2022 TDDW摘要手冊

2022 Taiwan Digestive Disease Week, TDDW

Chairman’s Lecture

CURRENT TREND IN ANTIVIRAL THERAPY FOR HBEAG-NEGATIVE CHRONIC HEPATITIS B

Rong-Nan Chien

Liver Research Unit, Chang Gung Memorial Hospital and University College of Medicine, Taoyuan, Taiwan

Since active hepatitis B virus (HBV) replication is the key driver of hepatic necroinflammation and disease progression, the treatment aim of chronic hepatitis B (CHB) is to suppress HBV replication permanently to prevent hepatic decompensation, liver cirrhosis and/or hepatocellular carcinoma and prolong survival. Currently entecavir (ETV), tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide (TAF) are the first-line drugs of choice. ETV, TDF and TAF can suppress HBV DNA profoundly but have no direct action on cccDNA of the HBV-infected hepatocytes, hence continuing long-term therapy is usually needed to maintain HBV suppression, but the ultimate goal of HBsAg loss was rarely achieved (10 year 2%). In addition, long-term NUC therapy comes with several concerns such as increasing cost, medication adherence and loss-to-follow-up. Studies, mainly from Taiwan, have shown that finite NUCs therapy of two to three years in HBeAg-negative patients

is feasible, safe and has a great benefit of much increasing HBsAg loss rate up to 30%/5 year. These have led an emerging paradigm shift to finite NUC therapy in HBeAg-negative patients globally. However, off-NUC relapse with hepatitis B flares may occur and have a risk of decompensation or even life-threatening outcomes. Therefore, proper monitoring, assessment, and retreatment decisions are crucial to ensure safety. Ideally, retreatment should be not too late to ensure safety and also not too early to allow further immune response for further HBsAg decline toward HBsAg loss. Assessment using combined HBsAg/ALT kinetics during hepatitis flare is better than biochemical markers alone to make a right retreatment decision. The strategy of finite NUC therapy has set a benchmark of high HBsAg loss rate to be achieved by the new anti-HBV drugs which are under preclinical or early phase study.

Special Lecture (I)

NATURAL COURSE AND IMMUNOPATHOLOGY OF CHRONIC HEPATITIS B INFECTION

Chia-Ming Chu

Liver Research Unit, Chang Gung Memorial Hospital, Taipei, Taiwan

As a result of the dynamic interplay of complex interactions involving HBV, hepatocyte and host immune response, the natural course of chronic HBV infection consists of distinct phases, characterized and diagnosed on the basis of HBeAg/anti-HBe serology, serum HBV DNA levels, ALT levels and liver histology. Typically, chronic infection acquired perinatally consists of four chronological phases: the initial immune tolerance (IT) phase, followed by immune clearance or active (IA) phase, and finally, the low replicative inactive immune control (IC) phase. In a subset of inactive carriers, HBV may reactivate and trigger immune mediated liver injuries. This reactivation phase can also be viewed as a variant of IA phase. In adult-onset chronic infection, there is usually no or very short initial IT phase.

In the IT phase, HBcAg is mainly distributed in the nucleus, while HBsAg is diffusely distributed on the plasma membrane and also focally in the cytoplasm. In the ensuing IA phase, the distribution of HBsAg in liver is the same as in the IT phase, but nuclear HBcAg expression is significantly reduced, with concomitant increase in cytoplasmic HBcAg expression. In the IC phase, HBcAg cannot

be detected anywhere, and HBsAg is only widely distributed in the cytoplasm. Membrane HBsAg expression does not appear to correlate with hepatitis activity. Subcellular localization of HBcAg is closely related to liver inflammation and liver cell regeneration (Gastroenterology 1987;92:220-5; 1995;109:1926-32).

The long-term outcomes of chronic HBV infection vary by viral (HBeAg, HBsAg levels, HBV DNA levels, genotype, mutant, HCV/HDV superinfection), host (immune status, age, gender, race, diabetes, fatty liver, ALT levels, cirrhosis, family history) and environmental (aflatoxin, alcoholic drinking, smoking) factors, ranging from inactive carrier state to development of cirrhosis, hepatic decompensation and HCC. The cumulative lifetime incidences of cirrhosis and HCC are estimated to be 40% and 18%, respectively.

Finally, 0.5%–2.0% of HBV carriers per year show HBsAg loss. HBV DNA is very low or undetectable in serum with persistent HBV DNA and cccDNA in liver. HBsAg clearance is a very favorable event and deemed a functional cure of chronic infection.

Special Lecture (II)

LOOKING TO THE FUTURE OF GASTROINTESTINAL ENDOSCOPY – EXPECTATIONS FOR AI ENDOSCOPY –

Hisao Tajiri President, World Endoscopy Organization

Department of Innovative Interventional Endoscopy Research, Jikei University School of Medicine, Tokyo, Japan

How far have we progressed in endoscopic medicine to date and how will the future change in the next 10-30 years? Since the spring of 2020, the global spread of corona virus infections has forced us changes in the endoscopic medicine and the education systems, including the introduction of the Web. Even if the corona virus infections subside in the future, we anticipate that there will be changes not only in clinical scenes, but also in the nature of academic societies and endoscopic medicine.

Japan Gastroenterological Endoscopy Society (JGES) was established as Japan Gastrocamera Society in 1959. The society had a membership of only 280 at its establishment, but it has grown to over 35,000 members in 2022. JGES is dedicated to advancing patient care and welfare, by promoting digestive disease research through endoscopy, developing and advancing endoscopic practice. In 2015, JGES started Japan Endoscopy Database (JED) Project. The aim of this project is to construct a “dream” database to benefit both doctors and patients. This will realize an ambitious strategy to create the world’s leading database with approximately 14 million additional data every year when it is fully operational. By JED, we seek to take an initiative in the construction of infrastructure to conduct international joint research and we indeed have been promoting several researches of AIassisted endoscopy with JED.

The ongoing issues we are working on are as follows;

1) While Image-Enhanced Endoscopy (IEE) has spread and contributed to the standardization of diagnosis at the global level, we aim to further improve the quality. For that purpose, we will further enhance our educational programs not only in Asian countries but also in other countries around the world and further promote internationalization projects. 2) By advancing the spread of endoscopic

screening, we are constructing an efficient screening system to detect and diagnose many early cancers and provide minimally invasive therapy to more patients, and as a result, contribute to medical cost reduction. 3) With respect to endoscopic therapy for GI malignancies, innovation has occurred every 15 years with polypectomy, EMR, ESD and third space endoscopy. Soon there will be an emergence of new technologies that will transform future endoscopic treatment.

AI is, without any doubt, an attractive option for standardizing endoscopy, which is inherently imperfect due to human error. AI has the potential to improve the quality of endoscopy and standardize endoscopy practice. It is expected to be able to detect lesions, determine the precise diagnosis, and display the exact margin of the lesion. AI research is underway to guide treatment during ESD and so AI will support endoscopic treatment as well as endoscopic examination. Endoscopy intelligent system is under construction according to the workflow of the endoscopy screening, to solve the various issues in the present endoscopy system. Technology development for the next generation is in progress, and concepts for the use of AI and ICT, IoT technologies are under consideration. In addition to the fusion of expert human skills and machinery (robot technology), it is important to advance next-generation technologies that combine AI and information systems.

The future of digestive endoscopy is summarized in 3 points;

1) introduction of effective screening system by AI-CAD and Liquid biopsy,

2) the progress of endoscopic therapy such as AIassisted robotic endoluminal therapy and genomic medicine, and

3) expansion of remote medicine in anticipation of the post-corona era.

Special Lecture (III)

GUT-LIVER AXIS IN ALCOHOLIC LIVER DISEASE

Bernd Schnabl

Department of Medicine, University of California San Diego, La Jolla, CA, USA

Alcohol-associated liver diseases (ALD) are accompanied by changes in the intestinal bacterial microbiota, mycobiota and virome. The importance of intestinal dysbiosis for ALD has been shown by fecal microbiota exchange. Mice transplanted with stool from patients with alcohol-associated hepatitis develop increased experimental liver disease. The intestinal microbiota contributes to ALD via various mechanisms, such as increased intestinal permeability in a subset of patients, changes in tryptophan-derived indole metabolites and bile acids. Bacterial virulence factors are proteins or peptides encoded by bacterial genes that help the organisms colonize the intestine or mediate disease. We have recently demonstrated

that an exotoxin secreted by Enterococcus faecalis (E. faecalis) to cause hepatocyte death and liver injury in humanized mouse models of ethanolinduced liver disease. The presence of exotoxinpositive E. faecalis correlated with liver disease severity and mortality in patients with alcoholic hepatitis. Conversely, there is no correlation between liver disease and positivity for exotoxin secreted from E. faecalis in a cohort of patients with non-alcoholic fatty liver disease (NAFLD). Gut microbiome centered treatment approaches might be able to restore intestinal homeostasis and eubiosis. This could be achieved by using bioengineered bacteria, supplementing metabolites or phage therapy that can target specific bacteria.

Special Lecture (IV)

RECENT UNDERSTANDING OF IBD

John Chang

Department of Medicine, University of California San Diego, La Jolla, CA, USA

Inflammatory bowel disease (IBD) encompasses a spectrum of gastrointestinal disorders driven by dysregulated immune responses against gut microbiota. Emerging single-cell technologies have recently been used extensively to probe the dynamic protein and

transcriptomic patterns within a wide range of immune cell types in health and disease. I will discuss recent findings using human cells and mouse models that elucidate key components and cellular states of the peripheral and gastrointestinal mucosal immune systems in health and IBD.

Special Lecture (V)

PERSONALIZED MEDICINE BASED ON DEEP HUMAN PHENOTYPING

Eran Segal Department of Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot, Israel

Recent technological advances allow large cohorts of human individuals to be profiled, presenting many challenges and opportunities. I will present The Human Phenotype Project, a large-scale (>10,000 participants) deep-phenotype prospective longitudinal cohort and biobank that we established, aimed at identifying novel molecular markers with diagnostic, prognostic and therapeutic value, and at developing prediction models for disease onset and progression. Our deep profiling includes medical history, lifestyle and nutritional habits, vital signs, anthropometrics, blood tests, continuous glucose and sleep

monitoring, and molecular profiling of the transcriptome, genetics, gut and oral microbiome, metabolome and immune system. Our analyses of this data provide novel insights into potential drivers of obesity, diabetes, and heart disease, and identify hundreds of novel markers at the microbiome, metabolite, and immune system level. Overall, our predictive models can be translated into personalized disease prevention and treatment plans, and to the development of new therapeutic modalities based on metabolites and the microbiome.

Special Lecture (VI)

HOW TO MANAGE REFRACTORY GERD ON 2022?

Edoardo Savarino

Division of Gastroenterology, Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy

Gastroesophageal reflux disease (GERD) is one of the most common gastrointestinal disorders, with a prevalence of 25-30% in Western Countries. Proton pump inhibitors (PPIs) are effective in mucosal heling and causing symptom relief in most cases, although up to 40% of GERD patients do not respond adequately to PPI therapy. Refractory GERD (rGERD) is one of the most challenging problems in clinical practice, given its impact on the quality of life and consumption of health care resources. The definition of rGERD is a controversial topic as it has not been unequivocally established. Indeed, patients who experience symptoms potentially related to GERD not responding to PPI therapy may not have GERD; in this case the definition could be replaced with “reflux-like PPI-refractory symptoms.” Patients with persistent reflux-like symptoms should undergo a diagnostic workup aimed at finding objective evidence of GERD through endoscopic (ie. Erosive esopgitis grade B-C-D or Barrett’s esophagus) and pH-impedance investigations (ie. increased esophageal acid exposure, abnormal mean nocturnal impedance baseline, positive symptom association analysis). The management strategies regarding rGERD, apart from a careful check of patient’s compliance with PPIs, a possible change in the timing of their administration and the choice of a PPI with a different metabolic pathway, include other pharmacologic treatments. These include histamine-2 receptor antagonists (H2RAs), alginate-based compounds, mucosal protective agents, potassium competitive acid blockers (PCABs), prokinetics, gamma aminobutyric acid-B (GABA-B) receptor agonists and pain modulators. If there is no benefit from medical therapy, but there is objective evidence of GERD, invasive antireflux options should be evaluated after having carefully explained the risks and benefits to the patient. The most widely performed invasive antireflux

option remains laparoscopic antireflux surgery, even if other, less invasive, interventions have been suggested in the last few decades, including endoscopic transoral incisionless fundoplication (TIF), magnetic sphincter augmentation (LINX) or radiofrequency therapy (Stretta). Due to the different mechanisms underlying rGERD, the most effective strategy can vary, and it should be tailored to each patient.

References:

1. Savarino E, de Bortoli N, De Cassan C, et al. The natural history of gastro-esophageal reflux disease: a comprehensive review. Dis Esophagus. 2017 Feb 1;30(2):1-9.

2. Savarino E, Zentilin P, Savarino V. NERD: an umbrella term including heterogeneous subpopulations. Nat Rev Gastroenterol Hepatol. 2013 Jun;10(6):371-80.

3. Zerbib F, Bredenoord AJ, Fass R, Kahrilas PJ, Roman S, Savarino E, Sifrim D, Vaezi M, Yadlapati R, Gyawali CP. ESNM/ANMS consensus paper: Diagnosis and management of refractory gastro-esophageal reflux disease. Neurogastroenterol Motil. 2021 Apr;33(4):e14075.

4. Kahrilas PJ, Savarino E, Anastasiou F, Bredenoord AJ, Corsetti M, Lagergren J, Mendive J, Nelson S, Roman S, Zerbib F, Hungin P. The tapestry of reflux syndromes: translating new insight into clinical practice. Br J Gen Pract. 2021 Sep 30;71(711):470-473.

5. Rettura F, Bronzini F, Campigotto M, Lambiase C, Pancetti A, Berti G, Marchi S, de Bortoli N, Zerbib F, Savarino E, Bellini M. Refractory Gastroesophageal Reflux Disease: A Management Update. Front Med (Lausanne). 2021 Nov 1;8:765061.

Special Lecture (VII)

MULTIOMICS FINDING OF HOST-MICROBE BIOMARKER FOR INFLAMMATORY BOWEL DISEASE

John Kao

Division of Gastroenterology & Hepatology, Department of Internal Medicine, University of Michigan, Ann Arbor, MI, USA

Inflammatory bowel disease (IBD) is a chronic inflammatory disease of the intestine associated with genetic susceptibility and alterations in the intestinal microbiome. Multiomics data developed and analyzed over the last several decades have yielded an unprecedented amount of genetic and microbial data. But how do we pinpoint mechanistic insight into the host-microbe relationship that will ultimately enable better care for patients with IBD?

Our recent work undertook a major decoding effort to decipher this multiomic data matrix. We analyzed anonymized data from more than 2800 individuals to discover a link between heterozygous carriers of deleterious DUOX2 variants and high levels of plasma IL-17C. These findings provide an example of how harnessing big data can drive mechanistic discovery to define disease biomarkers that have the potential to improve clinical care in IBD.

State-of-the-Art Lecture

NATIONAL POLICY AND ACHIEVEMENT OF HEPATITIS B AND C ELIMINATION IN TAIWAN

Chien-Jen Chen

Genomics Research Center, Academia Sinica, Taipei, Taiwan

Both hepatitis B virus (HBV) and hepatitis C virus (HCV) are major etiological factors for hepatocellular carcinoma (HCC) and endstage liver disease (ESLD) in Taiwan. The seroprevalence of HBV surface antigen (HBsAg) was 15-20% in Taiwan in late 1970s, while the seroprevalence of antibody against HCV (antiHCV) varied significantly from <1% to >20% among 358 townships/districts in Taiwan in mid2010s. Clinical trials on immunization of newborns with hepatitis B vaccine and immunoglobulin in early 1980s showed a high efficacy to prevent the development of persistent HBsAg carrier status in immunized newborns in Taiwan. National hepatitis B immunization program in Taiwan was launched in 1984. The vaccination coverage was over 90% after 1989. There has been a significant reduction (>80%) in HBsAg seroprevalence, infant fulminant hepatitis mortality, HCC incidence and mortality, and ESLD mortality in vaccinated birth cohorts. REVEAL Study has revealed several long-term risk predictors of HCC and cirrhosis for patients with chronic HBV or HCV infection in Taiwan. These predictors have been integrated to develop HCC

or cirrhosis risk calculators for patients with chronic viral hepatitis in Taiwan. The HCC risk calculators for chronic hepatitis B patients (REACH-B scores) have been internationally validated. Many clinical trials have documented the efficacy of antiviral therapy to reduce HCC risk among patients with chronic infection of HBV and/or HCV in Taiwan and other countries. National viral hepatitis therapy program in Taiwan was launched in 2003. Eligible viral hepatitis patients have received antiviral therapy completely reimbursed by National Health Insurance Administration. There has been a significant reduction (40%) in HCC incidence and mortality and ESLD mortality after the launch of the antiviral therapy program. National Hepatitis C Program (NHCP) was launched in 2017 with the aim to eliminate hepatitis C in Taiwan in 2025 through the mass screening, direct-acting antivirals (DAA) treatment, and reinfection prevention of chronic hepatitis C patients. In a recent analysis, there is a continuous reduction in mortality from HCC and ESLD in Taiwan which may be attributable to HBV vaccination and antiviral therapy of patients with chronic infection of HBV or HCV.

Prof. Teh-Hong Wang Memorial Lecture

MANAGEMENT OF COLORECTAL T1 (SM) CARCINOMA –CURRENT STATUS AND FUTURE PERSPECTIVE

Shinji Tanaka Department of Endoscopy, Hiroshima University Hospital, Hiroshima, Japan

Recent progress of colonoscopy and pathologic analysis based on the accumulation of many cases with SM colorectal carcinoma (CRC) have enabled the extension of the indication of endoscopic resection for SM CRC. Even for SM deep invasive CRC, if there are no other lymph node (LN) metastatic risk factors, LN metastatic risk after complete endoscopic resection is only about 1.3%. At present, the endoscopic complete resectable condition should be clarified in order to select the SM deep invasive CRC indicative for endoscopic resection.

Magnification and image-enhanced endoscopy (IEE) are useful in invasion depth diagnosis of early CRC. However, as the Japan NBI Expert Team (JNET) classification Type 2B includes the various histological lesions from LGD to SM-d lesion, therapeutic decisions are complicated. Moreover, Japanese Society for

Cancer of the Colon and Rectum (the 9th edition) states that “the risk of local recurrence might be low in cases of endoscopically resected SM CRC with the tumor vertical margin (VM) ≥500 μm”. Thus, the tumor-front to VM distance in the resected specimen has been focused. Recently we clarified the clinical significance of tumor free submucosal layer in endoscopic ultrasonography (EUS) for pathological VM in cases with colorectal endoscopic submucosal dissection (ESD) categorized as JNET Type 2B. In our proposal, the distance from the tumor-front to the muscle layer on EUS was defined as the tumor-free distance (EUS-TFD) and classified as follows: Type A (EUSTFD ≥1 mm) and Type B (EUS-TFD <1 mm). In my lecture, I will introduce the clinical significance of this new concept “EUS-TFD” including the recent progress and consensus about the management of SM CRC.

Prof. Juei-Low Sung’s Research Foundation 35th Annual Academic Meeting

DEVELOPMENT OF ANTI-CANCER AGENTS TARGETING THE MECHANISTICS OF IL-17B/IL-17RB DOWNSTREAM ONCOGENIC SIGNALING TO TREAT PANCREATIC CANCER

Heng-Hsiung Wu

The Program for Cancer Biology and Drug Discovery, China Medical University, Taichung, Taiwan

Interleukin 17 (IL-17) and its receptor (IL-17R) members play important roles in regulating proinflammatory responses. Among them, IL-17RB will form a heterodimer with IL-17RA after binding to IL-17E, thereby activating the Th2-mediated immune response of immune cells. In turn, the deletion of IL-17E or IL-17RB gene expression will impair Th2-mediated immune response and lead to infectious diseases.

Pancreatic cancer is the seventh leading cause of cancer death in Taiwan (MOHW 2020), and its five-year survival rate is only about 6%, indicating that research to find new therapeutic targets for pancreatic cancer is crucial. Our previous work has demonstrated the oncogenic role of IL-17B/IL-17RB in pancreatic tumors, and IL-17RB monoclonal antibody treatment can block tumor metastasis and prolong survival in mice with pancreatic cancer. These results suggest that IL17RB-targeted therapy is particularly effective in the treatment of pancreatic cancer (Wu et al., JEM 2015). However, systemic inhibition of IL-17RB leads to immunodeficiency, so we plan to further understand the molecular basis that initiates IL-

17B/IL-17RB oncogenic signaling to develop anticancer drugs that are more tumor-specific and do not affect normal immune responses.

Both IL-17B and IL-17E are the ligands of IL17RB. However, distinct from IL-17E which induces IL-17RA/IL-17RB to form heterodimers on Th2 cells, IL-17B induces IL-17RB homodimerization to enhance the malignancy of pancreatic cancer cells, because IL-17RB homodimers allow MLK4 binding to IL-17RB and phosphorylating tyrosine 447 of IL-17RB (P-Y447). In clinics, high expression of P-Y447 in pancreatic tumors is significantly associated to higher tumorigenicity and prevalence of post-operative metastasis. In turn, decreasing P-Y447 level through abrogating the interaction between IL-17RB and MLK4 could suppress pancreatic tumor progression to extend the lifespan of tumor-bearing mice without systemic effects on Th2 immunity (Wu et al., STM 2021). These results provide a feasible direction to develop anticancer drugs with high tumorspecificity for treating pancreatic tumors with high IL-17RB expression.

Prof. Juei-Low Sung’s Research Foundation 35th Annual Academic Meeting

COLORECTAL CANCER PREVENTION DISRUPTED BY COVID-19

PANDEMIC

Hsiu-Hsi Chen Institute of Epidemiology and Preventive Medicine, National Taiwan University, Taipei, Taiwan

In parallel with the evolution of COVID-19 pandemic as of March 2020, colorectal cancer prevention has been disrupted by a series of largescale outbreaks around the world. The current topic will begin with the presentation of health loss attributed to the disruption of colorectal cancer prevention care caused by COVID-19 pandemic. The respective short-term and long-term impacts of COVID-19 pandemic on preventive care for colorectal cancer will be shown with the framework of synthesis science integrating primary, secondary, and tertiary prevention as a whole. The machine learning such as dynamic Bayesian network (DBN) will be proposed for relating the primary prevention, screening, and treatment process to the yields and the effectiveness of preventive care amenable to

the underlying multistate disease natural history of colorectal neoplasm. The presentation of combining the proposed DBN with the Markov decision tree model will be given to assess how to minimize the loss affected by COVID-19 pandemic with different salvage decision strategies. The demonstration will be given to minimize the reduced long-term effectiveness attributed to the procrastinated screening and treatment schedule affected by COVID-19 pandemic and also to evaluate the possible reduced harm with the adaptation of precision prevention strategies, such as prioritize the referral by the cutoff of feacal hemoglobin concentration as a result of feacal immunochemical test using Taiwan colorectal cancer screening program as scenario.

Prof. Juei-Low Sung’s Research Foundation 35th Annual Academic Meeting

IMPACT OF COVID-19 ON INFLAMMATORY BOWEL DISEASES (IBDS)

Shu-Chen Wei Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan

Although COVID-19 is widely known for the hallmark respiratory symptoms, it also impacts the gut, causing gastrointestinal tract inflammation and diarrhea. COVID-19’s GI symptoms may be due to the high intestinal expression of angiotensin converting enzyme-2 receptors, which are for the binding of SARS-CoV-2 viral particles. Previous study showed that 48.1% of COVID-19 patients expressed viral SARS-CoV-2 mRNA in their stool. Given that the GI tract is a target tissue affected by COVID-19, this causes concern for those with

underlying GI pathologies, such as inflammatory bowel disease (IBD). Moreover, IBD patients often receive the treatment with immunosuppressive effects, which resulting in more concern about the risk of infection, prognosis after infection, and how to manage the IBD patients from diagnosis to treatment during the pandemic stage. During this presentation, we will discuss the above issues with the latest evidence. We will also share some study results from Taiwan about the impact of COVID-19 on IBD.

Prof. Juei-Low Sung’s Research Foundation 35th Annual Academic Meeting

THE IMPACT OF THE COVID-19 EPIDEMIC ON THE CONTROL OF VIRAL HEPATITIS GLOBALLY AND IN TAIWAN

Ming-Lung Yu

College of Medicine, National Sun Yat-Sen University, Kaohsiung, Taiwan Kaohsiung Medical University, Kaohsiung, Taiwan

In 2016, the World Health Organization (WHO) Global Health Sector Strategy (GHSS) on viral hepatitis set an ambitious goal for the global elimination of viral hepatitis B and C as a public health threat by 2030 – a 90% reduction in the incidence of viral hepatitis and a 65% reduction in viral-hepatitis-related mortality by 2030, compared with a 2015 baseline. Since the announcement by WHO, many academic, civil societies and governments are dedicated themselves on the track toward the elimination goals of viral hepatitis. Unfortunately, the outbreak of COVID-19 in early 2020 and the continuously pandemic worldwide have greatly impacted the global society, including the economy, transportation, communication, social behavior as well as health.

A recent large-scale investigation collected data from 32 European and 12 non-European clinical centers demonstrated that viral hepatitis

elimination programs have been held back by the COVID-19 pandemic. Each care cascade for HBV control decreased significantly during the pandemic of COVID-19, 26%-32% decrease in chronic HBV consultations, by 38%-39% decrease in new HBV referrals, 9%-30% decrease in HBV diagnosis and assessment, and 20%-44% in new HBV treatments. For HCV control there were 39%-50% for consultations, 49%-49% for new referrals, 11% -38% for diagnosis, and 51%-54% for antiviral treatments. COVID-19 pandemic has impacted in the disruptions to infrastructure, supply chains, services and interventions for viral hepatitis, leading to a long-term complications and onward transmission to future generations. Effective strategies are urgent needs to overcome the threat in the progress towards the goals of 2030 elimination.

Symposium (I)

COMPLICATED ACUTE CHOLECYSTITIS

TOKYO GUIDELINES 2018: DIAGNOSTIC CRITERIA AND SEVERITY GRADING OF ACUTE CHOLECYSTITIS

Jiann-Hwa Chen

Division of Gastroenterology & Hepatology, Department of Internal Medicine, Taipei Tzu Chi Hospital, Taipei, Taiwan

The Tokyo guidelines is to propose diagnostic criteria and severity assessment of acute cholecystitis, based on a systematic review of the literature and a consensus of experts, conducted initially in 2006 and published in 2007 as TG07. That validation study found that the sensitivity and specificity of a definitive diagnosis according to TG07 were 84.9% and 50.0%, respectively, whereas Murphy’s sign was of 20.5% sensitivity and 87.5% specificity. The authors pointed out that further improvement was required in the specificity of the diagnostic criteria for definitive diagnosis. Instead of changing the factors used for assessment, after thorough discussion, new diagnostic criteria led to the decision to change

the criteria by designating the presence of local and systemic signs of inflammation as indicating a suspected diagnosis. No major problems with the use of the TG07 severity assessment criteria had been reported and no new evidence was available; therefore, the severity assessment criteria were adopted unchanged in TG13. However, some studies found that severity grading plays a useful role in predicting vital prognosis, and others such as the length of hospitalization and the laparotomy conversion rate were significantly higher in more severe cases. The present revision (TG18) provides new information on diagnostic imaging in relation to diagnosis and severity grading.

Symposium (I)

COMPLICATED ACUTE CHOLECYSTITIS

THE COMPLEMENTARY ROLES OF IMAGING STUDIES IN COMPLICATED ACUTE CHOLECYSTITIS

Kao-Lang Liu

Department of Medical Imaging, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan

In this speech, I will focus on the pictorial essay of the complicated acute cholecysitis, in our own clinical practice and experience, including the CT findings of acute cholecysitis, complicated

cholecystitis, gallstone related Mirizzi syndrome, gallstone ileus, CBD stone and other mimicking as cholecystitis, such as adenomyomatosis.

Symposium (I)

COMPLICATED ACUTE CHOLECYSTITIS

SURGICAL MANAGEMENT OF PATIENTS WITH COMPLICATED ACUTE CHOLECYSTITIS

Shu-Hung Chuang

Division of General and Digestive Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan

Acute cholecystitis, one of the most common acute abdominal diseases, was a relative contraindication for minimally invasive cholecystectomy in the early laparoscopic era. It is related to procedural conversion from laparoscopy to open surgery and bile duct injury. Nevertheless, various modified laparoscopic techniques have been introduced to manage complicated cholecystitis, such as gallbladder decompression, meticulous dissection with a suction irrigation device, subtotal/partial cholecystectomy, fundus-

first cholecystectomy, and intracorporeal suturing. Nowadays, laparoscopic cholecystectomy is the gold standard surgery for acute cholecystitis even in complicated situations. Herein we show several video clips of laparoscopic surgery to treat difficult cases, including gangrenous cholecystitis, gallbladder empyema, liver abscess, biliary peritonitis, cholecystoenteric fistula, and Mirizzi syndrome type I. The procedures were carried out by single or multiple-incision approaches.

Symposium (I)

COMPLICATED ACUTE CHOLECYSTITIS

THE ROLE OF PERCUTANEOUS CHOLECYSTOSTOMY TUBE FOR ACUTE CHOLECYSTITIS

Shang-Yu Wang

Department of Surgery, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan

Percutaneous cholecystostomy (PC) has become an important procedure for treating acute cholecystitis (AC). PC is currently applied for patients who cannot undergo immediate laparoscopic cholecystectomy (LC). The efficacy and safety of PC tubes have been proved. Current clinical guidelines, such as Tokyo Guidelines 2018 (TG 18) and the World Society of Emergency Surgery (WSES) guidelines, placed PC as a treatment option for patients with AC.

After successful treatment of acute episode and resolution of acute inflammation, patients who can tolerate anesthesia and the surgical risk were suggested to undergo interval laparoscopic intended cholecystectomy as a definitive treatment,

without interval LC, a high incidence of recurrence can be expected.

While it is a straightforward strategy, “PC, then to interval LC”, there are several interesting issues that may be encountered by a clinician during the clinical course. These issues include techniques regarding PC placement, the natural course of patients undergoing PC without interval LC, the indications for cholangiography via PC, and the timing of interval LC. We will present a concise summary of several issues as mentioned above and will focus on the optimal timing of interval LC for definitive treatment after temporary PC application. Current evidence from the literature and experience of our institute will be presented.

Symposium (I)

COMPLICATED ACUTE CHOLECYSTITIS

THE ROLE OF ERCP TREATMENT IN COMPLICATED ACUTE CHOLECYSTITIS

Chi-Huan Wu

Division of Gastroenterology & Hepatology, Department of Internal Medicine, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan

Acute cholecystitis is the most common complication of biliary stone disease. The standard for treating acute cholecystitis is surgical cholecystectomy. Endoscopic retrograde cholangiopancreatography (ERCP) plays a great role in the treating lesion in common bile duct. In patient with acute cholecystitis who are also complicated with common bile duct stones, ERCP

could facilitate common bile duct stones removal before or after cholecystectomy. Beyond the common bile duct stones removal, ERCP could provide some diagnostic and therapeutic tools in complicated acute cholecystitis. We will focus on endoscopic therapies for gallbladder drainage and diagnostic or treatment of Mirizzi syndrome during this part of the presentation.

Symposium (I)

COMPLICATED ACUTE CHOLECYSTITIS

HOW TO PREVENT SURGICAL COMPLICATIONS IN COMPLICATED ACUTE CHOLECYSTITIS

Yu-Yin Liu

Division of General Surgery, Department of Surgery, Kaohsiung Chang Gang Memorial Hospital, Kaohsiung, Taiwan

The laparoscopic cholecystectomy (LC) was the standard treatment for gallbladder disease. The complications of LC still could not be prevented even this popular surgery especial acute cholecystitis. In acute cholecystitis, the anatomy would be misunderstood by inflammatory change. So severe procedure were developed to increased the successful rate, such as critical view, up to

down dissection, intraoperative cholangiography and near-infra red fluorescent cholangiography. The purpose of those technique was tried to prevent common bile duct injury. The emergent technology for artificial intelligence was also introduced to critical zone identification. We would review the current methods of acute cholecystitis treatment to prevent surgical complication.

Symposium (II)

ECONOMICAL APPRAISAL OF GI PRACTICES

STATE-OF-THE-ART LECTURE

HEALTH ECONOMICS IN THE FIELD OF GASTROENTEROLOGY

Uri Ladabaum

Division of Gastroenterology and Hepatology, Stanford University School of Medicine, Stanford, CA, USA

Health economic evaluations seek to understand the balance between clinical outcomes and economic expenditures. Common forms of analyses include cost-effectiveness, costbenefit, and cost-minimization analyses. These can range from simple analyses with short-term time horizons and very specific, non-generalizable measures of outcome, to complex modeling studies that synthesize available literature, include assumptions, extrapolate to long-term time horizons, and measure outcome with a metric that

can be used across diverse health conditions (e.g. life-years gained or quality-adjusted life-years gained). Standards for methodology have been published and will be reviewed. Key components of health evaluations include the perspective, the range of clinical outcomes, clinical journeys and costs that are considered, and sources informing inputs. The aims of a health economic evaluation can include to inform policy or future research. Specific applications in Gastroenterology will be discussed.

Symposium (II)

ECONOMICAL APPRAISAL OF GI PRACTICES

MASS ERADICATION OF HELICOBACTER PYLORI TO PREVENT GASTRIC CANCER: THE ROLE OF COST-EFFECTIVENESS ANALYSES

Yi-Chia Lee

Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan

Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan

Gastric cancer is an inflammation-related cancer triggered by Helicobacter pylori infection. Understanding of the natural disease course has prompted the hypothesis that gastric cancer can be prevented by administering a short-course antibiotic treatment to eradicate the H. pylori infection and interrupt this carcinogenic cascade. Results from randomized controlled trials and cohort studies have repeatedly confirmed this concept, which has moved attention from individual management of H. pylori infection to population-wide implementation of screening programs. Such a paradigm shift follows a threetier architecture. First, healthcare policy-makers determine the most feasible and applicable eligibility, invitation, testing, referral, treatment, and evaluation methods for an organized screening

program to maximize the population benefits and, most importantly, the cost-effectiveness. Second, provision of knowledge and effective feedback to frontline general practitioners, including choice of diagnostic tests, selection of eradication regimens, and the indication of endoscopic examination, ensures the quality of care and increases the likelihood of desired treatment responses. Third, initiatives to raise population awareness are designed regarding the impact of H. pylori infection and risky lifestyle habits on the stomach health. These programs, with increased accessibility and geographic coverage, will accelerate the decline in morbidity, mortality, and associated costs of this preventable malignancy. In this presentation, the role of cost-effectiveness analysis on the policy implementation will be demonstrated.

Symposium (II)

ECONOMICAL APPRAISAL OF GI PRACTICES

RETHINKING MANAGEMENT OF HEPATITIS: COSTEFFECTIVENESS PERSPECTIVES

Tsung-Hui Hu

Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan Medical School, Chang Gung University, Taoyung, Taiwan

Taiwan government has set an ambitious target of achieving 80% of treatment coverage for the patients with HCV by the year 2025. we selected a demonstration region, Changhua County, which is located in the central part of Taiwan, has 27 townships comprising a total of 1,289,000 residents. We developed a novel integrated model of HCV treatment delivery by combining the microelimination approach for special and general populations of patients since 2019 in Changhua county, led by the county’s health authority. The achievement of HCV micro-elimination: defined as the definition of HCV elimination by WHO criteria as diagnosis more than 90% and treatment more than 80% of the population. Until now, micro-elimination was achieved in four special populations, including

dialysis patients in 31 hemodialysis centers; HIV infected patients in five responsible hospitals; intravenous drug addicts with replacement therapy in five responsible hospitals; and prisoners. We are also going to achieve micro-elimination of diabetes or chronic kidney disease in 92175 patients in the near future. It is expected to accelerate the achievement of hepatitis C eradication via the novel and cost-effective community model established in this project. After the elimination of HCV, we plan to construct the Markov decision models to estimate the accumulated cost and effectiveness in terms of life years to evaluate the preventive strategies. The evaluation of the independent and incorporated approaches cancers and nonmalignant chronic liver disease will be conducted.

Symposium (II)

ECONOMICAL APPRAISAL OF GI PRACTICES

TOP-DOWN OR STEP-UP USE OF BIOLOGICS FOR INFLAMMATORY BOWEL DISEASES?

Chia-Hung Tu Health Management Center; Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan

In the last twenty more years the medical therapy for inflammatory bowel disease (IBD) has been dramatically improved by the advent of biologically engineered monoclonal antibodies targeted at specific inflammatory mediators that interfere with persistence of inflammatory mechanisms. Biologic agents are different from conventional drugs including mesalamine, corticosteroid, or immunosuppressant, by the capability of inducing remission of refractory inflammation, deeper healing of mucosal damage, maintenance of therapeutic achievement, and benefit in terms of long-term outcome. However, along with the rapid emergence of multiple biologic choices in real practice over most parts of the world, cost benefit issues become apparent. Aside from therapeutic gain, tremendous economic burden of

biologic therapy needs to be weighed against the limit of medical care resource and the very-likely existence of unnecessary extension of biologic use for maintenance therapy. In the presentation, the lately published studies addressed on this issue will be summarized. The focuses are the current scale of economic problems associated with biologics for IBD, and how likely the costbenefit ratio could be influenced by optimization of therapeutics, particularly by personalized decision-making on between top-down and stepup approaches when it comes to timing of biologic use in relation to more conventional agents. Finally the opportunity of more flexible strategy on long-term extension therapy while maintaining the success of initial achievement of anti-inflammation will be discussed.

Symposium (II)

ECONOMICAL APPRAISAL OF GI PRACTICES

EMERGING COST-EFFECTIVENESS ISSUES IN CRC SCREENING

Yu-Min Lin

Division of Gastroenterology, Department of Internal Medicine, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan

Implementation of Cancer Screening in the population usually requires considerable investment in equipment, personnel and information technology. This can strain a health system and potentially leading to greater inequalities. Accordingly, the cost-effectiveness of screening programs should be seriously evaluated.1

Current CRC screening guidelines recommend people at average risk get a colonoscopy, sigmoidoscopy, FIT or other test starting at age 45. Although abundant evidence indicates that colorectal cancer screening was cost-effective or even cost-saving compared with no screening,2,3 there are several challenging issues arising in the status quo:

• Precision CRC screening: Current onesize-fits-all method of identifying colorectal cancer is not perfect. Several recent reports combine environmental, lifestyle, metabolic and genetic information to create more tailored risk-prediction models. Though the concept of precision screening is charming, their applications in the public health system should be determined prospectively.

• New screening tests: Different types of invasive or non-invasive tests/strategies have been developed for CRC screening. There is controversy evidence about whether these tests or strategies are cost-effective compared with current screening programs. Do the new tests work well? There are more questions than answers, and their performance should be validated in the future.

• Other concerns: There are several unmet needs of current CRC Screening programs.

 The uptakes of the screening tests in the population remained have much room for improvement.

 The funding or payment models of CRC screening should be revised. Traditional feefor-service (FFS) model may not be costeffective. FFS model does not pay much attention to the quality of health delivery. Implementation of value-based payment model should be evaluated.

• Strategies in the future: Reallocation of the resources (such as funding, time or manpower) and creation of “learning screening programs” may improve the cost-effectiveness of the CRC screening. Patients enrolled in learning screening programs agree to be randomized into testing arms that assess different tests, intervals, or thresholds to identify the optimal screening test that improves population mortality without overdiagnosing patients for additional treatment.4

Reference:

1. Screening programmes: a short guide. Increase effectiveness, maximize benefits and minimize harm. Copenhagen: WHO Regional Office for Europe; 2020.

2. Effectiveness of Fecal Immunochemical Testing in Reducing Colorectal Cancer Mortality From the One Million Taiwanese Screening Program.

Han-Mo Chiu et al. Cancer, September 15, 2015, VOL 121, ISSUE 18.

3. Reducing the Burden of Colorectal Cancer: AGA Position Statements.

David Lieberman et al. Gastroenterology, June 14, 2022.

4. Improving cancer screening programs

- Evaluating diagnostic tests in learning screening programs could improve public health.

Mette Kalager and Michael Bretthauer. Science, January 10, 2020, VOL 367 ISSUE 6474.

Symposium (III)

MULTI-DISCIPLINARY APPROACHES FOR NAFLD/MAFLD

NAFLD VS. MAFLD: WHICH ONE IS BETTER FOR CLINICAL IMPLICATION?

Chia-Chi Wang

Department of Internal Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taipei, Taiwan School of Medicine, Tzu Chi University, Hualien, Taiwan

Non-alcoholic fatty liver disease (NAFLD) is the commonest cause of chronic liver disease in Western countries and its prevalence continues to increase in parallel with the epidemic of obesity and diabetes. It is an exclusive diagnosis without pointing out the underlying causes in nomenclature. Furthermore, it was easily misunderstanding due to the term of “non alcohol” for patients. A meeting organized by European liver patient’s association (ELPA) and European commission in 2018 proposed the disease name being changed from NAFLD to metabolic (dysfunction) associated fatty liver disease (MAFLD). In 2020, another international consortium of the 32 experts from 22 countries all over the world was convened to re-define the diagnostic criteria of MAFLD and

its spectrum of heterogeneity. The criteria are based on the evidence of hepatic steatosis by either imaging or histologic examinations, plus any of the following three conditions: overweight/ obesity, presence of type 2 diabetes mellitus (T2DM), or evidence of metabolic dysfunction. Due to the re-definition of MAFLD diagnosis, it has similar but different population compared with those of NAFLD. Thus, it should be considered as a brand new disease. This talk will discuss the shared features and potential differences between MAFLD and NAFLD in epidemiology, diagnosis, and the impacts on the funding and design of further clinical trials and studies. Finally, we will provide the benefits and shortcoming of the new nomenclature “MAFLD” compared with NAFLD.

Symposium (III)

MULTI-DISCIPLINARY APPROACHES FOR NAFLD/MAFLD

PHARMACOLOGIC THERAPY FOR NAFLD: AN UPDATE

Kuei-Chuan Lee

Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan

Department of Medicine, National Yang-Ming University School ofMedicine, Taipei, Taiwan

Non-alcoholic fatty liver disease (NAFLD) has been the most prevalent chronic liver disease in the world. The treatment includes life style modification, non-pharmacologic therapy, and pharmacologic therapy. The pharmacological agents predominantly target the following four mechanisms: (1) hepatic fat accumulation; (2) oxidative stress, inflammation, and apoptosis;

(3) gut-liver axis; and (4) hepatic fibrosis. In this talk, I will introduce new clinical trials in NAFLD including PPAR agonists, GLP1 agonist, FGF19 analogue, FGF21 analogue, ACC inhibitor, SCD1 inhibitor, selective thyroid hormone receptor-β agonist, Selonsertib, berberine ursodeoxycholate, FXR agonist, emricasan, belapectin and some experimental pharmaceutics for NAFLD.

Symposium (III)

MULTI-DISCIPLINARY APPROACHES FOR NAFLD/MAFLD

NON-PHARMACOLOGIC THERAPY FOR NAFLD: AN UPDATE

Ming-Ling Chang

Department of Gastroenterology and Hepatology, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan

Non-alcoholic fatty liver disease (NAFLD), defined by the non-alcoholic nature in the presence of fatty liver, is now considered the most common chronic liver disease worldwide. Individuals with NAFLD exhibited an increased risk of all-cause mortality driven by cardiovascular disease, extrahepatic cancers and liver diseases, particularly those with hepatic fibrosis. Multiple components and risk factors are thought to be

involved in the pathogenesis of NAFLD. Optimal therapy has not yet been found, but many advances have been made with the discovery of potential therapeutic options. A comprehensive update of upcoming treatment options for NAFLD, with a focus on non-pharmacologic therapy including lifestyle modifications (weight loss, dietary changes, physical exercise and cognitive-behavior therapy) and bariatric surgery is highlighted.

Symposium (III)

MULTI-DISCIPLINARY APPROACHES FOR NAFLD/MAFLD

INNOVATIVE THERAPY FOR NAFLD/MAFLD: PRECISION MEDICINE AND GUT MICROBIOTA

Bernd Schnabl Department of Medicine, University of California San Diego, La Jolla, CA, USA

The gut microbiota is linked to a wide range of diseases including not only luminal diseases such as inflammatory bowel disease, but also extraintestinal liver diseases such as non-alcoholic fatty liver disease (NAFLD). The prevalence of NAFLD is rising amid a worldwide increase in obesity and metabolic syndrome. NAFLD is considered a metabolic liver disease and driven by an accumulation of energy substrates in the liver. NAFLD is dependent on the gut microbiota, since

the phenotype is transmissible by fecal microbiota transfer in preclinical models. Dysbiotic microbiota changes and microbial derived metabolites have been implicated in disease mechanism. In this presentation, we cover the contribution of the gut microbiota to NAFLD and how different microbial mediators contribute to a similar metabolic outcome in the liver. Our aim is also to highlight therapeutic options that will modulate the intestinal microbiota and thereby improve hepatic metabolism.

Symposium (IV)

UPDATE OF HCC THERAPY IN 2022

CURRENT BEST OPTION OF SYSTEMIC THERAPY IN HCC

Masatoshi Kudo Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka, Japan

In advanced stage hepatocellular carcinoma (HCC), atezolizumab plus bevacizumab combination therapy (Atezo/Bev) is the best option among the 1st line treatment regimen in terms of prolonging overall survival, prolonging progression free-survival and high objective response rate (30% per RECIST 1.1). In addition, Atezo/Bev provide good quality of life and preserve liver function. However, intermediate-stage HCC, the goal of treatment is a cancer free and drug free status. Therefore, upfront systemic therapy followed by curative conversion is the treatment choice.

TACE has been the standard of care for intermediate-stage HCC until recently. However, this was based on evidence from a meta-analysis of 6 randomized controlled trials in which patients treated with TACE were compared with patients who did not receive therapy. Although 6 effective drugs are currently available, the data are insufficient to determine whether TACE or upfront systemic therapy followed by selective TACE, ablation, or resection after tumor necrosis and/or shrinkage has a greater overall survival (OS) benefit.

LEN-TACE sequential therapy was developed in proof-of-concept studies based on the marked prolongation of OS in patients with intermediatestage HCC beyond the up-to-seven criteria. OS was 37.9 months with upfront lenvatinib with subsequent selective TACE versus 21.3 months with TACE alone, indicating that LEN-TACE sequential therapy significantly improved OS (HR, 0.48; 95% CI, 0.16–0.79; p < 0.01). PFS, ORR per mRECIST, and preservation of liver function were also favorable in the lenvatinib-treated group. In addition, 5 of 30 patients (17%) who received LEN-TACE sequential therapy achieved cancer-free drug-free

status, indicating that this therapy can potentially achieve cure in patients with intermediate-stage HCC beyond the up-to-seven criteria. The results were reproduced in many other clinical studies, and LEN-TACE sequential therapy has become a well-established approach for TACE-unsuitable intermediate-stage HCC in Japan.

An ORR of 44% per RECIST v1.1 was achieved using Atezo/Bev combination therapy in patients with intermediate-stage HCC. This means that nearly one in two of these patients can potentially achieve curative conversion. Thus, in patients with intermediate-stage HCC receiving Atezo/Bev combination therapy, curative conversion must be implemented as soon as possible without hesitation upon achieving a sufficiently deep response instead of continuing the systemic therapy until progressive disease; real cure is not expected at this point. A pathological CR is rarely achieved with systemic treatment alone (e.g., lenvatinib or Atezo/ Bev); residual viable cancer is often found when resection is performed in patients who seemed to achieve CR according to mRECIST. In such cases, recurrence is most likely to occur when the systemic therapy is discontinued; to prevent this, curative conversion must be implemented whenever possible, even if imaging findings indicate CR or deep response. Of note, in patients who undergo resection as conversion surgery, bevacizumab needs to be discontinued at least 4–6 weeks before the procedure to prevent bleeding event, whereas a 3-week interval is sufficient when performing ablation or curative TACE. In either case, ABC conversion can be achieved in approximately 20–30% of patients with intermediate-stage HCC.

Symposium (IV)

UPDATE OF HCC THERAPY IN 2022

FUTURE PROMISING SYSTEMIC THERAPY IN HCC

Ann-Lii Cheng

President Emeritus, National Taiwan University Cancer Center, Taipei, Taiwan

In the wake of the success of atezo-bev, all sorts of combination therapy has emerged as a key focus. However, a breakthrough beyond atezo-bev has yet to be seen. Recently, the highly awaited results of ICI-TKI combination such as pembrolizumab/lenvatinib and ICI-ICI combination such as durvalumab/tremelimumab have only reported marginally supportive results. The combination of atezolizumab/cabozantinib has even reported a surprisingly negative result. The reasons for these failures are not known. However, a deep-dive research on the true mechanism of immunoregulatory effect of various ICIs and TKIs is mandatory.

Novel ICIs, such as ant-LAG3 and antiTIGIT, have recently reported promising activity in malignant melanoma and lung cancer, respectively, and are both under early clinical

trials in HCC. Antibody-drug conjugates (ADC) have exemplified surprising breakthrough in the treatment of HER-2 (+) breast cancer, triplenegative breast cancer, and urothelial cancer, are under preclinical studies in HCC. Bispecific T-cell engager (BiTE), has long been a part of our arsenals against hematologic malignancies, is currently under phase I trial in HCC. CAR-T has had tremendous success in hematologic malignancies, but encounters formidable obstacles in non-hematologic solid tumors. Nevertheless, around ten CRA-T trials are currently ongoing for the treatment of HCC. In addition, the combination of mRNA vaccination and CAR-T – CARVax, appears to offer a new hope for CAR-T technology. Systemic therapy for HCC is a dynamic and rapidly evolving field of research that holds great promise for the future.

Symposium (IV)

UPDATE OF HCC THERAPY IN 2022

UPDATE OF SURGICAL THERAPY IN HEPATOCELLULAR CARCINOMA 2022

Wei-Chen Lee

Department of General Surgery, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan

Hepatocellular carcinoma (HCC) is the most common primary liver malignancy. Although several treatment options are applied to treat HCC, surgical treatment remains the most effective and curable therapy. Surgical treatment includes liver resection and liver transplantation. Recent advance in liver resection includes surgical technique, prediction system for post-hepatectomy tumor recurrence, clinical trial of adjuvant therapy to prevent tumor

recurrence, etc. In liver transplantation, the efforts focus on down-staging of HCC to make liver transplantation possible.

The treatment of HCC has been changed greatly when immune checkpoint inhibitors were introduced to treat advanced HCC with promising effects. Surgical treatment is also altered and has to be updated.

Symposium (IV)

UPDATE OF HCC THERAPY IN 2022

UPDATE OF LOCAL ABLATION THERAPY: RFA, MWA, OR CRYOABLATION

Kai-Wen Huang

Department of Surgery & Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan

Center of Functional Image and Interventional Therapy, National Taiwan University Hospital, Taipei, Taiwan

Tumor ablation technology has evolved rapidly during the past several decades, with substantial technical and procedural improvements that can help improve clinical outcomes and safety profiles. With the significant evolution of imaging devices and ablation modalities during the last two decades, image-guided tumor ablation has become an ever more increasingly employed means for definitive treatment of focal malignancy, tumors in poor operative candidates, and for pain palliation in a minimally invasive manner. It has allowed larger ablation sizes with smaller instruments, and new technologies have enabled mini-invasive ablation with potential advantages in patient safety and treatment efficacy. As these technologies mature, the indications for percutaneous ablation continue to expand, and ablation promises to increasingly supplant surgery for local tumor therapy.

Numerous thermal and nonthermal ablation modalities are available, including radiofrequency

(RF) ablation, microwave ablation (MWA) and cryoablation. The benefits of these percutaneous approach include shortened hospital stay, lower morbidity, and decreased healthcare costs, as well as the ability to treat tumors in nonsurgical candidates. The mechanisms of action of various ablation modalities are at the center of many of the relative advantages, disadvantages, and limitations encountered in clinical practice. Familiarity with the basic scientific background and ablation technologies is necessary for interventional oncologist to practice safe and effective minimally invasive tumor ablation. As such, this speech aims to review the physical properties of tumor ablation technologies currently utilized, and to present a discussion of commercially available ablation devices to facilitate awareness with current technology. Future directions in the field will also be presented.

Symposium (V)

PANCREATIC CANCER: FROM BENCH TO BEDSIDE

“SUGAR”, SWEET POISON OF PANCREATIC CELLS, INITIATES TUMORIGENESIS

Chun-Mei Hu

Genomics Research Center, Academia Sinica, Taipei, Taiwan

Excess sugar’s impact on obesity and diabetes is well known. However, an area that may surprise many people is consuming excessive amounts of sugar can contribute to an increased risk of pancreatic ductal adenocarcinoma (PDAC). Previously, we have established a mechanistic link between disturbed glucose metabolism and genomic instability that induces oncogenic KRAS mutations and cell transformation preferably in pancreatic cells. Recently, we confirmed that excess sugar in daily drinks preferentially increases DNA damage and possibly cancer initiation in pancreatic tissue, according to experiments conducted on mice. The effect of high

sugar on the pancreatic tissue may be attributed to the intrinsic ratio of GFAT and PFK activity, a limiting factor that dictates UDP-GlcNAc levels. On the other hand, GlcNAc universally induces DNA damage in all six organs examined. Either inhibiting O-GlcNAcylation or supplementing the dNTP pool diminishes the induced DNA damage in these organs, indicating that the mechanism of action is similar to that of high glucose treatment in pancreatic cells. Collectively, these findings suggest the potential hazards of sugar-rich beverages and high glucosamine uptake to genomic instability and possibly cancer initiation.

Symposium (V)

PANCREATIC CANCER: FROM BENCH TO BEDSIDE

SCREENING AND EARLY DETECTION OF PANCREATIC CANCER: WHO, WHEN AND HOW?

Ming-Chu Chang

Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University, Taipei, Taiwan

Pancreatic cancer is a worldwide serious health issue with growing incidence. Patients with pancreatic cancer usually have poor survival. Over 80% of the patients are diagnosed in advanced disease stages. One major important reason is the lack of early detection of pancreatic cancer. Early detection is the most effective way to improve the prognosis of pancreatic cancer. Currently, screening for pancreatic cancer is often applied in high-risk individuals. Screening for pancreatic cancer is a desirable option for high-risk individuals to allow early detection and treatment of curable pancreatic neoplasms at a pre-invasive stage. Individuals with inherited pancreatic cancer predisposition syndromes (both owing to germline pathogenic alterations and family history of pancreatic cancer) may benefit from pancreatic cancer surveillance. Germline mutations include Peutz–Jeghers syndrome (associated with STK11 germline gene mutations) hereditary pancreatitis (predominantly PRSS1 mutations), familial atypical multiple mole melanoma syndromes (CDKN2A mutations), and Lynch syndrome (mismatch repair genes: MLH1, MSH2, MSH6) are thought to have a higher risk of pancreatic cancer. Families are considered to have familial pancreatic cancer (FPC) if there are at least 2 members of the family with pancreatic cancer who are first-degree relatives, or if there are at least 3 members of the family who have pancreatic cancer. Healthy individuals who come from a family with FPC

are likely to have an increased risk of developing pancreatic cancer in their lifetime.

The age of initiating screening is varied in different high-risk groups. Initiation of screening at the age 50 years or 10 years younger than the initial age of onset has been suggested in the guidelines of the American College of Gastroenterology and pursued in screening programs at Centers of Excellence. Screening has been initiated at age 35-40 years in PRSS1 mutation carriers with hereditary pancreatitis, in CKDN2A mutation carriers, in the setting of Peutz–Jeghers syndrome. New-onset diabetes mellitus in an individual older than 50 years with a history of smoking or weight loss is estimated to have an 8-fold increased risk of developing pancreas cancer. Patients with mucinous cystic tumors, including Intraductal papillary mucinous neoplasms and mucinous cystic neoplasms are regarded to have a higher risk of pancreatic malignancy compared to the normal population. Approximately 8% of all pancreatic ductal adenocarcinomas are believed to arise from premalignant mucinous cystic lesions of the pancreas.

Pancreatic imaging and/or biomarkers are the most commonly used methods in pancreatic cancer screening. Magnetic Resonance Imaging (MRI) or/and Endoscopic Ultrasonography (EUS) are currently the preferred imaging modalities for pancreas cancer screening. MRI with imaging construction pancreatogram (magnetic resonance

cholangiopancreatography, MRCP) is the best choice of noninvasive screening imaging. EUS could be another choice of screening or be a complementary method to MRI with concerning issues such as operator-dependent, intravenous general anesthesia et al. More and more efforts are made trying to discover novel serum biomarkers and exploring their use in combination with traditional marker, CA19-9, in the detection

of pancreatic cancer. Liquid biopsy involving circulating tumor cells (CTCs), circulating tumor DNA (ctDNA), microRNAs (miRNAs), and exosomes in blood and biomarkers in body fluid in pancreatic cancer diagnosis are ongoing. The potential diagnostic strategies for early pancreatic cancer screening have been established. The goal of surveillance is to identify and intervene in highrisk precursor lesions or early-stage cancers.

Symposium (V)

PANCREATIC CANCER: FROM BENCH TO BEDSIDE

NATURE HISTORY OF PANCREATIC CYSTIC NEOPLASMS: WEST VS EAST

Chih-Horng Wu

Department of Radiology, National Taiwan University Hospital, Taipei, Taiwan

The incidence of pancreatic cystic lesions (PCLs) is increasing due to advanced screening imaging modalities and extending life expectancy. Common pancreatic cystic lesions include pseudocyst, serous cystadenoma, intraductal papillary mucinous neoplasm (IPMN), mucinous cystic neoplasm, solid pseudopapillary neoplasm, cystic neuroendocrine tumor, pancreatic ductal adenocarcinoma with cystic degeneration, etc... In this study, we aimed to evaluate the long-term outcomes undergoing surveillance for PCLs and identify the risk of development of pancreatic malignancy during follow-up.

A prospective cohort study was conducted on patients with a clinical diagnosis of PCLs. The imaging modalities used to diagnose branch duct-IPMN (BD-IPMN) included computed tomography (CT), magnetic resonance imaging with cholangiopancreatography (MRI/MRCP), and/or endoscopic ultrasound (EUS). After initial diagnosis, patients had at least one cross-sectional imaging study (CT, MRI/MRCP, and/or EUS) done six months or longer after the initial diagnosis.

Diagnosis of BD-IPMN was based on the presence of unilocular or multilocular cysts of the pancreas and a non-dilated main pancreatic duct (MPD) (<10 mm) by imaging study. Cyst characteristics were evaluated, including location, size, septations, wall thickening, communication with the MPD, and solid component with or without enhancement. Reports of each patient were reviewed for high-risk stigmata (HRS) and worrisome features (WFs) according to the revised International Consensus Guidelines

1075 patients were diagnosed with PCLs. Among them, 934 (86.9%) were presumed as BDIPMN (clinical diagnosis). During follow-up, 163 (17.5%) patients had surgical intervention, and 48 (5.1%) had pancreatic malignancy. The cyst diameter (p < 0.0001), HRS (p < 0.0001), and WFs (p = 0.0001) were significantly associated with the presence of pancreatic malignancy.

In patients with PCLs, 5.1% will develop pancreatic malignancy during follow-up. In addition, the cyst diameter, HRS, and WFs were significant predictors of pancreatic malignancy.

Symposium (V)

PANCREATIC CANCER: FROM BENCH TO BEDSIDE

CELL THERAPY AND IMMUNOTHERAPY FOR PANCREATIC CANCER

Li-Yuan Bai

Division of Hematology and Oncology, China Medical University Hospital, Taichung, Taiwan Clinical Trial Center, China Medical University Hospital, Taichung, Taiwan

The projected number of pancreatic cancer death increases continuously, positioning pancreatic cancer as the second leading cause of cancer-related death in the United States before 2030. The incidence and mortality of pancreatic cancer also increase gradually in Taiwan. Currently, the pancreatic cancer death accounts the 7th cancer-related death in Taiwan. More than 70 percent of patients with newly diagnosed pancreatic cancer are ineligible to radical operation, leading chemotherapy the mainstay treatment modality for this population of patients. Personalized targeted therapy has been

utilized since the availability and affordability of next generation sequence technologies, but the application is limited only to a small portion of patients with pancreatic cancer. Immunotherapy especially checkpoint inhibitor has exciting success in hematological malignancies and some solid tumors. Unfortunately, the application of immunotherapy in patients with pancreatic cancer is not successful in past years. In this meeting, we will discuss the present situation, encountered obstacles, and the potential future of immunotherapy and cell therapy for patients with advanced/metastatic pancreatic cancer.

Symposium (VI)

GEST-KASID: MICROBIOME IN IBD

MAIN FACTORS FOR LARGE VARIATION BETWEEN MICROBIAL STUDIES IN IBD

Hsu-Heng Yen

Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan

The pathogenesis of inflammatory bowel disease is complex, involving the host genetic factor, environmental factor, and gut microbiota. The gut microbiota distribution differs between healthy populations and patients with IBD.

However, the findings are inconsistent and even contradictory. In this talk, I will review factors that account for the large variation between different microbial studies in IBD.

GEST-KASID: MICROBIOME IN IBD

CHANGES IN FECAL GUT MICROBIOTA BEFORE AND AFTER BIOLOGIC THERAPY IN CROHN’S DISEASE PATIENTS

Gyeol Seong Departement of Medicine, Gastroenterology, Nowon Eulji Medical Center, Seoul, Korea

Dysfunctional interaction between the intestinal mucosa and gut microbiota is thought to be associated with the development of Crohn’s disease (CD). Also, microbiota features of patients with remission state are distinguished from those whom with active state. In CD patients with remission, biodiversity is increased and specific bacteria, including Ruminococccus, Lachnospira, Lactobacillus, are increased.

Biologics is potent regulator of host’s immune responses to the gut microbiota. Therefore, it could be thought that the response to the biologics can be associated with gut microbiota in CD patients. Recent evidences support the relationship between the biologics and gut microbiota. Busquets D, et al. refered that the representative bacteria, such as E. coli and Faecalibacterium could be reliable indicators of healing state after adalimumab therapy. MK Doherty et al. showed

that the baseline fecal microbiota can be used to predict and monitor response to ustekinumab therapy. And Ashwin Ne et al. suggested that early changes of microbiome could be an indicator of response to vedolizumab therapy.

In fact, it is ambiguous that whether these changes are due to the direct relationship between the drug and gut microbiota, or simply a phenomenon that occurs as disease activity improves. At this time point, we cannot fully explain the change of gut ecology after biologics treatment, if it is a cause or consequence. However, fecal microbiota is noninvasive and useful source of biomarker to predict and evaluate the outcome of biologic therapy. Further longitudinal studies considering intra-individual variability, geographic locations, diet, and ethnicity will be needed to elucidate the interplay within the intestinal environment.

Symposium (VI)

GEST-KASID: MICROBIOME IN IBD

COMPARATIVE ANALYSIS STUDY OF SALIVA, TISSUE, AND FECAL BACTERIAL FLORA IN PATIENTS WITH IBD

Soo-Kyung Park

Division of Gastroenterology, Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea

Inflammatory bowel disease (IBD) is a chronic inflammatory gastrointestinal disorder mainly represented by Crohn’s disease (CD) and ulcerative colitis (UC). The incidence and prevalence of IBD have increased worldwide, and patients with IBD exhibit various symptoms, including abdominal pain, diarrhea, and hematochezia. Despite continuous efforts, the etiology and pathogenesis of IBD remain poorly understood. In recent years, the microbiome has become a major area of interest in the field of IBD research with the development of genome sequencing methods. Several studies have shown differences in the gut microbial community between patients with IBD and normal individuals, and increasing evidence suggests that they play a pivotal role in the pathogenesis of IBD. Inflammatory cascades induced by an imbalance of the gut microbial community, called dysbiosis, are the main elements of this hypothesis.

Research on IBD through metagenome analysis has mainly focused on dysbiosis in the intestinal tissue or stool samples, areas that are in the vicinity of where the disease occurs, and discovered several microbiome biomarkers for IBD. However, the CD can affect any location in the gastrointestinal tract, from the oral cavity to the anus; therefore, the symptoms of CD are not specifically found within the small intestine and colon. It can also lead to disease in the joints, skin, liver, biliary ducts, and kidneys beyond the entire gastrointestinal tract, known as extraintestinal

manifestations (EIMs). These bodily changes caused by CD make it possible to detect dysbiosis in sites other than intestinal tissue or stool samples. Recently, several studies have investigated the oral microbiome in saliva samples from patients with CD based on disease characteristics. Several oral mucosal diseases, including aphthous ulcers and stomatitis, are frequently found in patients with CD and are associated with disease activities. Salivary sample collection has the advantage of being safer, easier, and less uncomfortable for patients compared to other samples. Thus, understanding the salivary microbiome will improve patient compliance and expand our view of microbiota in patients with CD.

In our recent study, saliva, tissue, and stool samples from patients with CD were prospectively collected. Quantitative and phylogenetic analyses of 16s rRNA sequencing data were performed with bioinformatical pipelines. A total of 30 patients were enrolled in this study. The composition of major microbial taxa was similar between tissue and stool samples. 11 of the 20 most abundant microbiota were found in both samples. The microbial community in saliva was significantly distinct from that in tissue and stool. The major species of microbiota and their composition also differed significantly from those of tissue and stool samples. However, Streptococcus and Prevotella are common genera in saliva, tissue, and stool microbiome. The abundance of Streptococcus,

Pantoea, and Actinomyces from saliva sample group were significantly different, varying with the location of the inflammation. Saliva has a distinct microbial community compared with tissues and stools in patients with CD. Prevotella and Streptococcus, which are commonly observed in saliva, stool, and tissue, can be considered potential biomarker related to the diagnosis or prognosis of CD.

There are still many unanswered questions in the field of microbiomes of patients with IBD. Further studies could help expand our understanding of the microbiota in patients with CD.

Reference:

1. Danese, S.; Fiocchi, C. Ulcerative colitis. New England Journal of Medicine 2011, 365, 17131725.

2. Ungaro, R.; Mehandru, S.; Allen, P.B.; PeyrinBiroulet, L.; Colombel, J.-F. Ulcerative colitis. The Lancet 2017, 389, 1756-1770.

3. Mizoguchi, E.; Low, D.; Ezaki, Y.; Okada, T. Recent updates on the basic mechanisms and pathogenesis of inflammatory bowel diseases in experimental animal models. Intest Res 2020, 18, 151-167.

4. Pittayanon, R.; Lau, J.T.; Leontiadis, G.I.; Tse, F.; Yuan, Y.; Surette, M.; Moayyedi, P. Differences in gut microbiota in patients with vs without inflammatory bowel diseases: A systematic review. Gastroenterology 2020, 158, 930-946.e931.

5. Manichanh, C.; Rigottier-Gois, L.; Bonnaud, E.; Gloux, K.; Pelletier, E.; Frangeul, L.; Nalin, R.; Jarrin, C.; Chardon, P.; Marteau, P. et al. Reduced diversity of faecal microbiota in crohn’s disease revealed by a metagenomic

approach. Gut 2006, 55, 205-211.

6. Franzosa, E.A.; Sirota-Madi, A.; AvilaPacheco, J.; Fornelos, N.; Haiser, H.J.; Reinker, S.; Vatanen, T.; Hall, A.B.; Mallick, H.; McIver, L.J. et al. Gut microbiome structure and metabolic activity in inflammatory bowel disease. Nature Microbiology 2019, 4, 293305.

7. Vavricka, S.R.; Brun, L.; Ballabeni, P.; Pittet, V.; Vavricka, B.M.P.; Zeitz, J.; Rogler, G.; Schoepfer, A.M.; Group, a.t.S.I.C.S. Frequency and risk factors for extraintestinal manifestations in the swiss inflammatory bowel disease cohort. Official journal of the American College of Gastroenterology | ACG 2011, 106, 110-119.

8. Baima, G.; Massano, A.; Squillace, E.; Caviglia, G.P.; Buduneli, N.; Ribaldone, D.G.; Aimetti, M. Shared microbiological and immunological patterns in periodontitis and ibd: A scoping review. Oral diseases 2022, 28, 1029-1041.

9. Qi, Y.; Zang, S.-q.; Wei, J.; Yu, H.-c.; Yang, Z.; Wu, H.-m.; Kang, Y.; Tao, H.; Yang, M.-f.; Jin, L. et al. High-throughput sequencing provides insights into oral microbiota dysbiosis in association with inflammatory bowel disease. Genomics 2021, 113, 664-676.

10. Read, E.; Curtis, M.A.; Neves, J.F. The role of oral bacteria in inflammatory bowel disease. Nature Reviews Gastroenterology & Hepatology 2021, 18, 731-742.

11. Plauth, M.; Jenss, H.; Meyle, J. Oral manifestations of crohn’s disease: An analysis of 79 cases. Journal of Clinical Gastroenterology 1991, 13, 29-37.

Symposium (VI)

GEST-KASID: MICROBIOME IN IBD

THE THERAPEUTIC ROLE OF FECAL MICROBIOTA IN THE TREATMENT OF INFLAMMATORY BOWEL DISEASE

Puo-Hsien Le

Department of Gastroenterology and Hepatology, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan

FMT was approved by the USA Food and Drug Administration for clinical applications of recurrent or refractory Clostridioides difficile infection (CDI) in 2013. A shift in gut microbial composition in genetically susceptible individuals, an altered immune system, and environmental factors are all hypothesized to have a role in the pathogenesis of IBD. There are some studies that have proven

that FMT could emerge as a productive method to treat inflammatory bowel disease (IBD). Although recurrent or refractory CDI was the most common FMT indication, followed by ulcerative colitis (UC), Crohn’s disease (CD) and IBS in the latest systemic review published on Aliment Pharmacol Ther. We will discuss about the potential, benefits and possible risks of FMT in IBD treatment.

Symposium (VII)

WHEN HBV MEETS OTHER LIVER DISEASES

HBV AND HCV COINFECTION

Pin-Nan Cheng

Department of Internal Medicine, National Cheng Kung University Hospital, Tainan, Taiwan

HCV/HBV coinfection is common in HBV endemic area including Taiwan, because of similar routes of transmission of both viruses. Dual infection could lead to a higher risk of developing liver cirrhosis and hepatocellular carcinoma than mono-infection of each virus. In contrast to pegylated interferon/ribavirin treatment, current direct acting antiviral (DAA) treatment has the merits of simplicity, high efficacy, and excellent tolerance. HBV virologic reactivation (HBVr) is an important and critical concern for HCV/HBV dually infected patients receiving DAA treatment

for chronic hepatitis C. The risk of HBVr in HBsAg positive dually HCV/HBV infected patients is between 38% and 63.1% that can occur during DAA treatment or up to more than 3 months following DAA treatment. The clinical consequences of HBVr ranged from asymptomatic, mild hepatitis, symptomatic hepatitis, or even liver failure to death. A 12-week entecavir may have role in preventing HBVr. Current evidence showed that the long-term risk of liver related complications was reduced following interferon-based therapy in HCV/HBV dually infected subjects.

Symposium (VII)

WHEN HBV MEETS OTHER LIVER DISEASES

HBV AND HDV COINFECTION

Chien-Wei Su

Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan

Department of Internal Medicine, School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan

Hepatitis delta virus (HDV) is a defective virus that needs hepatitis B surface antigen (HBsAg) from hepatitis B virus (HBV) for viral assembly and transmission. It is estimated that around 1020 million subjects are co-infected with HBV and HDV in the world. With the successful implantation of vaccination for HBV and screening for high risk groups of HDV infections, some epidemiological surveys have shown that the prevalence rates of HDV are decreasing in previous highly endemic countries, such as Spain, Italy, Turkey, and Taiwan. However, HDV infections seemed to remerge in the Western Europe due to immigrants from Eastern Europe, Turkey and North Africa, where HDV remained endemic. Moreover, with

the increased awareness and improved diagnostic tools, more and more patients are diagnosed of HDV infections in some developing countries, such as Mongolia and Brazil, as well as in high risk groups of patients, including those are injections drugs user (IDU) or with human immunodeficiency virus (HIV) infections. Consequently, HDV infection is still an important public health issue worth of concern. Compared with those who are monoinfected by HBV, patients with chronic hepatitis D mad more aggressive clinical manifestations, including rapidly progressive to liver cirrhosis, portal hypertension, liver decompensation and HCC. Moreover, HDV infection is an important cause of fulminant hepatitis in the world.

Symposium (VII)

WHEN HBV MEETS OTHER LIVER DISEASES

SUPERINFECTION OF HEV IN HBV

Tai-Chung Tseng

Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan

Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan

Not only is it a remarkably widespread disease in Taiwan, viral hepatitis is also an important public health issue across the world. For patients already infected with chronic hepatitis B, however, recurring inflammation of the liver can lead to higher risks of complications in liver cirrhosis and liver cancer to varying degrees. Hepatitis E, on the other hand, has a radically different clinical profile. Patients infected with the hepatitis E virus (HEV) ordinarily develop acute hepatitis, which can lead to massive necrosis within a short span of time, resulting in a mortality rate between 1% and 2%. For chronic hepatitis B patients, whether or not the HEV superinfection will accelerate the progression of liver diseases remains unclear. Previous data mostly come from symptomatic patients with a relatively short follow-up period. The mortality of HEV superinfection in chronic hepatitis B patients is usually overestimated and the long-term outcome is unclear. To address this

issue, we adopted a large HBV cohort with a longterm follow-up and defined HEV superinfection by seroconversion of IgG-HEV. It is shown that HEV infection not only significantly increases the short-term liver-related mortality rate of cirrhotic patients but also increases the risk of cirrhosis and liver cancer in inactive hepatitis B carriers. This important finding was also confirmed by the follow-up cohort study of 414 cirrhotic patients. Combining these two cohort studies, we found that the mortality rate of chronic cirrhotic hepatitis B patients within one year into their infection with hepatitis E was 35.7%, which is much higher than that of non-cirrhotic hepatitis B patients, which is 2.4%. The clinical implication is that it is crucial to prevent chronic hepatitis B patients and cirrhotic patients from HEV superinfection, so that the risks of short- and long-term complications associated with hepatitis E may be reduced.

Symposium (VII)

WHEN HBV MEETS OTHER LIVER DISEASES

HBV AND NASH/NAFLD

Chun-Jen Liu

Hepatitis Research Center and Department of Internal Medicine, National Taiwan University College of Medicine and Hospital, Taipei, Taiwan

HBV infection is a major etiology of chronic liver disease worldwide. In the past few decades, NAFLD has emerged as a common liver disorder in general population including HBsAg carriers. Accordingly, the number of patients with co-existing CHB and NAFLD grows rapidly. Interestingly, patients with CHB were found to have a lower incidence of NAFLD in comparison with the general populations and the subjects with chronic HCV infection. Specifically, around 14~56% of patients with chronic HBV infection had evidence of fatty liver. The mechanism is possibly due to a lower frequency of dyslipidemia profile in patients with chronic HBV infection. Recent studies aimed to explore the relationship between CHB and NAFLD from different aspects, including the pathogenesis, molecular mechanisms, and the clinical observational/cohort studies. Briefly, it was found that although numerous cross-links have been suggested between HBV infection and

NAFLD pathogenesis, the associations of HBV with metabolic syndrome, insulin resistance, and the risk of arteriosclerosis are still inconclusive. In addition, obesity, diabetes, and metabolic syndrome instead of steatosis itself may accelerate the progression of liver disease in patients with chronic HBV infection and synergistically induce cirrhosis or even hepatocellular carcinoma development. Finally, from the therapeutic point of view, the presence of NAFLD, a recent review demonstrated that coexisting NAFLD did not influence the response to oral nucleos(t)ide analogue or interferon therapy. Overall, the presence of metabolic syndrome is associated with the progression of liver disease in patients with chronic HBV infection. Thus, in addition to the control of hepatitis B, metabolic derangement should be corrected. The treatment decision and the response to oral nucleos(t)ide analogue or interferon therapy are not influenced by co-existing NAFLD.

Symposium (VIII)

EVOLUTION OF COVID-19 PANDEMICS

EPIDEMIOLOGICAL EVOLUTION OF COVID-19 PANDEMICS

Hsiu-Hsi Chen Institute of Epidemiology and Preventive Medicine, National Taiwan University, Taipei, Taiwan

COVID-19 pandemic announced by WHO since March, 2020 has seen a series of epidemic outbreaks around the world in parallel with the evolution of SARS-CoV-2 mutants from the wild type/D614G of non-variant of concerns (VOCs) period to the periods of Alpha, Beta, Gamma, Delta, and Omicron VOCs in chronological order. The proposed mitigation strategies to contain the epidemic outbreaks have been also accompanied with the evolution of SARSCoV-2 variants. These include a suite of NPI, primary and booster vaccination, and various kinds of anti-viral therapy. The current speech will begin with the brief presentation of epidemic curves covering the evolution of SARS-CoV-2 variants from importation to community-acquired outbreaks. A spectrum of policies from “ zeropolicy” until “living with virus” accompanied

with SARS-CoV-2 variants will be briefly reviewed with the evolution of relevant mitigation strategies. Clinical outcomes associated with the evolution of epidemic outbreaks caused by each SARSCoV-2 variants are also presented. The short-term and long-term impacts of SARS-CoV-2 infections on gastroenterological patients will be presented. These include the common inflammatory pathway shared with the underlying gastrointestinal diseases and SARS-CoV-2 infection and the acceleration of disease progression leading to long-term chronic gastrointestinal diseases. The presentation will briefly cover whether and how the evolution of COVID-19 epidemic accompanied with SARS-CoV-2 variants result in long-COVID19 intestinal manifestation in relation to the dysbiosis of microbiota.

Symposium (VIII)

EVOLUTION OF COVID-19 PANDEMICS

EVOLUTION OF COVID-19 PANDEMICS: NATURAL VERSUS INTERVENED

Pei-Jer Chen

Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan Graduate Institute of Clinical Medicine, National Taiwan University Hospital, Taipei, Taiwan

The ongoing COVID-19 pandemic is once in a hundred-year event, after the 1918 influenza. The difference has been a much better scientific and medical capacities of human in understanding and responding to new pandemic. In this talk, three points will be discussed from evolution point of view.

The first regards the origin of SARSCoV2, at first outbreak in Wuhan, China. Distinct from SARS CoV in 2003 or MERS CoV which quickly disappeared from human society, SARSCoV2 continues its spreading and will become a seasonal common cold virus. The analysis of SARSCoV2 genomes evolutions, as compared with that of SARS CoV in 2003 or that of SARSCoV2 from humans to minks, suggested a virus already breaking the cross-species bottleneck when initially noted.

The second point discussed the evolution of SARS COV2 in humans from 2019 till now. The virus continuous generates new variants during infecting humans, some short live but other dominate. Extensive clinical and virological observations indicated an evolution direction from

higher transmission, but with lower virulence. Eventually SARS CoV2 will become the fifth member of seasonal common cold coronaviruses sometime in the future.

The third part examined the pandemic courses in the low vaccinated countries versus that in the highly vaccinated countries. In Africa/ India with low vaccine coverage, the peaks of COVID-19 infections caused higher mortality but diminish more quickly, and expected to come to equilibrium with other common cold in 2024 or 2025. In contrast, in Europe/USA/Japan, the peaks of COVID19 decline much slower or even surging up and the time to equilibrium is probably longer. The advantage of current vaccines has reduced the COVID-19 severity or death, however, not preventing infections for sufficient time periods. A scenario of vaccine-dependent enhancement of infection cannot be excluded, similar to dengue virus or RSV vaccines.

COVID-19 pandemic provides a window to examine the achievements and limitations of human culture. There is still a long way to go before we can manage next upcoming pandemic.

Symposium (VIII)

EVOLUTION OF COVID-19 PANDEMICS

GI-ASSOCIATED CLINICAL MANIFESTATIONS BY COVID-19 AND VACCINATION

Ming-Lung Yu

College of Medicine, National Sun Yat-Sen University, Kaohsiung, Taiwan Kaohsiung Medical University, Kaohsiung, Taiwan

The epidemic of COVID-19 by infection with SARS-CoV-2 has a wide clinical spectrum not only in the respiratory tract but also in extrapulmonary organs, such as GI systems. In the infectious process, SARS-CoV-2 shares the same cellular entry receptor, angiotensin-converting enzyme 2 (ACE2), which is mainly expressed in the alveolar epithelium as well as GI tract epithelial cells, such as colonic enterocytes and biliary cholangiocytes. The prevalence of GI symptoms has been reported from 2%-57% at diagnosis, including diarrhea, nausea/vomiting, abdominal pain, loss of appetite, and loss of taste, and up to 74% through the course of COVID-19 infection. Notably, antiviral treatment for COVID-19, such as hydroxychloroquine and Lopinavir/Ritonavir may lead to significant GI adverse events. Whether GI symptoms are associated with a different course of COVID-19 remains controversial. By contrast, liver injury has been associated with worse outcomes and mortality in COVID-19 patients, as observed in previous evidence of SARS and MERS infection.

Elevated serum aminotransferases and impaired liver function have been reported in 14.8% to 53% of patients in COVID-19 patients and up to 58% of patients with severe COVID-19. Alcoholic liver disease, decompensated cirrhosis and liver cancers are risks predictive of higher mortality among patients with CLD and COVID-19. The pandemic of COVID-19 might have a great impact on the screening and management of GI and liver cancers, as well as the control of viral hepatitis. The boosters of COVID-19 vaccines, although not completely preventing COVID-19 infections, have been associated with decreased severity once acquiring COVID-19 infection. Patients with immune-mediated inflammatory diseases under immunosuppressive therapy have a lower response to mRNA COVID-19 vaccines. COVID-19 vaccination was not associated with disease exacerbation of IBD, however, might induce immune-related hepatitis as well as HBV reactivation, even fatal hepatic failure.

Symposium (IX)

ADVANCES IN THE INVESTIGATION AND MANAGEMENT OF LIVER AND INTESTINAL FAILURE

PEDIATRIC LIVER FAILURE: EXPLORING THE RARE DISEASES AND NOVEL THERAPIES

Huey-Ling Chen

Division of Pediatric Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan

Pediatric acute liver failure is a devastating disease with high mortality. The most commonly applied definition is from the Pediatric Acute Liver Failure (PALF) study group: acute liver injury with coagulopathy: prothrombin time (PT) international normalized ratio (INR) ≥ 1.5 not corrected by vitamin K with presence of hepatic encephalopathy (HE), or a PT INR ≥ 2.0 regardless of the presence or absence of clinical hepatic encephalopathy (HE), without evidences of chronic liver diseases. Etiologies causing acute liver failure include viral infections, drug-related liver injury, immunemediated diseases, or metabolic/genetic liver disease (especially in infants and young children). With the advances of advanced genetic tools such as panel-based next generation sequencing or whole exome sequencing, more genetic causes of

liver diseases can be diagnosed, and may improve the treatment and outcome. Since April 2022, the World Health Organization reported warning on increased cases of idiopathic hepatitis in children (ALT > 500 U/L). Most cases were reported in UK, USA, Mexico, Japan, Spain, and also from other countries; some resulting in liver failure and mortality or received liver transplantation. Possible causes are being investigated including adenovirus infection, altered immunity after Covid-19 infection, or partial role of adeno-associated virus. Liver transplantation is still the mainstay of treatment for acute liver failure. Plasma exchange and other therapeutic modalities will be discussed. The continuing efforts to improve the outcome of liver failure in children is anticipated.

ADVANCES IN THE INVESTIGATION AND MANAGEMENT OF LIVER AND INTESTINAL FAILURE

INTESTINAL FAILURE: UPDATE ON MANAGEMENT AND TRANSPLANTATION IN TAIWAN

Yun Chen Division of Pediatric Surgery, Department of Surgery, Far Eastern Memorial Hospital, New Taipei City, Taiwan

Intestinal transplantation is considered as a definitive treatment for patients with irreversible intestinal failure (IF) or life-threatening complications after long-termed dependence on parenteral nutrition. In 2007, we initiated an intestinal transplant program in Taiwan. Herein are the program results during 2007-2022 at Far Eastern Memorial Hospital.

Thirty patients (8 children and 22 adults) received isolated intestinal transplantations, with one re-transplantation. Immunosuppression protocol included tacrolimus with combination of steroids. Infectious complications are monitored over the viral titer of CMV. Scheduled biopsy of the graft and biochemical analysis of blood samples were used for the surveillance on the patient

condition and graft function.

The indications for intestinal transplantation were repeated catheter-related sepsis (7/30, 23.3%), impairment of liver function (1/30, 3.3%), major vein thrombosis (5/30, 16.7%), and ultrashort bowel (17/30, 56.7%). The survival rates for 1-year, 3-year, and 5-year are 80.6%, 77.4%, and 71.0% for patients, and 67.7%, 61.3%, and 51.6% for grafts. The median time for weaning off TPN is 36 days.

These results suggest that intestinal transplantation is an effective therapy for patients with intestinal failure who cannot tolerate PN. We are now conducting human trials of living-related intestinal transplantation, hoping to help more patients with intestinal failure.

ADVANCES IN THE INVESTIGATION AND MANAGEMENT OF LIVER AND INTESTINAL FAILURE

NEW THERAPEUTIC APPROACH IN PEDIATRIC SHORT BOWEL SYNDROME

Olivier Goulet Division of Paediatric Gastroenterology-Nutrition, Necker-Enfants Malades Hospital, Paris, France

Intestinal failure (IF) is defined as a critical reduction of the gut mass or its function below the minimum needed to absorb nutrients and fluids required for adequate growth in children and weight maintenance in adults (1). Severe IF, results in the need for parenteral nutrition (PN). IF may be reversible or irreversible, depending on the underlying disease and also on the treatment used to develop or restore intestinal capacity. IF is most commonly due to congenital or neonatal intestinal diseases or malformations that can be divided into three groups: i) IF from reduced intestinal length and consequently reduced absorptive surface, such as in short bowel syndrome (SBS) or extensive aganglionosis (Long segment Hirschsprung disease); ii) IF related to an abnormal development of the intestinal mucosa such as congenital diseases of enterocyte development (CDED); iii) IF with intact length but with extensive motility dysfunction such as pediatric intestinal pseudo-obstruction syndromes (PIPOS).

IF conditions being rare, guidelines for PN may provide basic knowledge for the management of those complex patients (2,3). In clinical practice intestinal sufficiency may be indirectly measured by the level of PN required for normal or catch up growth (4). With optimal combinations of macronutrients and micronutrients, PN has become a safe and efficient feeding technique. However, long-term PN may be associated with

various complications including catheter related blood stream infections (CRBSIs), growth failure, metabolic disorders, and bone disease. “Intestinal Failure Associated Liver Disease” (IFALD), may lead to the so-called “nutritional failure” which is considered as a major indication for intestinal transplantation or combined liver-intestinal transplantation (5). Home-PN has become the corner stone for long term PN dependent patients (6). New treatment are nowadays available such as taurolidine for the prevention of CRBSIs (7), new generation of composite lipid emulsion for preventing IFALD (8) or GLP-2 analogs for SBS (9). Results of the Teduglutide Necker-study including 25 patients will be presented

References:

1. Goulet O, Ruemmele F. Causes and management of intestinal failure in children. Gastroenterology 2006; 130: S16-28.

2. Koletzko B, Goulet O, Hunt J, Krohn K, Shamir R; 1. Guidelines on Paediatric Parenteral Nutrition of the European Society of Paediatric Gastroenterology, Hepatology and Nutrition (ESPGHAN).

3. Mihatsch W, Shamir R, van Goudoever JB, et al; ESPGHAN/ESPEN/ESPR/CSPEN guidelines on pediatric parenteral nutrition: Clin Nutr. 2018 Jun 27. pii: S0261-5614(18)311622. doi: 10.1016/j.clnu.2018.06.943. [Epub ahead of print]

4. Goulet O, Olieman J, Ksiazyk J, et al. Neonatal short bowel syndrome as a model of intestinal failure: Physiological background for enteral feeding. ClinNutr 2013; 32:162-71.

5. D’Antiga L, Goulet O. Intestinal failure in children: the European view. J Pediatr Gastroenterol Nutr. 2013; 56: 118-26.

6. Goulet O, Breton A, Coste ME, et al. Pediatric Home Parenteral Nutrition in France: A six years national survey. Clin Nutr. 2021; 40: 5278-87. doi: 10.1016/j.clnu.2021.08.002.

7. Lambe C, Poisson C, Talbotec C, Goulet O. Strategies to Reduce Catheter-Related

Bloodstream Infections in Pediatric Patients Receiving Home Parenteral Nutrition: The Efficacy of Taurolidine-Citrate ProphylacticLocking. JPEN 2018; 42:1017-25.

8. Goulet OJ, Cai W, Seo JM. Lipid Emulsion Use in Pediatric Patients Requiring LongTerm PN. JPEN 2020;44 Suppl 1:S55-S67.

9. Goulet O, Abi Nader E, Pigneur B, Lambe C. Short Bowel Syndrome as the Leading Cause of Intestinal Failure in Early Life: Some Insights into the Management. Pediatr Gastroenterol Hepatol Nutr. 2019;22(4):303-329.

Symposium (X)

STATE-OF-THE-ART: MINIMALLY INVASIVE SURGERY IN GASTROENTEROLOGY AND HBP – HOW FAR WE CAN REACH

HEPATOBILIARY

Kuo-Hsin Chen

Department of Surgery, Far Eastern Memorial Hospital, New Taipei City, Taiwan

Hepatobiliary surgery has been considered one of the most challenging in the field of surgery, not only for the complexity of procedure, numerous variants of related anatomy but also for the delicate postoperative care involved.

Despite the first introduction of laparoscopic cholecystectomy by Dr. Erich Muhe of Germany in 1985, further development of minimally invasive surgery (MIS) in the hepatobiliary surgery has been slow. The first laparoscopic resection of benign liver tumor has been published by Dr. Reich H in 1991. Wider horizontal adaptation of MIS liver resection was observed after the two international consensus meetings held at Louisville in 2008 and at Morioka in 2014 respectively.

Currently, the application of LLR in HCC is suggested in patients with solitary tumor, less than 5 cm in diameter, without evident vascular invasion and extrahepatic spread.

Hepatocellular carcinoma (HCC) has become one of the commonest indications for laparoscopic liver resection (LLR), especially in Asian countries. Despite the difficulty, reports of LLR for advanced HCC, including major vascular invasion, nodal/ distant metastasis & in patients with poor performance status have been reported by experienced teams, although limited to sporadic case reports or small series.

Laparoscopic hepatectomy for HCC with vascular invasion

The prognosis of HCC with major vascular invasion is dismal. Treatment of HCC with

major vascular invasion is challenging. Systemic treatment with or without transarterial chemoembolization has been the current main streams according to BCLC recommendation. However, some retrospective studies revealed resection may offer better outcomes at least in highly selected patients. Current indications of surgical resection for HCC with vascular resection include vp3 lesion (unilateral involvement of first order of portal vein) with adequate liver reserve. Only very limited reports of LLR for HCC with vascular invasion can be found in the literature. Some of them included PV thrombectomy.

Considering the difficulties of laparoscopic thrombectomy of portal vein, it was suggested to start with lesion with adequate distance to the bifurcation.

Nevertheless, LLR for HCC with major vascular invasion which needs vascular exploration is a very advance procedure which should be reserved for well experienced surgeons. Laparoscopic resection of HCC with hepatic vein or IVC tumor thrombus has been reported in some case reports. However, it’s highly sophisticated procedure and should be for well experienced teams for now.

Regional lymph node dissection has been considered as an essential part of radical resection of biliary cancers including gall bladder cancer more than T1b, perihilar cholangiocarcinoma and intrahepatic cholangiocarcinoma. Despite more and more successful reports of laparoscopic gastrointestinal malignancy including gastric and pancreatic cancer, the feasibility and efficacy

of laparoscopic regional lymph node dissection of porta hepatitis remain to be established. Bile duct resection with free resection margin and subsequent reconstruction are two major obstacles of applying MIS in biliary cancer surgery. Although highly controversial, laparoscopic resection of

perihilar cholangiocarcinoma has been reported in some case report and small series.

In this presentation, literature review of MIS approach for advanced hepatobiliary surgery as well as our preliminary results will be included.

Symposium (X)

STATE-OF-THE-ART: MINIMALLY INVASIVE SURGERY IN GASTROENTEROLOGY AND HBP – HOW FAR WE CAN REACH

MINIMALLY INVASIVE SURGERY IN PANCREAS

Yi-Ming Shyr

Division of General Surgery, Taipei Veterans General Hospital, Taipei, Taiwan

Minimally invasive surgery (MIS) with smaller wounds and less pain has become a worldwide trend in many surgical fields, including pancreatic surgeries. Pancreatic surgery, especially Pancreaticoduodenectomy, is a technique-demanding and time-consuming complex procedure, which used to be performed only by traditional open method. Traditional open pancreaticoduodenectomy (OPD) always needs a large abdominal incision, which would cause severe pain and also result in cosmetic problem. Recently, several limitations using laparoscopic approach have been overcome by da Vinci Robotic Surgical System (Intuitive Surgical, Inc., Sunnyvale, CA, USA). Several advantages including favorable ergonomics, articulation of instruments with 540 of motion, elimination of surgeon tremor, and a high-quality 3-dimensional vision with 10–15 magnification view, robotic approach can facilitate a more delicate and complex procedure such as pancreaticoduodenectomy which is involved in extensive dissection and restoration of the digestive tract continuity for the pancreas, bile duct, and stomach.

In this presentation, we will share with you our experience of MIS in pancreas. The

topics will include 1. from RDP to RPD; 2. RDP (Robotic distal pancreatectomy); 3.RPD (Robotic pancreaticoduodenectomy); 4. RTP (Robotic total pancreatectomy); 5. RCP (Robotic central pancreatectomy); 6. RSPDDP (Robotic Simultaneous PD and DP); 7.RE (Robotic Enucleation).

Based on our studies, LDP is comparable to RDP in regard to surgical outcomes. LDP with spleen-preservation is highly recommended whenever possible and feasible for benign or low malignant lesions in terms of lower costs and less blood loss. RCP could be recommended as a feasible and safe MIS alternative without compromising the surgical outcomes and pancreatic functions. RPD did not increas the surgical risks and, moreover, might provide benefits of less blood loss, less delayed gastric emptying, lower wound infection rate and shorter length of postoperative stay, as compared with OPD. Survival outcome for pancreatic head adenocarcinoma was better in RPD group. At least, RPD seems not to compromise the survival outcomes. Therefore, RPD is not only justified but also feasible in the treatment of periampullary lesions.

STATE-OF-THE-ART: MINIMALLY INVASIVE SURGERY IN GASTROENTEROLOGY AND HBP – HOW FAR WE CAN REACH

De-Chuan Chan

Division of General Surgery, Department of Surgery, Tri-Service General Hospital, Taipei, Taiwan

Minimally invasive surgery (MIS) for gastric cancer has become common due to improvement of the surgical techniques and devices for laparoscopic surgery. Laparoscopic distal gastrectomy has been strongly recommended as a treatment option in clinical stage I gastric cancer in Japan and Korea, with no significant difference in overall survival. In addition, laparoscopic total gastrectomy (LTG) has also been evaluated in CLASS02 multicenter randomized prospective trial. The authors conclude that the safety of LTG with lymphadenectomy by experienced surgeons for clinical stage I gastric cancer was comparable to that of OTG.

MIS for locally advanced gastric cancer can be more difficult to perform because of the technical challenge and oncologic safety. Recently, there are many studies on laparoscopic approach in locally advanced gastric cancer. The KLASS-02 and CLASS-01 trials showed that laparoscopic gastrectomy is non-inferior to open gastrectomy in

terms of the 3-year disease-free survival rate. One large retrospective study comparing minimally invasive to open gastrectomy in a western country carried out at memorial Sloan-Kettering hospital, which showed there was a statistically significant improvement in the minimally invasive group in all patients.

Peritoneal relapse is the most common pattern of recurrence after radical gastrectomy in locally advanced GC. The use of HIPEC following a radical gastrectomy in patients without PM, but with a locally advanced GC, may prevent peritoneal recurrence. As we know, many patients have an unresectable PM at initial diagnosis and these cases frequently suffer from debilitating malignant ascites and poor life quality. These patients are always frail and may not tolerate aggressive treatment. Laparoscopic HIPEC may be a less aggressive treatment option for these fragile patients, which may lower peritoneal carcinomatosis, decrease ascites, and consequently improve performance status.

Symposium (X)

STATE-OF-THE-ART: MINIMALLY INVASIVE SURGERY IN GASTROENTEROLOGY AND HBP – HOW FAR WE CAN REACH

MINIMALLY INVASIVE SURGERY IN COLOPROCTOLOGY –CURRENT STATUS AND FUTURE

Po-Li Wei

Division of Colorectal Surgery, Department of Surgery, Taipei Medical University Hospital, Taipei, Taiwan

Laparoscopic colorectal surgery was first described by Jacobs in 1991. After three decades, minimally invasive surgery has become mainstay of surgical treatment for colorectal diseases.

Although the benefit of laparoscopic surgery for colorectal cancer has been demonstrated, inherent features of the laparoscopic procedure such as limited range of motion of the rigid instruments, amplification of tremor from the fulcrum effect, and 2 dimensional image add to the difficulty and limit its application. Radical resection and safety are still major concern of minimally invasive surgery.

Robotic platform for colorectal surgery is an emerging technique. The incorporation of advantageous features such as dexterity from articulated instruments, intuitive ergonomics, fine motion scaling, tremor filtration, steady retraction for exposure provided by the extra robotic arm, and a stable surgeon-controlled camera with

3-dimensional high-definition imaging may help overcome the limitations of laparoscopic surgery. Besides, concepts of TME for rectal cancer and CME with CVL for colon cancer were introduced to increase cancer clearance. Recently, fluorescence angiography using ICG has become the most promising technology that allows for real-time intraoperative objective evaluation of lymph status and bowel perfusion, which can further facilitate the nodal dissection and reduce the risk of anastomotic leakage.

For better recovery, reduced port surgery and nature orifice specimen extraction are also used for patients underwent minimally invasive colorectal surgery. In addition, there are a lot of new technologies including surgeon friendly laparoscopic instruments, smarter staples and robots to improve results of minimally invasive surgery. The prevalence of minimally invasive surgery will increase persistently.

Symposium (XI)

EMERGING ISSUES IN GASTROENTEROLOGY

FMT FOR INFLAMMATORY BOWEL DISEASES

Deng-Chyang Wu

Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan

Therapeutic strategies for inflammatory bowel disease (IBD) have increased over the past decade, but considerable unmet needs remain. The current treatment paradigm is based on the goal of altering the dysregulated immune response and decreasing inflammation in the gut by targeting various proteins in the inflammatory cascade. Although the available drugs have the potential to significantly improve patient symptoms, they are limited by their cost, side effects, and inconsistent efficacy. Dysbiosis is a decrease in gut microbial diversity owing to a shift in the balance between commensal and potentially pathogenic microorganisms of the gut microbial ecosystem and has long been characterized as a trait of IBD patients, so the prospect of modulating the microbiota in IBD is conceptually appealing and is based on sound rationale. One form of manipulating the microbiota is through fecal microbiota transplantation (FMT), where fecal microbiota from a healthy donor are transplanted

into the distal gastrointestinal tract of a patient. FMT has already emerged as a successful therapy for Clostridioides difficile infection, and is currently being explored as a potential treatment of IBD. With increasing numbers of studies, including randomized trials, of FMT for IBD, we will be faced with more clinical data in an area where a mechanistic understanding is lacking. At the moment, FMT cannot be considered a consistent therapy across trials. In fact, trials to date vary on the method of FMT delivery, bacterial dose, method of stool filtration, frequency of administration, and do not control for other donor factors such as diet. This diversity may ultimately be beneficial for deriving a mechanistic underpinning for FMT in IBD, though currently it limits our interpretation of FMT as a clinical success or failure. In the future, hopefully the numerous ongoing trials investigating FMT in IBD will help clarify the efficacy of this modality as a treatment option.

Symposium (XI)

EMERGING ISSUES IN GASTROENTEROLOGY

MODULATING GUT MICROBIOME FOR OBESITY AND METABOLIC DISORDERS

Chun-Ying Wu

College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan Division of Translational Research, Taipei Veterans General Hospital, Taipei, Taiwan President, Taiwan Microbiota Consortium

Gut microbiota has been shown to play important roles in obesity and metabolic syndrome. Altered gut microbiota is found associated with energy harvest and vulnerability to obesity and metabolic syndrome. Modulating gut microbiota or supplementing distinct bacterial species can restore responses to anticancer therapy.

Regardless of the valuable findings in animal experiments and clinical studies, a more thorough understanding of the interactions between gut microbiota and cancer therapy will be helpful

to identify more novel strategies and measures to treat cancer. In the present lecture, we will discuss the roles of gut microbiota in liver cancer and colon cancer oncogenesis, the impact of gut microbiota on the efficacy of anticancer therapy, and the potential development of gut microbiota intervention to improve cancer systematic therapy. This lecture will be helpful for physicians taking care of digestive cancers, researchers focusing on cancer systematic therapy, and young members interested in learning knowledge of gut microbiota.

Symposium (XI)

EMERGING ISSUES IN GASTROENTEROLOGY

YOUNG-ONSET COLORECTAL CANCER

Han-Mo Chiu

Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan

Globally, colorectal cancer (CRC) ranks third (1,849,518 new cases, 10.2% of total) as the most commonly diagnosed cancer after lung and breast, with it being second in women and third in men in 2018. It is also the second oncological cause of death worldwide. Screening was proven effective in reducing CRC and CRC death, and many countries with mid to high CRC incidence have implemented population screening in the past two decades and has contributed largely on controlling this devastating disease. In Taiwan, national screening program using fecal immunochemical test (FIT) was launched in 2004, and its effectiveness in reducing CRC mortality and the incidence of advanced stage CRC was reported to be 35% and 29%, respectively, comparing those who did and did not participate in FIT screening. CRC risk was traditionally considered to begin to rise after 50 but recent epidemiological

studies have demonstrated that CRC of 40 to 49 are increasing not only in the US but also in the Europe and the Asia-Pacific region. According to a study from the Asia-Pacific, increasing trend of young-onset CRC in both genders was demonstrated and the most pronounced change was observed with male rectal cancer. To confront such a situation, several guidelines adjusted their recommendation on the starting age of screening and lower from 50 to 45 in recent years but such a recommendation is, however, not supported by the results of randomized trials or cohort studies but mainly based on the results of simulation studies and previous experience of screening in the 50-75 age group.

In this presentation, updated evidences on the epidemiological trend of young-onset CRC will be introduced and the current status of prevention measures will also be discussed.

Symposium (XI)

EMERGING ISSUES IN GASTROENTEROLOGY

SCREENING FOR PANCREATIC CANCER: HOW FAR IS IT FROM HERE?

Wei-Chih Liao Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan

Pancreatic ductal adenocarcinoma (PDAC) is the most lethal cancer and comprises approximately 90% of pancreatic malignancies. Approximately 85% of PDAC patients present with unresectable locally advanced or metastatic cancer with dismal survival, whereas patients with localized stage I cancer have a 5-year survival rate of 42%. Therefore, early detection represents the most effective strategy to improve the prognosis of PDAC.

Screening for asymptomatic high-risk individuals (HRI, i.e., Peutz-Jeghers syndrome, familial pancreatic cancer with ≥ 3 first-degree relatives [FDR], familial atypical multiple mole melanoma, and hereditary pancreatitis) who carry more than 5% lifetime risk of PDAC is advocated. For HRIs, annually screening with magnetic resonance image (MRI) and/or endoscopic ultrasound (EUS) has been shown to downstage PDAC, but the benefit in survival and cost-effective need further study. By contrast, the US Preventive Service Task Force (USPSTF) recommended against regular screening for PDAC in the general population. For HRIs, annually screening with magnetic resonance image (MRI) or endoscopic

ultrasound (EUS) significantly down staged PDAC to stage I in the screening program.

Blood-based biomarkers such as tumor markers, circulating tumor cells, exosomes, circulating tumor DNA and cell-free DNA may offer promise for early detection. Pancreatic cancer-associated diabetes mellitus (PCDM) is a paraneoplastic phenomenon which occurs in approximately 40% of patients within 2 years before PDAC diagnosis. PCDM has been proposed as a window of opportunity for early detection, as the cancer are generally early at the onset of PCDM. Serum levels of PDAC-derived diabetogenic factors has been shown to distinguish PCDM from type 2 diabetes and might facilitate early detection of PDAC. Alternatively, artificial intelligenceassisted analysis of CT images has recently been shown to facilitate detection of early PDAC and might serve as a potential screening tool.

In summary, screening for HRIs may enable early detection of PDAC and improve survival. The potential of screening for PDAC with novel biomarkers and imaging analytics warrants further investigation.

Symposium (XII)

IMAGE ENHANCED ENDOSCOPY

PRECISION GI ENDOSCOPY APPLYING IEE: UPPER GI

Ching-Tai Lee

Department of Internal Medicine, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan

UGI tract malignancies, including esophageal, and gastric neoplasm, are among the most common causes of cancer death in Asia Pacific region and in Taiwan. Early detection in highrisk patients improved survival and quality of life. However, there are still some challenges for early diagnosis using conventional white-light endoscopy.

Since the development and evolution of image-enhanced endoscopy (IEE), early diagnosis of GI malignancies become more and more easy. To promote and standardize training of early GI

cancer diagnosis and therapy in the Asia Pacific region, and develop strategies and action plans for the professional development of endoscopists in the Asia Pacific region, the Asia Novel Bio-Imaging and Intervention Group (ANBIIG) was established for the purpose of furthering education for young endoscopists. Herein, I will briefly introduce the optimal diagnostic strategies for early UGI neoplasm (including esophageal squamous cell cancer, Barrett cancer and gastric cancer) using IEE according to the recommendation of ANBIIG.

Symposium (XII)

IMAGE ENHANCED ENDOSCOPY

PRECISION GI ENDOSCOPY APPLYING IEE: LOWER GI

Peng-Jen Chen

Division of Gastroenterology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan

Colorectal cancer (CRC) has become one of the most frequent malignancy in Taiwan. Adenoma detection rate (ADR) was inversely associated with the risks of interval CRC, advanced-stage interval CRC, and fatal interval CRC.

Image enhanced endoscopy (IEE) of colonoscopy includes dye spraying IEE and electronic IEE. Indigo carmine, as the most frequent use for dye spraying in colonoscopy, enhances the contrast of mucosal surface and highlights flat lesions in colon. Electronic IEE

techniques, such as narrow band imaging (NBI) by Olympus, blue light imaging (BLI) and linked color imaging (LCI) by Fujifilm, and i-scan optical enhancement (i-scan OE) by Pentax, intensify the mucosal structure details, and emphasize microvessels beneath the epithelium. IEE can improve adenoma detection. IEE incorporated into endoscopic magnification is able to characterize polyp surface and microvessels and predict the pathologic diagnosis.

Symposium (XII)

IMAGE ENHANCED ENDOSCOPY

HOW IEE CHANGED ENDOSCOPY CLINICAL PRACTICE? : UPDATES AND FUTURE PERSPECTIVES

Yen-Po Wang

Department of Internal Medicine, Endoscopy Center for Diagnosis and Treatment, Taipei Veterans General Hospital, Taipei, Taiwan

Image-enhanced endoscopy (IEE) means enhancing contrast during endoscopy using dye, optical filtering, and/or ultramagnification for various analyses of GI lesions from analysis of minute structures, epithelial capillaries on the mucosa surface, intensity of fluorescence emitted from intestinal tissue. These techniques help further identifying the tiny lesions or irregular abnormalities in GI tract lesions. IEE can be used to improve our endoscopic detection capability and characterization for diagnosis accuracy by highlighting the mucosal microstructure and microvascular features. Narrow-band imaging (NBI), Texture and Color Enhancement Imaging (TXI), Blue light laser imaging (BLI), LinkedColor Imaging (LCI), I-scan were useful optical-

digital methods in clinical practice. Confocal endomicroscopy and endocytoscopy provided higher magnifying function for optical pathologic evaluation and in-vivo GI function evaluation. With the development of Artificial intelligence, IEE had the potential to become a more easy and convenient application in clinical practice. Red Dichromatic Imaging (RDI), A newly introduced technique, further provided newer application in assistance of endoscopic hemostasis and help in endoscopic resection. With the advances of IEE, the endoscopic detection is better, diagnosis is more correct and predicted to be applicable in endoscopic resection and functional endoscopy in near future.

Symposium (XII)

IMAGE ENHANCED ENDOSCOPY

MOLECULAR GI ENDOSCOPY – HOW FAR IS IT FROM THE PRIME TIME FOR CLINICAL USE?

Thomas D. Wang Department of Medicine; Department of Biomedical Engineering; Department of Mechanical Engineering, University of Michigan, Ann Arbor, MI, USA

Molecular endoscopy is an emerging imaging technology that combines the use of a targeting ligand, such as a fluorescently-labeled antibody or peptide, with a wide-field endoscope that is sensitive to fluorescence. The ligand binds specifically to cell surface targets expressed uniquely by pre-malignant and malignant cells but not by normal ones. This approach generates an image that reflects the biological behavior of the mucosa as an adjunct to the conventional white light image that provides structural features. Ligands specific for EGFR, ErbB2, and VEGFA have been demonstrated in proof-of-concept

clinical studies, and more targets are being developed. Multiplexed imaging methods that either detect two or more ligands in separate channels concurrently or combine the ligands into a single biochemical entity are also in progress. This strategy is being advanced to address tumor molecular heterogeneity. The imaging agents are introduced into patients with rigorous regulatory oversight by the US FDA to ensure safety. Once the methodology has been validated in multicenter studies enrolling large numbers of subjects, clinical use in prime time becomes feasible.

Symposium (XIII)

MULTIDISCIPLINARY APPROACH FOR SMALL INTESTINAL DISEASE AND INFLAMMATORY BOWEL DISEASE

PATHOGENESIS OF IBD: CURRENT STATE OF THE ART

John Chang

Department of Medicine, University of California San Diego, La Jolla, CA, USA

The inflammatory bowel diseases (IBDs) are chronic intestinal disorders that are typically categorized as one of two subtypes: Crohn’s disease and ulcerative colitis. Treatment for IBD includes untargeted therapies, such as aminosalicylates, glucocorticoids, and immunomodulators, as well as targeted biologic therapies that act through one of several mechanisms, such as neutralization of cytokines that promote inflammation or drive the

differentiation and function of specialized immune subsets; blockage of signal transduction cascades downstream of these pathways; or modulation of lymphocyte trafficking. The pathophysiology of IBD involves complex genetic, environmental, epithelial, microbial, and immune factors. I will highlight recent advances in our understanding of the pathophysiology of IBD.

Symposium (XIII)

MULTIDISCIPLINARY APPROACH FOR SMALL INTESTINAL DISEASE AND INFLAMMATORY BOWEL DISEASE

REVIEW OF PREGNANCY IN IBD

Hsu-Heng Yen

Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan

Patients with IBD are usually of young age and pregnancy is a common program while handling these patients. Consideration before, during, and after pregnancy is required to provide high-quality

care for these patients. In this talk, I will review the up-to-date information regarding issues of pregnancy in IBD

Symposium (XIII)

MULTIDISCIPLINARY APPROACH FOR SMALL INTESTINAL DISEASE AND INFLAMMATORY BOWEL DISEASE

IBD MIMICS

Chia-Jung Kuo

Department of Gastroenterology and Hepatology, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan

Inflammatory bowel disease (IBD) is a chronic and idiopathic inflammatory disease of the digestive tract showing a remitting and relapsing disease course. Ulcerative colitis (UC) and Crohn’s disease (CD) are two major forms of IBD.A single reference standard for the diagnosis of IBD does not exist. The diagnosis of IBD is based on a combination of clinical, biochemical, stool, endoscopic, cross-sectional imaging, and histological investigations. Since there is no gold standard diagnostic test, there are many disease processes that can be misdiagnosed as IBD, given its often non-specific symptoms.

The symptoms of CD and UC are largely nonspecific, and multiple other disease states may have presentations similar to those of IBD. There is a broad differential diagnosis IBD, however most of the etiologies generally fall into two categories: infectious and non-infectious. Endoscopy is an

important diagnostic and therapeutic modality in IBD. Endoscopy is used to make an initial diagnosis of IBD, distinguish CD from UC, assess the disease extent and activity and monitor response to therapy. Clinicians can accurately diagnose most cases by fully understanding the typical endoscopic findings. In some cases, however, it is difficult to differentiate IBD due to an atypical presentation. Therefore, not only endoscopic features but also clinical symptoms, as well as laboratory, pathological, and radiological findings should be considered in order to make a correct diagnosis.

Therefore, the differential diagnosis of IBD is quite broad. A careful history and physical examination may help to both narrow the differential diagnosis and order specific testing that will culminate in a diagnosis.

Symposium (XIII)

MULTIDISCIPLINARY APPROACH FOR SMALL INTESTINAL DISEASE AND INFLAMMATORY BOWEL DISEASE

WHAT CLINICIAN SHOULD KNOW ABOUT TREATMENT IN IBD

Ching-Pin Lin

Hepatic Disease Center, Chung Shan Medical University Hospital, Taichung, Taiwan

Inflammatory bowel disease (IBD), including ulcerative colitis (UC) and Crohn’s disease (CD), is a chronic and recurrent inflammatory disease that mainly relates to the intestinal tract. Over recent decades, the epidemiology of IBD has changed considerably. The early twenty-first century has witnessed a rapidly rising incidence.

American College of Gastroenterology (ACG) clinical guidelines recommend IBD management based upon disease extent, severity, and prognosis. Clinicians should risk-stratify patients based on the likelihood of severe clinical course, including assessment of perianal or penetrating phenotype, long-segment small bowel involvement (CD), extensive colitis (UC), anemia, hypoalbuminemia, elevated inflammatory markers, and weight loss, to determine an appropriate therapeutic strategy, Screening before the initiation of medical therapy for IBD including assessment of hepatic and renal function, presence of latent tuberculosis or hepatitis B infection, and assessment of thiopurine methyl transferase status before thiopurine use. Clinicians should facilitate adherence to vaccination schedules, If possible, vaccination should be scheduled before starting immunosuppression.

Conventional treatments control symptoms through pharmacotherapy, including aminosalicylates, corticosteroids (CSs), immunomodulators, and other general measures and/or surgical resection if necessary.

Recent progress in therapeutic approaches, especially the emergence of biologics, Biologics are divided into four classes based on mechanism of action. The first and largest class of biologics are agents targeting TNF, A different type of biologic is the anti-leukocyte trafficking agent vedolizumab, engineered to block α4β7, this gut specificity makes for an improved side effect profile when compared to the anti-TNFs, Another type of biologic is ustekinumab, which targets the common p40 subunit of receptors for IL-12 and 23 cytokines. New therapeutic strategies are emerging, involving small molecules: JAK inhibitor presently approved is tofacitinib, other JAK inhibitors are under investigation and development and include upadacitinib, filgotinib.

Despite biologics, around 11% of patients with UC will still require colectomy due to medically refractory disease, acute severe ulcerative colitis, mucosal dysplasia, or malignancy, and up to 3050% of patients with CD will require surgery due to medically refractory disease, or complications that respond poorly to medical management. Care for the patient with IBD should be multidisciplinary, actively engaging gastrointestinal specialists, primary care providers , other medical subspecialists ,mental health professionals, general or colorectal surgeons, nutritionists, and pharmacists. Engaging with family and caregivers may also be appropriate in formulating a plan.

Symposium (XIV)

GUT MICROBIOTA AND PRECISION MEDICINE

NOVEL INSIGHTS INTO GUT MICROBIOME IN ACUTE AND POSTACUTE COVID-19 SYNDROME

Siew C. NG

Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong

Although COVID-19 is primarily a respiratory illness, there is mounting evidence suggesting that the gastrointestinal tract is involved in this disease. We found altered gut microbiome and showed that depletion of immunomodulatory gut microorganisms may contribute to severe COVID-19 disease. The dysbiotic gut microbiota that persists after disease resolution could be a factor in developing persistent symptoms and/ or multisystem inflammation syndromes that occur in some patients after clearing the virus. Bolstering of beneficial gut species depleted in COVID-19 could serve as a novel avenue to mitigate severe disease, underscoring importance of managing patients’ gut microbiota during and after COVID-19. In a pilot study to assess the effects of a novel microbiome formula (SIM01) as an adjuvant therapy on immunological responses and changes in gut microbiota of hospitalized COVID-19 patients, the use of a novel microbiome formula SIM01 hastened antibody formation against SARS-CoV-2, reduced pro-inflammatory immune markers and restored gut dysbiosis

in hospitalized COVID-19 patients compared with subjects on standard care. The evidence of involvement of SARS-CoV-2 in the gut, the role play by gut microbiota and COVID-19 severity, and modulation of microbiota for prevention, treatment and vaccine response in COVID-19 will be discussed in this talk.

References:

1. T Zuo, …SC Ng, Alterations in Gut Microbiota of Patients With COVID-19 During Time of Hospitalization. Gastroenterology 2020.

2. YK Yeoh, T Zuo, ...SC Ng, Gut Microbiota Composition Reflects Disease Severity and Dysfunctional Immune Responses in Covid-19 Patients. Gut 2020.

3. T Zuo, …SC Ng. Depicting SARS-CoV-2 faecal viral activity in association with gut microbiota composition in patients with COVID-19. Gut 2020.

4. SC Ng and H Tilg. COVID-19 and the gastrointestinal tract: more than meets the eye. Gut 2020.

Symposium (XIV)

GUT MICROBIOTA AND PRECISION MEDICINE

GUT MICROBIOTA AND THE EFFECTIVENESS OF FMT

Cheng-Hsun Chiu

Chang Gung Microbiota Therapy Center, and Division of Pediatric Infectious Diseases, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan, Taiwan

There has been increasing interest in understanding the role of the human gut microbiome to elucidate the therapeutic potential of its manipulation. Fecal microbiota transplantation (FMT) is the administration of a solution of fecal matter from a donor into the intestinal tract of a recipient in order to directly change the recipient’s gut microbial composition and confer a health benefit. Because of the increasing use of broadspectrum antibiotics, Clostridioides difficile infection rates are soaring in frequency and severity, and the spectrum of susceptible patients is expanding beyond the traditional scope of hospitalized patients receiving antibiotics. FMT is becoming increasingly accepted as an effective and safe intervention in patients with recurrent disease, likely due to the restoration of a disrupted microbiome. Cure rates of > 90% are being consistently reported from multiple centers in different countries. FMT can be provided through a variety of methodologies,

either to the lower proximal, lower distal, or upper gastrointestinal tract. The human gut microbiome provides colonization resistance from bacterial pathogens such as C. difficile. The everincreasing understanding of how the microbiome affects health and disease suggests that human microbiome data should be included in precision medicine approaches. Understanding how broadly host–microbe associations are maintained across populations is revealing individualized host–microbiome phenotypes that can be integrated with other ‘omics’ data sets to enhance precision medicine. The presentation will focus on the role of gut microbiota in C. difficile infection and colonization and summarize the application, reported results, factors in donor selection, appropriate patient criteria, and the recent advances of FMT in the treatment of recurrent or refractory C. difficile infection and as a treatment modality in precision medicine.

Symposium (XIV)

GUT MICROBIOTA AND PRECISION MEDICINE

GUT MICROBIOTA AND THE EFFECTIVENESS OF CANCER SYSTEMATIC THERAPY

Chun-Ying Wu

College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan Division of Translational Research, Taipei Veterans General Hospital, Taipei, Taiwan President, Taiwan Microbiota Consortium

Gut microbiota has been shown to play important roles in cancer oncogenesis and the efficacy of anticancer therapy. Altered gut microbiota is found associated with resistance to chemotherapy and immune checkpoint inhibitors. Modulating gut microbiota or supplementing distinct bacterial species can reduce the risk and severity of obesity and metabolic syndrome.

Regardless of the valuable findings in animal experiments and clinical studies, a more thorough understanding of the interactions between gut microbiota and metabolic syndrome will be helpful to identify more novel strategies and measures

to treat obesity and metabolic syndrome. In the present lecture, we will discuss the roles of gut microbiota in obesity and metabolic syndrome pathogenesis, the impact of gut microbiota on the development of obesity and metabolic syndrome, and the potential development of gut microbiota intervention to treat or prevent obesity and metabolic syndrome.

This lecture will be helpful for physicians taking care of patients with metabolic syndrome, researchers focusing on metabolic syndromerelated diseases, and young members interested in learning knowledge of gut microbiota.

Symposium (XIV)

GUT MICROBIOTA AND PRECISION MEDICINE

GUT MICROBIOTA AND THE EFFECTIVENESS OF BARIATRIC SURGERY

Wei-Kai Wu

Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan

Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan

Bariatric surgery is highly effective in treating metabolic disease, including obesity, type II diabetes and non-alcoholic fatty liver disease, and has been proved to decrease the incidence of major adverse cardiovascular events. Despite a significant weight loss was usually achieved by bariatric surgery, it has been shown that some of the metabolic outcomes, such as glucose intolerance, improve earlier than the weight reduction after bariatric surgery, suggesting potential weight loss-independent mechanisms contributing to the improved metabolic effects. Recently, studies revealed a permanent alteration of gut microbiome caused by dramatic gut

anatomical changes after bariatric surgery. Of note, the altered gut microbial composition, such as increased gene richness, enriched Akkermansia muciniphila, Faecalibacterium prausnitzii and Roseburia intestinalis, as well as the changes of microbiota-dependent metabolomics, including short chain fatty acids and bile acids, have been shown to favorably correlated to the metabolic improvement. These observations suggest the effectiveness of bariatric surgery on metabolic disorder may be partly contributed by the alteration of gut microbiota and the underlying mechanisms require further investigations to be uncovered.

GI VASCULAR INTERVENTION

IR FOR VASCULAR COMPLICATION AFTER LIVER TRANSPLANTATION

Yu-Fan Cheng

Department of Radiology and Liver Transplantation Center, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan

Living donor liver transplant is an optimal solution for the urgent demand for liver graft. But recent follow-up studies revealed the potential threats that may eventually lead to graft loss. Although portal vein (PV) abnormalities are rather uncommon and merely occur in 2–13% of transplant recipients, some devastating complications are troublesome and have been an imperative challenge for postoperative management. There are certain factors that put recipients in the risk of developing PV complications, including small PV size, type of liver graft used, graft positional factors and venous conduits that are used to connect the PV of the donor and the recipient. Furthermore, previous studies have shown that PV stenosis is more commonly seen in partial than in whole-size liver grafts. Obstruction of the PV contributes to thrombus or stenosis formation at the anastomosis

site. The onset of ascites, variceal bleeding, splenomegaly and pancytopenia are the typical clinical scenarios associated with PV stenosis. Although these symptoms could also be a result of occlusion of the hepatic vein, statistically, the PV bears a relatively higher tendency for occlusion. In the past few years, these complications have been well documented and widely discussed in order to reach an ultimate solution. Interventional stent placement has shown promising results and eliminated the need for further surgical revision and metallic stent placement is being used as an initial treatment for PV occlusion. The aim of this study is to refine the technical procedures and develop a strategy to overcome the complications associated with interventional stent placement in PV occlusions in LDLT after and even during operation in both adult and children.

Symposium (XV)

GI VASCULAR INTERVENTION

EFFECTS OF TRANSJUGULAR INTRAHEPATIC PORTOSYSTEMIC SHUNT ON ABDOMINAL MUSCLE MASS IN PATIENTS WITH DECOMPENSATED CIRRHOSIS

Chih-Horng Wu

Department of Radiology, National Taiwan University Hospital, Taipei, Taiwan

Sacopenia is a common finding in patients with decompensated cirrhosis without effective therapy. These patients also suffer from complications of cirrhosis, such as variceal bleeding and refractory ascites. We aimed to examine whether a transjugular portosystemic shunt (TIPS) could improve the abdominal muscle mass assessed by cross-sectional images in patients with decompensated cirrhosis and to investigate the association of imaging-defined sarcopenia with the prognosis of such patients.

In this retrospective observational study, we enrolled 25 decompensated cirrhosis patients aged >20 who received TIPS for the control of variceal bleeding or refractory ascites between April 2008 and March 2021. All of them underwent preoperative computed tomography or magnetic resonance imaging, which was used to determine psoas muscle (PM) and paraspinal muscle (PS) indices at the third lumbar vertebra. First, we compared baseline muscle mass with muscle mass at 6 and 12 months after TIPS placement

and analysed PM- and PS-defined sarcopenia to predict mortality.

Among 25 patients, 20 (80.0%) and 12 (48.0%) had PM- and PS-defined sarcopenia, respectively, at baseline. In total, 16 and 8 patients were followed up for 6 and 12 months, respectively. By 6 months after TIPS placement, the PM area and index had significantly larger than baseline images (13.82 ± 6.84 to 16.21 ± 7.18 cm2, p = 0.013, and 4.78 ± 1.95 to 5.61 ± 2.02 cm2/m2, p = 0.013, respectively). All imaging-based muscle measurements performed 12 months after TIPS placement were significantly greater than the baseline measurements (all p < 0.001). Unlike patients with PS-defined sarcopenia (p = 0.529), patients with PM-defined sarcopenia had poorer survival than did patients without (p = 0.036).

PM and PS mass in patients with decompensated cirrhosis may increase by 6 or 12 months after TIPS placement. Patients with preoperative PM-defined sarcopenia may suggested poorer survival.

GI VASCULAR INTERVENTION

CURRENT TRENDS IN THE TRANSCATHETER MANAGEMENT OF GASTRIC VARICEAL AND OTHER PORTAL HYPERTENSION RELATED HEMORRHAGE

Chien-An Liu

Division of abdominal imaging, Department of Radiology, Taipei Veterans General Hospital, Taipei, Taiwan

Portosystemic shunt (PS), commonly seen in cirrhosis, includes splenorenal, gastrorenal, and dilated paraumbilical veins. A spectrum of clinical manifestations can happen, ranging from recurrent hepatic encephalopathy, and variceal hemorrhage to progressive hepatic failure. Among them, bleeding caused by varices is one of the major complications of portal hypertension. Gastric varices (GVs) own a higher mortality rate because there is more severe blood loss and a higher

recurrence. Techniques of shunt embolization such as balloon-assisted retrograde transvenous occlusion (BRTO), plug-assisted retrograde transvenous occlusion (PARTO), or coil-assisted retrograde transvenous obliteration (CARTO) are efficacious in controlling bleeding, and associated with minimal complications. In this talk, the pathophysiology of portal hypertension-related varices and various techniques for managing hemorrhage will be presented.

Symposium (XVI)

NOVEL AND EMERGING DIAGNOSIS OF GERD

THE ADDED VALUE OF IMPEDANCE-PH IN THE DIAGNOSIS OF GERD

Edoardo Savarino Division of Gastroenterology, Department of Surgery, Oncology and Gastroenterology, University of Padua, Padua, Italy

The prevalence of GERD based on symptom perception in individual cross-sectional surveys ranges from 2.5% to more than 25%, being it much lower in Asia than in Western countries. Moreover, it is worth noting that the overall prevalence of GERD has increased since 1995 and consequently also the disease burden is enhanced. Proton pump inhibitors represent the mainstay of GERD treatment. However, although they are effective for symptoms relief in most cases, approximately 40% of the patients do not respond or respond partially to acid suppressive therapy. Further investigation identifies three broad patterns of symptom generation: true reflux disease, symptoms triggered by reflux episodes without pathologic reflux, and non-GERD mechanisms of symptom generation, including functional symptoms. Reflux monitoring allows characterization of esophageal reflux burden and subsequent customization of management.

Combined pH-impedance monitoring has impedance electrodes in addition to pH sensor(s), and allows identification of reflux episodes irrespective of pH. Additionally, pH-impedance monitoring can separate reflux episodes from swallows, measure the proximal extent of reflux, evaluate air movement, and identify supragastric belching and rumination episodes. However, interpretation is labor-intensive, and many of the existing impedance-driven metrics have not been demonstrated to predict treatment outcome. Novel

impedance metrics have the potential to improve the clinical utility of ambulatory pH-impedance monitoring. Numbers of reflux episodes can be accurately recorded during impedance-based reflux monitoring, but this has limited value as a stand-alone metric in predicting treatment outcome. Instead, this can provide supplementary evidence for or against pathological GERD, where >80 episodes are abnormal, <40 episodes are physiological, and in-between values are inconclusive. Numbers of reflux episodes are also utilized in determining symptom–reflux association. Symptoms occurring within 2 min of a reflux episode are considered associated with the reflux episode. A simple proportion of associated symptoms to all symptoms defines the symptom index (SI), and is positive when >50%. A more robust metric consists of the Symptom Association Probability, which takes into account the presence or absence of reflux and/or symptoms for each 2-min segment of the study, and computes a statistical probability of symptoms and reflux episodes occurring just by chance. When the likelihood just by chance is <5% (i.e., P < 0.05), symptom association probability (SAP) is >95%, and hence positive. Symptom–reflux association is more robust when both SI and SAP are positive, and may predict better outcome from antireflux therapy when present in settings with pathological AET. When symptom reflux association is positive with physiological reflux (i.e., AET < 4%), reflux

hypersensitivity (a functional esophageal disorder) is diagnosed; in contrast, negative symptom reflux association with physiological reflux defines functional heartburn (FH). Symptom reflux association is considered a supplementary metric that complements borderline AET in defining GERD. In addition, two novel metrics can be extracted from pHimpedance studies, and are gaining importance as supplementary indicators of pathological GERD when abnormal. The first is baseline impedance, which can be accurately measured over three 10-min periods during sleep (mean nocturnal baseline impedance, MNBI). Baseline impedance is thought to be a marker of esophageal mucosal integrity, as values are low when there is mucosal inflammation, and recover when the mucosa heals. Normal values have been reported as higher than 2292 Ohms. MNBI is low in erosive and nonerosive GERD, compared to reflux hypersensitivity, FH, or normal controls. A low MNBI correlates with high AET, and can predict successful outcome from antireflux therapy. The second novel metric is the postreflux swallowinduced peristaltic wave (PSPW), which represents a reflux-triggered primary peristaltic sequence that brings salivary bicarbonate to neutralize esophageal mucosal acidification from reflux episodes. This can be identified as anterograde progression of impedance decline following a retrograde impedance episode (reflux). The proportion of reflux episodes followed by PSPW defines the PSPW index. This correlates with contraction reserve on esophageal manometry, and has impressive performance characteristics in segregating erosive and nonerosive GERD from reflux hypersensitivity, FH, and healthy controls. These novel metrics add to confidence in a reflux mechanism for symptoms, especially when AET is borderline.

References:

1. Savarino E, de Bortoli N, De Cassan C, et al. The natural history of gastro-esophageal reflux disease: a comprehensive review. Dis Esophagus. 2017 Feb 1;30(2):1-9.

2. El-Serag HB, Sweet S, Winchester CC, Dent J. Update on the epidemiology of gastrooesophageal reflux disease: a systematic review. Gut. 2014 Jun;63(6):871-80.

3. Savarino E, Zentilin P, Savarino V. NERD: an umbrella term including heterogeneous subpopulations. Nat Rev Gastroenterol Hepatol. 2013 Jun;10(6):371-80.

4. Gyawali CP, de Bortoli N, Clarke J, Marinelli C, Tolone S, Roman S, Savarino E. Indications and interpretation of esophageal function testing. Ann N Y Acad Sci. 2018 Dec;1434(1):239-253.

5. Frazzoni M, Frazzoni L, Ribolsi M, Bortoli N, Tolone S, Russo S, Conigliaro R, Penagini R, Fuccio L, Zagari RM, Savarino E. Applying Lyon Consensus criteria in the work-up of patients with proton pump inhibitory-refractory heartburn. Aliment Pharmacol Ther. 2022 Jun;55(11):1423-1430.

6. Gyawali CP, Tutuian R, Zerbib F, Rogers BD, Frazzoni M, Roman S, Savarino E, de Bortoli N, Vela MF, Sifrim D. Value of pH Impedance Monitoring While on Twice-Daily Proton Pump Inhibitor Therapy to Identify Need for Escalation of Reflux Management. Gastroenterology. 2021 Nov;161(5):14121422.

7. Gyawali CP, Kahrilas PJ, Savarino E, Zerbib F, Mion F, Smout AJPM, Vaezi M, Sifrim D, Fox MR, Vela MF, Tutuian R, Tack J, Bredenoord AJ, Pandolfino J, Roman S. Modern diagnosis of GERD: the Lyon Consensus. Gut. 2018 Jul;67(7):1351-1362.

Symposium (XVI)

NOVEL AND EMERGING DIAGNOSIS OF GERD

INTELLIGENT ANALYSIS OF IMPEDANCE STUDIES

Benjamin D. Rogers

Division of Gastroenterology, Hepatology, and Nutrition, University of Louisville School of Medicine, Louisville, KY, USA

Artificial Intelligence is frequently being employed across medical specialties, with Gastroenterology in particular seeing a rapid expansion of its usage. Ambulatory reflux monitoring can be performed via wireless pH catheters or capsules but is frequently carried out using combined pH and impedance analysis. Although this provides an in-depth evaluation of

esophageal events, analysis is time consuming and requires significant expertise. Further, existing commercially available software is known to have imperfect sensitivity and specificity in the identification of reflux events. Machine learning may provide an opportunity to both reduce analysis times and improve diagnostic accuracy.

Symposium (XVI)

NOVEL AND EMERGING DIAGNOSIS OF GERD

ARTIFICIAL INTELLIGENCE FOR MEASURING IMPEDANCE-PH METRICS

Ming-Wun Wong

Division of Gastroenterology, Department of Medicine, Hualien Tzu Chi Hospital, Hualien, Taiwan

Reflux episodes and postreflux swallowinduced peristaltic wave (PSPW) index are useful impedance metrics that can augment the diagnosis of gastroesophageal reflux disease (GERD). However, manual analysis of pH-impedance tracings is time-consuming, resulting in limited use of these novel impedance metrics. Recently, a supervised learning artificial intelligence (AI) model was established for identifying reflux

episodes and PSPW index, which achieved more than 80% overall accuracy and excellent inter-rater agreements between AI and manual interpretations for individual numbers of reflux episodes and PSPW index. AI has the potential to accurately and efficiently measure novel impedance metrics for augmenting diagnosis and guiding personalized management of GERD.

Symposium (XVI)

NOVEL AND EMERGING DIAGNOSIS OF GERD

OBJECTIVE DIAGNOSIS OF EXTRAESOPHAGEAL REFLUX

Han-Chung Lien

Division of Gastroenterology, Taichung Veterans General Hospital, Taichung, Taiwan

Conceptual discrepancies exist between gastroenterology specialty and otolaryngology specialty, regarding management of extraesophageal reflux disease or laryngopharyngeal reflux. The major obstacles in this field include a lack of gold standard tests and lack of reliable data to support clinical response to anti-reflux treatments. With the advancement of reflux monitoring techniques, detection of supra-esophageal reflux may gradually become feasible in clinical settings, thus may be able to distinguish reflux from non-reflux etiologies

in this heterogenous patient group who suffer from various chronic reflux-related respiratory symptoms. Using 3-pH-sensor or pharyngeal impedance-pH monitoring, we recently found that patients with suspected LPR and pathological reflux are more likely to response to proton pump inhibitor therapy. In addition, validation of pharyngeal reflux episodes may be crucial in the diagnosis of laryngopharyngeal reflux. Given the limited use of reflux monitoring in the clinical settings, mucosal impedance measurement may also play a role for wide spread use in the future.

Symposium (XVII)

ENDOSCOPIC BARIATRIC THERAPY

EVOLUTION AND CURRENT STATE OF BARIATRIC ENDOSCOPY: FOCUSING ON INTRA-GASTRIC BALLOONS

Wey-Ran Lin

Department of Gastroenterology and Hepatology, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan

Endoscopic bariatric therapies (EBTs) have played a significant role in obesity treatment over the last decades, successfully filling the gap between lifestyle modification/pharmacotherapy and bariatric surgery. Among EBTs procedures, intra-gastric balloons (IGBs) have generally been considered as an effective, reversible, less invasive and non-surgical bariatric procedure. These IGBs can provide a continuous sensation of satiety that help maintenance of small amount diet and result

in body weight loss. A wide variety of balloon types have been developed due to their easy application, reversibility and good short-term results. However, some studies show that IGBs have limited longterm effects after balloon removal. This talk will discuss six most commonly used IGBs, the liquidfilled balloons Orbera, Spatz3, ReShape Duo and Elipse, and the gas-filled Heliosphere and Obalon, and further focus on Orbera since this is currently the only choice of IGBs in Taiwan.

Symposium (XVII)

ENDOSCOPIC BARIATRIC THERAPY

CLINICAL DEVELOPMENTS AND METABOLIC INSIGHTS IN BARIATRIC SURGERY

Po-Jen Yang

Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan

The first bariatric surgery, the jejunoileal bypass, was performed in the 1950s. The surgery bypasses most of the intestines to reduce body weight, but leads to many complications because of severe malabsorption. A lot of surgical procedures were developed by reducing the gastric volume and intestinal absorption to control the body weight in the patients with morbid obesity afterwards. However, many of the procedures, such as vertical banded gastroplasty, biliopancreatic diversion, and adjustable gastric band, are abandoned as time passes. Laparoscopic sleeve gastrectomy and gastric bypass are the most common bariatric surgeries nowadays. There are still several modified and novel surgical procedures developed in the recent years, which are trying to reduce the complications and improve the quality of life.

Bariatric surgery is the only effective treatment for the patients with severe obesity to achieve long-term weight loss. Besides, bariatric surgery also significantly improves many obesity related disorders, such as type 2 diabetes, hypertension, dyslipidemia, obstructive sleep apnea, and nonalcoholic fatty liver diseases. Therefore, it is also named as metabolic surgery. Bariatric surgery induces a lot of physiologic alterations. The levels of gut hormone, bile acid, vagal signals, gastrointestinal motility, and gut microbiota are all changes after operation. Besides, the patients have reduced hunger and increased satiety, and change their favors of food. Studies for the pathophysiology of bariatric surgery will be helpful for the treatment of obesity and metabolic diseases.

Symposium (XVII)

ENDOSCOPIC BARIATRIC THERAPY

ENDOSCOPY: A GREAT CLOSER FOR POST-BARIATRIC SURGERY COMPLICATIONS

Chi-Ming Tai

Division of Gastroenterology and Hepatology, Department of Internal Medicine, E-Da Hospital, Kaohsiung, Taiwan

Bariatric surgery remains the only therapy that reliably achieves sustained weight loss and significant reduction in obesity-related comorbidities. The rising prevalence of obesity and the success of surgical interventions lead to a marked increase in the number of bariatric surgeries, including Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG). A multidisciplinary team is needed to provide better care for bariatric surgical patients, and the role of the endoscopists has been gradually increasing in the management of these patients. It is therefore essential for the endoscopists to be knowledgeable in all areas of their care, including preoperative evaluation,

intraoperative endoscopy, and the postoperative recognition and management of complications. The most common complications after SG are leak, stricture, and erosive esophagitis. Complications at the bypassed stomach or common bile duct are especially challenging in post-RYGB patients. Endoscopists caring for these patients should become familiar with the post-bariatric surgical anatomy, potential complications, common presenting symptoms, anticipated endoscopic findings, and endoscopic management. In addition, endoscopists should collaborate early with the surgeon of the patient when managing complications.

The 6th Joint Session between TDDW – JDDW – KDDW

LOWER GI: CURRENT TREND OF THE MANAGEMENT OF POLYPOSIS SYNDROME: ENDOSCOPIC AND SURGICAL PERSPECTIVES

CURRENT STATUS OF POLYPOSIS SYNDROME IN SMALL INTESTINE

Chen-Wang Chang

Department of Gastroenterology and Hepatology, Mackay Memorial Hospital, Taipei, Taiwan

Colorectal cancer is the commonest gastrointestinal neoplasia and up to 1 % develop in the context of gastrointestinal polyposis syndromes. There are some health-related policies for colorectal cancer screening now, but no specific policies for intestinal polyposis syndromes screening. Due to intestinal polyposis syndromes, and also the small bowel cancer are relatively rare, and ignored easily. Even though, it is important for clinicians to recognize the potential risks of intestinal polyposis syndromes.

Intestinal polyposis syndromes include both nonhereditary and hereditary types and are relatively rare. They are associated with considerable morbidity and mortality from both malignant and non-malignant manifestations such as bleeding, intussusception and bowel obstruction. Based on histology, intestinal polyposis syndromes can be classified into hamartomatous polyposis syndromes, in which the polyps are predominantly hamartomatous, familial adenomatous polyposis (FAP), in which the polyps are predominantly adenomatous, and other rare polyposis syndromes.

The hamartomatous polyposis syndromes

are uncommon and account for less than 1% of colorectal cancer cases in North America. Hamartomatous polyposis syndromes encompass several syndromes, including: Peutz-Jeghers Syndrome, juvenile polyposis syndrome and PTEN hamartoma tumor syndromes etc. The endoscopic findings and the prognosis were different in the current reports. FAP is caused by a mutation in the APC gene located on chromosome 5q21 and has an incidence of 1: 10000. Patients with FAP and patients with Lynch syndrome have an increased risk of developing small intestinal neoplasia. In both conditions, the lifetime risk to develop small bowel cancer is estimated to be around 5%. Current studies in FAP patients have revealed that jejunal and ileal polyps occur frequently, especially in those with extensive duodenal polyposis. Nevertheless, the clinical relevance of small bowel polyps beyond the duodenum appears to be limited.

The clinical features of intestinal polyposis syndromes are divergent, but some of them sometimes lethally. Timely diagnosis of the polyposis syndromes allows for appropriate surveillance and management.

The 6th Joint Session between TDDW – JDDW – KDDW

LOWER GI: CURRENT TREND OF THE MANAGEMENT OF POLYPOSIS SYNDROME: ENDOSCOPIC AND SURGICAL PERSPECTIVES

THE MANAGEMENT OF SURGICAL TREATMENT AND EXTRAINTESTINAL LESIONS IN PATIENTS WITH FAMILIAL ADENOMATOUS POLYPOSIS BASED ON JAPANESE COHORT

Kensuke Kumamoto

Department of Gastroenterological Surgery, Kagawa University, Kagawa, Japan

The diagnosis of familial adenomatous polyposis (FAP) can be made clinically, and prophylactic colectomy is usually performed at an appropriate time after diagnosis. In addition, although ileal pouch-anal anastomosis (IPAA) has the lowest cancer risk, prophylactic colectomy for FAP may be acceptable for ileorectal anastomosis (IRA) depending on the case, as complications such as defecation control and sexual dysfunction

are observed. In selecting this technique, it is desirable to understand the advantages and disadvantages of each method. Surveillance for desmoid tumors and duodenal adenomas (adenocarcinoma) that affect life prognosis after colectomy is also important in patients with FAP. We also report on the frequency of occurrence and treatment strategies for these in Japan.

The 6th Joint Session between TDDW – JDDW – KDDW

LOWER GI: CURRENT TREND OF THE MANAGEMENT OF POLYPOSIS SYNDROME: ENDOSCOPIC AND SURGICAL PERSPECTIVES

CURRENT APPROACHES IN MANAGING SERRATED POLYPOSIS SYNDROME IN KOREA

Hyun Jung Lee

Department of Internal Medicine, Department of Gastroenterology, Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea

Serrated polyposis syndrome (SPS) is characterized by numerous colorectal serrated polyps and is associated with a high risk of colorectal cancer (CRC). The diagnosis of SPS is based on the cumulative lifetime number of HPs, TSAs, and SSPs in a patient who meets 1 of the 2 following World Health Organization (WHO) criteria including: at least 5 serrated lesions or polyps proximal to the rectum, all >5 mm, with 2 or more that are >10 mm, or more than 20 serrated lesions or polyps of any size distributed throughout the large bowel, with at least 5 proximal to the rectum.1 SPS is the most common polyposis syndrome that recent evidence suggests a prevalence of up to 1:127 (0.8%) individuals in screening cohorts based on fecal occult blood testing and up to 1:238 (0.42%) in primary screening cohorts by subsequent surveillance colonoscopies.2

The etiology of SPS is still unknown, however, seems multifactorial and includes the consequences of lifestyle-associated environmental factors such as smoking and high body mass index.3 Genetic studies have not identified high-penetrance germline mutations yet, although pathogenic germline variants of RNF43 have been reported in very small numbers of SPS patients.4

Current estimates of CRC incidence in SPS

based on several cohort studies range widely, between 15% and 35%, with which most were diagnosed before or at the moment of SPS diagnosis. In addition, even during surveillance in prediagnosed SPS patients, the CRC risk is increased (5-year cumulative risk 1.5%–1.9%).5 In a recent meta-analysis, CRC risk at the time of diagnosis was 14.7% (95% CI, 11.4%–18.8%), while risk during surveillance was 2.8% (95% CI, 1.8%–4.4%). In addition, SPS patients had a high incidence of history of CRC prior to SPS diagnosis (7.0%; 95% CI, 4.6%–11.7%).6 Regarding extracolonic cancers, four retrospective studies reported high risk of extracolonic cancers in SPS patients compared to the general population. However, results are conflicting and all studies are of older age and performed retrospective analyses.

Crucial in preventing CRC development in SPS patients are consistent, proper clearing of all clinically relevant polyps followed by strict endoscopic surveillance is key in the management of SPS. In most recent ESGE guideline, endoscopic removal of all polyps ≥5mm and all polyps of any size with optical suspicion of dysplasia in individuals with SPS is recommended before and after entering surveillance. A surveillance interval of 1 year is advised after the resection of ≥1 advanced polyp or ≥5 non-advanced clinically relevant polyps. A

surveillance advice of 2 years is advised in any other situation.7 Like other polyposis syndromes, surgical management should be considered when endoscopic management is no longer feasible. Furthermore, CRC risk was elevated 5-fold in firstdegree relatives of patients with SPS and any-site adenoma/carcinoma risk was also increased 2.6fold.8 Therefore, these individuals are advised to undergo screening colonoscopy every 5 years starting at the age of 45 years.

References:

1. World Health Organisation. Classification of Tumours of the Digestive Tract. Lyon: IARC Press.

2. JEG IJ, Bevan R, Senore C, et al. Detection rate of serrated polyps and serrated polyposis syndrome in colorectal cancer screening cohorts: a European overview. Gut 2017;66:1225-1232.

3. Carballal S, Rodríguez-Alcalde D, Moreira L, et al. Colorectal cancer risk factors in patients with serrated polyposis syndrome: a large multicentre study. Gut 2016;65:1829-1837.

4. Yan HHN, Lai JCW, Ho SL, et al. RNF43 germline and somatic mutation in serrated neoplasia pathway and its association with BRAF mutation. Gut 2017;66:1645-1656.

5. JE IJ, Rana SA, Atkinson NS, et al. Clinical risk factors of colorectal cancer in patients with serrated polyposis syndrome: a multicentre cohort analysis. Gut 2017;66:278-284.

6. Muller C, Yamada A, Ikegami S, et al. Risk of Colorectal Cancer in Serrated Polyposis Syndrome: A Systematic Review and Meta-analysis. Clin Gastroenterol Hepatol 2022;20:622-630.e7.

7. van Leerdam ME, Roos VH, van Hooft JE, et al. Endoscopic management of polyposis syndromes: European Society of Gastrointestinal Endoscopy (ESGE) Guideline. Endoscopy 2019;51:877-895.

8. Kanth P, Yu Z, Keener MB, et al. Cancer Risk in Patients With and Relatives of Serrated Polyposis Syndrome and Sporadic Sessile Serrated Lesions. Am J Gastroenterol 2022;117:336-342.

The 6th Joint Session between TDDW – JDDW – KDDW

LOWER GI: CURRENT TREND OF THE MANAGEMENT OF POLYPOSIS SYNDROME: ENDOSCOPIC AND SURGICAL PERSPECTIVES

ROLE OF ENDOSCOPISTS IN HAMARTOMATOUS POLYPOSIS SYNDROME

Chen-Shuan Chung

Division of Gastroenterology and Hepatology, Department of Internal Medicine, Far Eastern Memorial Hospital, New Taipei City, Taiwan

Hamartomatous polyposis syndrome (HPS) is a rare disease entity composing of genetic syndromes in an autosomal dominant manner, which includes Peutz-Jeghers syndrome, Juvenile polyposis syndrome, PTEN hamartoma tumor syndrome, hereditary mixed polyposis syndromes as well as other syndromes such as Gorlin syndrome and multiple endocrine neoplasia syndrome 2B. It is characterized by the development of multiple hamartomatous polyps in the gastrointestinal tract and several

extra-intestinal findings such as dermatological and dysmorphic features or intestinal and extraintestinal cancers. The initial clinical manifestation and diagnosis of HPS are commonly related to complications from gastrointestinal polyposis, such as bleeding, obstruction and intussusception of intestines. In this lecture, I will be reporting the role of endoscopists in HPS in terms of disease diagnosis, management of complications as well as surveillance for malignancy.

The 6th Joint Session between TDDW – JDDW – KDDW

LOWER GI: CURRENT TREND OF THE MANAGEMENT OF POLYPOSIS SYNDROME: ENDOSCOPIC AND SURGICAL PERSPECTIVES

CURRENT CLINICAL PRACTICE FOR FAMILIAL ADENOMATOUS POLYPOSIS IN JAPAN

–A NATIONWIDE MULTICENTER STUDY–

Naohito Beppu

Division of Lower Gastrointestinal Surgery, Department of Surgery, Hyogo College of Medicine, Hyogo, Japan

In Japanese patients with familial adenomatous polyposis (FAP), colectomy tends to be postponed or avoided. This study aimed to clarify the current clinical practice from a Japanese multi-center cohort study database. We analyzed the records of 250 patients with non-dense FAP who did not require colorectal cancer removal. The clinical outcomes were compared between patients who received colectomy (n=142) (Group A) and those who did not receive colectomy (n=108) (Group B). The colectomy rate based on the age at the final follow-up examination was 46%, 60%, 54%, 65%, at ≤29, 30–39, 40–49 and ≥50 years, respectively. The development of colorectal cancer did not differ between Groups A and B (25% vs. 34% p=0.19); however, colorectal cancer was diagnosed at the

Tis stage in 95% of the patients with colorectal cancer in Group B, and 48% of the patients with colorectal cancer in Group A (p<0.01). Regarding survival, all patients in Group B were alive at the final follow-up examination. In contrast, 6 patients in Group A died, including 3 patients with desmoid tumors and one with colon cancer. Over onethird of patients with non-dense FAP in Japan did not receive colectomy at >30 years of age, and patients managed without colectomy showed acceptable survival with the early diagnosis of colorectal cancer, and a very low incidence of desmoid tumor development, indicating that this approach represents a potential option for the management of selected non-dense FAP patients.

The 6th Joint Session between TDDW – JDDW – KDDW

LOWER GI: CURRENT TREND OF THE MANAGEMENT OF POLYPOSIS SYNDROME: ENDOSCOPIC AND SURGICAL PERSPECTIVES

CLINICAL PERSPECTIVES IN THE MANAGEMENT OF SERRATED POLYPOSIS SYNDROME

Min Seob Kwak

Division of Gastroenterology, Internal Medicine, Kyung Hee University Hospital, Seoul, Korea

Colorectal cancer (CRC) mainly occurs through two pathways. The colorectal adenomacarcinoma sequence represents the predominant process by which CRC originates and it refers to the development of CRC from a precursor dysplastic polypoid adenomatous lesion. The risk of CRC development from an adenoma has been associated with the size of the adenoma and the growth pattern (Prescence of villous component).

On the other hand, a minority of CRC seems to develop from serrated polyps, whereas the serrated mechanism may be culpable for the origin of 1015% of all CRC.

Serrated polyps represent a miscellaneous group of polyps with specific histologic, morphologic and molecular genetics features, which include the following three subsets: hyperplastic polyps, sessile serrated lesions (SSLs) and traditional serrated adenomas (TSAs). In particular, hyperplastic polyps represent the most common subgroup of serrated polyps and are frequently flat, <5 mm in size and situated mainly in the distal colon. Moreover, endoscopically they are identified as lesions with a pale color or a color approximating to the normal mucosa and their boundaries are not always distinct.

Serrated polyposis syndrome (SPS) is a clinical phenotype characterized by the presence

of multiple serrated polyps, which is known to be a high-risk condition for CRC.

The World Health Organization (WHO) has recently updated the diagnostic criteria for SPS to include either of the following:

1) ≥5 serrated polyps ≥ 5 mm in size proximal to the rectum with ≥ 2 being ≥ 10 mm; or

2) >20 serrated polyps of any size throughout the bowel with ≥ 5 proximal to the rectum.

SPS has been considered a very rare disease, showing a prevalence of up to 1:111 (0.9%) individuals in screening cohorts based on fecal occult blood testing and up to 1:238 (0.42%) in primary screening cohorts by subsequent surveillance colonoscopies.

Therefore, the evidence for SPS is scanty and controversial and its management is a debated topic and requires colonoscopy surveillance at regular intervals and removal of precursor CRC lesions.

SPS remains an underestimated and undetected condition, which is strongly associated with CRC development via the serrated pathway.

Increased awareness, the rapid development of endoscopic techniques, and application of WHO’s criteria are required for timely identification of patients with SPS. Moreover, surveillance at regular intervals and removal of precursor CRC lesions are mandatory for the management of SPS.

The 6th Joint Session between TDDW – JDDW – KDDW

UPPER GI: UPDATES ON THE DIAGNOSIS, MANAGEMENT AND SURVEILLANCE OF BARRETT’S ESOPHAGUS

ENDOSCOPIC TREATMENT OF BARRETT’S ESOPHAGUS WITH DYSPLASIA

Wen-Lun Wang

Division of Gastroenterology, Department of Internal Medicine, E-Da Hospital, Kaohsiung, Taiwan

Barrett’s esophagus (BE), a precursor for esophageal adenocarcinoma (EAC), is defined as salmon-colored mucosa extending more than 1 cm proximal to the gastroesophageal junction with histological evidence of intestinal metaplasia. The actual risk of EAC in nondysplastic Barrett’s esophagus (NDBE) is low with an annual incidence of 0.3%. The mainstay in the management of NDBE is control of gastroesophageal reflux disease along with enrollment in surveillance programs. However, BE with dysplasia has a higher cancer progression risk, and the management of Barrett’s dysplasia or early cancers has evolved in recent years. Endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD)

are the initial interventions of choice for nodular BE, with ESD reserved for endoscopists highly trained in the technique and for larger lesions that would warrant en bloc resection. Resection should then be followed by ablative therapy, which remains first line in the treatment of BE with visible dysplasia. Although there is a myriad of ablation techniques available to the endoscopist, recent review has found that radiofrequency ablation (RFA) continues to have the most robust safety and efficacy data to support its use despite a relatively high rate of recurrence. We will review and update the guidelines and quality indicators of endoscopic management for Barrett’s esophagus with dysplasia.

The 6th Joint Session between TDDW – JDDW – KDDW

UPPER GI: UPDATES ON THE DIAGNOSIS, MANAGEMENT AND SURVEILLANCE OF BARRETT’S ESOPHAGUS

PERSPECTIVES ON CUTTING-EDGE ENDOSCOPY FOR DIAGNOSING SUPERFICIAL BARRETT’S ESOPHAGUS-RELATED NEOPLASIA IN JAPAN

Kenichi Goda Department of Gastroenterology, Dokkyo Medical University, Tochigi, Japan

Barrett’s esophagus (BE) is a precursor of esophageal adenocarcinoma, which includes BErelated neoplasms (BERN), one of the most rapidly increasing cancers in Western countries. BERN are currently rare in Japan; however, patients with BE and BERN are increasing gradually as the prevalence of gastroesophageal reflux disease has increased. Early detection of BERN is essential for good prognosis; however, superficial BERN where invasion is confined to the submucosal layer is often hard to detect if only white-light endoscopy is used. Random biopsy using white light endoscopy is recommended for detecting superficial BERN in western countries. In Japan, we commonly perform target biopsy directed by magnification endoscopy. Studies have shown that magnification endoscopy is a potential tool for detecting and characterizing superficial BERN. Several magnification endoscopic classifications have been proposed that are based on the surface and vascular patterns visualized by Narrow Band Imaging (NBI). However, none of the classifications are widespread because the classifications were all complicated. A simplified NBI classification, namely the BING classification, was recently proposed, but the classification may be too simple and to fully understand because of a lack of adequate description of diagnostic criteria.

We developed a new simplified classification system for magnification endoscopy, namely the Japan Esophageal Society [JES] BE classification, to identify superficial BERN. The classification incorporated diagnostic criteria for early gastric cancer that is easily understood by Asian endoscopists who are familiar with endoscopic diagnosis of early gastric cancer and proposed an optimal diagnostic algorism for practical endoscopy. A nationwide multicenter study showed that all values of diagnostic accuracy and interobserver agreement were significantly or substantially high both in experts and non-experts (Sensitivity 87% and 87%, Specificity 97% and 98%, κ-value 0.75 and 0.79, respectively). In addition to utility in the detection, Japanese guideline recommended to use magnification endoscopy for diagnosing lateral extent of superficial BERN prior to endoscopic resection.

Recently, artificial intelligence (AI) systems applied for the endoscopic diagnosis of BERN were first developed and validated in western countries. Most recently, AI system was developed in Japan and showed the potential to enable the real-time detection of superficial BERN. AI-driven diagnostic systems will be a challenge that we should address now.

The 6th Joint Session between TDDW – JDDW – KDDW

UPPER GI: UPDATES ON THE DIAGNOSIS, MANAGEMENT AND SURVEILLANCE OF BARRETT’S ESOPHAGUS

BARRETT’S ESOPHAGUS: THE GAP IN PERSPECTIVES BETWEEN ASIAN AND WESTERN COUNTRIES

Kee Wook Jung

Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea

Endoscopists consider Barrett esophagus (BE) to be a tongue-like projection above the esophagogastric junction (EGJ).1,2 The guidelines from Western countries suggest the use of the upper end of the gastric mucosal folds as the border of the EGJ; conversely, some Japanese studies suggest the use of the distal extent of the palisade vessels.1,3-5 Moreover, the criteria for pathological diagnosis of BE still differs among the countries.5,6 British and Japanese guidelines do not accept the presence of intestinal metaplasia as the diagnostic criteria of BE.6-8 However, the presence of intestinal metaplasia usually depends on the number of biopsies.9 The American College of Gastroenterology recently published new guidelines that necessitate columnar mucosa of at least 1 cm in length for a diagnosis of BE.10 However, in some Japanese studies, the biopsy was performed at a length of less than 1 cm, and it was called an ultrashort segment BE.6 Moreover, BE cases in most Asian countries are less than 1 cm above EGJ.11 Finally, BE surveillance is clinically important for identifying the adenocarcinoma risk from BE.10,12 Western countries have a significantly higher prevalence of esophageal adenocarcinoma due to prevalent gastroesophageal reflux disease (GERD).10,12 In contrast, in Asian countries, esophageal adenocarcinoma is still rare compared

with squamous cell carcinoma.11,13,14 A difference in perspectives remains between Western and Asian countries. However, owing to changing dietary habits and increasing obesity, GERD is now becoming an issue even in Asian countries.11 We, Asian doctors, therefore, may soon confront the threat of increased BE risk, and thus, exercising caution in the detection and surveillance of BE is necessary.11

References:

1. Sharma P. Barrett Esophagus: A Review. JAMA 2022;328:663-671.

2. Singh R, Jayanna M, Wong J, et al. Narrowband imaging and white-light endoscopy with optical magnification in the diagnosis of dysplasia in Barrett’s esophagus: results of the Asia-Pacific Barrett’s Consortium. Endosc Int Open 2015;3:E14-18.

3. Scholvinck DW, Goto O, Seldenrijk CA, et al. Detection of palisade vessels as a landmark for Barrett’s esophagus in a Western population. J Gastroenterol 2016;51:682-690.

4. Lee YC, Cook MB, Bhatia S, et al. Interobserver reliability in the endoscopic diagnosis and grading of Barrett’s esophagus: an Asian multinational study. Endoscopy 2010;42:699704.

5. Soh YSA, Lee YY, Gotoda T, Sharma P, Ho KY, Asian Barrett’s C. Challenges to diagnostic standardization of Barrett’s esophagus in Asia. Dig Endosc 2019;31:609-618.

6. Ishimura N, Okimoto E, Shibagaki K, Ishihara S. Endoscopic diagnosis and screening of Barrett’s esophagus: Inconsistency of diagnostic criteria between Japan and Western countries. DEN open 2022;2:e73.

7. Zhang L, Sun B, Zhou X, et al. Barrett’s Esophagus and Intestinal Metaplasia. Front Oncol 2021;11:630837.

8. Fitzgerald RC, di Pietro M, Ragunath K, et al. British Society of Gastroenterology guidelines on the diagnosis and management of Barrett’s oesophagus. Gut 2014;63:7-42.

9. Harrison R, Perry I, Haddadin W, et al. Detection of intestinal metaplasia in Barrett’s esophagus: an observational comparator study suggests the need for a minimum of eight biopsies. Am J Gastroenterol 2007;102:11541161.

10. Shaheen NJ, Falk GW, Iyer PG, et al. Diagnosis

and Management of Barrett’s Esophagus: An Updated ACG Guideline. Am J Gastroenterol 2022;117:559-587.

11. Tan PO, Soh AYS, Kusano C, Lee YY, Gotoda T. Is There an Increasing Incidence of Gastroesophageal Junctional Adenocarcinoma and Barrett Esophagus in Asia? A Review of Diagnostic Conundrums. Digestion 2022;103:37-44.

12. Jung KW, Talley NJ, Romero Y, et al. Epidemiology and natural history of intestinal metaplasia of the gastroesophageal junction and Barrett’s esophagus: a population-based study. Am J Gastroenterol 2011;106:14471455; quiz 1456.

13. Chung JW, Lee GH, Jung HY, et al. Clinicopathologic Characteristics of Barrett’s Cancer in Korea. Gut Liver 2008;2:193-198.

14. Jung HK, Tae CH, Lee HA, et al. Treatment pattern and overall survival in esophageal cancer during a 13-year period: A nationwide cohort study of 6,354 Korean patients. PLoS One 2020;15:e0231456.

The 6th Joint Session between TDDW – JDDW – KDDW

UPPER GI: UPDATES ON THE DIAGNOSIS, MANAGEMENT AND SURVEILLANCE OF BARRETT’S ESOPHAGUS

IDENTIFY THE HIGH-RISK POPULATION OF BARRETT’S ESOPHAGUS

Ming-Wun Wong

Division of Gastroenterology, Department of Medicine, Hualien Tzu Chi Hospital, Hualien, Taiwan College of Medicine, Tzu Chi University, Hualien, Taiwan

Barrett’s esophagus (BE) is the only known precursor lesion to esophageal adenocarcinoma (EAC). Early recognition and intervention could potentially reduce the societal burden of EAC by detecting cancers at an earlier stage and improving outcomes. However, nearly 90% of patients with EAC do not have known BE at the time of cancer diagnosis, and up to 25% of BE patients are asymptomatic, and 20% to 50% of EAC patients have no prior gastroesophageal

reflux disease (GERD) symptoms. Since patients with BE have less esophageal sensitivity and vigilance, a targeted strategy only for symptomatic subjects may be insufficient because more than half of the subjects with histologic BE did not have any GERD symptoms. Emerging AI and noninvasive modalities have the potential to improve BE identification. Thus, identifying the high-risk population of BE in Asia is warranted for costeffectiveness screening.

The 6th Joint Session between TDDW – JDDW – KDDW

UPPER GI: UPDATES ON THE DIAGNOSIS, MANAGEMENT AND SURVEILLANCE OF BARRETT’S ESOPHAGUS

WHAT IS THE BEST TREATMENT STRATEGY FOR BARRETT’S ADENOCARCINOMA? – A JAPANESE PERSPECTIVE

Yugo Iwaya

Department of Advanced Therapeutic Endoscopy, Shinshu University School of Medicine, Nagano, Japan

The incidence of Barrett’s adenocarcinoma (BAC) has been increasing in Western countries and in Eastern countries as well. The strategy of treatment for early stage BAC has also evolved dramatically from esophagectomy to endoscopic therapies in recent decades.

There is a significant discrepancy in the treatment strategy for BAC between the East and West. The resection methods differ, with ESD being more common in Japan and EMR more prevalent in the West. In our recent JGES guideline for ESD/EMR of esophageal cancer, we performed a systematic literature search and systematic review comparing ESD with EMR. We concluded that ESD was preferable for the treatment of lesions amenable for endoscopic resection (ER) owing to its higher rates of en bloc and R0 resections and a lower rate of local recurrence.

In terms of suitable candidates for ER, our guideline suggested that differentiated mucosal adenocarcinoma without lymphovascular invasion could be a good candidate. Additionally, two multicenter retrospective studies from Japan revealed that patients with submucosal adenocarcinoma ≤500 µm, without lymphovascular

invasion, without a poorly differentiated component, and measuring ≤30 mm were unlikely to exhibit lymph node metastasis. Thus, ER candidates might eventually be extended to patients who meet those criteria.

A multimodality approach that combines ER and radiofrequency ablation (RFA) has been widely adopted in the West, whereas accessibility to RFA treatment is limited in the East, including Japan. Especially for LSBE, management after ER is always challenging due to the higher incidence of metachronous cancer compared with that of SSBE and the difficulty in detecting adenocarcinoma. Since RFA is not commercially available in Japan, endoscopists have no choice but to closely monitor the remaining Barrett’s esophagus after ER. However, several advanced Japanese institutions have attempted stepwise ESD for both BAC and the residual Barrett’s esophagus, a technique in which the entire Barrett’s segment is removed in consecutive ESD sessions. As this technique requires a high level of skill, patients with BAC arising from LSBE should be aggregated at tertiary referral centers in the future.

The 6th Joint Session between TDDW – JDDW – KDDW

UPPER GI: UPDATES ON THE DIAGNOSIS, MANAGEMENT AND SURVEILLANCE OF BARRETT’S ESOPHAGUS

ESOPHAGEAL EPITHELIAL BARRIER IN BARRETT’S ESOPHAGUS

Ju Yup Lee

Division of Gastroenterology, Department of Internal Medicine, Keimyung University School of Medicine, Daegu, Korea

The tight junction complex actively regulates paracellular permeability of ions, and demarcates the boundary between basolateral and apical cell surface. The complex is made up of numerous proteins that span across the cell membranes and connect with the intracellular cytoskeleton. These proteins include claudin, occludin, zonulin, and junctional adhesion molecules (JAM), which are central proteins to tight junctions in most types of epithelia. The transmembrane claudins are thought to be the key to barrier function, because claudin-1 knockout mice typically die within 24 hours of birth given loss of fluids and electrolytes through their epithelium. Occludin is also thought to be critical in defining the barrier characteristic of the tight junction. The zonulin proteins do not traverse the space between the cells but instead provide an intracellular foundation for the tight junction. The JAM protein also has a role in tight junction regulation. An in vitro study performed in a variety of human epithelia including intestine

has shown that exposure to anti-JAM monoclonal antibodies results in a delay in occludin assembly, and decreased transepithelial resistance.

Barrett’s esophagus, as defined by >1 cm of intestinal metaplasia above the EGJ, is another pathologic condition that is associated with changes in the esophageal barrier function. Once Barrett’s esophagus has formed, the barrier structure resembles that of small bowel in that the intercellular space is dilated. While the spaces are dilated, this form of mucosa may be better at defending against acid injury. Some theorize that the structural protein change, including the inclusion of claudin-18 in Barrett’s esophagus epithelium, which is essentially missing in normal squamous epithelium, enhances its resistance to paracellular acid transport. Other studies of Barrett’s esophagus claudin composition have shown that Barrett’s esophagus has more claudin-2 and claudin-3 and less claudin-1 and claudin-5 when compared with their control subjects.

The 6th Joint Session between TDDW – JDDW – KDDW

LIVER: FINITE NUCLEOS(T)IDE ANALOGUE THERAPY: A STRATEGY TO ACHIEVE HBV FUNCTIONAL CURE

THE LONG-TERM INCIDENCES AND PREDICTORS OF HBSAG LOSS AFTER FINITE THERAPY

Chien-Hung Chen

Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan

Long-term nucleos(t)ide analogue (NA) therapy can effectively prevent the development of liver cirrhosis and HCC. Patients who achieve Hepatitis B surface antigen (HBsAg) loss have a more favorable clinical course and very low risk of HCC and HBsAg loss is considered as an ideal endpoint to cease administration of NAs. However, HBsAg loss during NA treatment is uncommon among patients with chronic hepatitis B (CHB).

Researchers have demonstrated that the HBsAg loss rate significantly increases after discontinuation of NA therapy. Recent studies showed that HBeAg-negative patients with CHB who achieved a sustained response (no virologic relapse) after cessation of NA therapy have the highest rate of HBsAg seroclearance. Moreover, patients who were not retreated for clinical relapse had higher HBsAg seroclearance rates than those who received retreatment. However, the long-term rates of HBsAg loss in patients with a sustained response or patients who experience HBV relapse

but do not require retreatment are rarely reported. Our recent study showed that the cumulative incidence of HBsAg loss at 8 years after EOT was 57.3% in Group I (sustained responders), 24.1% in Group II (virological relapse without clinical relapse and retreatment) and 35.9% in Group III (clinical relapsers without retreatment) in HBeAgnegative patients after entecavir or TDF cessation. Cox regression analysis showed NA experience, lower HBsAg levels at end-of-treatment (EOT) and higher HBsAg decline at 6 months after EOT were independently associated with HBsAg loss in Group I and Groups II+III. In Group I, the rate of HBsAg loss at 5 years for patients with HBsAg ≤40 IU/mL at EOT and HBsAg decline >0.2 log IU/mL at 6 months after EOT was 90.1%. In Group II and Group III, the rates of HBsAg loss at 6 years for patients with HBsAg decline of ≤0.15 versus >0.15 log IU/mL at 6 months after EOT were 10.7% and 47.1%, respectively (p<0.001).

The 6th Joint Session between TDDW – JDDW – KDDW

LIVER: FINITE NUCLEOS(T)IDE ANALOGUE THERAPY: A STRATEGY TO ACHIEVE HBV FUNCTIONAL CURE

DEVELOPMENT OF INTRANASAL THERAPEUTIC VACCINE TO ELIMINATE HBS ANTIGEN AND ACHIEVE FUNCTIONAL CURE IN PATIENTS WITH HEPATITIS B

Yoichi Hiasa

Department of Gastroenterology and Metabology, Ehime University Graduate School of Medicine, Ehime, Japan

HBs antigen (HBsAg) loss with anti-HBs acquisition is regarded as a functional cure, and is recognized as an ideal treatment goal for chronic hepatitis B patients (CHB). However, achieving this functional cure in these patients by nucleos(t) ide analogs (NAs) or interferon is difficult. Further, hepatitis B virus (HBV) asymptomatic carriers (ASC) are not recommended for anti-HBV therapy under current guidelines, and require drugs to achieve functional cure and minimize the risk of hepatocellular carcinoma and progression of liver injury. We have developed an intranasal therapeutic vaccine, CVP-NASVAC, which contains both HBsAg and HBcAg mixed with the mucoadhesive excipient carboxyl vinyl polymer (CVP), and have performed a phase I clinical trial in Japan.

After receiving written consent, 29 CHB with NA treatment (NA group) and 42 ASC without treatment (ASC group) were enrolled in an open-label clinical trial at Ehime University Hospital. The study design was approved by the institutional ethics committee (approval no. IRB#E18-27) and registered to jRCT (registration #jRCTs061180100). CVP-NASVAC was administered once every 2 weeks, for a total of 10 times, using a special device for nasal administration. We analyzed the data at 30 months

after the final administration.

In the NA group, 22 of 29 patients (75.9%) displayed HBsAg reduction at 6 months after end of treatment (EOT), and 2 of 29 (6.9%) achieved HBsAg loss. At 30 months, 17 of 17 patients (100%) showed HBsAg reduction. In the ASC group, HBsAg reduction was observed in 32 of 42 patients (76.2%) at 6 months, and in 19 of 24 (79.2%) at 30 months. Notably, 5 of 24 patients (20.8%) achieved HBsAg loss and functional cure. Anti-HBs was positive in 34.5% of NA and in 59.5% of ASC after treatment, and the amount of HBeAg was also decreased (-53.9% from baseline) in HBeAgpositive patients. HBcrAg was significantly reduced, and an HBV-DNA reduction of 28.6% was observed in ASC. No serious adverse events were observed among enrolled patients. Transient elevations in ALT were observed in 3 ASC patients, but resolved spontaneously without NA treatment.

The new intranasal therapeutic vaccine CVPNASVAC could offer one strategy to achieve functional cure in HBV patients, with or without NA treatment. Since the phase I trial confirmed the safety of CVP-NASVAC, we are now moving to a phase II, multi-center randomized controlled trial in Japan.

The 6th Joint Session between TDDW – JDDW – KDDW

LIVER: FINITE NUCLEOS(T)IDE ANALOGUE THERAPY: A STRATEGY TO ACHIEVE HBV FUNCTIONAL CURE

NOVEL ANTIVIRAL AND IMMUNOMODULATORY STRATEGIES IN THE QUEST TO CURE HEPATITIS B VIRUS

Su Jong Yu

Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea

The landscape for chronic hepatitis B virus (HBV) therapy is rapidly evolving. The latest generation of antiviral drugs provide robust virus suppression with a high barrier to resistance that facilitates long-term treatment. However, low rates of hepatitis B surface antigen (HBsAg) loss demonstrate that additional strategies are needed to consistency achieve a functional cure. Functional cure of HBV is defined as sustained undetectable circulating HBsAg and HBV DNA after a finite course of treatment. Barriers to functional cure of HBV include the reservoirs for HBV replication and antigen production (covalently closed circular DNA [cccDNA] and HBV DNA integration into the host genome), the high viral burden (HBV DNA and HBsAg) and the impaired host innate and adaptive immune responses against HBV. Current HBV therapeutics, 1 year of PEGylated-interferon-α (PEG-IFNα) and long-term nucleos(t)ide analogues (NUCs), rarely achieve functional cure of HBV. Stopping NUC therapy may lead to functional cure of HBV in some Caucasian patients but rarely in Asian patients. Switching from a NUC to IFN after HBV DNA suppression increases the chance of HBsAg clearance mainly in those with low HBsAg levels. Because functional cure of HBV is accompanied by recovery of antiviral immunity, a combination of direct-acting antiviral agents and immunotherapy are likely to be required. Novel

antiviral strategies that inhibit viral entry, translation and secretion of HBsAg, HBV-targeted RNA interference (RNAi), modulate capsid assembly, or target cccDNA transcription/degradation have shown promise in clinical trials. The immune system can clear HBV and establish long-term control over the virus. Sufficiently boosting HBV immunity in chronic patients has been very difficult due to immune exhaustion, immune dysregulation, and inhibitory pathways suppressing the immune response. Novel immunomodulatory approaches including checkpoint inhibitors, metabolic modulation of T cells, therapeutic vaccines, adoptive transfer of genetically engineered T cells, and stimulation of innate and B-cell immune responses are being explored and may be able to overcome exhaustion via eliciting direct antiviral effects and cancelling inhibitory mechanism. These novel approaches may be further combined with NUCs or PEG-IFNα in personalized strategies, according to virological and disease characteristics, to maximize the chance of HBV cure. The development of curative HBV therapies should be coupled with the development of standardized and validated virological and immunologic assays to confirm target engagement and to assess response. In addition to efficacy, curative therapies must be safe and affordable to meet the goal of global elimination of HBV.

The 6th Joint Session between TDDW – JDDW

– KDDW

LIVER: FINITE NUCLEOS(T)IDE ANALOGUE THERAPY: A STRATEGY TO ACHIEVE HBV FUNCTIONAL CURE

FROM FINITE THERAPY TO HBV CURE

Wen-Juei Jeng

College of Medicine, Chang Gung University, Taoyuan, Taiwan Clinical Trial Center, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan, Taiwan

The road to HBV cure by current antiviral therapy is a challenging task since the minimal HBsAg decline and only ~0.33% annual incidence of HBsAg seroclearance during nucleos(t)ide analogue (Nuc) treatment. The booming evidence of much increased HBsAg seroclearance after stopping Nuc in HBeAg negative chronic hepatitis B (CHB) patients has support the possibility to increase viral clearance by re-challenging the host immune system after a period of viral suppression

to restore the host exhausted immunity. However, relapse is not an uncommon problem after stopping Nuc and how to manage the relapse is a hot topic for too early retreatment halt the occurrence of HBsAg seroclearance but too late may lead to catastrophic events. In this session, we’ll review the updated information for the strategy of finite therapy and how to predict the flare, especially ineffective flare, during the off-therapy follow-up

The 6th Joint Session between TDDW – JDDW – KDDW

LIVER: FINITE NUCLEOS(T)IDE ANALOGUE THERAPY: A STRATEGY TO ACHIEVE HBV FUNCTIONAL CURE

THE RISK FACTOR OF HEPATOCELLULAR CARCINOMA IN CHRONIC HEPATITIS B PATIENTS ON NUCLEOS(T)IDE ANALOGUES THERAPY

Shun Kaneko

Department of Gastroenterology and Hepatologyy, Tokyo Medical and Dental University, Tokyo, Japan

Hepatitis B virus (HBV) infection remains a major public health concern. HBV infects 296 million people worldwide putting them at risk for cirrhosis and hepatocellular carcinoma (HCC). Nucleos(t)ide analogs (NA) suppress HBV replication and reduce the risk of hepatocellular carcinoma (HCC). However, NA cannot suppress carcinogenesis completely in patients with chronic hepatitis B (CHB). Although most CHB management guidelines recommend HCC surveillance every 6–12 months, it is still critical to accurately identify patients at high risk of HCC occurrence. Furthermore, surveillance leads to early detection of HCC and reduces cancerrelated death in CHB patients. There have been some reports about risk factors and predictive risk scores for HCC development. The main risk factors for HCC are host factors (age, gender),

fibrosis-related factors (cirrhosis, liver stiffness measurement, platelet counts, albumin, bilirubin), and viral factors [HBV DNA, ALT, hepatitis B e antigen (HBeAg), HBV core-related antigen (HBCrAg)]. There are also reports on metabolic factors (diabetes, obesity) and lifestyle (alcohol, smoking). Risk prediction models may estimate an individualized probability of developing HCC, which may aid in the efficiency and implementation of screening surveillance strategy. We have identified risk factors for HCC development of CHB patients particularly at baseline and during NA therapy, and have confirmed usefulness of predictive HCC risk score with Japanese nationwide cohort. In this session, we talk about the risk factor of HCC in CHB patients on NA therapy and a surveillance strategy.

The 6th Joint Session between TDDW – JDDW – KDDW

LIVER: FINITE NUCLEOS(T)IDE ANALOGUE THERAPY: A STRATEGY TO ACHIEVE HBV FUNCTIONAL CURE

A MACHINE LEARNING MODEL FOR PREDICTING HEPATOCELLULAR CARCINOMA RISK IN PATIENTS WITH CHRONIC HEPATITIS B

Hye Won Lee Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea

Machine learning (ML) algorithms can be used to overcome the prognostic performance limitations of conventional hepatocellular carcinoma (HCC) risk models. We established and validated an MLbased HCC predictive model optimized for patients with chronic hepatitis B (CHB) infections receiving antiviral therapy (AVT).

Treatment-naïve CHB patients who were started entecavir (ETV) or tenofovir disoproxil fumarate (TDF) were enrolled. We used a training cohort (n = 960) to develop a novel ML model that predicted HCC development with 5 years, and validated the model using an independent external cohort (n = 1,937). ML algorithms consider all potential interactions and do not use predefined hypotheses. The prognostic performance of our model was compared to current models.

The mean age of the patients in the training

cohort was 48 years and males predominated (68.9%). During follow-up, 69 (7.2%) patients developed HCC. Our ML-based HCC risk prediction model had an area under the receiver operating characteristic curve (AUC) of 0.930, which was better than those of the mPAGE-B (AUC = 0.773) and CAMD (AUC = 0.801) models (both P < 0.05). The better performance of our model was maintained (AUC = 0.946 vs. 0.663 for mPAGE-B and 0.674 for CAMD) in the validation cohort. Using cut-off probabilities of 0.3 and 0.5, the cumulative incidence of HCC development was differed significantly among the three risk groups (P < 0.001).

Our new ML model performed better than models in terms of predicting the risk of HCC development in CHB patients receiving AVT.

The 6th Joint Session between TDDW – JDDW – KDDW

PANCREAS, BILIARY: EARLY DETECTION, SCREENING, AND MANAGEMENT OF PANCREATIC CANER

EARLY DETECTION AND SCREENING FOR PANCREATIC CANER

Wei-Chih Liao

Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan

Pancreatic ductal adenocarcinoma (PDAC) is the most lethal cancer and comprises approximately 90% of pancreatic malignancies. Approximately 85% of PDAC patients present with unresectable locally advanced or metastatic cancer with dismal survival, whereas patients with localized stage I cancer have a 5-year survival rate of 42%. Therefore, early detection represents the most effective strategy to improve the prognosis of PDAC.

Screening for asymptomatic high-risk individuals (HRI, i.e., Peutz-Jeghers syndrome, familial pancreatic cancer with ≥ 3 first-degree relatives [FDR], familial atypical multiple mole melanoma, and hereditary pancreatitis) who carry more than 5% lifetime risk of PDAC is advocated. For HRIs, annually screening with magnetic resonance image (MRI) and/or endoscopic ultrasound (EUS) has been shown to downstage PDAC, but the benefit in survival and cost-effective need further study.

Blood-based biomarkers such as tumor markers, circulating tumor cells, exosomes, circulating tumor DNA and cell-free DNA may offer promise for early detection. Pancreatic

cancer-associated diabetes mellitus (PCDM) is a paraneoplastic phenomenon which occurs in approximately 40% of patients within 2 years before PDAC diagnosis. PCDM has been proposed as a window of opportunity for early detection, as the cancer are generally early at the onset of PCDM. Serum levels of PDAC-derived diabetogenic factors has been shown to distinguish PCDM from type 2 diabetes and might facilitate early detection of PDAC.

Early PDACs are often obscure on imaging studies, with approximately 40% of tumors < 2cm missed on computed tomography (CT). Artificial intelligence has recently shown great promise in medical image analysis. We have recently shown that an AI-based computer-assisted detection (CAD) tool could detect 92% of PDACs missed by radiologists in a tertiary center and achieved 91.4% accuracy in detecting PDAC in a nationwide realworld test dataset.

In summary, screening for HRIs may enable early detection of PDAC and improve survival. The potential usefulness of novel biomarkers and imaging analytics in facilitating early detection and warrants further investigation.

The 6th Joint Session between TDDW – JDDW – KDDW

PANCREAS, BILIARY: EARLY DETECTION, SCREENING, AND MANAGEMENT OF PANCREATIC CANER

IMPORTANCE OF SURVEILLANCE FOR HIGH-RISK GROUPS FOR DETECTION OF EARLY STAGE PANCREATIC CANCER

Susumu Hijioka

Department of Hepatobiliary and Pancreatic

National Cancer Center Hospital, Tokyo, Japan

Pancreatic cancer is still a leading incurable cancer with a poor prognosis, with a five-year survival rate of approximately 8%.

However, the five-year survival rate for tumors less than 1 cm in diameter is approximately 80%, and early detection of pancreatic cancer is thought to directly improve prognosis.

Various efforts are being made for early

Oncology,

diagnosis of pancreatic cancer, but in principle, the basic approach is to identify risk groups and conduct periodic surveillance. There are various factors that are considered to be high-risk factors for pancreatic cancer. This time, I would like to introduce some of these high-risk factors, especially familial pancreatic cancer and IPMN, and how to survey for these high-risk individuals.

The 6th Joint Session between TDDW – JDDW – KDDW

PANCREAS, BILIARY: EARLY DETECTION, SCREENING, AND MANAGEMENT OF PANCREATIC CANER

THE USE OF IMMUNOLOGIC BIOMARKERS IN THE DIAGNOSIS OF PANCREATIC CANCER

Sung Ill Jang

Department of Internal Medicine, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul, Korea

Pancreatic ductal adenocarcinoma (PDAC) is aggressive cancer and the fourth-leading cause of cancer-related mortalities worldwide. Despite enormous efforts, other than CA19-9, no definite biomarkers for PDAC detection and progression are used clinically. Identifying cancers through blood sampling is one of the most exciting advances in the cancer treatment paradigm, especially for intractable cancers, including PDAC. The goal of PDAC diagnosis is to identify cancer at an optimal stage for successful treatment for longterm survival. The immune surveillance hypothesis suggests that the immune system plays a crucial role in tumor development and progression. Crosstalk occurs between cancer and immune cells during cancer development and progression. In addition, inflammatory and angiofibrotic cytokines are unregulated and play a critical role during PDAC development and progression.

Among cytokine studies for diagnosis of PDAC, the defined cytokines were IL-1β, IL-6, IL8, IL-10, TGF, and VEGF, which are all elevated in pancreatic cancer. Individual cytokines exhibit poor diagnostic performance. In contrast, cytokine panels have superior diagnostic performance when compared to CA19-9 alone. Furthermore, cytokine panels exhibit improved diagnostic performance

when combined with CA19-9 as a biomarker. These results suggest that cytokine secretion reflects the host immunocompetence during the early stages of PDAC. As cancer progresses, the host may become immunocompromised; therefore, cytokine secretion may decrease. Conversely, CA19-9 levels increase as PDAC progress, which suggests that immune markers and CA19-9 may have a complementary relationship. Thus, a biomarker panel that combines immune markers for both cancer development and progression may increase PDAC diagnostic performance.

We reported the potential role of IL-7R in the diagnosis of PDAC as a biomarker. IL-7R is significantly upregulated in PDAC-PBMCs, and it may be a novel diagnostic marker for PDAC. Combining IL-7R and CA19-9 enhanced PDAC diagnostic performance. However, a single IL-7R cytokine is insufficient as a diagnostic, predictive, or prognostic PDAC biomarker. Instead, a panel of cytokines could provide a comprehensive tool to discriminate between patients with PDAC from healthy individuals, individuals with other nonmalignant pancreatic diseases, and individuals with other systemic malignancies. Additional prospective studies are needed to validate and build upon the findings previously presented.

The 6th Joint Session between TDDW – JDDW – KDDW

PANCREAS, BILIARY: EARLY DETECTION, SCREENING, AND MANAGEMENT OF PANCREATIC CANER

ROBOTIC SURGERY FOR PANCREATIC CANCER

Shin-E Wang

Departments of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan National Yang Ming Chiao Tung University, Taipei, Taiwan

RPD working inside the abdominal cavity with a close and limited space raises the concerns of survival and oncological outcomes in the absence of randomized trials. This study is to clarify the feasibility and justification of robotic pancreaticoduodenectomy (RPD) on survival and oncological outcomes for pancreatic adenocarcinoma.

A propensity score-matched study comparing RPD and open pancreaticoduodenectomy (OPD) was conducted, based on 6 covariates commonly used to predict survival outcomes.

A total of 130 patients with pancreatic adenocarcinoma were recruited after 1 : 1 propensity score-matching. RPD took longer operation time than OPD, with a median of 8.3 vs. 7.0 hours, P = 0.002. RPD was associated with less blood loss, lower overall surgical complication rate

and lower incidence of delayed gastric emptying. Oncologically, radicality of resection was similar between RPD and OPD, and RPD harvested more lymph nodes, with a median lymph node yield of 18, vs. 16, P = 0.038. Before propensity score matching, survival outcome was better in RPD group than OPD, with 5-year survival of 27.0% vs. 17.6%, P = 0.006. After propensity score matching, there was still a trend towards improved overall survival in RPD although difference between RPD and OPD was not significant, with 5-year survival of 24.5% vs. 19.7%, P = 0.088.

RPD is not only feasible but also justified without increasing the surgical risk and with improved survival outcome. The survival and oncological outcomes by RPD is not inferior to OPD.

The 6th Joint Session between TDDW – JDDW – KDDW

PANCREAS, BILIARY: EARLY DETECTION, SCREENING, AND MANAGEMENT OF PANCREATIC CANER

CURRENT STATUS AND FUTURE PERSPECTIVES OF EARLY DETECTION AND MANAGEMENT OF PANCREATIC CANCER IN JAPAN

Nao Fujimori

Department

of

Medicine and Bioregulatory Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan

The incidence of pancreatic ductal adenocarcinoma (PDAC) has been increasing all over the world and PDAC is the fourth leading cause of cancer-related deaths in Japan. PDAC remains as one of the most lethal malignancies, with a 5-year survival rate of approximately 8%. Early detection and appropriate management of patients with PDAC is essential to improve this dismal prognosis.

Japanese guideline for pancreatic cancer recommends cytological or histological diagnosis by pancreato-biliary endoscopy using EUS-FNA and ERCP. EUS-FNA is a gold standard method for patients with pancreatic mass, however, reports regarding needle tract seeding (NTS) after EUSFNA has been increasing especially from Japan. A recent nationwide survey in Japan revealed that the overall incidence of NTS was 0.33%, and all NTS were observed in patients who underwent transgastric EUS-FNA.1 On the other hand, ERCP is useful for the patients with main pancreatic duct stenosis because endoscopic nasopancreatic duct drainage tube placement enabled repeated pancreatic juice cytology. But ERCP has the potential risk of severe post-ERCP pancreatitis, which can be fatal although it is rare. Therefore, endoscopists should carefully decide whether to

perform ERCP or EUS-FNA, considering the risks and benefits of each case.

Appropriate management of patients with advanced PDAC is another important issue. Biliary obstruction and gastric outlet obstruction are common complications of advanced PDAC, and endoscopic treatments such as ERCP, EUS-guided biliary drainage (EUS-BD) and duodenal stent (DS) placement are required to resolve symptoms and perform subsequent chemotherapy. We recently conducted two multicenter retrospective studies regarding EUS-BD2 and DS3 for patients with malignant diseases including PDAC. From these studies, we elucidated suitable patients for respective procedures. EUS-BD will play an important role in biliary drainage as well as ERCP by overcoming issues such as procedure standardization and management of complications. We should consider inserting DS especially for suitable patients such as Glasgow Prognostic Score of 0–1 and D3 (distal part of the papilla) stricture. Advancement of not only chemotherapy but also endoscopic treatments is essential for improving the prognosis of PDAC. In this session, I would like to present the current status and future perspectives of early detection of PDAC in Japan, as well as the management of PDAC in our hospital.

References:

1. Kitano M, Yoshida M, Ashida R, et al. Needle tract seeding after endoscopic ultrasoundguided tissue acquisition of pancreatic tumors: A nationwide survey in Japan. Dig Endosc. 2022 (in press).

2. Ohno A, Fujimori N, Kaku T, et al. Feasibility and Efficacy of Endoscopic UltrasoundGuided Hepaticogastrostomy Without Dilation:

A Propensity Score Matching Analysis. Dig Dis Sci. 2022 (in press).

3. Takamatsu Y, Fujimori N, Miyagahara T, et al. The Glasgow Prognostic Score and stricture site can predict prognosis after endoscopic duodenal stent placement for malignant gastric outlet obstruction. Sci Rep. 2022; 12: 9746.

The 6th Joint Session between TDDW – JDDW – KDDW

PANCREAS, BILIARY: EARLY DETECTION, SCREENING, AND MANAGEMENT OF PANCREATIC CANER

EXOSOMAL PROTEIN PROFILING TO PREDICT THE MALIGNANT POTENTIAL OF PANCREATIC CYSTIC LESIONS

Woo Hyun Paik

Department of Internal Medicine, Seoul National University Hospital, Seoul, Korea

Pancreatic cancer has a grave prognosis because early detection is difficult. Although there are premalignant lesions of pancreatic cancer, predicting the malignant potential of these lesions is highly dependent on imaging findings, and the level of evidence for this is low. Exosomes are small extracelluar vesicles secreted by all cell types. They participate in local and systemic cellto-cell communication with cellular cargo, such as

DNA, microRNA, or proteins. Recent advances in cell specific markers and exosomal purification methods allow for determining the cellular origin of exosomes. Based on potential roles of exosomes in pathophysiology, analyzing protein component of circulating exosomes could open a new avenue to predict and identify pancreatic cystic lesions with malignant potential.

Young Investigator Award (YIA)

CONCURRENT METABOLIC DYSFUNCTION-ASSOCIATED FATTY LIVER DISEASE REDUCES THE RISK OF HEPATOCELLULAR CARCINOMA IN PATIENTS WITH UNTREATED CHRONIC HEPATITIS B

Shang-Chin Huang1,2,3,4, Tung-Hung Su2,3, Tai-Chung Tseng3,5, Chi-Ling Chen4, Shih-Jer Hsu2,3, Sih-Han Liao6, Chun-Ming Hong7, Chen-Hua Liu2,3, Ting-Yuan Lan8, Hung-Chih Yang2, Chun-Jen Liu2,3,4, Pei-Jer Chen2,3,4,5, Jia-Horng Kao1,2,3,4

1Department of Internal Medicine, National Taiwan University Hospital Bei-Hu Branch, Taipei, Taiwan

2Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan

3Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan

4Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan

5Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan

6National Taiwan University Cancer Center, Taipei, Taiwan

7Division of Hospital Medicine, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan

8Division of Rheumatology, Department of Internal Medicine, National Taiwan University Hospital Hsin-Chu Branch, Hsinchu, Taiwan

6 國立臺灣大學醫學院附設醫院癌醫中心分院

7 國立臺灣大學醫學院附設醫院內科部整合醫學科

8 國立臺灣大學醫學院附設醫院新竹分院內科部風

濕免疫科

Background: Chronic hepatitis B (CHB) and metabolic dysfunction-associated fatty liver disease (MAFLD) have been recognized as the main causes of hepatocellular carcinoma (HCC) worldwide. However, the impact of concurrent MAFLD on the risk of HCC in patients of CHB remains unclear.

Aims: Considering the increasing prevalence of MAFLD in patients with CHB, this study aimed to investigate the impact of MAFLD on CHB patients for the development of HCC.

Methods: Patients with CHB were consecutively recruited from the Integrated Medical Database of the National Taiwan University Hospital (NTUHiMD). MAFLD was defined by concurrent steatosis and either obesity, diabetes mellitus, or other metabolic risk abnormalities according to the proposed criteria. Cumulative incidence of HCC and associated factors were compared between the MAFLD and non-MAFLD groups.

2 國立臺灣大學醫學院附設醫院內科部胃腸肝膽科

3 國立臺灣大學醫學院附設醫院肝炎研究中心

4 國立臺灣大學醫學院臨床醫學研究所

5 國立臺灣大學醫學院附設醫院醫學研究部

Results: From January, 2006 to September, 2021, a total of 10,546 treatment-naïve CHB patients were included with a median followup of 5.1 years. CHB patients with MAFLD (n = 2212) had significantly fewer hepatitis B e antigen (HBeAg)-positivity, lower HBV DNA levels and Fibrosis-4 index compared with the non-MAFLD group (n = 8334). After adjustment for HBV activity and other confounding factors, concurrent MAFLD was associated with a 60% reduced risk of HCC (adjusted hazard ratio [aHR]: 0.40, 95% confidence interval [CI]: 0.24 – 0.66, p < 0.001). Further investigations demonstrated steatosis and metabolic dysfunction had distinct effects on HCC. Steatosis was protective for HCC (aHR: 0.44, 95% CI: 0.30 – 0.65, p <0.001); while greater burden of metabolic dysfunction increased the risk of HCC (aHR: 1.39 per dysfunction increase, 95% CI: 1.18 – 1.65, p < 0.001). The protective effect of MAFLD was further validated in CHB patients receiving antiviral therapy and those with probable MAFLD. Conclusions: In untreated CHB patients, concurrent MAFLD is independently associated with a lower risk of HCC; however, greater burden of metabolic dysfunction increases the risk of HCC regardless of the presence of MAFLD.

PRE-TREATMENT ENDOSCOPIC BILIARY DRAINAGE WITH METALLIC STENT CAN IMPROVE THE SURVIVAL IN PANCREATIC CANCER PATIENTS WHO RECEIVED NEOADJUVANT TREATMENT: A RETROSPECTIVE COHORT STUDY

Chien-Jui Huang1, Yao-Shan Wang1, Jhong-Han Wu1, Jui-Wen Kang1, Chiao-Hsiung Chuang1, Yan-Shen Shan2, Chiung-Yu Chen1

1Division of gastroenterology and hepatology, Department of internal medicine, National Cheng Kung University Hospital, Tainan, Taiwan

2Division of general surgery, Department of surgery, National Cheng Kung University Hospital, Tainan, Taiwan

有效延長胰臟癌病人存活率：一個回朔

in the head and neck who received endoscopic biliary drainage due to obstructive jaundice in a tertiary center in Southern Taiwan from Feb/2012Nov/2021. All patients had non-metastatic tumor at the initial diagnosis, and they all received systemic neoadjuvant chemotherapy as the first treatment choice. The primary outcome was the overall survival of the patients, and the secondary outcome was also analyzed.

Results: Total 120 patients were enrolled in this study and divided to 2 groups based on the stent choice during the initial endoscopic biliary draiage. The plastic stents group included 45 patients and the metallic stents group had 75 patients. 9 patients (7.5%) were stage I, 37 patients (30.8%) were stage II, and 74 patients (61.7%) were stage III. Hifer successfully curative or conversion surgery rate were noted in the metallic stent group (26.7% VS 45.3%, p = 0.05). However, no difference of the major surgical complications in the two groups. Longer stent patency were noted in the metallic stents regardless of the disease stage (PS VS MS = 113 days VS 221 days, p = 0.001). Most importantly, the overall survival was much longer in the metallic stents group (PS VS MS= 328 days VS 507 days, p = 0.008).

1 國立成功大學醫學院附設醫院內科部消化內科 2 國立成功大學醫學院附設醫院外科部一般外科

Background: Pancreatic cancer is still one of the most difficult cancer to treat in the world. Curative surgery is the gold standard of treatment of pancreatic cancer. Biliary tract obstruction is one of the common complications of pancreatic cancer. However, neoadjuvant chemotherapy is now the gold standard for the borderline resectable and locally advanced disease and will also be applied in the resectable disease soon in the future due to the promising outcome. Thus, pre-treatment biliary drainage plays an important role during the treatment course of the neoadjuvant treatment because infection due to recurrent bile duct obstruction will delay the treatment course.

Aims: In this study, we investigated the role of the stent choice in pre-treatment endoscopic biliary drainage and the effect of the disease outcome, especially the overall survival.

Methods: We retrospectively collected the patients with pancreatic adenocarcinoma located

Conclusions: Pre-treatment endoscopic biliary drainage with metallic stents can improve the overall survival of all pancreatic cancer patients no matter whether they received surgical intervention or not. Thus, endoscopic biliary drainage with metal stents should be applied as the first choice for pre-treatment drainage.

THE INCIDENCE AND PREDICTORS OF 28-DAY MORTALITY IN PATIENTS WITH ACUTE ON CHRONIC LIVER FAILURE

Pao-Yuan Huang, Chien-Hung Chen, Tsung-Hui Hu, Jing-Houng Wang, Chao-Hung Hung, Sheng-Nan Lu

Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan

慢性肝炎急性發作病患 28 天的死亡率 及預測因子

INR, high total bilirubin, bacterial infection, and major hemorrhage during hospitalization were independent predictors of 28-day mortality. The HR of 28-day mortality for bacterial infection was 2.267 (95% CI: 1.205-4.267, p = 0.011), and that for major hemorrhage was 2.159 (95% CI: 1.2543.716, p = 0.005)

Conclusions: Short-term mortality of patients with ACLF was high. Liver transplantation should be promptly evaluated especially in those with severe coagulopathy and hyperbilirubinemia. Prevention and treatment of infections and hemorrhage should be executed vigorously.

Background: Acute-on-chronic liver failure (ACLF) is an acute deterioration of liver function in patients with chronic liver disease. The characteristics of ACLF included its association with a systemic inflammatory response, organ failures, and high 28-day mortality.

Aims: To analyze the incidence and predictors of 28-day mortality in patients with ACLF.

Methods: The cohort study was conducted on the basis of Chang Gung Research Database (CGRD). We enrolled the patients with ACLF in Kaohsiung CGMH between January 2009 and December 2018. The study patients were selected based on discharge diagnosis of acute liver failure or cirrhosis (ICD-9-CM codes 570 and 571, or ICD-10-CM codes K70, K71, K72, K74) and 27910 patients were retrieved from CGRD. Of them, 27679 patients who didn’t have ACLF defined from APASL ACLF Research Consortium or met the exclusion criteria were excluded. Finally, 231 patients who met the criteria of ACLF were included for analysis. The severity of ACLF upon admission was analyzed according to the CLIF Consortium Organ Failure score.

Results: Of the 231 patients with ACLF, 26 received liver transplantation during admission. The major etiology of ACLF was HBV related (158/231, 68.4%). The 28-day mortality rate in non-transplanted patients with ACLF was 32% (25.6% for grade 0, 29.5% for grade 1, 56.9% for grade 2, and 70% for grade 3). All transplanted patients survived at the first month. Old age, high

黃寳源 陳建宏 胡琮輝 王景弘 洪肇宏 盧勝男 高雄長庚紀念醫院胃腸肝膽科系

PREDICTORS OF ACHIEVING HBV SURFACE ANTIGEN LEVEL < 100 IU/ML AT END OF FINITE NUC TREATMENT IN HEPATITIS B E ANTIGEN-NEGATIVE PATIENTS

Yen-Chun Liu1,2, Wen-Juei Jeng1,2, Chien-Wei Peng1,2, Rong-Nan Chien1,2,3, Yun-Fan Liaw2,3

1Department of Gastroenterology and Hepatology, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan

2Chang Gung University

3Liver Research Unit, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan 慢性

logistic regression showed pretherapy ALT ≥5X ULN [adjusted odds ratio (aOR): 2.47 (1.72-3.55), P < 0.01], TDF use [versus ETV, aOR: 1.72 (1.132.63), P = 0.01] and HBsAg reduction from baseline ≥1 log10 IU/mL [aOR: 38.60 (5.30-281.25), P < 0.01] were favorable predictors for EOT HBsAg <100 IU/mL while those with pretherapy HBsAg ≥3 log10 IU/mL [aOR: 0.34 (0.24-0.50), P < 0.01] and time to HBV DNA undetectable ≥6 months during Nuc treatment [aOR: 0.88 (0.60-1.30), P = 0.035] were unfavorable factors for achieving EOT HBsAg <100 IU/mL. After stratified by cirrhotic status or types of Nuc, pretherapy ALT >5X ULN, or ALT <5x ULN combined with HBsAg <3 log10 IU/mL were independent factors for achieving EOT HBsAg <100 IU/mL across different subgroups.

Conclusions: HBeAg negative CHB patients with pretherapy ALT <5X ULN and HBsAg ≥3 log10 IU/ mL were the least likely to achieve EOT HBsAg <100 IU/mL. To start therapy in HBeAg negative CHB patients with hepatitis flare is more likely to achieve the goal of EOT HBsAg <100 IU/mL.

3 林口長庚紀念醫院肝病研究中心

Background: Quantitative HBsAg (qHBsAg) level at end-of-treatment (EOT) <100 IU/mL is an independent predictor for off-therapy sustained response or HBsAg loss in chronic hepatitis B (CHB) patients stopping nucleos(t)ide analogue (Nuc). Little information is known about factors contributing to the achievement of EOT HBsAg level <100 IU/mL.

Aims: This study aims to investigate this issue.

Methods: HBeAg-negative CHB patients who stopped Entecavir (ETV) or Tenofovir (TDF) after consecutive undetectable HBV DNA ≥1 year were enrolled. Patients with pretherapy qHBsAg <100 IU/mL were excluded from the analysis. Pretherapy host and virological factors as well as liver biochemistry were analyzed. Logistic regressions were analyzed for predictors of EOT HBsAg <100 IU/mL.

Results: The 1188 enrolled patients, mean age: 53 years, 84% male, 40% liver cirrhosis, were treated for a median duration of 2.99 (IQR: 2.41-3.08) years. One hundred and sixty-seven patients (14%) achieved HBsAg <100 IU/mL at EOT. Patients with EOT HBsAg <100 IU/mL had higher proportion of genotype B, use of TDF, higher pretherapy ALT, bilirubin and longer consolidation duration than those with EOT HBsAg ≥100 IU/mL. Multivariate

HIGHER FECAL HB CONCENTRATION PREDICTS RISK OF METACHRONOUS ADVANCED NEOPLASIA AT SURVEILLANCE IN SUBJECTS WITH NEGATIVE BASELINE COLONOSCOPY

Hsuan-Ho Lin1,3, Wei-Yuan Chang2,3, Li-Chun Chang3, Wen-Feng Hsu3,4, Ming-Shiang Wu3, Han-Mo Chiu3

1Department of Internal Medicine, Saint Paul’s Hospital, Taoyuan, Taiwan

2Department of Internal Medicine, National Taiwan University Hsin-Chu Hospital, Hsinchu, Taiwan

3Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan

4Department of Internal Medicine, National Taiwan University Cancer Center, Taipei, Taiwan

應用糞便免疫潛血法量性數值於正常

篩檢大腸鏡後之精準追蹤

1 聖保祿醫院內科部

2 台大醫院新竹分院內科部

3 台大醫院內科部

4 台大醫院癌醫中心分院內科部

Background: Higher fecal hemoglobin concentration (FHbC) is associated with advanced neoplasm at diagnostic colonoscopy but whether baseline FHbC could be a predictor of metachronous advanced neoplasia (AN) after a negative colonoscopy remains unclear. We aim to elucidate the association between baseline FHbC and the subsequent risk of AN, in order to tailor the surveillance after negative colonoscopy.

Aims: Tailor surveillance interval based on better risk stratification method (baseline FHbC) after negative colonoscopy.

Methods: Those who received both screening (baseline) and surveillance colonoscopy from 2010 to 2018 in National Taiwan University Hospital with negative baseline colonoscopic findings were enrolled. We analyzed those 4,567 consecutive subjects who had concurrently received fecal immunochemical test (FIT) and with

negative baseline colonoscopy. Stool samples were collected within two days prior to the baseline colonoscopy. Demographic and clinical information, including gender, age, FHbC, body mass index, and smoking at the timing of baseline colonoscopy were analyzed. FHbC ≥100 ng/ml was defined as high FHbC and FHbC <100 ng/ ml was defined as low FHbC group. Besides, we divided high FHbC groups into subgroups averagely. Comparison of metachronous AN risk between FHbC subgroups was conducted using Kaplan-Meier analysis for univariate analysis and Cox-regression models for multivariable analysis. Results: Of those 4,567 subjects, a total of 678 subjects had metachronous colorectal neoplasm at surveillance colonoscopy. Among them, 592 (87.3%), 81 (12.0%), and 5 (0.7%) subjects had non-advanced adenoma (non-AA), advanced adenoma (AA), and invasive cancer, respectively. There were 49 (7.2%) subjects had FHbC of 100 ng/mL or higher among the metachronous CRN group. Comparing the group of metachronous AN to group of non-AN, the mean age (p = 0.05), level of FHbC (p < 0.001), proportion of high FHbC (p < 0.001) and BMI (p = 0.04) were significantly higher. The Cox Regression model revealed that subjects with high FHbC and BMI ≥ 25 had significantly higher risk of metachronous AN at surveillance colonoscopy with hazard ratio (HR) of 4.16 (95% CI = 2.26-7.66) and 1.56 (95% CI = 1.02-2.39) respectively. In the multivariate analysis, only high FHbC was associated with significantly higher risk of metachronous AN, with adjusted hazard ratio (aHR) of 3.95 (95% CI = 2.13-7.35). In the subgroup of FHbC (100-199; n = 62), FHbC (200-399, n = 48) and FHbC (≥400, n = 54), the aHR was 1.50 (95% CI = 0.36-6.15), 5.90 (95% CI = 2.13-16.33) and 6.02 (95% CI = 2.59-13.97) respectively.

Conclusions: Subjects who had higher baseline FHbC (especially ≥200 ng/ml) had a significantly higher risk for developing metachronous AN at surveillance after negative baseline colonoscopy. Tailored surveillance interval based on FHbC may be beneficial but requires further study.

COMPARISON OF HBV RELAPSE AFTER CESSATION OF ENTECAVIR, TENOFOVIR DISOPROXIL FUMARATE OR TENOFOVIR ALAFENAMIDE IN CANCER PATIENTS WITH HBEAGNEGATIVE CHRONIC HEPATITIS B UNDER ANTI-VIRAL PROPHYLAXIS FOR CHEMOTHERAPY

Hsin-Wei Fang, Chien-Hung Chen, Po-Lin Tseng, Tsung-Hui Hu, Jing-Houng Wang, Chao-Hung Hung, Sheng-Nan Lu

Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan 慢性

DNA levels at baseline was the most important factor of VR and CR, patients were classified as high (> 2000 IU/mL), intermediate (between 2000 and 20 IU/mL) and low (< 20 IU/mL) viremia three groups based on baseline HBV DNA levels. In high viremia group, TAF group had higher rates of VR and CR than entecavir group. In intermediate viremia group, TAF group had a higher rate of CR than entecavir and TDF groups. In low viremia group, there was no significant difference in VR or CR between entecavir, TDF and TAF groups.

Conclusions: As antiviral prophylaxis use in cancer patient with CHB, TAF had a trend to have higher possibility of HBV relapse after NA cessation, particularly in patients with high or intermediate viral load at baseline.

長庚醫療財團法人高雄長庚紀念醫院胃腸肝膽科系

Background: It is ambiguous that HBV relapse rates after cessation of tenofovir alafenamide (TAF), a new prodrug of tenofovir, in cancer patients with HBeAg-negative chronic hepatitis B (CHB) under anti-viral prophylaxis for chemotherapy.

Aims: To compare HBV relapse rate after cessation of entecavir, tenofovir disoproxil fumarate (TDF) and TAF in cancer patients with CHB under antiviral prophylaxis for chemotherapy.

Methods: A total of 201 HBeAg-negative cancer patients without cirrhosis who previously received entecavir (n=124), TDF (n=35) or TAF (n=42) for antiviral prophylaxis were enrolled. All patients had post-treatment follow-up for at least 6 months.

Results: Of the 201 patients, the cumulative rates of virological relapse (VR) and clinical relapse (CR) at 3 years were 44.8% and 18.1%, respectively. The multivariate analysis shows that baseline HBV DNA level, use of rituximab and different nucleos(t)ide analogues (NA) therapy were independent factors of VR and CR. Because HBV

FECAL

Puo-Hsien Le1, Cheng-Hsun Chiu2, Chien-Chang Cheng3, Chia-Jung Kuo1, Cheng-Tang Chiu1

1Department of Gastroenterology and Hepatology, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan

2Division of Pediatric Infectious Diseases, Department of Pediatrics, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan

3Department of Pediatric Gastroenterology, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan

糞便微菌移植可降低發炎性腸病患者

罹患困難梭菌感染之併發症

李柏賢

1 林口長庚紀念醫院胃腸肝膽科

2 林口長庚紀念醫院小兒感染科

3 林口長庚紀念醫院小兒胃腸科

Background: Clostridiodes difficile (C. difficile) infection (CDI) increases the risks of hospitalization, colectomy, and mortality in inflammatory bowel disease (IBD).

Aims: There has been no study comprehensively evaluating the impact of fecal microbiota transplantation on the complications of IBD.

Methods: In this retrospective case-control study, we enrolled hospitalized IBD patients with the culture or toxin A/B results for C. difficile in a medical center between April 2007 and April 2021. They were divided into CDI group and control groups. The risk factors, clinical presentations and outcomes were analyzed.

Results: A total of 144 IBD inpatients (45 CDI group and 99 control group) were enrolled for analysis. The median follow-up duration was 15.5 months. The incidence of CDI in IBD inpatients was 31%. The risk factors of CDI included longer IBD duration, biological failure, and biological user. More patients presented as abdominal pain in CDI

group (77.8% vs 55.6%, P = 0.011). After antibiotics treatment and fecal microbiota transplantation (FMT), 83.3% patients had negative result, and 61.9% had improved clinical symptoms. Regarding clinical outcomes, CDI led to more hospitalizations (median 2 times (range 0-12 times) vs median 1 time (range 0-19 times), P = 0.008), lower steroid free remission rate (46.7% vs 67.7%, P = 0.017) and higher Mayo score (median 5 points (range 2-12 points) vs median 3 points (range 0-12 points)). Compared to antibiotics treatment, the patients receiving FMT had less times of hospitalization and less IBD related complications during follow-up.

Conclusions: CDI led to more hospitalizations, lower steroid free remission rate and higher Mayo score in IBD inpatients. FMT should be considered in refractory or recurrent CDI in IBD to improve the clinical outcomes.

MICROBIOTA TRANSPLANTATION LEADS TO LOWER IBD RELATED COMPLICATIONS IN HOSPITALIZED INFLAMMATORY BOWEL DISEASE PATIENTS WITH CLOSTRIDIODES DIFFICILE INFECTION

OUTCOMES OF SYSTEMIC THERAPY FOR HEPATOCELLULAR CARCINOMA WITH MAJOR PORTAL VEIN THROMBOSIS

Hsien-Chen Mon1, Chi-Jung Wu2,3,4, Chien-An Liu5, Pei-Chang Lee2,4, Ya-Wen Hung2, Chieh-Ju Lee2, Chen-Ta Chi2,3,4, I-Cheng Lee2,4, Ming-Chih Hou2,4, Yi-Hsiang Huang2,3,4

1Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan

2Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan

3Institute of Clinical Medicine, National Yang Ming Chiao Tung University School of Medicine, Taipei, Taiwan

4Faculty of Medicine, National Yang Ming Chiao Tung University School of Medicine, Taipei, Taiwan

5Department of Radiology, Taipei Veterans General Hospital, Taipei, Taiwan

line setting.

Methods: One hundred and five consecutive HCC patients with vp3/ vp4 portal vein thrombosis received sorafenib or lenvatinib with or without immunotherapy in the first-line setting in Taipei Veteran General Hospital from Jan. 2018 to Sep. 2021 were retrospectively recruited. The tumor and portal vein specific response rates were assessed by an independent radiologist according to RECIST 1.1 criteria.

3 國立陽明交通大學臨床醫學研究所

4 國立陽明交通大學醫學系

5 臺北榮民總醫院放射線部

Background: Hepatocellular carcinoma (HCC) with major portal vein invasion, including Vp3 and Vp4, indicates poor survival outcome and systemic therapy is the key treatment option for such condition. However, high-risk patients such as main portal vein thrombosis (Vp4) were mostly excluded from previous clinical trials, including REFLECT and Keynote 240. Whether these patients could be beneficial from sorafenib or lenvatinib-based treatment and their responses to the thrombosed portal vein were unclear.

Aims: This study aim to assess the tumor and portal vein specific response rates and survival outcomes in patients with major portal vein thrombosis receiving systemic therapy in the first-

Results: Of them, 61 patients received sorafenib monotherapy, 20 received lenvatinib monotherapy, and 24 received lenvatinib plus pembrolizumab. Significantly better overall objective response rate (ORR: 29.5% vs. 8.2%, p = 0.004), disease control rate (DCR: 77.3% vs. 29.5%, p < 0.001), median PFS (5.8 vs. 2.2 months, p < 0.001) and median OS (12.2 vs. 6.3 months, p = 0.043) were observed in patients received lenvatinib-based treatment as compared with sorafenib treatment. The portal vein specific ORR (70% vs. 16.1%, p < 0.001) and DCR (95% vs. 61.3%, p = 0.007) were also significantly higher in the lenvatinib-based treatment subgroup. The findings were consistent in the 51 patients with main portal vein (Vp4) thrombosis. In multivariate analysis, extrahepatic metastasis (HR = 1.799, p = 0.020) and lenvatinibbased treatment (HR = 0.491, p < 0.009) were significant factors associated with OS. However, a higher risk of hepatic encephalopathy (15.9% vs. 3.3%, p = 0.033) was noted in lenvatinib-based treatment as compared with sorafenib treatment. Conclusions: Lenvatinib-based treatment could provide better ORR, PFS, and OS for HCC patients with Vp3/Vp4 portal vein invasion. However, the risk of hepatic encephalopathy by lenvatinib treatment should be aware.

ARTIFICIAL INTELLIGENCE BASED ON SERUM BIOMARKERS PREDICTS THE EFFICACY OF LENVATINIB FOR UNRESECTABLE HEPATOCELLULAR CARCINOMA

Po-Yao Hsu1, Po-Cheng Liang1, Ming-Ying Lu1, Yu-Ju Wei1,2, Tyng-Yuan Jang1, Ming-Lun Yeh1, Ching-I Huang1, Yi-Hung Lin1, Chih-Wen Wang1, Ming-Yen Hsieh1,2, Nai-Jen Hou1,2, Meng-Hsuan Hsieh1, Zu-Yau Lin1, Shinn-Cherng Chen1,2, Chung-Feng Huang1, Jee-Fu Huang1, Wan-Long Chuang1, Chia-Yen Dai1, Ming-Lung Yu1

1Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan

2Department of Internal Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan

lenvatinib.

Results: Of 82 patients with uHCC (median 68.5 years; 68.3% male; 82.9% first-line systemic therapy), the median OS and PFS were 12.8 months and 5.3 months, respectively. Of 74 patients with assessable tumor responses, the ORR was 24.3%. An AFP reduction ≥ 40% from baseline within 8 weeks after lenvatinib induction was associated with a higher ORR. With baseline biomarkers using a decision tree-based model, we identified patients with high, intermediate, and low ORRs (84.6%, 21.7% and 0%, respectively; odds ratio, 53.04, p < 0.001, high versus intermediate/ low groups). Based on the decision tree-based survival predictive model, baseline AFP was the most important factor for OS, followed by ALBI grade and FGF21.

Conclusions: Baseline CAFs and early AFP decline were associated with tumor response rates, while the baseline levels of FGF21, AFP, and ALBI grade were factors predictive of OS with lenvatinib by decision tree-based models.

Background: Lenvatinib has been effective as the first-line systemic therapy for unresectable hepatocellular carcinoma (uHCC).

Aims: We aimed to investigate the impact of serum biomarkers on the treatment outcomes of patients with uHCC treated with lenvatinib in a real-world setting using an artificial intelligence algorithm.

Methods: Serum biomarkers, including alphafetoprotein (AFP), albumin-bilirubin (ALBI) grade, and circulating angiogenic factors (CAFs [i.e., vascular endothelial growth factor, angiopoietin-2, fibroblast growth factor-19 [FGF19], and FGF21]), were measured. Treatment outcomes, including objective response rate (ORR), progression-free survival (PFS), and overall survival (OS), were analyzed in patients with uHCC treated with

基於血清生物標記的人工智能可預測 Lenvatinib 在不可手術切除之肝細胞 癌上之治療結果

高雄市立大同醫院內科部

GUT MICROBIAL METABOLITES MITIGATE ACETAMINOPHENINDUCED LIVER INJURY BY ACTIVATING NRF2-MEDIATED SIGNALING AND MITOPHAGY

Chun-Ju Yang, Hao-Chun Chang, Pin-Cheng Sung, Wen-Yuan Yang, Sen-Yung Hsieh

Department of Gastroenterology and Hepatology, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan 腸道菌代謝產物藉由活化

indicating some metabolites generated by specific gut microbes, rather than microbes, contributed to the therapeutic effects. Comparative metabolomics on mice plasma revealed the difference between control and SMT-treated mice. A panel of differentially expressed metabolites was screened for protection from APAP-induced hepatocyte toxicity. We found that APAP induces mitochondrial dysfunction, ROS accumulation, and ferroptosis. MetS, a gut microbe metabolite, enhanced the Nrf2-mediated antioxidant signaling pathways. Simultaneously, MetS provoked mitophagy to clean up the damaged mitochondria and promoted mitochondrial biogenesis. Further studies revealed that both the MetS-induced hepatocyte protection signaling pathways are orchestrated through the activation of p62 (also known as sequestosome-1, SQSTM1) by MetS.

Background: Acetaminophen (APAP)-induced liver injury (AILI) is the most common cause of drug-induced acute liver failure. Although the gutliver axis plays a vital role in maintaining normal liver physiology and pathogenesis of liver diseases, including AILI, the mechanisms remain largely unknown. Clinically, N-acetylcysteine (NAC) is the only pharmacologic option for AILI patients, but its efficacy is restricted not later than eight hours after intoxication. Developing better treatments for AILI is a clinically unmet need.

Aims: This study aims to elucidate the impacts of gut microbiota on the severity of AILI and the underlying mechanisms to develop new therapies for AILI in the near future.

Methods: The conventional and germ-free housed mice were received with or without fecal microbiota transplantation (FMT) or pasteurized FMT (SMT) after APAP treatment to induce acute liver failure. The survival rate, severity of liver damage, microbiota changes, and metabolite profiles were measured by ELISA, H&E staining, and HPLC. For in vitro study, NeHepLxHT cells and HepG2 cells were used to investigate the mechanisms of how the gut microbes modulate the severity of AILI.

Results: The mice depleted gut microbiota by antibiotic treatment reduced the liver damage in AILI. However, FMT mitigated the severity of AILI. Interestingly, the alleviation of AILI severity was even more prominent by SMT than by FMT,

Conclusions: Although the commensal gut microbes could exacerbate AILI severity, MetS, a gut microbe metabolite, protects mice against APAP-induced ferroptosis via activation of Nrf2mediated signaling and mitophagy. These findings advanced our understanding of the molecular basis of the gut-liver axis and the acetaminopheninduced liver pathogenesis. MetS is a potential treatment for AILI.

楊淳如 張皓竣 宋品承 楊雯媛 謝森永

Free Paper

Section：HCV

LIVER GRAFT PATHOLOGY AND LOW SERUM 25-HYDROXYVITAMIN D AFTER LIVING DONOR LIVER TRANSPLANTATION

Shu-Hsien Lin1,2, Chih-Chi Wang2, Kuang-Tzu Huang3, Hock-Liew Eng4, King-Wah Chiu1,2

1Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan

2Liver Transplantation Program, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan

3Institute for Translational Research in Biomedicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan

4Department of Pathology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan

活體肝臟移植後肝臟病理變化與血清

25-

羥基維生素 D 濃度低下

林淑賢1,2 王植熙

黃廣慈

邢福柳

1 高雄長庚紀念醫院胃腸肝膽科系

2 高雄長庚紀念醫院肝臟移植中心

3 高雄長庚紀念醫院生物轉譯中心

4 高雄長庚紀念醫院解剖病理科

Background: Most cases of advanced liver diseases are associated with low serum 25-hydroxyvitamin D and vitamin D deficiency. This phenomenon may occur in living donor liver transplantation (LDLT).

Aims: We conducted this study to explore the interplay between VDR and CYP2R1 in liver graft and compared our findings with the pathological interpretation of serum 25(OH)D concentration.

Methods: In total, 60 patients received liver graft biopsy after LDLT and were separated (1:1) into two groups: graft rejection group and graft nonrejection group. We extracted both of the recipients’ and donors’ serum DNA to investigate the vitamin D receptor (VDR) rs2228530 and CYP2R1 rs10741657 single nucleotide polymorphisms (SNPs) using real-time polymerase chain reaction. We also extracted DNA from liver graft tissues to explore the genetic alleles of VDR rs2228530

and CYP2R1 rs10741657 after LDLT. Serum biochemistry profile and 25(OH)D concentrations were measured before and after LDLT.

Results: There were no significant differences in serum VDR rs2228530 and CYP2R1 rs10741657 genetic alleles between recipients and donors. The percentage of genetic modification was 33.4% (10/30) for the rejection and non-rejection groups in VDR rs2228530, and 66.7% (20/30) for both groups in CYP2R1 rs10741657. Serum 25(OH) D concentrations were significantly lower after LDLT D30 than that before LDLT in the rejection (p = 0.0001) and non-rejection graft pathology (p = 0.0017) groups.

Conclusions: The presence of low serum 25(OH) D concentrations after LDLT suggested that posttransplant low serum 25(OH)D concentrations may develop with the homogenous phenomenon of VDR rs2228530 and CYP2R1 rs10741657 genetic modifications in recipients regardless of graft pathology.

COMBINATION OF POST-DAA FIB-4 AND NEUTROPHIL-TOLYMPHOCYTE RATIO HELP

PREDICT THE DEVELOPMENT OF DE NOVO LIVER-ASSOCIATED COMPLICATIONS AFTER HCV ERADICATION

Chun-Ming Hong1, Ming-Lung Yu2, Tung-Hung Su3, Shih-Jer Hsu3, Tai-Chung Tseng3, Chen-Hua Liu3, Hung-Chih Yang3, Jia-Horng Kao3, Pei-Jer Chen3, Yu-Syuan Zeng2, Chun-Jen Liu3

1Division of Hospital Medicine, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan

2Division of Hepatobiliary, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan

3Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan

結合口服抗病毒藥物治療後之 FIB-4 指 標和嗜中性球與淋巴球的比率有助於

併發症

1 台大醫院內科部整合醫學科

Background: Direct-acting antiviral agents (DAAs) can achieve high sustained virologic response (SVR) in chronic hepatitis C (CHC) patients; yet a proportion of patients still experience liverassociated complications after SVR. Identification of prediction factors is clinically important. FIB4 index is a useful noninvasive tool to assess fibrosis. Besides, neutrophil-to-lymphocyte ratio (NLR) is a biomarker for systemic inflammation.

Aims: To investigate the association between the combination of post-SVR FIB-4 and NLR and liver-associated complications in post-SVR CHC patients.

Methods: We recruited patients with the platform

of Taiwan HCV Registry (TACR). The inclusion criteria were patients who achieved SVR12 after DAA therapy and were followed at least 24 months after SVR12.

Results: Totally 2093 patients were recruited from 2017/01/01 to 2019/12/31. Among these patients, 412 patients (19.7%) were cirrhotic and 295 (14.1%) had prior treatment. 1018 patients (48.7%) were infected with genotype 1, followed by genotype 2 (39.3%). Sofosbuvir/ledipasvir, glecaprevir/pibrentasvir, and elbasvir/grazoprevir were the main DAA regimens. During 2-year follow-up after SVR 12, 25 patients developed HCC, ascites, variceal bleeding, or spontaneous bacterial peritonitis. Among these 25 patients, 22 patients (88.0%) were cirrhotic at baseline and 17 patients (68%) had Fib-4 > 3.25 after SVR 12. 21 patients with combined FIB-4 > 3.25 and NLR > 4 had higher incidence of de novo liver-associated complications (9.5%) than the 1687 patients with combined FIB-4 < 3.25 and NLR < 4 (0.5%).

Conclusions: The overall incidence of de novo hepatocellular carcinoma, ascites, variceal bleeding, spontaneous bacterial peritonitis, or hepatic encephalopathy after SVR is low during short-term follow-up after HCV eradication. Long term follow-up for cumulative incidence is still needed. Combination of post-SVR FIB-4 and NLR is a useful indicator for liver-associated complications in this group of patients.

PRETREATMENT AND POSTTREATMENT SPLEEN STIFFNESS VALUES AS SIGNIFICANT PREDICTORS OF LIVER-RELATED EVENTS IN PATIENTS WITH CHRONIC HEPATITIS C AFTER DIRECTACTING ANTIVIRAL THERAPY

Sheng-Hung Chen1,2, Hsueh-Chou Lai1,3, Wei-Fan Hsu1,3, Hung-Wei Wang1,2, Po-Heng Chuang1, Cheng-Yuan Peng1,2

1Center for Digestive Medicine, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan

2School of Medicine, China Medical University, Taichung, Taiwan

3Department of Chinese Medicine, China Medical University, Taichung, Taiwan

beyond the SVR visit.

Background: Posteradication surveillance is fundamental for patients with chronic hepatitis C (CHC). Residual liver fibrosis burden may contribute to the common and critical upstream pathways that drive both portal hypertension-related decompensation and hepatic carcinogenesis. Combined utility of diagnostic measures may enhance the diagnostic performances. Long-term risk stratification using combined spleen stiffness (SS) acquired beyond the sustained virologic response (SVR) visit for CHC patients receiving direct-acting antiviral (DAA) therapy has not been thoroughly characterized.

Aims: Therefore, this preliminary study used prespecified protocols to obtain SS values from treatment baseline to time points further beyond the SVR visit to retrospectively investigate the utility of longitudinal measurements of precancerous SS measurements in the prognostics of post-SVR liver-related events (LREs) from baselines further

Methods: The LRE of interest was defined as the first de novo occurrence of any LRE. The liver decompensation events recorded were portal hypertensive gastrointestinal bleeding (diagnosed by endoscopy), portal hypertension-related ascites (diagnosed through paracentesis or imaging), spontaneous bacterial peritonitis (diagnosed through paracentesis), hepatic encephalopathy (diagnosed clinically), hepatorenal syndrome (diagnosed clinically), acute-on-chronic liver failure necessitating transplantation (diagnosed clinically), and liver-related mortality (diagnosed clinically). Hepatocellular carcinoma (HCC) was diagnosed following pathologic confirmation or by using at least one imaging technique (contrastenhanced computed tomography, contrastenhanced magnetic resonance imaging, or contrast-enhanced ultrasound) for liver nodules at least 1 cm in diameter in patients with cirrhosis. The participants with missing data were excluded from the modeling. Collinearity between the covariates was evaluated using a variance inflation factor. A Cox regression model identified the key factors that could predict LREs, including HCC, during prespecified follow-ups from 2012 to 2022. Univariate significance, timing, collinearity, and clinical relevance of factors were considered for inclusion in a multivariate analysis. The optimal threshold values maximizing a Youden index were employed to implement the survival analysis. Kaplan–Meier survival analysis estimated the significance of between-group risk stratification. Results: Of the entire eligible cohort (n = 1001), the median age was 61 years (interquartile range, 52–69), and 567 (56.6 %) of the participants were male. Fifty-one (5.1%) patients developed LREs over a median follow-up duration of 31.6 months (interquartile range = 11.8–47.9) after the SVR baseline (PW12, Week 12 after the SVR visit). The incidence rate was 1.93 per 100 personyears. Forty-six (4.6%) patients developed LREs over a median follow-up duration of 28.6 months (interquartile range = 8.8–44.9) after PW24. Delta checks revealed that the SS values (meter per second) were: 2.61 (2.23–3.18) at baseline (TW0), 2.66 (2.21–3.18) at the end of treatment, 2.52 (2.18–3.12) at the SVR visit, 2.49 (2.14–3.08) at PW24. The pairwise difference between SS values measured at preceding and next visits was only significant (P = 0.031) (declining) from SVR to PW24 visits. Spleen size index and

peak systolic flow velocity of the main portal vein exhibited insignificant declines in longitudinal values over time. Through aforementioned criteria, multivariate Cox regression analysis identified six significant predictors of LREs after SVR baseline (event n = 46, multivariate analysis): age (adjusted hazard ratio = 1.038, 95% confidence interval = 1.007–1.071, P = 0.017), sex (2.472, 1.306–4.679, P = 0.005), aspartate aminotransferase (SVR visit) (1.049, 1.021–1.078, P = 0.001), platelet (SVR) (0.990, 0.983–0.997, P = 0.004), α-fetoprotein (SVR) (1.000, 0.999–1.001, P = 0.002), and SS (SVR), (1.641, 1.082–2.487, P = 0.020). Kaplan–Meier survival analysis revealed that SS values (m/s) were all significantly sensitive (all Log-rank P < 0.05) in predicting LREs. To predict postSVR LREs, the cutoff values of SS were 2.985, and 2.705, for SS (TW0) (Log-rank P < 0.001), and SS (SVR) (Log-rank P < 0.001), respectively. Moreover, to predict post-PW24 LREs, the cutoff values of SS were 3.000, 2.865, and 2.492, for SS (TW0) (Log-rank P < 0.001), SS (SVR) (Log-rank P < 0.001), and SS (PW24) (Log-rank P = 0.025), respectively. The subgroups with higher SS values in the cohort all exhibited higher risks of LRE development from the corresponding baselines of follow-up.

Conclusions: SS values exhibited a significant discriminative performance for risk stratification in the present CHC cohort receiving DAAs. We recommend the combined utility of concurrent SS in future prediction models for LREs. A recall policy comprising intense surveillance should be activated for patients with high SS values on and off treatment. Future studies should employ a larger cohort to validate results of SS-combined LRE predictions.

Wen-Hsiu Su1, Ciniso Sylvester Shabangu2, Chia-Yen Dai3, Jee-Fu Huang3, Wan-Long Chuang3, Ming-Lung Yu3, Shu-Chi Wang1

1Department of Medical Laboratory Science and Biotechnology. Kaohsiung Medical University, Kaohsiung, Taiwan

2Graduate Institute of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan

3Division of Hepatobiliary, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan

探討持續 HCV 感染表達 miRNAs 和臨 床肝癌相關基因的相關性

蘇玟秀1 Ciniso Sylvester Shabangu2 戴嘉言3 黃志富3 莊萬龍3 余明隆3 王述綺1

1 高雄醫學大學醫事檢驗生物技術學系

2 高雄醫學大學醫學研究所

3 高雄醫學大學附設中和紀念醫院肝膽胰內科

Background: Chronic hepatitis C infection is one of the leading chronic infectious factors that cause liver cancer. In chronic hepatitis C infected patients’ liver tissue, it has been observed that not all hepatocytes are infected with HCV, and only about 40% of the cells can be detected the expression of hepatitis C protein. Although there are effective treatments for hepatitis C and the eradication of the HCV rate has reached more than 95%, there are still a certain proportion of patients with long-term infection but undiagnosed or untreated. Clinical studies have confirmed that long-term HCV-infected patients respond poorly to ledipasvir and daclatasvir, NS5A inhibitors. The sensitivity of the detection will also ignore the inability of host immunity to clear the virus, resulting in the persistence of low viral load and the change of epigenetic genes to induce virusrelated liver cancer.

Aims: To explore whether HCV infection can also affect gene expression and slow down the formation of liver cancer. We hope that it can

④

TO INVESTIGATE THE CORRELATION BETWEEN MIRNAS AND CLINICAL LIVER CANCERRELATED GENES EXPRESSED BY PERSISTENT HCV INFECTION

provide a new strategy for preventing liver cancer caused by chronic hepatitis C in the future, reduce the incidence of liver cancer caused by chronic HCV-infected and achieve the purpose of precision medicine.

Methods: Used an miRNA array for the initial identification of possible candidates. The systematic integrative analysis included analysis of the identified miRNA via ENCORE for expression in LIHC; The identified significant (p<0.01) miRNAs were combined and analyzed via Oncomir for survival. Significantly (p <0.05) associated with survival and hazard ratio (HR) > 1.0 of the miRNAs were analyzed associated KEGG pathways via DIANA.

Results: Five miRNAs were significantly correlated with survival in long-term HCV infection. In followup studies, we used mirPathDB to analyze the three miRNAs most significantly associated with survival. We obtained 11,008 genes, which overlapped with our previous NGS data to get 102 genes affected by hsa-miR-215-5p, hsa-miR-10b5p, and hsa-miR-7a-5p regulation. The systematic integrative results show that the STA2, FZD5, CDH1and PMAIP1 genes are related to HCC and associated with hsa-miR-215-5p.

Conclusions: The main reason cause of HCC is that HCV inhibits the expression of hsa-miR-2155p, and it has a significant effect on survival so that hsa-miR-215-5p may play an essential role in virus-related liver cancer.

⑤HEPATITIS C VIRUS REINFECTION IN PEOPLE LIVING WITH HUMAN IMMUNODEFICIENCY VIRUS IN TAIWAN AFTER ACHIEVING SUSTAINED VIROLOGIC RESPONSE WITH ANTIVIRAL TREATMENT: THE RECUR STUDY

Chen-Hua Liu1,2,3, Hsin-Yun Sun1, Cheng-Yuan Peng4,5, Szu-Min Hsieh1, Sheng-Shun Yang6,7,8, Wei-Yu Kao9,10,11, Yu-Lueng Shih12, Chih-Lin Lin13, Chun-Jen Li1,2,14, Wang-Hui Sheng1, Yi-Chun Lo15, Wen-Chun Liu1, Jo-Hsuan Wu16, Tung-Hung Su1,2, Tai-Chung Tseng1,2,17, Pei-Jer Chen1,2,14, Chien-Ching Hung1,18, Jia-Horng Kao1,2,17

1Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan;

2Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan;

3Department of Internal Medicine, National Taiwan University Hospital, Yun-Lin Branch, Yunlin, Taiwan; 4Center for Digestive Medicine, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan; 5School of Medicine, China Medical University, Taichung, Taiwan; 6Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan; 7School of Medicine, Chung Shan Medical University, Taichung, Taiwan; 8Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan; 9Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taipei Medical University Hospital, Taipei, Taiwan; 10School of Medici, Taipei Medical University College of Medicine, Taipei, Taiwan;

11Graduate Institute of Clinical Medicine, Taipei Medical University College of Medicine, Taipei, Taiwan; 12Division of Gastroenterology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan; 13Department of Gastroenterology, Taipei City Hospital, Ren-Ai Branch, Taipei, Taiwan; 14Graduate Institute of

Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan; 15Centers for Disease Control, Taipei, Taiwan; 16Hamilton Glaucoma Center, Shiley Eye Institute and Viterbi Family Department of Ophthalmology, University of California, San Diego, CA, USA; 17Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan; 18Department of Tropical Medicine and Parasitology, National Taiwan University College of Medicine, Taipei, Taiwan

who achieved SVR12 with interferon (IFN) or direct-acting antivirals (DAAs) between 2005 and 2021 underwent HCV RNA measurements at SVR24 and then biannually. HCV reinfection was defined as the detection of different HCV strains beyond SVR12. HIV-negative, low-risk individuals with SVR12 served as reference patients. Crude reinfection rates and secular trends were assessed. Multivariate Cox regression analysis was performed to identify baseline factors associated with HCV reinfection.

盛望徽1

羅一均15 劉文君1 吳若玄16 蘇東弘1,2 曾岱宗1,2,17

陳培哲1,2,14 洪健清1,18 高嘉宏1,2,17

1 國立臺灣大學醫學院附設醫院內科部

2 國立臺灣大學醫學院附設醫院肝炎研究中心

3 國立臺灣大學醫學院附設醫院雲林分院內科部

4 中國醫藥大學附設醫院消化醫學中心

5 中國醫藥大學醫學系

6 臺中榮民總醫院內科部胃腸肝膽科

7 中山醫學大學醫學系

8 國立中興大學生命醫學科學研究所

9 臺北醫學大學內科部胃腸肝膽科

10 臺北醫學大學醫學系

11 臺北醫學大學臨床醫學研究所

12 國防醫學中心三軍總醫院內科部胃腸科

13 臺北市立聯合醫院仁愛分院胃腸科

14 國立臺灣大學醫學院臨床醫學研究所

15 疾病管制署

16 美國加州大學聖地牙哥分校眼科部

17 國立臺灣大學醫學院附設醫院醫學研究部

18 國立臺灣大學醫學院熱帶醫學暨寄生蟲學科

Background: Data on hepatitis C virus (HCV) reinfection in East Asian people living with human immunodeficiency virus (HIV) after treatmentinduced sustained virologic response (SVR) are limited.

Aims: To prospectively asses the risk of HCV reinfection in HIV/HCV-coinfected patients who achieve SVR with antiviral therapies.

Methods: HIV/HCV-coinfected patients in Taiwan

Results: A total of 216 HIV-positive and 1589 reference patients were recruited with median follow-up durations of 3.0 and 6.0 years. During a total of 772 person-years of follow-up (PYFU), the HCV reinfection rate in HIV-positive patients was 4.02 per 100 PYFU (95% confidence interval [CI]: 2.85-5.65), while the HCV reinfection rate in reference patients was 0.14 per 100 PYFU (95% CI: 0.09-0.23) during 10862 PYFU. HIV-positive patients had a higher risk of HCV reinfection than reference patients (hazard ratio [HR]: 17.63; 95% CI: 7.10-43.80, p < 0.001). No baseline factors were predictive of HCV reinfection in HIV-positive patients. The incidence of HCV reinfection in HIVpositive patients increased after 2015 when DAAs were available in Taiwan.

Conclusions: The risk of HCV reinfection remains high in HIV/HCV-coinfected patients with treatmentinduced SVR12. In addition to mass screening and treatment scale-up, strategies to reduce reinfection are needed for HCV microelimination in HIV-positive patients in Taiwan.

THE ELEVATED ELECTRONEGATIVE LOW-DENSITY LIPOPROTEIN IN PATIENTS WITH CHRONIC HEPATITIS C

Chia-Yen Dai1,2, Chung-Feng Huang1,2, Ching-I Huang1,2, Ming-Lun Yeh1,2, Po-Cheng Liang1, Po-Yao Hsu1, Jee-Fu Huang1,2, Wan-Long Chuang1,2, Ming-Lung Yu1,2

1Division of Hepatobiliary, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan

2College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan

C 型肝炎病患有較高之陰電性低 密度脂蛋白濃度

of therapy with the definition of the sustained virological response (SVR12). Laboratory data were collected and plasma was tested for the LDL 5 sub-fractions (L1, L2, L3, L4, and L5) using the increasing negative charge on anion-exchange columns. L5% means the percent of L5 in total LDL. L5 concentration ([L5]) estimated by L5%* LDL-C.

Background: Patients with chronic hepatitis C virus (HCV) infections have shown to have significantly higher mortality such as increased incidence of cancer and cancer-related mortality and extrahepatic diseases such as cardiovascular diseases and cerebral vascular diseases (CVD) than the general population. Nevertheless, patients with HCV infection display significantly decreased triglyceride, total cholesterol, highdensity lipoprotein-cholesterol (LDL-C) and lowdensity lipoprotein-cholesterol (LDL-C) levels in plasma. Plasma LDL has been classified into five charge-defined sub-fractions LDL L1, L2, L3, L4 and L5 using anion-exchange chromatography and L5, the most negatively charged LDL, is more abundant in patients with increased cardiac risks than in the healthy population.

Aims: The present study aimed to investigate the relationship between the HCV infection and serum LDL L5 level and the impact of antiviral therapy on the serum LDL L5 level.

Methods: Patients with CHC and controls were enrolled in the present study. Patients treated with direct antiviral agents (DAAs) were enrolled for testing the serial change of the L5 at baseline, end-of-treatment (EOT), and end-of-follow-up (EOF) which is the 12 weeks after cessation

Results: A total of 477 subjects were enrolled in the study. There were 167 (35.0%) with negative anti-HCV and 310 (65.0%) with positive anti-HCV and 73 subjects with the baseline, EOT, and EOF samples after DAA treatment for testing the L5% and [L5]. The L5% was an independent risk factor associated with HCV infection (the risk of L5% >1.8 was approximately ten-fold (OR = 10.28) and the risk of L5% >5 (OR = 8.1) was approximately eight-fold after adjusting the other risk factors. The anti-HCV positivity was the only factor significantly associated with the risk of L5% >1.8 in multivariate analyses. Among patients with HCV infection, L5% was significantly associated with ALT and platelet levels. For patients with DAA therapy, plasma L5 (%) and [L5] significantly decreased by successful anti-viral treatment (p < 0.0001 for L5% and p = 0.0018 for [L5]).

Conclusions: LDL L5, showing an increased level compared to controls, indicates that it can be used as a new biomarker for liver-related disease caused by HCV infection. Although the elevated serum lipid profile has been noted after successful DAA therapy, the decreased levels of L5 after the cure of the HCV RNA implicate a role in the decreased risk of CVD.

A NOVEL MORPHOLOGICAL ENDOSCOPIC CLASSIFICATION OF COLORECTAL LYMPHOMA: A RETROSPECTIVE STUDY AT A SINGLE MEDICAL CENTER

Yi-Hsuan Wong1, Tze-Sian Chan1,2, Min-Shung Wu1,2, Fat-Moon Suk1,2, Gi-Shih Lien1,2, Chun-Nan Chen1

1Division of Gastroenterology, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan

2Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan

辦理消化內科

2 臺北醫學大學醫學系內科學科

Background: Colorectal lymphomas (CRL) represent only 10–20% of gastrointestinal lymphomas, which are much more frequent in stomach (50–60%) and small intestine (20–30%). Meanwhile, colorectal lymphoma only accounts for 0.2–1.2% of all colorectal tumors. The endoscopic features of CRL are variable and nonspecific; a timely diagnosis of the disease is usually difficult. We recently performed a retrospective survey of patients with CRL at our hospital from 2002 to 2021; endoscopic features of CRL were collected and analyzed.

Aims: To evaluate the endoscopic features of patients with CRL at a medical center in Northern Taiwan.

Methods: Clinical and endoscopic records of patients with CRL were analyzed retrospectively at a single medical center from 2002 to 2021. Endoscopic features such as the morphology, locations, and initial endoscopic impressions of each of enrolled patients were retrieved. The endoscopic pictures were read and analyzed by at least two experienced board-certified gastrointestinal endoscopy specialists at the medical center.

Results: Due to the rarity of the disease, only 10 cases of patients with CRL were identified. The median age of patients was 72 years (range: 5490 years) and the male-to-female ratio was 1:1. The most frequently encountered symptoms/ signs were abdominal fullness, pain, bloody stool and positive fecal occult blood test. Rectum and cecum are the most common locations. The endoscopic features of CRL were classified as (1) submucosal tumor type, (2) ulcero-infiltrative type, and (3) multiple lymphomatous polyposis type after careful evaluations of the endoscopic images. Among them, the ulcero-infiltrative type was the predominant feature in patients with CRL (50%), followed by submucosal tumor type (40%) and multiple lymphomatous polyposis type (10%). Moreover, the most common histological subtypes were diffuse large B-cell lymphoma (DLBCL) in 5 patients (50%), followed by mantle cell lymphoma in 2 patients (20%), mucosa-associated lymphoid tissue lymphoma in 2 patients (20%) and follicular lymphoma in 1 patient (10%). Remarkably, 80% of colorectal DLBCL were ulcero-infiltrative type on endoscopy. There were no significant differences between histological type and the location of CRL lesion.

Conclusions: CRL should be considered in any ulcerative submucosal lesions encountered during colonoscopic examinations. We proposed a novel morphological classification of CRL that might be helpful in the diagnosis of the diseases: submucosal tumor type, ulcero-infiltrative type and multiple lymphomatous polyposis type. Remarkably, ulcero-infitrative type tumors are predominant in DLBCL Further study with a larger sample size would be required to confirm the trend of histological correlation.

類：一個單一醫學中心之回朔性研究

ADENOMA DETECTION USING REAL-TIME COMPUTER-AIDED COLON POLYP DETECTION SYSTEM TO COMPARE

WATER EXCHANGE AND AIR INSUFFLATION – A PILOT CONTROLLED STUDY

Chis-Pei Tang1,2, Tu-Liang Lin3, Yu-Hsi Hsieh1,2, Felix Leung4

1Department of Gastroenterology, Dalin Tzu Chi Hospital, Chiayi, Taiwan

2School of Medicine, Tzu Chi University, Hualien, Taiwan

3Department of Management Information Systems, National Chiayi University, Chiayi, Taiwan

4David Geffen School of Medicine at University of California at Los Angeles, CA, USA

set to 0.96 and 0.97, respectively. The positive predictive value was 0.98 and negative predictive value was 0.93. The algorithm was validated by a video analysis study. To assess the real-time application, in a pilot study, 100 eligible patients were prospectively recruited to undergo realtime CADe colonoscopies inserted with either WE or air insufflation method. The resected polyps were evaluated by a blinded pathologist. The colonoscopy procedure was recorded as CADe over-laid videos and reviewed for FP characteristics afterward.

3 嘉義大學資訊管理學系

Background: In a retrospective video analysis, we showed that the strengths of water exchange (WE) and computer-aided detection (CADe) complemented the weaknesses of each other. CADe increased WE polyp detection rate and WE reduced false positive per colonoscopy (FPPC) of CADe compared with the air insufflation.

Aims: We applied the CADe model to conduct a pilot real-time colonoscopy study to compare the ADR and FPPC between the WE and air insufflation method.

Methods: By mimicking the methods established to identify diseases in plants, we developed a CADe model using convolutional neural network with transfer learning approach (YOLOv4) to detect colon polyps. The CADe algorithm achieved a mean average precision of 94.0% and the area under receiver operating characteristic curve of 0.98. The sensitivity and specificity were

Results: The real time CADe colonoscopies included patients inserted with either WE (n = 50) or air insufflation (n = 50) methods. The mean colon Boston Bowel Preparation Scale score graded by the endoscopist was (8.37 [0.6] and 6.91 [1.25], P < 0.001) for WE and air insufflation, respectively; the WE group was significantly higher than the air insufflation group. Table 1 shows that the WE group had significantly higher polyp detection rate (PDR) and mean total number of polyps (88.0% versus 68.0%, P = 0.028; 3.34 [3.29] versus 1.98 [2.24], P = 0.010), respectively). Adenoma detection rate (ADR) (70.0% versus 46.0%, P = 0.025) and mean number of adenomas (1.80 [2.30] versus 1.02 [1.57], P = 0.021) were higher in the WE group than those in the air insufflation group. The mean FPPC related to feces (2.34 [2.54] vs. 5.58 [5.35], P < 0.001) and bubbles (0.44 [0.97] vs.1.92 [2.33], P < 0.001) in the WE group were significantly lower than those in the air insufflation group. The mean number of FPPC for the WE group was significantly lower.

Conclusions: This first real-time CADe comparison revealed PDR and ADR were significantly higher in WE than the air insufflation. The FPPC related to feces and bubbles was significantly lower in the WE group. The locally developed CADe algorithms validated in video analyses was applicable in realtime colonoscopy.

4

METAGENOMIC ANALYSIS OF FECAL MICROBIOTA TRANSPLANTATION FOR RECURRENT CLOSTRIDIUM

DIFFICILE INFECTION: A COHORT STUDY

Hao-Tsai Cheng1,2,3,5, Yuan-Ming Yen5, Cheng-Tang Chiu2,5, Sen-Yung Hsieh2,5, Cheng-Hsun Chiu4,5

1Division of Gastroenterology and Hepatology, Department of Internal Medicine, New Taipei Municipal Tucheng Hospital, Tucheng, New Taipei City, Taiwan

2Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University, Taoyuan, Taiwan

3Graduate Institute of Clinical Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan

4Division of Pediatric Infectious Diseases, Department of Pediatrics, Chang Gung Memorial Hospital, Chang Gung University, Taoyuan, Taiwan

5Chang Gung Microbiota Therapy Center, Chang Gung Memorial Hospital, Taoyuan,

Taiwan

用宏基因組學分析困難梭桿菌感染病

FMT.

Methods: Six patients who received FMT for rCDI in Chang Gung Memorial Hospital from Nov 2018 to June 2019. FMT was delivered by gastroenterologists using colonoscope. Metagenomic shotgun sequencing of fecal samples for donor, and also recipient before and after FMT 7days, 3M and 6M. Resistance gene of microbiota is focus on this subject.

Results: A prominence of Proteobacteria, Firmicutes and Actinobacteria were noted in the feces of rCDI patients. But, Bacteroidetes and Firmicutes were prominent in donor. The dynamic change of fecal microbiota from Proteobacteria to Bacteroidetes as donor after FMT could be persisted over six months. Microbiota with efflux pump complex or subunit conferring antibiotic resistance gene were abundant in rCDI patients and rare in donors. After FMT, the reducing abundance of microbiota with efflux pump complex or subunit conferring antibiotic resistance gene was found after FMT till six months. One patient used antibiotics for leg cellulitis treatment many times during following up and the Escherichia became more abundant then other rCDI patients. Conclusions: Gut dysbiosis including abundant drug-resistance microbiota exists in rCDI patients. Using FMT to restore gut microbiota in rCDI patients can reduce the drug-resistance microbiota and the effective time is persisted over six months.

Background: Fecal microbiota transplantation (FMT) is an effective treatment for recurrent or refractory Clostridioides difficile infection (rCDI) patients. The change of microbiota and association with long follow-up outcome after FMT is not well study.

Aims: The study reported the six-months clinical outcome associated with microbiota change after

THE SERRATED COLONIC POLYP CLASSIFICATION USING ENDOSCOPY IMAGES WITH ARTIFICIAL INTELLIGENCE MODEL AND TENSOR FLOW CHART

Tsung-Hsing Chen1, Chieh Lee2, Chang-Fu Kuo3

1Department of Gastroenterology and Hepatology, Linkou Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan, Taiwan

2Department of Information Management, National Sun Yat-sen University, Kaohsiung, Taiwan

3Division of Rheumatology, Allergy, and Immunology, Linkou Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan, Taiwan

陳聰興

1 林口長庚紀念醫院胃腸肝膽科系

2 國立中山大學資訊管理學系

3 林口長庚紀念醫院風濕免疫科

Background: Cancer is one of the top 10 causes of death around the world. Colonic cancer is among the top three most comely observed cancer in Taiwan. It has the been well documented that early detection of precancerous lesion can reduce the mortality rate of colonic cancer and cost of healthcare.

Aims: In this study, we implement artificial intelligence model such as convolutive neuron network to help physicians to classified colonic polyps into traditional serrated adenoma (TSA), sessile serrated adenoma (SSA), and hyperplastic. Where both TSA and SSA are potential precancerous polyps that should be removed during endoscopy.

Methods: We collected endoscopy images under both white and NBI lights. Under the white light, 257 images of hyperplastic, 423 images of SSA and 60 images of TSA were collected. Under the NBI light, 238 images of hyperplastic, 284 images of SSA and 71 images of TSA were collected.

Results: In this study, we implement artificial

intelligence to build a model for classifying the type of colonic polyps. We found with AI model our prediction of colonic type under the white light is 94% and the discriminability of the model (area under curve) is 98%.

Conclusions: Thus, we can conclude that our model can effectively help physicians to distinguish between TSA, SSA and hyperplastic polyps.

利用人工智慧及張量流程圖可幫助大 腸鋸齒狀息肉辨別診斷

FRAMEWORK AND MASTERY LEARNING

Yen-Nien Chen1, Silvia Sanduleanu2,3, Tiffany Nguyen-Vu4, Wen-Feng Hsu5, Li-Chun Chang5, Ravishankar Asokkumar3,6, Yu-Min Lin7, Carl Wieman8,9, Argenta Price8, Candice Kim10, William McGaghie11, Tonya Kaltenbach3,12, Han-Mo Chiu3,4, Roy Soetikno3,12

1Department of Medicine, National Taiwan University Cancer Center, Taipei, Taiwan; 2Maastricht University, Maastricht, Netherlands; 3Academy of Endoscopy CA, USA; 4Department of Medicine, University of California, San Francisco, CA USA;

5Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan;

6Department of Gastroenterology and Hepatology, Singapore General Hospital, Singapore; 7Department of Internal Medicine, Shin Kong Wu Ho Su Memorial Hospital, Taipei, Taiwan; 8Department of Physics, Stanford University, Palo Alto, CA USA;

9Graduate School of Education, Stanford University, Palo Alto, CA USA; 10School of Medicine & Graduate School of Education, Stanford University, Stanford, CA USA;

11Feinberg School of Medicine, Northwestern University, Chicago, IL USA;

12Department of Gastroenterology and Hepatology, San Francisco Veterans Affairs Medical Center, San Francisco, CA USA

Background: Current gastroenterology training focuses on the know-what (content and facts) and places less emphasis on translating the know-what to know-how (applying facts) in clinical practice. We developed a curriculum that trains the knowhow using a novel framework based on problemsolving decisions made by experts, which were made by 3 methods: expert performance approach

(EPA), decisions framework, and mastery learning (ML).

Aims: We hypothesized that implementation of our curriculum leads to a moderate to large learning effect. Herein, we report our experience training hereditary colorectal cancer (HCRC) and familial colorectal cancer (FCRC) using this framework.

Methods: We developed the curriculum using ML methodology. Pre-meeting learning materials were provided online. We conducted a virtual meeting (2-hours) and used real-world clinical cases to simulate decision making with deliberate practice and feedback. The minimum passing standard (MPS) is 80% for the pre-test and post-test. Our primary outcome was to evaluate the learning gained using Cohen’s D coefficient (large effect ≥ 0.8). We compared the test performance using paired t-tests. Our secondary outcome was the proportion of participants who reached the MPS post-course using Fisher’s exact test.

Results: We enrolled 18 board certified gastroenterologists from 8 sites in Taiwan: median age 40.9 (range 29-56) years; 76% from academic/ cancer center. We observed a significant gain in knowledge (Cohen’s D: 1.91-5.08). Mean post-test score was significantly higher than pre-test score (78.7% ± 11.8% vs. 65.1% ± 8.5%, p < 0.001). After the course, we continued case-based training on social media to consolidate knowledge till the rest of the participants reach the MPS. All agreed that our curriculum advanced their knowledge and has changed their decision-making process in clinical practice.

Conclusions: Our experience using this framework has shown significant gain in transferring knowhow on recognition and managing HCRC and FCRC among gastroenterologists. The framework can be scaled to teach other concepts of gastroenterology.

TEACHING CLINICAL DECISION MAKING FOR RECOGNITION AND MANAGEMENT OF PATIENTS WITH HEREDITARY AND FAMILIAL COLORECTAL CANCER USING EXPERT PERFORMANCE APPROACH, DECISION MAKING

EXPLORATION

Li-Chun Chang1, Yi-Chiung Hsu2, Han-Mo Chiu1, Ming-Shiang Wu1, Chiun-How Kao3, Tang-Long Shen4

1Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan

2Department of Biomedical Science and Engineering, National Central University, Taoyuan, Taiwan

3Department of Statistics, Tamkang University, Taipei, Taiwan

4Department of Plant Pathology and Microbiology, National Taiwan University, Taipei, Taiwan

1 國立臺灣大學醫學院附設醫院內科部

2 國立中央大學生醫科學與工程學系

3 淡江大學統計學系

4 國立臺灣大學植物病理與微生物學系

Background: Patient participation in colorectal cancer (CRC) screening via a stool test and colonoscopy is suboptimal, but participation can be improved by the development of a blood test. However, the suboptimal detection abilities of blood tests for advanced neoplasia, including advanced adenoma (AA) and CRC, limits their application.

Aims: We aimed to investigate the proteomic landscape of small extracellular vesicles (sEVs) from the serum of patients with colorectal neoplasia and identify specific sEV proteins that could serve as biomarkers for early diagnosis.

Methods: We enrolled 100 patients including 13 healthy subjects, 12 non-AAs, 13 AAs, 16 stage-I, 15 stage-II, 16 stage-III, and 15 stage-IV CRCs. These patients were classified as normal control, early neoplasia, and advanced neoplasia. The sEV proteome was explored by liquid chromatography-

tandem mass spectrometry. Generalized association plots were used to integrate the clustering methods, visualize the data matrix, and analyze the relationship. The specific sEV biomarkers were identified by a decision tree via Orange3 software. Functional enrichment analysis was conducted by using the Ingenuity Pathway Analysis platform.

Results: The sEV protein matrix was identified from the serum of 100 patients and contained 3353 proteins, of which 1921 proteins from 98 patients were finally analyzed. Compared with the normal control, subjects with early and advanced neoplasia exhibited a distinct proteomic distribution in the data matrix plot. Six sEV proteins were identified, namely, GCLM, KEL, APOF, CFB, PDE5A, and ATIC, which properly distinguished normal control, early neoplasia, and advanced neoplasia patients from each other. Functional enrichment analysis revealed that APOF+ and CFB+ sEV associated with clathrin-mediated endocytosis signaling and the complement system, which have critical implications for CRC carcinogenesis.

Conclusions: Patients with colorectal neoplasia had a distinct sEV proteome expression pattern in serum compared with those patients who were healthy and did not have neoplasms. Moreover, the 6 identified specific sEV proteins had the potential to discriminate colorectal neoplasia between earlystage and advanced neoplasia. Collectively, our study provided a six-sEV protein biomarker panel for CRC diagnosis at early or advanced stages. Furthermore, the implication of the sEV proteome in CRC carcinogenesis via specific signaling pathways was explored.

OF THE PROTEOMIC LANDSCAPE OF SMALL EXTRACELLULAR VESICLES IN SERUM AS BIOMARKERS FOR EARLY DETECTION OF COLORECTAL NEOPLASIA

血清中胞外體蛋白質對大腸直腸腫瘤 早期偵測之探討

Section：HBV ⑬

MATERNAL HIGH FAT DIET WITH MICROPLASTICS EXPOSURE IN NEONATE OFFSPRING LIVER INJURY VIA OXIDATIVE STRESS

Mao-Meng Tiao

Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital, and Chang Gung University College of Medicine, Kaohsiung, Taiwan

⑭TREATMENT WITH TENOFOVIR ALAFENAMIDE FOR CHRONIC HEPATITIS B WITH MILDLY ELEVATED ALANINE AMINOTRANSFERASE AND SIGNIFICANT LIVER INJURIES – A 48-WEEK ANALYSIS

Yi-Ning Lo1, Pin-Nan Cheng1, Ming-Lung Yu2, Yao-Chun Hsu3, Chun-Jen Liu4

1Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan

高雄長庚紀念醫院兒科

Background: Prenatal nutrition or toxic exposure will affect the health of offspring. Prenatal high-fat diet or exposure of microplastics can impact the accumulation of liver fat in the offspring, which can cause liver cirrhosis.

Aims: To study the neonate offspring fatty liver injury through maternal high-fat diet (1st hit) and microplastics exposure (2nd hit) was with oxidative stress.

Methods: After confirmation of pregnancy on the 14th day after mating, pregnant females SpragueDawley rats are randomly divided for the maternal high-fat diet exposure paradigm (HFD) or normal diet (NC) until delivery. The other NC and HFD were fed with microplastics as NCMP1: NC + microplastics (5 um, 100 ug/L), NCMP2: NC + microplastics (5 um, 1000 ug/L), HFDMP1: HFD + microplastics (5 um, 100 ug/L), HFDMP2: HFD + microplastics (5 um, 1000 ug/L). The offspring was sacrificed 7 days after delivery (PD7).

Results: In liver histology, the PD7 offspring increased more hepatic lipid accumulation in the HFDMP1,2 than HFD and NCMP1,2 groups. The offspring liver TUNEL stain, cellular apoptosis were increased more in HFDMP1,2 than HFD group. The MDA, lipid peroxidation, expression were increased in HFD, HFDMP1, HFDMP2 and was highest in HFDMP2 group (P < 0.05). The Glutathione peroxidase, antioxidant enzyme were decreased in HFD, HFDMP1 and HFDMP2 groups (P < 0.05).

Conclusions: Oxidative stress with cellular apoptosis plays a vital role in the neonate offspring liver after maternal microplastics with HFD and this may shed light on future therapeutic strategy.

2Hepatitis Center and Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, School of Medicine and Hepatitis Research Center, College of Medicine, and Cohort Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan

3Division of Gastroenterology and Hepatology, Department of Internal Medicine, E-Da Cancer Hospital/I-Shou University, Kaohsiung, Taiwan

4Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan

Background: The recommendations of antiviral treatment for chronic hepatitis B (CHB) subjects with mildly elevated alanine aminotransferase (ALT) are different among various international guidelines. For this kind of patients with significant liver injury, the effect of tenofovir alafenamide (TAF) treatment on clinical and biochemical features is not well studied.

Aims: This interim study aimed to evaluate a 48week TAF treatment and associated changes in

母體高脂肪飲食與微塑料暴露引起的 新生兒肝損傷中與氧化壓力的作用

CHB patient with mildly elevated ALT and significant liver injury.

Methods: Patients with chronic HBV infection with HBV DNA >2000 IU/mL of HBeAg negative or HBV DNA >20000 IU/mL of HBeAg positive, naïve to any antiviral treatment, and an ALT level between 1-2 folds of ULN within one year before liver biopsy participated in a phase IV study (NCT04674423) were enrolled. For those patients with histology activity index (HAI) HAI score ≥4 of Knodell necroinflammantion scoring system or fibrosis stage 2 or 3 of Metavir scoring system were treated with oral TAF 25mg per day. Meanwhile, liver stiffness measurement (LSM) by FibroScan at same day of liver biopsy and at study week 48 were performed. Demography, biochemical, hematology, and virology assessments were measured.

Results: From July 2019 to May 2022, 20 CHB patients with mean age of 57.2 years and 10 males were enrolled for TAF treatment. At baseline, the levels of HBV DNA and HBsAg were 5.7 ± 1.5 log10 IU/mL and 2.6 ± 0.8 log10 IU/mL. Three patients exhibited HBeAg positivity. The grading of HAI was 5.1 ± 16 and distribution of fibrosis was seven patients of stage 1 (35%), four patients of stage 2 (20%), and nine patients of stage 3 (45%). Among them, 19, 16, and 15 patients completed 12 weeks, 36 weeks, and 48 weeks of TAF treatment, respectively. Of those patients completed 48 weeks of TAF treatment, 14 patients (93.3%) had undetectable HBV DNA. Comparing with baseline level of ALT (50.2 ± 22.5 U/L), there were significant decline of ALT levels at week 12 (29.0 ± 11.9, p < 0.001), week 24 (32.0 ± 12.9, p = 0.001), week 36 (29.9 ± 12.7, p = 0.002), and week 48 (28.1 ± 10.8, p < 0.001). The percentage of ALT normalization was 68.4% (13/19) at week 12, 75% (12/16) at week 24, 81.3% (13/16) at week 36, and 73.3% (11/15) at week 48, respectively. In addition, liver stiffness measured by fibroscan (7.9 ± 3.5 kPa vs. 5.9 ± 1.9 kPa, p = 0.003) and Fibrosis-4 score (1.9 ± 1.3 vs. 1.7 ± 1.2, p = 0.003) were improved following a 48-week of TAF treatment.

Conclusions: For CHB patients with mildly elevated ALT and significant liver injury, a 48-week TAF treatment resulted in decline of ALT levels, ALT normalization in a large proportion of patients, and improvement of liver stiffness and Fibrosis-4 score. These results indicated that 48-week TAF treatment may improve liver inflammation and fibrosis.

⑮

ARTHROSPIRA ENHANCES SEROCLEARANCE IN PATIENTS WITH CHRONIC HEPATITIS B RECEIVING NUCLEOS(T)

IDE ANALOGUE THROUGH MODULATION OF TNF-α/IFN-γ PROFILE

Wei-Hsiang Wang1, Ming-Shun Wu1,2, Sheng-Jie Shiue1, Chao-Ling Cheng1, Chun-Nan Chen1, Tze-Sian Chan1,2

1Division of Gastroenterology, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan

2Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan

慢性 B 肝病人接受抗病毒藥物治療後

TNF-α/IFN-γ 狀態促進表面抗原的血清清除

王威翔1 吳明順1,2 薛聖潔1 鄭照霖1 陳俊男1

張智翔1,2

1 臺北市立萬芳醫院—委託財團法人臺北醫學大學

辦理消化內科

2

Background: Hepatitis B virus infection not only causes chronic hepatitis but also immune dysfunction and is the first class carcinogen for hepatocellular cancer. Arthrospira species, a cyanobacterium has been used frequently as a dietary supplement, have ability to maintain natural killer (NK) cell growth, enhance B cells maturation, activate macrophages and T cells.

Aims: Our study is to investigate how Arthrospira enhances quantitative hepatitis B surface antigen (qHBsAg) reduction in Chronic hepatitis B (CHB) patients under maintenance nucleos(t)ide analogues (NA)

Methods: Sixty CHB patients who have been receiving NA for at least one year with undetectable HBV DNA were open-labelled randomization into three groups. The control group received NA alone. The low dose and standard dose groups received NA plus Arthrospira 3 g and 6 g daily, respectively. All patients were followed for 6 months. Meanwhile, orally Arthrospira diet mice were established to investigate the possible

補充節螺藻可調節血中

immunological mechanism of Arthrospira against HBV

Results: Within 6 months of Arthrospira supplement, declined mean qHBsAg associated with increased interferon gamma (IFN-γ), decreased TNF-α, interleukin 6 (IL-6), hepatic fibrosis and steatosis. In mice, Arthrospira enhanced both innate and adaptive immune system, especially NK cell cytotoxicity, B cells activation and the interleukin 2 (IL-2) and IFN-γ immune responses.

Conclusions: Arthrospira may modulate IL-2 and TNF-α/IFN-γ mediated B and T cell activation to reduce qHBsAg and enhance seroclearance.

⑯

PROGNOSIS OF SEVERE FLARES OCCURRED WITHIN 6 MONTHS AFTER COVID-19 VACCINATION IN CHRONIC HEPATITIS B PATIENTS WAS WORSE THAN THOSE WITHOUT RECENT VACCINATION

Chia-Hung Tai1,2, Yen-Chun Liu1,2, Wen-Juei Jeng1,2, Rong-Nan Chien1,2,3, Yun-Fan Liaw2,3

1Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan, Taiwan

2College of Medicine, Chang Gung University, Taoyuan, Taiwan

3Liver research unit, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan, Taiwan

B 型肝炎患者在接種新冠肺炎疫

Background: Recent case reports had disclosed acute hepatitis occurred after COVID-19 vaccination in patients without viral hepatitis. In 2021, we have observed several cases of acute severe hepatitis flare in chronic hepatitis B patients with recent COVID vaccine exposure.

Aims: This study aims to investigate the presentation and prognosis of severe flare or hepatic decompensation between chronic hepatitis B patients with and without recent (<6 months) exposure to COVID-19 vaccination during Nov 2020-Nov 2021.

Methods: From the Nuc application registry during Nov 2020-Nov 2021 in Chang Gung Memorial Hospital, Linkou medical center, patients with acute hepatitis flare, defined as ALT ≥ 5x upper limit of normal (ULN), with serum bilirubin ≥ 2 mg/dL and/or prothrombin time >3 second were recruited. Age, gender, liver biochemistry, HBV viral load as well as adverse outcomes including liver transplantation or mortality were compared between chronic hepatitis B patients with and

without COVID-19 vaccination within 6 months prior to hepatitis flare. Patients with acute hepatitis B were excluded from this study.

Results: A total of 68 patients were enrolled. Nine patients (13.2%) had recent COVID vaccine exposure history (vaccine group) within 6 months. Compared these two groups, there is no significant difference between age, gender, cirrhosis, and HBeAg positivity. The median level of HBV DNA at flare was numerically higher in the nonvaccine group (7.4 vs 6.3 log10 IU/mL, P = 0.4) while the vaccine group more frequently showed low viremia (<5 log10 IU/mL) (22.2% vs 8.5%, P = 0.26). In addition, the vaccine group patients have significantly higher peak INR (3.2 vs 1.9, P = 0.044), peak AST (1789 vs 918, P = 0.017), peak ALT (2079 vs 1507, P = 0.027) during the event. Higher proportion of peak ALT > 3000 U/L (44.4% vs 8.5%, P = 0.014), INR ≥ 1.5 (89% vs 78.0%, P = 0.677) and MELD score ≥32 (33.3% vs 6.8%, P = 0.06) in vaccine group than non-vaccine arm was observed. The vaccine group patients have higher rates of mortality or liver transplant (55.6% vs 33.9%, P = 0.138).

Conclusions: Chronic hepatitis B patients who encountered severe flare in 6 months after COVID-19 vaccine had comparable HBV viral load but higher proportion of MELD score ≥32 and higher rate of mortality/liver transplantation.

CARCINOMA

Shen-Yung Wang1,2, Yen-Hua Huang3, Yuh-Jin Liang4, Jaw-Ching Wu2,4

1Division of Gastroenterology and Hepatology, Department of Medicine, MacKay Memorial Hospital, Taipei, Taiwan

2Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan

3Institute of Biomedical Informatics, National Yang Ming Chiao Tung University, Taipei, Taiwan

4Medical Research Department, Taipei Veterans General Hospital, Taipei, Taiwan

基因共同表現網絡分析發現 B 型肝炎

病毒相關肝細胞癌之樞紐

王勝永

1

2 國立陽明交通大學臨床醫學研究所

3 國立陽明交通大學生物醫學資訊研究所

4

Background: Hepatocellular carcinoma (HCC) is among the leading causes of cancer-related death worldwide. The molecular pathogenesis of HCC involves multiple signaling pathways.

Aims: This study aims to investigate the pathogenesis of HCC with systems and bioinformatic approaches.

Methods: Gene expression microarray data were obtained from 50 patients with chronic hepatitis B and HCC. The 1649 differentially expressed genes were inferred from tumorous and nontumorous datasets. Weighted gene co-expression network analysis (WGCNA) was performed to construct clustered co-expressed gene modules. Statistical analysis was used to study the correlation between gene co-expression networks and demographic features of patients. Functional annotation and pathway inference were explored for each coexpression network. Network analysis identified hub genes of the prognostic gene co-expression network. The hub genes were further validated with a public database.

Results: Five distinct gene co-expression

⑰

GENE CO-EXPRESSION NETWORK ANALYSIS IDENTIFIES HUBS IN HEPATITIS B VIRUS-ASSOCIATED HEPATOCELLULAR

networks were identified by WGCNA. A distinct co-expressed gene network was significantly correlated with HCC prognosis. Pathway analysis of this network revealed extensive integration with cell cycle regulation. Ten hub genes of this gene network were inferred from protein-protein interaction network analysis and further validated in an external validation dataset. Survival analysis showed that lower expression of the 10gene signature had better overall survival and recurrence-free survival.

Conclusions: This study identified a crucial gene co-expression network associated with the prognosis of HBV-related HCC. The identified hub genes may provide insights for HCC pathogenesis and may be potential prognostic markers or therapeutic targets.

RATE OF HBSAG LOSS AFTER DISCONTINUING

VERSUS ENTECAVIR IN CHRONIC HEPATITIS B PATIENTS

Chien-Hung Chen, Tsung-Hui Hu, Jing-Houng Wang, Chao-Hung Hung, Sheng-Nan Lu

Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan

失率

陳建宏 胡琮輝 王景弘 洪肇宏 盧勝男

長庚醫療財團法人高雄長庚紀念醫院胃腸肝膽科

Background: HBsAg lossrate remains unclearafter discontinuing tenofovirdisoproxilfumarate (TDF) versus entecavir in chronic hepatitis B (CHB) patients.

Aims: To compare HBsAg loss rate inHBeAgpositive and HBeAg-negativeCHB patients without cirrhosis who discontinued entecavirversus TDF treatment.

Methods: A total of 892 patients (285HBeAgpositiveand 607 HBeAg-negative patients) who received entecavir (n = 555) and TDF (n = 337) therapy previously and had post-treatment followup for at least 12 months were included in this study. The end of follow-up was either the time retreatment began or the last visit among patients without retreatment. The propensity scorematching method (PSM) was used by creating a ratio of 1:1 to 1:2 (TDF:entcavir) to adjust age, sex, HBV DNA, HBeAg and NA-naïve status, treatment and consolidation duration, and HBsAg levels at baseline and end of treatment (EOT).

Results: Of the 892 patients, 425 received retreatment during follow-up. The cumulative incidences of HBsAg loss at 6 years were17.7% and 25.8% in the entecavirand TDF groups, respectively (p = 0.019). Multivariate analysis showed that TDF group (HR: 1.722, 95% CI:

⑱

HIGHER

TENOFOVIR

慢性 B 型肝炎病人停止惠立妥治療比 停止貝樂克治療有較高的表面抗原消

系

Section：Pancreas / Biliary

1.101-2.692, p = 0.017), longer treatment duration and lower HBsAg levels at EOT were independent predictors of HBsAg loss for all patients. After PSM, TDF group still had a higher HBsAg loss rate than entecavir group (p = 0.031). For the analysis of subgroups, TDF group had a higher HBsAg loss rate than entecavir group in patients with sustained virological remissionafter entecavir or TDF cessation (the cumulative rate of 6 years: TDF vs. entecavir: 48.6% vs. 29.4%; p = 0.001). After PSM, TDF group still had a higher HBsAg loss rate than entecavir group (p = 0.005) in patients with sustained virological remission.

Conclusions: Patients who discontinued TDF therapy had significantly higher rates ofHBsAg loss than those who discontinuedentecavir therapy, especially in patients without HBV relapse after entecavir or TDF cessation.

ENCOUNTERED

Sheng-Fu Wang, Chi-Huan Wu, Mu-Hsien Lee, Yung-Kuan Tsou, Cheng-Hui Lin, Kai-Feng Sung, Nai-Jen Liu

Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan, Taiwan

Background: Periampullary diverticulum is frequently encountered especially in elderly when performing ERCP that may lead to difficult selective biliary cannulation in some previous studies and several classifications were created according to the location between the diverticulum and the papilla vater. Precut method with needle knife fistulotomy or papillotomy is proved to be an effective and safe method when initial cannulation failed. But scarce study to evaluate precut method in patients with periampullary diverticulum.

Aims: We want to recognize if there’s risk factors influence the precut success or failure in patients with periampullary diverticulum.

Methods: We retrospectively collected 592 patients undergoing ERCP with needle knife precut since January 2004 till December 2020 and then included 122 patients had periampullary diverticulum. We analyze factors including common bile duct diameter, hemorrhage during needle knife precut, morphology of papilla, classification of periampullary diverticulum, diverticulum size and we also evaluate if post ERCP complications (pancreatitis, cholangitis, bleeding and perforation) would be different between precut success or failure.

Results: Our result revealed that the type of papilla morphology may influence precut success (p = 0.01), when approaching type II papilla (small orifice), precut is more difficult to success compared to the type I (regular papilla) (p = 0.032, OR: 0.264, 95% CI: 0.08-0.89) and when

FACTORS INFLUENCE NEEDLE KNIFE PRECUT SUCCESS WHEN PERIAMPULLARY DIVERTICULUM

探討當有乳突周圍憩室時影響針刀切 開成功率的因素

王昇富 吳季桓 李沐憲 鄒永寬 林政輝

宋皚峰 劉乃仁

林口長庚紀念醫院胃腸肝膽科

approaching type III (protruding papilla), precut is much easier to success compared to type I (regular papilla) (p = 0.043, OR: 14.028, 95% CI: 1.08-182.16). Increased diverticulum size makes precut more difficult (p = 0.041, OR: 0.233, 95% CI: 0.06-0.94) and bleeding during precut also prone to failure (p = 0.000, OR: 13.991, 95% CI: 3.66-53.56) but the classification of periampullary diverticulum had no clinical significance. Bleeding is the only complication had clinical significance more in group of precut failure (p = 0.003).

Conclusions: The success or failure of precut in patients with periampullary diverticulum may related to the size of diverticulum, type of papilla and if bleeding occurred when ERCP but not related to the classification of periampullary diverticulum. The complications are comparable between success or failure of precut except the bleeding underwent ERCP. Therefore, we suggest considering alternative therapy earlier if these risk factors exist.

⑳

TIMING OF ERCP IN THE TREATMENT OF ACUTE CHOLANGITIS OF DIFFERENT SEVERITY

Chi-Huan Wu, Sheng-Fu Wang, Mu-Hsien Lee, Cheng-Hui Lin, Kai-Feng Sung, Nai-Jen Liu, Yung-Kuan Tsou

Department of Gastroenterology and Hepatology, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan

劉乃仁 鄒永寬

林口長庚紀念醫院胃腸肝膽科

Background: The optimal timing for an early ERCP has been unclear. Aims: This study aimed to report whether timing of ERCP is associated with outcomes in different severity of acute cholangitis (AC) patients.

Methods: According to the 2018 Tokyo guidelines, 683 patients who met the definite diagnostic criteria for AC were retrospectively identified. Results were first compared between patients receiving ERCP ≤24 hours (h) and >24 h, and then between patients receiving ERCP ≤48 h and >48 h. Subgroup analyses were performed on patients with grade III, II, or I AC. The primary outcome was 30-day mortality. Secondary outcomes were intensive care unit (ICU) admission rate, length of hospital stay (LOHS), and 30-day readmission rate.

Results: Taking 24 h as the critical value, compared with ERCP and >24 h, the proportion of cardiovascular dysfunction (11.2% vs. 2.6%), respiratory dysfunction (14.2% vs.5.3%), and ICU admission (11.2% vs. 4%) in the ERCP ≤24 h group was significantly higher, while the LOHS was significantly shorter (median, 6 vs. 7 days). Stratified by severity of AC, higher ICU admission was only observed in grade III AC; shorter LOHS was only observed in grade II and I AC. There were no significant differences in 30-day mortality between groups, either in the overall population or in patients with grade III, II, or I AC. With 48 h as the critical value, compared with ERCP >48 h, the ERCP ≤48 h group had significantly lower

管攝影之時機

吳季桓 王昇富 李沐憲 林政輝 宋皚峰

30-day mortality (0 vs 1.9%) and shorter LOHS (6 vs 8 days). Stratified by AC severity, higher 30-day mortality (0 vs. 6.1%) and CU admission rate (22.2% vs. 10.2%) were only observed in grade III AC; shortened LOHS was only observed in grade II and I AC. In multivariate analysis, cardiovascular dysfunction and time to ERCP were two independent factors associated with 30day mortality.

Conclusions: ERCP ≤48 h conferred a survival benefit in patients with grade III AC. Early ERCP shortened hospital stay in patients with grade II and I AC.

Yu-Ling Pan1,5, Pei-Shan Wu1,2,5, Jung-Hsuan Chen3,5, Wen-Liang Fang4,5, Gar-Yang Chau4,5, Kuei-Chuan Lee1,5, Ming-Chih Hou1,2,5

1Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan

2Endoscopy Center for Diagnosis and Treatment, Taipei Veterans General Hospital, Taipei, Taiwan

3Department of Radiology, Taipei Veterans General Hospital, Taipei, Taiwan

4Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan

5Department of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan

Background: Acute cholecystitis (AC) is a lifethreatening infectious/inflammatory disease in elderly patients. The mortality rate is about 1% and the related complications such as gallbladder rupture, gallbladder abscess and acute pancreatitis, are associated with increased overall, cardiovascular disease and cancer mortality. Cholecystectomy is the standard treatment of acute cholecystitis. In Tokyo guideline 2018, it should be evaluated whether the patients with acute cholecystitis need immediate cholecystectomy according to disease

EARLY CHOLECYSTECTOMY FOLLOWING PERCUTANEOUS TRANSHEPATIC GALLBLADDER DRAINAGE IS EFFECTIVE FOR MODERATE TO SEVERE ACUTE CHOLECYSTITIS IN EXTREMELY ELDERLY PATIENTS

severity and preoperative factors. The inoperable patient could receive medical antibiotics treatment or percutaneous transhepatic gallbladder drainage (PTGBD) first, then arrange surgical intervention after clinical conditions stabilized. In previous studies, PTGBD has been known as a safe option and an alternative treatment in severe septic patients or patients with serious comorbidities not responding to conservative treatment and/or unfit to undergo surgery. However, there is still unknown about how long the drainage tube should remain and whether subsequent cholecystectomy is necessary in elderly patients. The clinical predictors of outcome for patients with acute cholecystitis treated with PTGBD are also unclear.

Aims: This study aimed to investigate the safety and optimal timing of surgery in extremely elderly patients with moderate to severe AC who have undergone percutaneous transhepatic gallbladder drainage (PTGBD).

Methods: From January 2008 to February 2021, 152 extremely elderly patients with moderate to severe AC who had undergone subsequent cholecystectomy following PTGBD were retrospectively enrolled in Taipei Veterans General Hospital. The clinical outcomes of cholecystectomy, including operationrelated complications and mortality, were analyzed. Results: Among the 152 patients, 67 (44.1%) underwent laparoscopic cholecystectomy (LC), 62 (40.8%) underwent open cholecystectomy (OC), and 23 (15.1%) underwent conversion surgery from LC to OC. Operation-related complications and mortality rates did not differ among the three types of surgery; however, LC group had shorter operative time than the other groups. Eighty-two (53.9%) patients underwent early cholecystectomy (<6 weeks after PTGBD), while 70 (46.1%) underwent delayed cholecystectomy (≥6 weeks after PTGBD). There were no differences in operative time, operationrelated complications, and mortality rates between the groups. However, higher rates of recurrent AC and biliary events were observed in the delayed cholecystectomy group (52.9% vs. 4.9% and 57.1% vs. 8.5%, p < 0.001). On multivariate analysis, delayed cholecystectomy was a significant risk factor for recurrent AC (odds ratio [OR] = 20.7, p < 0.001) and further biliary events (OR = 16.18, p < 0.001).

Conclusions: Early cholecystectomy within 6 weeks of PTGBD is recommended for extremely elderly patients with moderate to severe AC who have undergone acute episodes of PTGBD.

EFFICACY OF 100 MG AND 25 MG PERIPROCEDURAL DICLOFENAC SUPPOSITORIES IN PREVENTING POST-ERCP PANCREATITIS: A RANDOMIZED CONTROL TRIAL

Keng-Han Lee1, Chih-Jen Chen1, Ching-Chung Lin1,2, Chien-Yuan Hung1, Cheng-Hsin Chu1, Jian-Han Lai1, Chia-Yuan Liu1,2,3, Ming-Jen Chen1,2,3

1Division of Gastroenterology, Department of Internal Medicine, Mackay Memorial Hospital, Taipei, Taiwan

2Mackay Medical College, Taipei, Taiwan

3Mackay Junior College of Medicine, Nursing, and Management, New Taipei City, Taiwan

比較術後

Background: Post-ERCP pancreatitis is an important iatrogenic complication in the daily practice, accounting for substantial morbidity, occasional mortality, increased health care expenditure and even legal problem; it was proposed that rectal NSAID administration is the most cost-effective prophylactic strategy used to prevent post- ERCP pancreatitis. Standard 50100 mg NASID dose is considered to have toxic effects on the gastric and renal functions, and previous Japanese study had evaluated the safety and efficacy of 25 mg rectal dose of diclofenac in preventing post-ERCP pancreatitis, but local data is lacking.

Aims: The aim was to compare the efficacy between different dose (100 mg and 25 mg) rectal diclofenac after ERCP to prevent post ERCP pancreatitis.

Methods: The prospective randomized control trial underwent in Taipei and Tamsui MacKay Memorial Hospital during January 2020 to January 2021. Patients were eligible for this study if they

㉒

100 毫克與 25 毫克 Diclofenac 塞劑降低逆行性膽胰管攝

aged 20~90 years and had been arranged ERCP. The exclusion criteria were patients with acute or chronic pancreatitis, p-duct stent used, allergy to NSAID, active peptic ulcer disease and severe cardiac, renal, or hepatic comorbidities. The participants were randomly assigned to either high dose (rectal Diclofenac 100 mg) or low dose group (rectal Diclofenac 25 mg). All procedurerelated interventions were dictated by the performing endoscopist. The suppositories were administered right after ERCP while the patient still in the procedure room. The primary outcome of the study was the development of post-ERCP pancreatitis (defined as a new onset epigastric pain, an elevation in pancreatic enzymes of at least three 3 times the upper limit of the normal range, and hospitalization for at least 2 nights). Patient demographics, risk factors, ERCP procedural elements, and follow-up data were recorded. Statistical analyses were performed using the SPSS 12.0 statistical package (SPSS, Chicago, IL). All statistical analyses were based on twosided hypothesis tests with a significance level of p < 0.05.

Results: Total 134 patients were recruited in this study, with 73 (54.5%) assigned to 25 mg group and 61 (45.5%) to the 100 mg group. Acute pancreatitis happened in 20 (14.9%) patients, while 6 (4.5%) patients encountered post-ERCP bleeding. Diclofenac dose did not significantly influence the incidence of post-ERCP pancreatitis (p = 0.159) and bleeding (p = 0.058). Previous ERCP + EPT was identified as a risk factor in developing post-ERCP pancreatitis (p = 0.026). In the case for post-ERCP bleeding, cannulation attempts (p = 0.038) and procedural duration (p = 0.013) were predicting factors with statistical significance.

Conclusions: High dose and low dose rectal Diclofenac administration provide similar efficacy of preventing post-ERCP pancreatitis, and both cannulation attempts and ERCP procedural duration were significant predicting factors of developing post-ERCP bleeding. However, this is a single center, small sample size study conducted during COVID-19 pandemics, further multi-center study with larger sample size is warranted to make the conclusions.

㉓

EFFICACY AND SAFETY OF INTERNAL DRAINAGE BY ENDOSCOPIC ULTRASOUND GUIDED LUMEN APPOSING METAL STENT PLACEMENT FOR PANCREATIC FLUID COLLECTIONS: A MULTICENTER STUDY IN TAIWAN

Yu-Ti Chang1, Chen-Shuan Chung1,2, Yu-Ting Kuo3, Yi-Chun Chiu4, Yang-Chao Lin2,5, Chi-Ying Yang6, Kuan-Chih Chen1, Szu-Chia Liao7, Cheuk-Kay Sun8, Yen-Chih Lin9, Hsiu-Po Wang3

1Division of Gastroenterology and Hepatology, Department of Internal Medicine, Far Eastern Memorial Hospital, New Taipei City, Taiwan

2College of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan

3Department Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan

4Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung

Chang Gung Memorial Hospital and Chang

Gung University College of Medicine, Kaohsiung, Taiwan

5Department of Gastroenterology and Hepatology, Fu Jen Catholic University Hospital, New Taipei City, Taiwan

6Department of Internal Medicine, Digestive Medicine Center, China Medical University Hospital, Taichung, Taiwan

7Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taichung

Veterans General Hospital, Taichung, Taiwan

8Department of Internal Medicine, Shin Kong

Wo Ho-Su Memorial Hospital, Taipei, Taiwan

9Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan

屬支架內引流治療胰臟週邊積液之有 效性及安全性：一台灣多中心研究

1 亞東紀念醫院肝膽胃腸科

2 輔仁大學醫學院

3 國立臺灣大學醫學院附設醫院胃腸肝膽科

4 高雄長庚紀念醫院胃腸肝膽科

5 輔仁大學附設醫院胃腸肝膽內科

6 中國醫藥大學附設醫院消化醫學中心

7 臺中榮民總醫院胃腸肝膽科

8 新光吳火獅紀念醫院胃腸肝膽科

9 彰化基督教醫院胃腸肝膽科

Background: Pancreatic fluid collections (PFCs) are one of the complications after pancreatitis. Conventional management by percutaneous drainage or surgical debridement brings high rates of re-intervention and unplanned hospitalization as well as perioperative complication and mortality.

Aims: This study aimed to evaluate the efficacy and safety of endoscopic ultrasound (EUS) guided lumen-apposing metal stent (LAMS) for internal drainage of PFC.

Methods: Between June 2019 and February 2022, patients with symptomatic PFCs, including pancreatic pseudocyst (PP) and walled-off necrosis (WON), who underwent EUS-guided HotAxios placement for internal drainage were enrolled retrospectively from 8 tertiary centers in Taiwan. Clinical, radiological and endoscopic data were reviewed and analyzed.

Results: Totally 26 patients [9 (34.62%) PP and 17 (65.38%) WON] were enrolled. The gender (female/male) and mean (±SD) age were 11 (42.31%)/15 (57.69%) and 24.62 (±5.16) years old. The most common etiology for pancreatitis was gallstone (34.62%), followed by alcohol (26.92%) and hypertriglyceridemia (15.38%). The PFC related symptoms included abdominal pain (69.23%), infection (23.08%) and enteral obstruction (7.69%). The mean size of PFC and proportion of necrotic parts of WON were 11.57 (±5.51) cm and 63.33% (±24.25%). The majority (80.77%) was unilocular and 5 (19.23%) patients had paracolic gutter extension. All the enrolled patients received 15mm HotAxios placement with technical and clinical success rates of 100% and 96.15%, respectively. Regarding the transluminal route, 23 (88.46%) patients were from gastric body, followed by 2 (7.69%) antrum and 1 (3.85%) fundus. The mean procedure time and direct endoscopic necrosectomy (DEN) session was 32.31 (±17.57) minutes and 2.83 (±2.01) times. Complications from index procedure included one (3.85%) self-

limited bleeding without mortality and the mean LAMS indwelling time was 22.85 (±9.56) days. Seven (26.92%) patients developed recurrence with follow-up period of 446.81 (±428.41) days. Patients with disconnected pancreatic duct syndrome (DPDS) had a higher recurrence rate after removal of LAMS than those without DPDS (71.43% vs. 31.58%, p=0.03). Among DPDS patients after LAMS removal, the migration rate of transmural double pigtail plastic stent (DPS) (100% vs. 33.33%, p = 0.04) was higher in those with recurrence and placement of transpapillary pancreatic stent could lower recurrence (100% vs. 40%, p=0.05).

Conclusions: EUS-guided LAMS internal drainage for symptomatic PFCs is efficient and safe. LAMS replacement with transmural DPS and transpapillary pancreatic stenting in DPDS patients was associated with lower recurrence rate.

THE

DISEASES

Fai-Meng Sou1, Chien-Ning Hsu2,3, Yi-Chun Chiu1, Cheng-Kun Wu1, Chen-Hsiang Lee4, Seng-Kee Chuah1, Chih-Ming Liang1

1Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan

2Department of Pharmacy, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan

3School of Pharmacy, Kaohsiung Medical University, Kaohsiung, Taiwan

4Division of Infectious Diseases, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan

Those who had an International Classification of Diseases, Ninth and Tenth Revision (ICD9 and ICD10) codes of choledocholithiasis were enrolled (n = 68,384). After strict exclusions, 32,696 patients were further divided into the non-statin user (≤28 cDDD, cumulative defined daily doses) group (n = 27,929) and statin user (>28 cDDD) group (n = 4,767) for analysis. The group-based trajectory modeling technique was used to estimate serum cholesterol trajectories (n = 8,410). There were 3,254 participants (38.7 %, group 1) with low level of cholesterol, 4,038 participants (48.0%, group 2) with intermediate level of cholesterol, and 1,118 participants (13.3%, group 3) with high level of cholesterol.

1 高雄長庚紀念醫院內科部胃腸肝膽科系 2 高雄長庚紀念醫院藥劑科

Background: Statins can reduce hepatic cholesterol biosynthesis and thereby decrease biliary cholesterol secretion. Animal studies have indicated that statins can prevent gallstone formation. Few epidemiological studies have investigated the association between statin use and the risk of gallstone disease, and results have been inconsistent.

Aims: to evaluate whether statin doses and serum cholesterol were associated with a decreased risk of recurrent biliary stone disease after the first event index.

Methods: This study was based on the Chung Gung Research Database (CGRD) between January 1, 2001 and December 31, 2020.

Results: The statin user group had higher CCI (Charlson Comorbidity Index) scores and age distribution than the non-statin user. Time (15 years)-dependent Cox regression analysis showed that statin user >365 cDDD was associated with significantly lower risk of recurrent biliary stone disease after adjusting for other risk factors (Adjusted hazard ratio [aHR] = 0.28, 95% CI: 0.240.34; p < .0001 for recurrent biliary stone) (aHR = 0.24, 95% CI: 0.17-0.32, p < .0001 for acute pancreatitis ) (aHR = 0.28, 95% CI: 0.25-0.32, p < .0001 for cholangitis). Cholecystectomy was also a protective factor for recurrent biliary stone diseases (aHR = 0.41, 95% CI: 0.37-0.46; p < .0001 for recurrent biliary stone) (aHR = 0.53, 95% CI: 0.45-0.63, p < .0001 for acute pancreatitis) (aHR = 0.39, 95% CI: 0.36-0.42, p < .0001 for cholangitis). In trajectory model analysis, the level of serum cholesterol was unable to predict the risk of recurrent biliary stones diseases.

Conclusions: The statin treatment and cholecystectomy after the first biliary stone index play a protective role in the recurrence of biliary stones diseases, such as recurrent stone, acute pancreatitis, and cholangitis.

ASSOCIATION BETWEEN TRAJECTORY MODEL ANALYSIS OF SERUM CHOLESTEROL, STATIN DOSAGE, AND THE RISK OF RECURRENT BILIARY STONE

3 高雄醫學大學藥學系

4 高雄長庚紀念醫院感染醫學科

Section：Cirrhosis & HCC

PERIPHERAL IMMUNOPROFILING ANALYZED BY MACHINE LEARNING ALGORITHM SERVES AS PREDICTIVE BIOMARKERS OF IMMUNE CHECKPOINT INHIBITORS FOR ADVANCED HEPATOCELLULAR CARCINOMA TREATMENT

Chun-Yang Lee1, Yi-Ping Hung2,3, Jan-Mou Lee4, Kai-Yuan Chou4, Cheng-Yun Lee4,5, Yu-Yun Shao5,6, Chiun Hsu5,6, Chih-Hung Hsu6, Yee Chao3

1Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan

2School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan

3Department of Oncology, Taipei Veterans General Hospital, Taipei, Taiwan

4FullHope Biomedical Co., Ltd, New Taipei City, Taiwan

5Graduate Institute of Oncology, College of Medicine, National Taiwan University, Taipei, Taiwan

6Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan

surveillance and improving therapy ultimately. Methods: In the current study, we took advantage of a flow cytometry-based immunoprofiling platform published previously to analyze a possible variety of fifty peripheral immune cell subsets among aHCC patients with disease control and disease progression responses after nivolumab treatment. Results: Via the Mann-Whitney U test, the disease control group carried significantly higher amounts of PDL1+ monocytes, PD-L1+ CD8 T cells, PDL1+ CD8 NKT cells, but fewer PD-1+ CD8 NKT cells than those of the disease progression group. We subsequently integrated multi-omic biomedical data into a dataset and used artificial intelligence tools to select potential feature subsets, which led to discrimination of the disease control group and disease progression group. Interestedly, the selected feature subsets, including CD4 NKTreg, PD-1+ CD8 T cells, PD-1+ CD8 NKT cells, PD-L1+ CD8 T cells, and PD-L1+ monocytes, are highly overlapping with ones identified via Mann-Whitney U test, consolidating that selectively expressing PD-L1 on peripheral monocytes and effector CD8 T and NKT cells render aHCC more sensitive to ICI treatment. Machine learning algorithms committed valuable AUC from 0.8417 to 0.875 to significantly separate the disease control group from the disease progression group through these five feature subsets. The SHAP value ranking also revealed that PD-L1+ monocytes and PD-L1+ CD8 T cells exclusively and significantly contributed to this discrimination. Altogether, the current study enables the amalgamation of complicated immune cell profiling with the multi-omics datasets and subsequently machine learning algorithm processing to drive feasible precision medicine.

Conclusions: Synergies of peripheral immune cell profiling and computational analyses are expected to improve patient stratification in immuno-oncology.

Background: The efficiency of immune checkpoint inhibitor (ICI) therapy using monoclonal antibodies has been well proven and documented in substantial clinical studies and approaches.

Aims: Accurately profiling systemic immune responses before and after ICI treatment, and even progression is necessary for understanding tumor

5 國立臺灣大學腫瘤醫學研究所

6 台大醫院腫瘤醫學部

COMPARISON OF EIGHT HEPATOCELLULAR CARCINOMA RISK PREDICTION MODELS IN COMPENSATED CIRRHOTIC PATIENTS WITH CHRONIC HEPATITIS B RECEIVING LONGTERM NUCLEOS(T)IDE ANALOGUE THERAPY

Hung-Wei Wang1, Chien-Hung Chen2, Hsueh-Chou Lai1, Chi-Yi Chen3, Jing-Houng Wang2, Cheng-Yuan Peng1

1Center for Digestive Medicine, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan

2Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan

3Division of Hepatogastroenterology, Department of Internal Medicine, Chia-Yi Christian Hospital, Chiayi, Taiwan

針對代償肝硬化慢性 B 型肝炎患者接

predictive performance was evaluated using the receiver operating characteristic (ROC) curve. The AUROC of AFDA model was compared with those of other prediction models by DeLong test.

Results: In the present cohort, 161 patients (13.9%) developed HCC during a median followup period of 4.6 years. The cumulative incidences of HCC at 3, 5 and 10 years were 8.1%, 13.2% and 24.1%, respectively. The AFDA model showed numerically higher performance in predicting HCC development (C-statistic AUROC = 0.6828) than aMAP (C-statistic AUROC = 0.6591), modified PAGE-B (C-statistic AUROC = 0.6465), CAMD (C-statistic AUROC = 0.6379) and THRI (C-statistic AUROC = 0.6356) by DeLong test. Compared with PAGE-B (C-statistic AUROC = 0.6246), AASL-HCC (C-statistic AUROC = 0.6242), and HCC-RESCURE (C-statistic AUROC = 0.6242), the AFDA model showed significantly higher performance in predicting HCC development. According to the AFDA model, patients with a total score of 0 (n = 187, 16.1% of cirrhotic patients) had the lowest cumulative incidence of HCC at 2 to 5 years of 1.1%, 2.6%, 3.4% and 3.4%, respectively. In our cirrhotic cohort, no patient fulfilled the criteria for the low-risk group defined by CAMD (<8 points) or AASL-HCC (≤5 points). The top 3 models of which the low-risk group exhibited the lowest HCC incidence at 5 years of antiviral therapy in ascending order were AFDA (3.4%), HCC-RESCURE (4.8%) and aMAP (6.4%), accounting for 16.1%, 2.5% and 10.2% of our cohort, respectively.

Background: We recently proposed a hepatocellular carcinoma (HCC) risk model, AFDA, based on 4 variables: a combination of albuminbilirubin score (ALBI) and FIB-4, diabetes mellitus, and alpha-fetoprotein (AFP) in predicting HCC development in compensated cirrhotic patients with chronic hepatitis B (CHB) receiving long-term nucleos(t)ide analogue (NA) therapy.

Aims: We investigated the predictive performance of the AFDA model for HCC development in the same cohort, and compared with 7 other prediction models of HCC, including aMAP, PAGE-B, CAMD, THRI, PAGE-B, AASL-HCC, HCC-RESCURE because the components of these models all consist of baseline characteristics and blood tests.

Methods: We enrolled 1158 NA-naïve, compensated cirrhotic patients with CHB treated with entecavir or tenofovir from 2008 to 2018. The

Conclusions: The AFDA model demonstrated higher ability than the other prediction models to stratify the risk of HCC and assess the low-risk group in compensated cirrhotic patients with CHB receiving long-term NA therapy.

Te-Wei Tseng1, Chen-Yu Hsu1, Chen-Yang Huang2, Cheng-Heng Wu1, Pin-Jung Chen1, Yung-Chang Lin2, Chun-Yen Lin1

1Department of Hepatogastroenterology, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan

2Division of Medical Oncology/Hematology, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan

2 林口長庚紀念醫院血液腫瘤科

Background: Presence of tumor-associated neutrophils (TANs) is known as a negative prognostic factor for hepatocellular carcinoma and other cancer types. TANs phenotypic classification has been challenged with the emerging evidence leveraging single cell RNA sequence (scRNAseq) technologies. Besides, blood low-density neutrophils (LDNs) with immune suppression also accumulated as tumor progress, but the relation between TANs and LDNs remained unclear.

Aims: This study aimed to clarify the possible peripheral origin, classification, differentiation and immune phenotype of TANs.

Methods: A total of 3x105 BNL cells were injected into livers of BALB/c mice as murine hepatoma model. 21 days after injection, peripheral neutrophils were obtained and separated by density centrifugation and TANs were harvested, subsequently analyzed by flow cytometry. The suppression function of neutrophils was evaluated by cocultured with T-cell ex vivo. Bulk RNA and scRNA sequencing were done.

Results: The frequency of neutrophils increased in

blood and liver tumors as tumors progressed. TANs and blood LDNs displayed immune suppression. By scRNAseq technology, we reclassified TANs into TAN1 with immature neutrophil phenotype, TAN2 with mature neutrophil phenotype, TAN3 and TAN4 with immune suppression. Gene profile of blood LDNs resembled TAN1 and high-density neutrophils resembled TAN2, indicating the origin of TANs. Trajectory analysis showed a continuous maturation process from TAN1 to TAN4 paralleled with increasing immune suppression, deceasing anti-tumor function and metabolic responses including decreased oxidative phosphorylation (OXPHOS), adipogenesis and increased glycolysis, hypoxia signaling. Increased hypoxia in tumor-microenvironment induces a metabolic switch from OXPHOS to glycolysis and lactate is generated and exported extracellularly in hypoxic cancer cell. Lactate induces PDL1 expression through MCT/COX2/NFKB signaling in TANs. The mechanisms mentioned above were observed in TAN4.

Conclusions: Our study indicated a possible origin of TANs in murine hepatoma model and demonstrated a new classification of TANs based on maturation stage and immune suppression, evidenced from transcriptomic profiles. Furthermore, the pathway analysis suggested the importance of metabolic alteration of TANs to acquire suppressive ability. Our study provides novel evidence for the relationship between metabolic alteration and immune suppression which can be taken as a reference of tumor immunotherapy.

RE-CLASSIFICATION OF TUMOR ASSOCIATED NEUTROPHILS BASED ON THE MATURATION STAGES IS HIGHLY CORRELATED WITH SUPPRESSION FUNCTION AND METABOLIC PROFILE IN A MURINE HEPATOMA MODEL

小鼠肝腫瘤相關性嗜中性球的分化分 類與抑制功能和代謝呈高度相關

META-ANALYSIS OF SURVIVAL PROGNOSIS OF

STRATEGY FOR INTRAHEPATIC RECURRENT HEPATOCELLULAR CARCINOMA AFTER HEPATECTOMY: REPEATED HEPATECTOMY OR LIVER TRANSPLANTATION

Cho-Hsun Lee, Jen-Lung Chen, Chen-Guo Ker, Yaw-Sen Chen

Department of General Surgery, E-Da Hospital, Kaohsiung, Taiwan

Background: Hepatocellular carcinoma (HCC) was common and having a high frequency in the most patients and reflex a life threatening status, Precise surgical strategy with repeated hepatectomy (RH) or liver transplantation (LT) for recurrent hepatocellular carcinoma (HCC) after resection still remains controversy. Hence, we try to apply a systemic review and meta-analysis method for evaluation the survival prognosis.

Aims: We attempted to apply a systemic review and meta-analysis method for evaluation of repeated hepatectomy or liver transplantation for recurrent hepatocellular carcinoma after resection.

Methods: A systematic literature was searched from PubMed, EMBASE, and Cochrane Library databases, published from 2010 to 2021, to identify all of the relevant intrahepatic recurrent HCC after resection and treated with RH or LT. The Comprehensive Meta-Analysis (CMA) version 3 software was used to perform all analyses.

Results: There were 24 articles (5 with 2-arm of RH and LT, 12 of RH and another 7 of LT) enrolled for analysis. After meta regression analysis, the disease free survival rates of LT patients had a better results compared with RH patients and their β = 1.181 (95% CI = 0.55-1.812, p < 0.001) and β = 1.258 (95% CI = 0.623-1.893 p < 0.001) for 3-year and 5-year with significant difference respectively. But, the overall survival rates of LT patients also had a better results in LT patients compared with RH patients and their β = 0.04, (95% CI = -0.479-0.55, p = 0.881) and 0.392 (95% CI = -0.192-0.975, p = 0.188) for 3-year and 5-year without significant difference.

Conclusion: Either RH or LT were considered for recurrent HCC after surgical resection. These patients accepted LT usually had better results in the disease free survival with a significant difference, but not in the overall survival.

㉙

RADIOLOGICAL PATTERN DETERMINES OUTCOMES OF TRANSARTERIAL

CHEMOEMBOLIZATION AND RISK OF TACE REFRACTORY IN INTERMEDIATE STAGE HEPATOCELLULAR CARCINOMA

Ya-Wen Hung1, I-Cheng Lee1,2, Chen-Ta Chi1,2,3, Rheun-Chuan Lee4, Chien-An Liu4, Nai-Chi Chiu4, Hsuen-En Hwang4, Yee Chao5, Ming-Chih Hou1,2, Yi-Hsiang Huang1,2,3

1Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan

2Faculty of Medicine, National Yang Ming Chiao Tung University School of Medicine, Taipei, Taiwan

3Institute of Clinical Medicine, National Yang

Ming Chiao Tung University, Taipei, Taiwan

4Department of Radiology, Taipei Veterans General Hospital, Taipei, Taiwan

5Cancer Center, Taipei Veterans General Hospital, Taipei, Taiwan

Background: The tumor burdens and outcomes of unresectable intermediate-stage hepatocellular carcinoma (HCC) are heterogenous and diverse. For patients with high tumor burden, transarterial chemoembolization (TACE) might not be beneficial. Recently, we propose 7-11 criteria to redefine tumor burden. However, the role of tumor morphology and its relationship with tumor burden and outcomes of TACE was still unclear.

Aims: This study was aimed to compare the outcomes of repeated TACE in unresectable intermediate HCC by different radiological features and delineate which tumor morphology is likely to

SURGICAL

become TACE-refractory.

Methods: From January 2007 to September 2021, 640 treatment-naïve HCC patients with intermediate-stage HCC undergoing TACE were retrospectively enrolled. Among them, 386 patients received repeated TACE. The radiological features of HCC were evaluated by two radiologists. Tumor patterns were classified into single/multi nodular type, simple nodular type with extranodular growth, confluent multinodular type, and infiltrative type. We compared the objective response rate and survival among patients with different radiologic morphology.

Results: Of the 640 HCC patients treated by TACE, single/multi nodular type HCC exhibited the best radiologic response (objective response rate, ORR 58%), followed by extranodular type (45.8%), confluent multinodular type (29%), and infiltrative type HCC (19.5%). Importantly, the radiological pattern was highly associated with tumor burden. Tumor burden defined by 7-11 criteria and tumor morphology were significant factors associated with ORR and overall survival (OS) by TACE in multivariate analysis. For 386 patients received repeated TACE, single/multi nodular type HCC had the best ORR (48.7%), followed by extranodular type (37.3%), confluent multinodular type (26.2%), and infiltrative type HCC (10%). In multivariate analysis, radiological features were significant independent predictors of ORR and OS. The median OS in patients by repeated TACE was 34.8 months for single/multi nodular type, 19.1 months for extranodular growth, 16.5 months for confluent multinodular type and 12.9 months for infiltrative type HCC.

Conclusions: Radiological features can determine outcomes of TACE, and select patients who are likely to become TACE-refractory. Systemic therapy might be introduced for unresectable intermediate stage HCC with poor tumor morphology.

PATTERNS OF AFP KINETICS

CORRELATE WITH OUTCOMES OF IMMUNE CHECKPOINT

INHIBITORS-BASED COMBINATION TREATMENT FOR UNRESECTABLE HEPATOCELLULAR CARCINOMA

Chi-Jung Wu1,2,3, Pei-Chang Lee1,3, Ya-Wen Hung1, Chieh-Ju Lee1, Chen-Ta Chi1,2,3, I-Cheng Lee1,3, Ming-Chih Hou1,3, Yi-Hsiang Huang1,2,3

1Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan

2Institute of Clinical Medicine, National Yang

Ming Chiao Tung University, Taipei, Taiwan

3Faculty of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan

Background: Immuno-oncology (IO) combinations by immune checkpoint inhibitors (ICIs) plus antiVEGF or muti-kinase inhibitor (MKI) are promising for unresectable hepatocellular carcinoma (uHCC). Alpha-fetoprotein (AFP) response is different between IO monotherapy and combinations. Whether pattern of AFP kinetics can predict outcomes of IO combinations for uHCC is unclear.

Aims: This study aim to evaluate whether pattern of AFP kinetics can predict outcomes of IO combinations for uHCC.

Methods: One hundred and twenty-three consecutive uHCC patients who received lenvatinib plus pembrolizumab or atezolizumab plus bevacizumab in Taipei Veteran General Hospital from Jul. 2019 to Apr. 2022 were prospectively enrolled. Patients with baseline AFP less than 10ng/ml, follow-up period less than 6 weeks, missing evaluable images were excluded from this analysis. Finally, there were 87 patients recruited in this study. The tumor responses were

不可手術切除肝癌接受免疫節點抑制 劑合併治療中胎兒蛋白變化形態與預

assessed according to RECIST 1.1 criteria. AFP on-treatment kinetics were classified into four patterns: (1) Decrease ≥ 80% at week 6, with AFP normalization (<10 ng/ml) thereafter (2) Decrease < 80% initially with maintain steady abnormal AFP level (3) Decrease initially but rebound within 3 months (4) Persistent elevation after IO combinations.

Results: The median age of the patients was 63 years (range, 28-92) at the start of ICI treatment, 68 (78.2%) patients were male, and 10 (11.5%) used atezolizumab plus bevacizumab. Of them, 22 (25.3%) were AFP kinetic pattern 1, 32 (36.8%) were pattern 2, 19 (21.8%) were pattern 3, and 14 (16.1%) were pattern 4. The objective response rate (ORR) and disease control rate (DCR) were significantly higher in the AFP kinetic pattern 1 (81.8% vs. 30.8%, p < 0.001, and 100% vs. 73.8%, p < 0.007, respectively) as compared to the other AFP patterns. For patients with AFP pattern 1, the median progression-free survival (PFS) was 25.1 (95% CI: 2.5-47.7) months and the median overall survival (OS) was still not reached at 34.8 months. In multivariate analysis, AFP kinetic pattern 1 (HR = 0.178, p = 0.005) was the only significant factor associated with OS.

Conclusions: AFP kinetic correlates with outcomes of IO combinations for uHCC. Week 6 AFP reduction for at least 80% confers excellent outcomes.

Section：UGI

PYLORI INFECTION

Chia-Jung Kuo1,2, Cheng-Yu Lin1,2, Sen-Yung Hsieh1,2, Cheng-Tang Chiu1,2, Chih-Ho Lai3

1Department of Gastroenterology and Hepatology, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan

2School of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan

3Department of Microbiology and Immunology, Chang Gung University, Taoyuan, Taiwan

Penicillin-Binding Protein-1A 的氨基 酸變異與頑固性幽門桿菌感染其 Amoxicillin 抗藥性之關聯性

2

3 長庚大學微生物及免疫學科

Background: Amoxicillin resistance in Helicobacter pylori is mainly associated with mutations in penicillin-binding protein-1A (PBP-1A). However, the specific amino acid substitutions in PBP-1A that confer amoxicillin resistance in H. pylori remain to be investigated.

Aims: This study aimed to investigate the molecular mechanism underlying amoxicillin resistance in patients with refractory H. pylori infection.

Methods: Esophagogastroduodenoscopy (EGD) was performed in patients with persistent H. pylori infection after at least two courses of H. pylori eradication therapy between January-2018 to March-2021. Refractory H. pylori was cultured from the gastric biopsy specimens. Antibiotic susceptibility testing was conducted to determine the minimum inhibitory concentrations (MICs). Sequence analysis of pbp-1A was performed for amoxicillin-resistant strains.

Results: Thirty-nine successfully cultured isolates were classified as refractory H. pylori isolates, and seventeen isolates were resistant to amoxicillin (MIC > 0.125 mg/L). Sequence analysis of

MULTIPLE AMINO ACID SUBSTITUTIONS IN PENICILLINBINDING PROTEIN-1A CONFER AMOXICILLIN RESISTANCE IN REFRACTORY HELICOBACTER

resistant strains showed multiple mutations in the C-terminal region of PBP-1A that conferred amoxicillin resistance in H. pylori. However, the number of PBP-1A mutations did not correlate with the high MICs of amoxicillin-resistant isolates. Notably, D479E amino acid substitution was identified in all Taiwanese isolates with history of eradication failure but not in published amoxicillinsusceptible strains, suggesting that these strains were localized and the mutation may play a role in conferring to eradication failure.

Conclusions: Our results show that amoxicillin resistance in refractory H. pylori is highly correlated with numerous PBP-1A mutations that are strain specific. Continuous improvements in diagnostic tools, particularly molecular analysis approaches, can help to optimize current antimicrobial regimens.

TRIAL

Hsi-Chang Lee1,11, Deng-Chyang Wu2,11, Jyh-Chin Yang3,11, Seng-Kee Chuah4,11, Kuan-Yang Chen1,11, Feng-Woei Tsay5,11, Yu-Hwa Liu6,11, Chien-Lin Chen7,11, Chia-Long Lee8,11, Hong-Zen Yeh9,11, Chao-Hung Kuo2,11, Wei-Chen Tai4,11, Chang-Bih Shie10,11, Sz-Iuan Shiu9,11, Ping-I Hsu10,11

1Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taipei City Hospital, Renai Branch, Taipei, Taiwan;

2Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan;

3Division of Gastroenterology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; 4Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan; 5Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan; 6Division of Gastroenterology, Department of Internal Medicine Shin Kong Wu Huo-Shih Memorial Hospital, Taipei, Taiwan; 7Division of Gastroenterology, Department of Medicine, Buddhist Tzu Chi General Hospital, Hualien, Taiwan; 8Division of Gastroenterology and Hepatology, Department of Internal Medicine Cathay General Hospital, Taipei, Taiwan; 9Division of Gastroenterology, Department of Medicine, Tainan Municipal An Nan Hospital, China Medical University, Tainan, Taiwan; 10Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan; 11Taiwan Acid-related Disease & Microbiota (TARD-M) Consortium

㉜

HYBRID, HIGH-DOSE DUAL AND BISMUTH QUADRUPLE THERAPIES FOR FIRST-LINE TREATMENT OF HELICOBACTER PYLORI INFECTION: A MULTICENTRE, OPEN-LABEL, RANDOMISED

混合療法、高劑量二合療法與鉍劑四合

assessed in the intention-to-treat population. This trial was registered with ClinicalTrials.gov, number NCT03779074.

高雄

3 國立臺灣大學醫學

4 高雄長庚紀念醫院胃腸肝膽

5 高雄榮民總醫院胃腸肝膽科；6 新光吳火獅

紀念醫院胃腸肝膽科；7 花蓮慈濟醫院肝膽胃腸

科；8 國泰綜合醫院腸胃內科；

Background: The relative effectiveness of highdose dual therapy, bismuth quadruple therapy and hybrid therapy as first-line treatment of Helicobacter pylori infection remains unclear. The study aimed to compare the efficacy and safety of 14-day hybrid therapy, 14-day high-dose dual therapy and 10-day bismuth quadruple therapy in the first-line treatment of H. pylori infections.

Aims: To compare the efficacy and safety of 14day hybrid therapy, 14-day high-dose dual therapy and 10-day bismuth quadruple therapy in the firstline treatment of H. pylori infection.

Methods: In this multicentre, open-label, randomised trial, we recruited adult H. pyloriinfected patients (age 20 years) from nine centers in Taiwan. Eligibility included positive tests of both rapid urease test and histology, or a positive result of culture. Subjects were randomly assigned (1:1:1) to 14-day hybrid therapy (rabeprazole 20 mg twice daily and amoxicillin 1 g twice daily for 7 days, followed by rabeprazole 20 mg, amoxicillin 1 g, clarithromycin 500 mg, and metronidazole 500 mg twice daily for 7 days), 14-day high-dose dual therapy (rabeprazole 20 mg and amoxicillin 750 mg, both given four times a day for 14 days) or 10day bismuth quadruple therapy (rabeprazole 20 mg twice daily, tripotassium dicitrato bismuthate 300 mg four times a day, tetracycline 500 mg four times a day and metronidazole 250 mg four times a day for 10 days). A computer-generated permuted block randomization sequence with a block size of six was used for randomization. Investigators were masked to treatment allocation. The primary outcome was the eradication rate of H. pylori

Results: Between August 1 2018 and December 2021, 3095 patients were screened for eligibility. Among them, 918 patients were randomly assigned in this study. The intention-to-treat eradication rates were 91.5% (280/306 [88.4 to 94.6%]) for 14-day hybrid therapy, 83.3% (255/306 [87.8 to 95.0%]) for 14-day high-dose dual therapy, and 90.2% (276/306 [87.8 to 95.0%]) for 10-day bismuth quadruple therapy. Both hybrid therapy (difference: 8.2%; 95% confidence interval [CI]: 4.5 to 11.9%; p = 0.002) and bismuth quadruple therapy (difference: 6.9%; 95% CI: 1.6 to 12.2%; p = 0.012) were superior to high-dose dual therapy, and were similar to one another. The frequency of adverse events was 27% (81/303) with 14-day hybrid therapy, 13% (40/305) with 14-day highdose dual therapy, and 32% (96/303) with 10-day bismuth quadruple therapy. Patients receiving high-dose dual therapy had the fewest adverse events (both p < 0.001).

Conclusions: 14-day hybrid therapy and 10day bismuth quadruple therapy are preferable to 14-day high-dose dual therapy in the first-line treatment of H. pylori infection in the face of rising prevalence of antibiotic resistance. High-dose dual therapy must be further optimized before it can be used as a first-line treatment of H. pylori infections.

9 臺南市立安南醫 院暨中國醫藥大學消化內科；10 臺中榮民總醫院 胃腸肝膽科；11 台灣胃酸相關疾病暨微菌叢聯盟

EFFICACIES OF POTASSIUMCOMPETITIVE ACID BLOCKERBASED TRIPLE THERAPY, POTASSIUM-COMPETITIVE ACID BLOCKER-BASED HIGH-DOSE DUAL THERAPY AND PROTON PUMP INHIBITOR-BASED REVERSE HYBRID THERAPY IN THE FIRSTLINE ANTI-H. PYLORI TREATMENT – A PRELIMINARY REPORT

Chang-Bih Shie1,10, Ping-I Hsu1,10, Chien-Lin Chen2,10, Chao-Hung Kuo3,10, Kuan-Yang Chen4,10, Chia-Long Lee5,10, Wei-Yi Lei2,10, Hsi-Chang Lee4,10, Chih-An Shih6,10, Seng-Kee Chuah7,10, Jyh-Chin Yang8,10, Feng-Woei Tsay9,10, Deng-Chyang Wu3,10

1Division of Gastroenterology, Department of Medicine, Tainan Municipal An Nan Hospital, China Medical University, Tainan, Taiwan; 2Division of Gastroenterology and Hepatology, Department of Medicine, Hualien Tzu Chi Hospital, Hualien, Taiwan;

3Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan;

4Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taipei City Hospital, Renai Branch, Taipei, Taiwan; 5Division of Gastroenterology and Hepatology, Department of Internal Medicine, Cathay General Hospital, Taipei, Taiwan; 6Division of Gastroenterology and Hepatology, Department of Internal Medicine, Antai Medical Care Corporation, Antai

Tian-Sheng Memorial Hospital, Pingtung, Taiwan; 7Division of Hepatogastroenterology, Department of Medicine, Kaohsiung Chang

Gung Memorial Hospital, Kaohsiung, Taiwan;

8Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan;

9Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung

Veterans General Hospital, Kaohsiung, Taiwan; 10Taiwan Acid-related Disease & Microbiota (TARD-M) Consortium

轉式混合療法」在第一線幽門螺旋桿菌 除菌治療之療效比較 一先期報告

2 花蓮慈濟醫院內科部肝膽胃腸科

3 高雄醫學大學附設醫院胃腸內科

4 臺北市立聯合醫院仁愛院區消化內科

5 國泰綜合醫院腸胃內科

6 安泰醫院內科部胃腸肝膽科

7 高雄長庚紀念醫院胃腸肝膽科

8 國立臺灣大學醫學院附設醫院內科部胃腸科

9 高雄榮民總醫院胃腸肝膽科

10 台灣胃酸相關疾病暨微菌叢聯盟

Background: Vonoprazan is a new gastric acid suppression agent, classified as potassiumcompetitive acid blocker (PCAB). Its acid inhibition efficacy is superior to that of proton pump inhibitor. The Japanese guidelines on the management of H. pylori infections recommend replacing proton pump inhibitor (PPI) with vonoprazan in the firstline strand triple therapy. Currently, whether vonoprazan-based high-dose dual therapy and vonoprazan-based triple therapy are more effective or have fewer adverse effects than PPIbased anti-H. pylori therapies remains unclear.

Aims: To compare the efficacies of 14-day PCABbased high-dose dual therapy, 14-day PCABbased triple therapy, and 14-day PPI-based reverse hybrid therapy in the first-line treatment of H. pylori infection.

Methods: For this multi-center, randomized, openlabel, superiority trial, adult patients with H. pylori infection from eight centers in Taiwan. Using a computergenerated randomized sequence, we randomly allocated patients (1:1:1) to either 14day vonoprazan-based triple therapy, 14-day vonoprazan-based high-dose dual therapy, or 14day rabeprazole-based reverse hybrid therapy. Patients were asked to return at the second week to assess drug adherence and adverse events. Post-treatment H. pylori status was assessed by

「鉀離子競爭性酸阻斷劑 / 三合療 法」、「鉀離子競爭性酸阻斷劑 / 高劑 量二合療法」與「質子幫浦抑制劑 /

13C-urea breath test at week 6.

Results: Between August 1 2021 and April 2022, 150 patients were randomly treated by vonoprazanbased triple therapy, 14-day vonoprazan-based high-dose dual therapy, or 14-day rabeprazolebased reverse hybrid therapy. The intention-totreat eradication rates were 84.0% (42/50) for vonoprazan-based high-dose dual therapy, 90.0% (45/50) for vonoprazan-based triple therapy, and 92.0% (46/50) for rabeprazole-based reverse hybrid therapy. Three treatment groups had comparable eradication rates (P = 0.812). Perprotocol analysis yielded similar result (85.7%, 91.8% and 93.7%, respectively). Additionally, there were no differences in the frequencies of adverse events (14.6%, 14.8% and 13.0%, respectively) and drug adherence (98.0%, 98.0% and 96.0%, respectively) among the three treatment groups.

Conclusions: The preliminary data suggest that 14-day vonoprazan-based high-dose dual therapy, vonoprazan-based triple therapy and rabeprazolebased reverse hybrid therapy have comparable eradication efficacy and safety in the first-line treatment of H. pylori infection.

㉞

EFFECT OF ESOPHAGEAL CANCER SCREENING ON SURVIVAL IN PATIENTS WITH ORAL CANCER AND SECOND PRIMARY ESOPHAGEAL CANCER IN TAIWAN: ANALYSIS FROM TAIWAN NATIONAL HEALTH INSURANCE RESEARCH DATABASE

Yi-Hsun Chen1, Wen-Hung Hsu1,2, Hui-Min Hsieh3, I-Chen Wu1,2

1Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan

2Department of Medicine, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan

3Department of Public Health, Kaohsiung Medical University, Kaohsiung, Taiwan

3

Background: Oral and esophageal cancer are the fourth and fifth leading causes of cancer deaths in Taiwan. The direct medical costs and indirect costs from the mortality of esophageal and oral cancer ranked as top 3 among ten mostly cost cancers. Despite a good prognosis in oral cavity cancer (OCC) patients, those developing second primary esophageal cancer (SPEC) had a worse survival. The consensus from guidelines and published studies for screening strategy is still controversial.

Aims: Our study aims to compare the 5-year mortality between screening and non-screening groups among patients with OCC and SPEC.

Methods: This study was conducted by analyzing Taiwan Cancer Registry (TCR) and National Health Insurance Research Database (NHIRD) from 2004 to 2018. We identified 522 patients with OCC (ICD-O-3: C00-C06) and SPEC (ICD-O-3: C15), and 217 and 305 patients were in screening and non-screening groups, respectively. We compared the 5-year mortality from the diagnosis date of

食道癌篩檢於口腔癌病人產生第二種 食道癌存活率的效應：台灣健保資料庫 分析

SPEC between screening and non-screening groups among patients with OCC and SPEC.

Results: Endoscopic screening was significantly improved early detection of SPEC (adjusted odds ratio: 0.34, 95% confidence interval [CI]: 0.23-0.49) and reduced all-cause mortality (adjusted hazard ratio: 0.80; 95% CI: 0.66-0.98). Early detection of SPEC by endoscopic exam is crucial to reduce OCC mortality.

Conclusions: Endoscopic screening achieved early detection of SPEC among OCC patients, and further decreased OCC mortality. To improve screening effect on stage shift, patients with early stage of OCC are also encouraged to undergo routine endoscopic screening.

THE IMPACT OF CONTRASTENHANCED HARMONIC ENDOSCOPIC ULTRASOUNDGUIDED FINE-NEEDLE BIOPSY (CH-EUS-FNB) VERSUS STANDARD FINE-NEEDLE BIOPSY (FNB) IN PANCREATIC SOLID MASSES ON DIAGNOSTIC YIELD AND MACROSCOPIC ONSITE EVALUATION (MOSE): A RETROSPECTIVE STUDY IN SINGLE-MEDICAL CENTER OF MIDDLE TAIWAN

Szu-Chia Liao1, Hong-Zen Yeh1,2,3, Yi-Chun Liao1, Hui-Chun Chang1, Chi-Shun Yang4, Sheng-Shun Yang1,2

1ivision of Gastroenterology and Hepatology, Department of Internal Medicine, Taichung

Veterans General Hospital, Taichung, Taiwan

2School of Medicine, National Yang Ming

Chiao Tung University, Taipei, Taiwan

3Division of Gastroenterology and Hepatology, Tungs’ Taichung MetroHarbor Hospital, Taichung, Taiwan

4Department of Pathology and Laboratory Medicine, Taichung Veternas General Hospital, Taichung, Taiwan

使用對比劑顯影做為內視鏡超音波指 引下細針切片術的導引在胰臟腫瘤對 於診斷率及檢體宏觀質量之影響：單一 醫學中心之回溯性研究

Background: Contrast-enhanced harmonic endoscopic ultrasound (CH-EUS) can visualize necrotic areas and vessels inside lesions. CHEUS findings combined with EUS-guided fineneedle biopsy (EUS-FNB) improves diagnosis in pancreatic solid masses. CH-EUS can also guide EUS-FNA (CH- EUS-FNA), potentially improving the diagnostic yield. However, the superiority in

CH-EUS-FNA is still controversial according to previous prospective studies and meta-analysis. The adequacy of histologic cores on MOSE obtaining from EUS-FNB can also increase the diagnostic accuracy. Due to the importance of next-generation sequencing (NGS) for the choice of chemotherapy, the adequacy of the histologic cores is important to make sure the feasibility of analysis for NGS.

Aims: Our aim was to compare CH-EUS-FNB versus standard EUS-FNB about the diagnostic accuracy in solid pancreatic lesions. The relationship between the macroscopic visible core (MVC) on in the EUS-FNB specimen and the use of CH-EUS were studied.

Methods: This retrospective study in one single medical center was conducted between Jan. 2022 to Jun. 2022. The patients with pancreatic solid masses on CT or MRI scan were enrolled. The diagnostic sensitivity was anaylzed. The length of MVC on MOSE was recorded. The primary outcome was to evaluate the diagnostic accuracy between CH-EUS-FNB and standard EUS-FNB. The secondary outcomes were to compare the difference in the length of MVC between these two groups.

Results: 50 patients were evaluated. 17 patients receiving CH- EUS-FNB and 33 patients receiving standard CH-EUS-FNB showed diagnostic accuracy of 100 % and 96.9 %, respectively (not significantly different) and the diagnostic accuracy of the first pass was 94.1 % and 84.8 %, respectively (not significantly different). The length of MVC between CH-EUS-FNB and standard EUS-FNB showed no difference (2.8 ± 0.5 vs 2.9 ± 0.7 cm, p = 0.307) and the length of the first pass also showed no difference (17.4 ± 6.9 vs 14.3 ± 5.7 mm, p = 0.122). The procedure time was significantly longer in CH-EUS-FNB group (57.6 ± 13.3 vs 45.8 ± 9.1 min, p = 0.001). No adverse event was found during CH-EUS-FNB.

Conclusions: The diagnostic yield and the length of MVC on MOSE from sampling obtained using CH-EUS-FNB showed no significantly difference compared with standard EUS-FNB if the procedure was performed by the experienced endosonographer. However, further study is needed to confirm the result.

NEUTROPHILE–LYMPHOCYTE RATIO AS PREDICTION MARKER OF SHORT-TERM POSTOPERATIVE BODY WEIGHT LOSS AFTER LAPAROSCOPIC SLEEVE GASTRECTOMY

Kun-Ta Wu2, Chao-Ming Hung1,3, Chung-Yen Chen2,4, Hui-Ming Lee2, Jian-Han Chen2,4

1E-Da Cancer Hospital, Kaohsiung, Taiwan

2Division of General Surgery, Department of Surgery, E-Da Hospital, Kaohsiung, Taiwan

3Division of General Surgery, Department of Surgery, E-Da Cancer Hospital, Kaohsiung, Taiwan

4Bariatric and Metabolism International Surgery Center, E-Da Hospital, Kaoshiung, Taiwan

Background: As the prevalence of obesity increases worldwide, bariatric surgery (BS) has become a major practice for the management of the morbid side of the entire obesity spectrum. However, approximately 10%–20% of patients are at risk of inadequate weight loss after surgery, which may attenuate the metabolic effect of BS. Poor postoperative weight loss may also influence the metabolic effect of BS, thus limiting the expected health benefits. Identifying patients who may have inadequate weight loss and offering supportive therapy postoperatively to facilitate adequate weight loss in these patients as early as possible are crucial. The neutrophil–lymphocyte ratio (NLR) has been widely applied as a prognostic marker in oncology. An elevated NLR value is associated with poorer prognoses of ischemic coronary disease, heart failure, peripheral vascular disease, and obesity. On the other hand, higher NLR was observed in obese patients with higher insulin resistance than in healthy individuals.

嗜中性球 - 淋巴球比值作為預測袖狀胃 切除術後短期減重預後之臨床指標

However, only a few studies have demonstrated the relation between NLR and body weight loss. Our study examined the differences between patients with adequate and inadequate weight loss, which was defined as Excessive body weight loss(EBWL) > 37.7% at post-operative 3rd month, and these differences were compared with their immunological profile changes, namely the quantity and ratio of white blood cells in preoperative and various postoperative intervals, in morbidly obese patients who underwent laparoscopic sleeve gastrectomy (LSG). We identified the difference between patients who did and did not achieve adequate body weight loss and received upgraded medical nutritional therapy after LSG.

Aims: To evaluate the neutrophil–lymphocyte ratio (NLR) as a clinical marker for evaluating the effect of laparoscopic sleeve gastrectomy (LSG).

Methods: Retrospectively, we included patients who had undergone LSG at our institution between January 2019 and April 2021. An excessive body weight loss (EBWL) of >37.7% at 3 months postoperatively (POM3) was defined as a successful operation. We analyzed the correlation between NLR and postoperative weight change after LSG.

Results: A total of 100 patients were included. Compared with the success group (POM3 EBWL > 37.7%), the failure group exhibited a significantly higher initial bodyweight, body mass index, incidence of dyslipidemia, and NLR. Preoperative NLR exhibited considerable prediction efficacy for EBWL of 37.7% at POM3. The cutoff value of preoperative NLR was 2.36 in POM3 (sensitivity: 67.7%, specificity: 62.5%, area under the curve = 0.635, 95% confidence interval: 0.532–0.729, P = .032). In the multivariate analysis, preoperative NLR < 2.36 exhibited a positive effect for predicting successful weight loss in patients. However, higher preoperative body weight (P = .0009) and preoperative dyslipidemia (P = .0045) demonstrated a negative effect in achieving EBWL < 37.7% at POM3.

Conclusions: Preoperative NLR < 2.36 exhibited a positive effect in predicting successful EBWL at POM3. Early prediction of postoperative EBWL in POM3 may aid in decision-making for the surgical procedure and for initiating early nutrition interventions.

3

P.001

FINITE THERAPY DECREASED HCC INCIDENCE COMPARING TO LONG-TERM NUC SUPPRESSED CHRONIC HEPATITIS B PATIENTS WITH CIRRHOSIS

Wen-Juei Jeng1,2, Rong-Nan Chien1,2,3, Yi-Cheng Chen1,2,3, Chih-Lang Lin2,4, Chia-Ying Wu1, Yen-Chun Liu1,2, Chien-Wei Peng1,2, Yun-Fan Liaw2,3

1Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan, Taiwan

2College of Medicine, Chang Gung University, Taoyuan, Taiwan

3Liver research unit, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan, Taiwan

4Department of Gastroenterology and Hepatology, Keelung Chang Gung Memorial Hospital, Keelung, Taiwan

arm. Pre-therapy age, ALT, platelet, HBsAg, HBV DNA levels were compared between these two groups and between those with and without HCC development. Propensity score matching(PSM) of pretherapy age, gender, pretherapy platelet count and HBV DNA level was done at 1 to 1 ratio between these two arm. Kaplan Maier and Log-rank test analysis for cumulative incidence of HCC. Cox regression analysis for predictors of HCC were applied.

Results: A total of 1022 patients were enrolled (506 in the interrupted arm, 516 in the continuous arm). During a median of follow-up of 10.5 and 6.1 years in interrupted arm and continuous arm, the annual, 5- and 10-year incidence of HCC was 1.27%, 6.6% and 13% versus 2.0%, 9.1% and 20.9% in the interrupted arm and continuous arm (Log rank test, P = 0.016). Multivariate Cox regression analysis showed older age [adjusted HR (aHR): 1.05, P < 0.001] and interrupted therapy [aHR: 0.69, P = 0.48] were favorable and unfavorable factors for HCC development. After PSM, there were 338 patients in continuous and interrupted arms. The mean age was 55 year-old, 69% were male, 68% were genotype B. The demographic features of age, gender, HBV genotype, FIB-4, platelet count, pretherapy HBsAg and HBV DNA levels were comparable between the matched two arms. The annual, 5- and 10-year incidence of HCC were both lower in the interrupted arm than the continued arm (1.35%, 6.8% and 12.8% versus 2.15%, 11% and 23.6%, P = 0.004).

2

Background: Long-term nucleos(i)tide analogue (Nuc) treatment decreased HCC incidence in chronic hepatitis B (CHB) patients with cirrhosis. Two hospital-based cohorts of patients with cirrhosis (HBV-LC) showed a 5-6 years cumulative incidence of HCC in patients receiving finite Nuc therapy was not higher than that in patients who continued long-term Nuc therapy.

Aims: This study aims to validate these finding using a large-scale multi-center cohort with longer follow-up.

Methods: HBeAg negative HBV-LC from two medical centers were recruited and categorized into two arms: finite(interrupted) arm and continuous arm. Patients who still under treatment but less than 3-year were excluded from the continued

Conclusions: Our results suggest that, compared with HBV-LC on continuing Nuc therapy, the incidence of HCC was even lower in HBeAgnegative HBV-LC patients who received finite therapy strategy.

P.002

CCR5 EXPRESSED ACTIVATED REGULATORY T CELLS ACCUMULATED IN TUMOR MICROENVIRONMENT AND PREDICT SURVIVAL IN PATIENTS WITH HEPATOCELLULAR CARCINOMA

Chien-Hao Huang1,2, Jayashri Mahalingam1,2, Wei-Ting Ku1,2, Jian-He Fan1, Cheng-Heng Wu1, Tsung-Han Wu3, Po-Ting Lin1, Wei Teng1, Wen-Juei Jeng1,2, Wei-Ting Chen1,2, Chen-Chun Lin1,2, Shi-Ming Lin1,2, I-Shyan Sheen1,2, Yung-Chang Lin2,4, Chun-Yen Lin1,2

1Division of Hepatology, Department of Gastroenterology-Hepatology, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan, Taiwan

2College of Medicine, Chang Gung University, Taoyuan, Taiwan

3Department of General Surgery, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan, Taiwan

4Department of Hematology-Oncology, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan, Taiwan

Tyrosine kinase inhibitor imatinib had been shown to deplete aTreg cells in several cancers such as leukemias, melanoma and gastrointestinal stromal tumors.

Aims: We hereby investigated the relationship between aTreg and the progression of HCC, and whether imatinib could deplete aTreg and expand antigen-specific CD4/CD8.

Methods: 107 HCC patients and 53 healthy donors were enrolled and peripheral blood mono-nucleated cells were obtained and isolated. Liver tumor tissue and non-tumor tissue were processed immediately after surgery for patients with HCC. The phenotype and functional relevance of aTreg were analysed by flow cytometric method and genetic data.

Results: The percentages of aTreg but not rTreg significantly increased in peripheral blood (PB) and accumulated in the tumor parts in patients with HCC. These aTreg had higher expressions of cytotoxic T-lymphocyte antigen-4, tumor necrosis factor-a receptor II, HLA-DR and Ki67 but very few effector cytokines like IFN-g, IL-2 and IL-17A than Foxp3- CD4+T cells. To explore the underlying mechanisms of aTreg cells accumulation in tumor microenvironment (TME), we found Interestingly, CCL5, the chemokine for CCR5, increased significantly in tumor tissues as well. Furthermore, CCL5 could attract these aTreg but not rTreg by in-vitro migration assays. Analyzing the impact of aTreg cells on the outcome, we also showed the Treg could predicted overall survival by KaplanMeier survival analysis in our cohort. Since average 90% of CCR5+Foxp3+Treg cells were aTreg cells (aTreg/CCR5+Foxp-3+T cells vs. rTreg/ CCR5+Foxp-3+T cells: 90.0 ± 16.0% vs. 2.8 ± 0.8%, p < 0.001), we analysed the TCGA database taking CCR5+Foxp3+Treg cells as aTreg and found that patients with CCR5+Foxp3+Treg cells intratumor accumulation had significantly better survival prediction than those with CCR5-Foxp3+Treg cells (Figure A). Finally, the tyrosine kinase inhibitor, imatinib, was shown to decrease aTreg cells and to expand antigen-specific CD4+ and CD8+ T cells after peptide stimulation in vitro in patients with HCC (Figure B).

Background: CD4+Foxp3+regulatory T cells (Treg cells) are associated with tumor progression, including hepatocellular carcinoma (HCC), and are considered a potential target for tumor immunotherapy. However, CD4+Foxp3+T cells were not functionally homogenous. CD45RA- Foxp3hi activated Treg (aTreg) cells were claimed more potent suppressors with tissue-migration tendency than resting Treg(rTreg, CD45RA+Foxp3low) cells.

Conclusions: CCR5 expressed activated Treg cells increased in peripheral blood, accumulated more in tumor sites of HCC patients possibly through CCR5CCL5 interaction.CCR5+ aTreg could predicted patients’ overall survival in our cohort and validated by TCGA data. In addition, imatinib could decrease the inhibition ability of aTreg. These result implied immunotherapy targeted at these aTreg cells may be promising.

2 長庚大學醫學院

3 林口長庚紀念醫院一般外科

4 林口長庚紀念醫院血液腫瘤科

USEFUL BIOMARKERS FOR PREDICTING POOR PROGNOSIS OF PATIENTS WITH DRUGINDUCED LIVER INJURY: A RETROSPECTIVE COHORT STUDY

Hsueh-Chien Chiang, I-Chin Wu

Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan

P.004 SMOKING AS A RISK FACTOR FOR RECURRENCE EVEN AFTER 5 RECURRENCE-FREE YEARS IN EARLY-STAGE HEPATOCELLULAR CARCINOMA PATIENTS AFTER PRIMARY RESECTION

An-Che Liu1, Ming-Chao Tsai1,2, Chih-Chi Wang3, Chih-Che Lin3, Yueh-Wei Liu3, Yi-Hao Yen1

1Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang

Gung University College of Medicine, Kaohsiung, Taiwan

國立成功大學醫學院附設醫院消化內科

Background: Drug-induced liver injury (DILI) plays an important role in liver failure and causes mortality. Patients with DILI compatible with Hy’s law are associated with a poorer outcome. However, the predicting accuracy of Hy’s law is not good enough in clinical practice.

Aims: Our study aimed to investigate the optimal values of biomarkers associated with the prognosis of DILI.

Methods: From 2014/06/01 to 2022/05/30, the patients with reported DILI were included. We assessed the patients’ characteristics, drug type, DILI type, liver enzymes, renal function, and comorbidities. Their associations with DILI-related mortality and overall survival were analyzed.

Results: A total of 95 patients with DILI were enrolled, 5 patients died of liver failure, and 23 patients died within 56 weeks after DILI. This study found 15 mg/ dL of total bilirubin, 1000 U/L of ALT, and 2 of PT-INR were optimal cut-off values in predicting DILI-related mortality, with sensitivity of 100%, 80%, 80%, and specificity of 92%, 88.5%, and 81.1%, respectively. In the contrast, Hy,s Law had sensitivity of 40% and specificity of 85.2% for DILI-related mortality. For the overall survival, patients with sepsis (HR: 5.053, 95% CI: 1.594–16.018, p = 0.006), malignancy (HR: 4.371, 95% CI: 1.573–12.147, p = 0.005), or end-stage renal disease (HR: 7.409, 95% CI: 1.404–39.103, p = 0.018) were independent poor prognostic factors in multivariate Cox regression analysis.

Conclusions: Total bilirubin > 15 mg/dL, ALT > 1000 U/L, and PT-INR > 2 are useful biomarkers in predicting DILI-related mortality. DILI patients with sepsis, malignancy, or end-stage renal disease are associated with worse overall survival.

2Graduate Institute of Clinical Medical Sciences, Chang Gung University College of Medicine, Taoyuan, Taiwan

3Liver Transplantation Center and Department of Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan

吸煙仍是早期肝細胞癌經初次切除後 5 年無復發之患者再次復發的危險因素

Background: Although hepatocellular carcinoma (HCC) is notorious for its high recurrence rate, very late recurrence (more than 5 years) of HCC is sometimes seen after curative resection. For those with five recurrence-free period, the risk of HCC recurrence within the next 5 years remains unknown.

Aims: This study assesses prognostic factors in HCC patients with recurrence-free survival (RFS) for 5 years after primary resection.

Methods: A total of 337 HCC patients who diagnosed with early-stage HCC and received primary tumor resection between January 2001 and December 2016 and achieved more than 5 years without recurrence after resection were analyzed.

Results: After a median follow-up of 126 months,

評估各種生物標記以預測藥物性肝炎

吳毅晉

3 高雄長庚紀念醫院暨長庚大學醫學院肝移植外科 中心

77 patients (22.8%) had recurrent HCC. The cumulative recurrence rates increased to 6.9%, 11.7%, and 16.6% at 6, 7, and 8 years, respectively. Multiple tumor number and smoking were associated with very late HCC recurrence among patients who did not experience recurrence for more than 5 years. In subgroup analysis, patients with smoking cessation had better RFS than those with current smoking (p = 0.061)

Conclusions: In HCC patients without recurrence for 5 years after curative resection, the recurrence rate was still high, indicating that HCC patients warrant continued HCC surveillance, even after 5 recurrence-free years. Smoking is a risk factor for very late HCC recurrence, and quitting smoking can reduce this risk.

P.005 SACCHAROMYCES BOULARDII AMELIORATES NON-ALCOHOLIC STEATOHEPATITIS IN MICE INDUCED BY A METHIONINECHOLINE-DEFICIENT DIET THROUGH GUT-LIVER AXIS

An-Ming Yang1, Chien-Yu Lin2, Shih-Hao Liu3, Guan-Da Syu4, Hao-Jhe Sun5, Kuei-Chuan Lee5,6, Han-Chieh Lin5,6, Ming-Chih Hou5,6

1Division of Gastroenterology and Hepatology, Department of Internal Medicine, En Chu Kong Hospital, New Taipei City, Taiwan

2Division of Nephrology, Department of Internal Medicine, En Chu Kong Hospital, New Taipei City, Taiwan

3Division of Pathology, En Chu Kong Hospital, New Taipei City, Taiwan

4Department of Biotechnology and Bioindustry Sciences, National Cheng Kung University, Tainan, Taiwan

5Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan

6School of Medicine, National Yang Ming Chiao Tung University School of Medicine, Taipei, Taiwan

Background: Non-alcoholic steatohepatitis (NASH) is affecting people worldwide. Changes in the intestinal microbiome are crucial to NASH. A previous study showed eradicating intestinal fungi ameliorates alcohol-induced steatohepatitis; However, the role of intestinal fungi in non-alcoholic steatohepatitis is unclear. Saccharomyces

Boulardii (SB), a dietary supplement yeast, has been reported to restore the integrity of intestine. The effect of SB on NASH is not known.

Aims: Here, we aimed to test the effect of SB in the prevention of NASH.

Methods: For this study, we fed eight-week-old C57/BL6 male mice either a methionine-choline deficient (MCD) diet or a normal chow diet (NCD) for eight weeks. Half of the MCD diet-fed mice were gavaged with SB (5 mg/day) once daily. The remainder of the NCD–fed mice were gavaged with normal saline as a control. The degree of liver function, hepatic steatohepatitis and liver fibrosis were evaluated. Inflammation and integrity of the intestine were tested. Then, deep sequencing of the fecal microbiome was done. MCD-fed mice on SB supplement showed better liver function, less hepatic steatosis and inflammation. The hepatic inflammatory genes and fibrogenic genes were suppressed in mice with SB gavage. Intestinal damage caused by MCD was tampered, the inflammation of intestine was decreased, and gut permeability was improved on SB supplement mice. Deep sequencing of fecal microbiome showed enriched potentially beneficial gut microbiota and increased diversity.

Results: The MCD diet-fed mice on SB supplement showed better liver function, less hepatic steatosis, and decreased inflammation. Both hepatic inflammatory gene expression and fibrogenic gene expression were suppressed in mice with SB gavage. Intestinal damage caused by the MCD diet was tampered with, intestine inflammation decreased, and gut permeability improved in mice that had been given the SB supplement. Deep sequencing of the fecal microbiome showed a potentially increased beneficial gut microbiota and increased microbiota diversity in the SBsupplemented mice.

Conclusions: The SB supplement maintains gut integrity, increases microbial diversity, and increases the number of potentially beneficial gut microbiota. Thus, the SB supplement attenuates gut leakage and exerts a protective effect against NASH. Our results provide new insight into the prevention of NASH.

Chun Li1,2, Tsuo-Hsuan Chien1, Tien -Shin Chou1, Cheng-Hung Chien1,2, Ching-Chih Hu1, Shuo-Wei Chen1, Li-Wei Chen1, Ching-Juen Liu1, Paul Wei-Che Hsu2,3, Yu-Chiau Shyu2,4, Rong-Nan Chien1,2,5, Chih-Lang Lin1,2

1Department of Gastroenterology and Hepatology, Keelung Chang Gung Memorial Hospital, Keelung, Taiwan

2Community Medicine Research Center, Keelung Chang Gung Memorial Hospital, Keelung, Taiwan

3Institute of Molecular and Genomic Medicine, National Health Research Institute, Miaoli, Taiwan

4Institute of Molecular Biology, Academia Sinica, Taipei, Taiwan

5Liver Research Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan

UGT1A

1 基隆長庚紀念醫院胃腸肝膽內科

2 基隆長庚紀念醫院社區醫學科研中心

3 國立衛生研究院分子與基因組醫學研究所

4 中央研究院分子生物研究所

5 林口長庚紀念醫院肝臟研究中心

Background: At present, Gilbert’s syndrome is mainly diagnosed through genetic analysis and is primarily detected through a mutation in the promoter region of the UGT1A1 gene. However, most of the research has been conducted on Caucasian populations.

Aims: In this study, we studied the Han Chinese population in Taiwan to investigate the possibility of other mutations that could cause Gilbert’s syndrome.

Methods: This study comprised a test group of 45 Taiwanese individuals with Gilbert’s syndrome and

P.006 THE MUTATION HOTSPOTS AT UGT1A LOCUS MAY BE ASSOCIATED WITH GILBERT’S SYNDROME AFFECTING THE TAIWANESE POPULATION

180 healthy Taiwanese individuals as the control group. We extracted DNA from the subjects’ blood samples and then used Axiom GenomeWide TWB 2.0 array plates for genotyping. Lastly, machine learning methods, such as Support Vector Machine, Random Forest, and XGBoost, were used to develop the predictive models.

Results: Out of 302,771 candidate single nucleotide polymorphisms (SNPs) from 225 subjects studied, we detected 57 SNPs with the most significant shift in allele frequency; 27 SNPs among them were located in UGT1A region of the genome. Most of the detected SNPs highly correlated with each other and are located near the first exon of UGT1A1, UGT1A3, UGT1A6, and UGT1A7. We used these SNPs as an input to the machine learning algorithms and developed prediction models based on the area under the receiver operating characteristic curve that reached up to 91%.

Conclusions: Our study reveals a strong association between the 27 SNPs detected in the Han Taiwanese and Gilbert’s syndrome. Hence, this study provides a reference for diagnosing Gilbert’s syndrome in the Taiwanese population in the future.

IDE ANALOGUE THERAPY

Chien-Wei Peng1,3, Wen-Juei Jeng1,3, Yen-Chun Liu1,3, Rong-Nan Chien1,2,3, Yun-Fan Liaw2

1Division of Gastroenterology and Hepatology, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan

2Liver Research Unit, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan

3College of Medicine, Chang Gung University, Taoyuan, Taiwan

E 抗原陽性病人停止核苷（酸）類似物 後發生嚴重肝炎發作之發生率與預測 因子

2

3

Background: Hepatitis flare may occur in nearly half of the HBeAg-positive patients stopping nucleot(s)ide analogue (Nuc) therapy. Severe hepatitis flare (SHF) is the most critical safety concern. Little is known about the incidence and predictors of SHF in HBeAg-positive patients who stop Nuc.

Aims: This study aimed to investigate the incidence and the predictive factors of severe hepatitis flare in HBeAg-positive patients who stop Nucleot(s)ide analogue therapy.

Methods: HBeAg-positive patients who stopped Nuc therapy with > 1-year consolidation therapy after HBeAg loss in a tertiary medical center. Pretherapy age, gender, liver cirrhosis (LC), ALT, HBV genotype, HBsAg, and HBV DNA levels were analyzed. SHF was defined as an event with ALT level > 1000 U/L, or total bilirubin (T.Bil) level > 3.5 mg/dL and/or INR > 1.5. Hepatic decompensation (HD) was defined as apparent symptoms with T.Bil level > 2 mg/dL and INR > 1.5. Kaplan-Meier analysis was applied for the cumulative incidence (CI) of events. Cox regression analysis was done for the predictors of SHF.

P.007 INCIDENCE AND PREDICTIVE FACTORS OF SEVERE HEPATITIS FLARE IN HBEAG-POSITIVE PATIENTS WHO STOP NUCLEOT(S)

Results: SHF occurred in 31 of 295 patients enrolled during a median follow-up of 3 years. The 1-, 2-, 3-year CI of SHF was 10.9%, 13.1%, and 13.1%, respectively. Among the 31 SHF patients,16 (51.6%) had HBeAg sero-reversion (HBeAg-rev), 15 remained HBeAg-negative (HBeAg-Neg), 6 suffered from HD, and 3 died, while none of the remaining 246 patients had adverse events. The 2-year CI of HD and mortality was 2.4% and 1.3%. Multivariate Cox regression showed that male [adjusted HR (aHR): 3.6, P = 0.02], pre-therapy LC(aHR: 2.5, P = 0.02), pre-therapy HD (aHR: 3.6, P < 0.01), and Tenofovir (TDF) (aHR: 3.4, P < 0.01) were independent predictors of SHF. The 2-year CI of SHF was higher in LC than non-LC (22.8% vs. 11.1%, P < 0.01), in off-TDF than off-Entecavir (ETV) (20.6% vs. 10%, P < 0.01), in off-Nuc HBeAg-rev than HBeAg-Neg (31.5% vs. 8.7%, P < 0.01), but comparable between with and without EOT HBeAg seroconversion (11% vs. 16%, P = 0.33). The 2-year CI of HD and mortality were comparable between those with off-Nuc HBeAgrev and HBeAg-Neg (HD: 4% vs. 2%; mortality: 1% vs. 1%, both P > 0.1) and between patients with HBeAg seroconversion and seroclearance by EOT (HD: 1% vs. 2 %; mortality: 1% vs 1%, both P > 0.5). The 2-year CI of SHF, HD, and mortality was highest in patients with LC/off-TDF, followed by LC/off-ETV, non-LC/off-TDF and lowest in nonLC/off-ETV.

Conclusions: SHF occurred in 10.5% of HBeAg positive patients stopping Nuc. Stringent monitor is important, especially for those with HBeAg-rev, cirrhosis and stopping TDF.

P.008 CORRELATION OF FERROPTOSIS AND HEPATOCYTE INJURY INDUCED BY HIGH LIPID AND HIGH OXIDATIVE STRESS ENVIRONMENT

Chi-Sheng Chen1, Jee-Fu Huang2, Chia-Yen Dai2, Wan-Long Chuang2, Ming-Lung Yu2, Shu-Chi Wang1

1Department of Medical Laboratory Science and Biotechnology. Kaohsiung Medical University, Kaohsiung, Taiwan

2Division of Hepatobiliary, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan

高脂和高氧化壓力環境誘導肝細胞損 傷和鐵依賴性凋亡的相關性

Background: Ferroptosis (an iron-dependent mechanism of cell death) differs from apoptosis and occurs during intracellular iron accumulation and is related to lipid peroxidation. The irons in the human body mainly come from the degradation of hemoglobin, ferritin, and other iron sources in blood. About 60% of the irons are stored in the liver by transferrin; ferroportin (FPN) can cause reticuloendothelial cell macrophages to release irons and return irons to circulation. Once hepatocytes are damaged, they may go towards ferroptosis.

Aims: To study the ferroptosis in a high-fat accompanied carbon tetrachloride animal model and used hepatocytes to co-culture with adipocytes “3T3L1” in order to simulate a highfat environment, then observe the possibility of steatosis caused by ferroptosis in hepatocyte.

Methods: To collect the adipocyte culture medium (ACM) for Hepatocyte co-culture environments, IBMX (3-isobutyl-1-methylxanthine), Dexamethasone, and Insulin (10 ug/ml) were added to differentiate pre-adipocyte. The medium was replaced every two days, and Insulin (5 ug/ ml instead of 10 ug/ml) was added simultaneously. On the eighth day after 3T3L1 cell differentiation, the supernatant was collected to obtain an ACM.

Results: In the animal model of high-fat

accompanied carbon tetrachloride experiments, it was found that in addition to histological fibrosis, iron accumulation was indeed found in the liver slices of mice in 7 months. To investigate highfat-induced hepatocyte damage by ferroptosis effect, the ACM co-culture was found to increase ferroptosis-related genes in hepatocyte cells compared to the medium-only control cells after 48 hrs. The H2O2 cytotoxicity assay demonstrates that the ACM increased the cell cytotoxicity. The ferroptosis inhibitors and inducers will further analyze the effect of the ROS-related liver cell damage and ferroptosis-related gene expression.

Conclusions: In this study, we can further clarify the relationship between ferroptosis, steatosis and even fibrosis in non-alcoholic fatty liver disease (NAFLD). The results can provide the development of precise health prevention strategies through the inhibition of ferroptosis to reduce liver disease.

P.009 ADD-ON GEFITINIB FOR UNRESECTABLE HEPATOCELLULAR CARCINOMA AFTER LENVATINIB FAILURE

Chih-Cheng Tan1, Chi-Jung Wu1,2,3, Pei-Chang Lee1,3, Ya-Wen Hung1, Chieh-Ju Lee1, Chen-Ta Chi1,2,3, I-Cheng Lee1,3, Ming-Chih Hou1,3, Yi-Hsiang Huang1,2,3

1Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan

2Institute of Clinical Medicine, National Yang

Ming Chiao Tung University, Taipei, Taiwan

3Faculty of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan

Gefitinib 用於 Lenvatinib 治療失敗之

不可手術肝細胞癌

2

3

Background: Lenvatinib is the key multi-kinase inhibitor (MKI) by targeting not only vascular endothelial growth factor receptors (VEGFR)1-3 but also fibroblast growth factor receptors (FGFR)1-4 for unresectable hepatocellular carcinoma (uHCC) with a better objective response rate (ORR) and non-inferiority in overall survival as compared with sorafenib. There are several choices after lenvatinib failure, including switching to immune checkpoint inhibitors (ICIs) or other MKIs. As epidermal growth factor receptor (EGFR) pathway activation might be the mechanism of lenvatinib failure based on one recent research from Nature, which showed meaningful clinical responses by co-blocking EGFR with gefitinib and FGFR with lenvatinib in patients who progressed after lenvatinib treatment.

Aims: This study aims to analyze the outcomes of gefitinib for uHCC patients failed by lenvatinib treatment.

Methods: Ten consecutive uHCC patients who received add-on gefitinib after progression on lenvatinib monotherapy or in combination with pembrolizumab in Taipei Veteran General Hospital

from Sep. 2021 to Apr. 2022 were retrospectively reviewed. Of them, 9 had evaluable imaging studies after gefitinib were enrolled in this analysis. The tumor responses were assessed according to RECIST 1.1 criteria.

Results: The median age of the patients was 57 years (range, 23-87) at the start of lenvatinib treatment, all 9 patients were male, and 6 (66.7%) used lenvatinib as the first-line systemic treatment. Of them, 3 received lenvatinib monotherapy and the other 6 used lenvatinib/pembrolizumab combinations. The median treatment duration for lenvatinib was 12.6 (range, 3.5-25.2) months, including 2 (22.2%) had ever objective response, and the other 7 (78.8%) maintained in stable disease before progression. At lenvatinib progression, there were 3 (33.3%) in BCLC stage B, and 8 (88.9%) in Child-Pugh class A liver function. After a median duration of 5.5 (range, 2.8-10.2) months of follow-up, the best ORR was 33.3% and the disease control rate was 100% by add-on gefitinib treatment. The median time to response was 2.6 months (range, 1.8-5.2) for responders. The median progression-free survival was 7.8 months, and the median overall survival was still not reached yet. Two patients suffered from grade 2 hand-foot-skin reaction and the other 1 patient experienced grade 2 diarrhea. No patient discontinued gefitinib due to adverse effects. Conclusions: Add-on gefitinib treatment is a promising strategy for lenvatinib failure with satisfactory responses and tolerability. Further analysis by recruitment for more patients and observation for longer duration is still required.

P.010 DIRECT-ACTING ANTIVIRALS AMELIORATE THE DE NOVO DEVELOPMENT OF ESOPHAGEAL VARICES IN PATIENTS WITH HEPATITIS C RELATED LIVER CIRRHOSIS

Yung-Yu Hsieh1,2, Wei-Ming Chen1,2, Kao-Chi Chang1,2, Te-Sheng Chang1,2, ChaoHung Hung1,3, Yao-Hsu Yang4,5,6, Shui-Yi Tung1,2, Kuo-Liang Wei1,2, ChenHeng Shen1, Jing-Hong Hu7, YuTing Huang1, Yuan-Jie Ding1, Meng-Hung Lin4, Chung-Kuang Lu1, Cheng-Shyong Wu1

1Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chang Gung Memorial Hospital, Chiayi, Taiwan

2College of Medicine, Chang Gung University, Taoyuan, Taiwan

3Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan

4Health Information and Epidemiology Laboratory, Chang Gung Memorial Hospital, Chiayi, Taiwan

5Department of Traditional Chinese Medicine, Chang Gung Memorial Hospital, Chiayi, Taiwan

6School of Traditional Chinese Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan

7Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chang Gung Memorial Hospital, Yunlin, Taiwan

1 嘉義長庚紀念醫院胃腸肝膽科

2 長庚大學醫學系

3 高雄長庚紀念醫院胃腸肝膽科

4 嘉義長庚紀念醫院健康資訊暨流行病學研究室

5 嘉義長庚紀念醫院中醫科

6 長庚大學中醫系

7 雲林長庚紀念醫院胃腸肝膽科

Background: The real-world benefits of directacting antiviral (DAA)-induced sustained virologic response (SVR) on the de novo occurrence and progression of esophageal varices (EV) in patients with hepatitis C (HCV) related liver cirrhosis (LC) remain unclear.

Aims: We aimed to assess the association between DAA-induced SVR and occurrence/ progression of EV.

Methods: This is a retrospective cohort study evaluating all patients with Child-Pugh class A HCV-related LC during 2013 to 2020 in the Chang Gung Medical System. The primary end point was the de novo development of EV defined by esophagogastroduodenoscopy (EGD). The inverse probability of treatment weighting (IPTW) with the propensity score was used to evaluate the association between DAA-induced SVR and EV occurrence/progression.

Results: A total of 215 patients fit the inclusion criteria and were enrolled. Of them, 132 patients achieved DAA induced-SVR and 83 did not receive anti-viral treatment. During a median follow-up of 18.4 (interquartile range, 10.1-30.9) months, the 2-year incidence of de novo EV occurrence was 8 (7.0%) in the SVR group and 7 (12.7%) in the treatment-naïve group. Compared to the treatment-naïve group, the SVR group was associated with a significantly lower incidence of EV occurrence (adjusted hazard ratio [aHR]: 0.47, p = 0.030), and a significantly lower incidence of EV progression (aHR: 0.55, p = 0.033). The risk of EV progression strongly correlated to the baseline EV presence (p < 0.001).

Conclusions: DAA-induced SVR is associated with decreased risk of 2-year de novo EV occurrence and progression in HCV patients with early cirrhosis.

LEVEL

Tai-Chung Tseng1,2,3, Chun-Jen Liu1,2,5, Chun-Ming Hong1,4, Tung-Hung Su1,2, Hung-Chih Yang1,5,6, Wan-Ting Yang2, Chen-Hua Liu1,2, Pei-Jer Chen1,2,5, Jia-Horng Kao1,2,3,5

1Division of Gastroenterology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan

2Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan

3Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan

4Division of Hospital Medicine, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan

5Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan

6Department of Microbiology, National Taiwan University College of Medicine, Taipei, Taiwan

B 肝患者，較低 B

1 國立臺灣大學醫學院附設醫院內科部消化內科

2 國立臺灣大學醫學院附設醫院肝炎研究中心

3 國立臺灣大學醫學院附設醫院醫學研究部

4 國立臺灣大學醫學院附設醫院內科部整合醫學科

5 國立臺灣大學醫學院臨床醫學研究所

6 國立臺灣大學醫學院微生物學系

Background: Clearance of hepatitis B surface antigen (HBsAg) indicates functional cure of hepatitis B virus (HBV) infection. However, little is known about the association between hepatitis B core-related antigen (HBcrAg) levels and HBsAg seroclearance.

Aims: We aimed to explore the association

P.011

LOW HEPATITIS B CORE-RELATED ANTIGEN LEVELS ASSOCIATED WITH HIGHER SPONTANEOUS SEROCLEARANCE OF HBSAG IN CHRONIC HEPATITIS B PATIENTS WITH HIGH HBSAG

between hepatitis B core-related antigen (HBcrAg) levels and HBsAg seroclearance.

Methods: We conducted a retrospective cohort study including 2614 CHB patients [2111 hepatitis B e antigen (HBeAg)-negative and 503 HBeAgpositive patients], who received long-term followup at the National Taiwan University Hospital. The primary endpoint was HBsAg seroclearance. We aimed to explore whether HBcrAg levels could predict HBsAg seroclearance, especially for patients with high HBsAg levels.

Results: There were 465 patients clearing HBsAg among 32414.72 person-years of follow-up. Lower HBcrAg levels at baseline were shown to be associated with increased chance of HBsAg seroclearance. When restricting to 1539 patients with HBsAg levels >1000 IU/mL, who are difficult to clear HBsAg, only lower HBcrAg level served as an independent viral predictor for HBsAg seroclearance. In contrast to a late decline of HBsAg levels (5-10 years before HBsAg seroclearance), we found an early decline of HBcrAg (15-20 years before HBsAg seroclearance), which achieved <1000 U/mL 10-15 years before HBsAg serolcearance. This finding was supported by the surge of HBsAg seroclearance rate after 10 years of follow-up in patients who achieved HBcrAg <1000 U/mL.

Conclusions: Lower serum HBcrAg levels were associated with increased chance of HBsAg seroclearance. In patients with HBsAg levels >1000 IU/mL, undetectable HBcrAg developed long before HBsAg seroclearance.

P.012

KLHL23 NEGATIVELY REGULATES

CDC42 BIOACTIVITIES THROUGH UBIQUITIN-DEPENDENT PROTEASOMAL DEGRADATION FOR TUMOR INVASION AND METASTASIS

Hao-Chun Chang, Yung-Hsiang Yi, Sen-Yung Hsieh

Department of Gastroenterology and Hepatology, Linkuo Chang Gung Memorial Hospital, Taoyuan, Taiwan

KLHL23 透過泛素化蛋白質 酶 降解機 制負向調控 CDC42 生物活性以抑制腫

瘤侵襲和轉移

張皓竣 易永祥 謝森永

林口長庚紀念醫院胃腸肝膽科系

Background: High invasiveness is a hallmark of cancer. Using a genome-wide screen, we identified a novel metastasis suppressor, KLHL23, often down-regulated in patients with pancreatic and liver cancers and associated with tumor metastasis and poor clinical outcomes.

Aims: Here, we aim to investigate the mechanisms of how KLHL23 orchestrates actin cytoskeleton remodeling for invasion and metastasis.

Methods: Proteomic screening and biochemistry analysis were carried out to identify the binding partners of KLHL23 during actin remodeling. The signaling pathways regulated by KLHL23 were also studied in vivo using patient-derived tumor xenografts in mice.

Results: KLHL23 is an actin-binding protein suppressing F-actin, filopodium, and lamellipodium formation. Since CDC42, a small Rho GTPase, is crucial for actin polymerization, we hypothesized that KLHL23 negatively regulates CDC42. Indeed, overexpressed KLHL23 partially prevented filopodium formation by inhibiting CDC42. The KLHL23-mediated CDC42 downregulation can be restored by MG132 treatment, suggesting that the ubiquitin-dependent proteasomal degradation was involved. Further analysis using in vitro and in vivo ubiquitination assays revealed that KLHL23 ubiquitinated CDC42 at K163/K166 via a K11-ubiquitin linkage. Interestingly, KLHL23 selectively targets the active GTP- but not inactive GDP-bound CDC42 for degradation. In addition,

KLHL23 downregulation drives the epithelialmesenchymal transition (EMT) of tumor cells for metastasis through activating HIF/NOTCH signaling in a cell-density-dependent manner. Mechanistically, oxygen-overconsumption during actin polymerization and overwhelmed hypoxic stress in high-cell-density environment, promote EMT and tumor metastasis. Actin-polymerization inhibition or ATP supplement interrupts the HIF/ NOTCH-mediated EMT and tumor metastasis.

Conclusions: We identified KLHL23 as a tumormetastasis suppressor, by acting as an E3 ligase targeted GTP-bound CDC42 for proteasomal degradation. Downregulation of KLHL23 in tumors drives downstream F-actin remodeling/EMT/tumor metastasis events in a cell density-dependent context. Our findings elucidate a long-term biological and clinical enigma “why large tumors tend to metastasis”, explain how CDC42 bioactivity is regulated during cell migration, and provide a new paradigm for anti-metastasis therapy.

P.013

FACTORS ASSOCIATED WITH ANTIVIRAL THERAPY AMONG PATIENTS WITH CHRONIC HEPATITIS B – A QUESTIONNAIRE-BASED STUDY

Pei-Yuan Su1,2, Wen-Yuan Chen3

1Center for Gastroenterology, Changhua Christian Hospital, Changhua, Taiwan

2Division of Gastroenterology and Hepatology, Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan

3Department of Pharmacy, Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan

慢性 B 型肝炎個案服用抗病毒藥物治 療之相關因子問卷調查

3

1 彰化基督教醫院消化系中心

2 彰化基督教醫院胃腸肝膽科

3 彰化基督教醫院藥學部

Background: Adherence to medication is an important aspect of avoiding the development of drug resistance among patients receiving anti-viral therapy for chronic hepatitis B.

Aims: To explore the factors related to patient adherence to nucleoside/nucleotide analogues therapy in chronic hepatitis B treatment in a single medical center.

Methods: The study enrolled 152 chronic hepatitis B patients who had been receiving nucleoside/ nucleotide analogues for ≥3 months were invited for the questionnaire study. A questionnaire was completed by patients themselves, and adherence was evaluated based on patients’ self-reporting. The use of at least 95% of the drugs in the previous month was considered as adequate adherence.

Results: Most of the patients received tenofovir disoproxil fumarate (65.1%) followed by entecavir 0.5 mg (26.3%). Cirrhosis was present among 77.6% of the patients and 21.1% of the patients have history of hepatoma. Adherence was adequate in 91.4% of patients. Younger age (p = 0.002) and permanent employment (p = 0.038) were related to lower adherence. The need of work and patient perception of good disease control are patients reported factors associated with drug incompliance.

Conclusions: Patients in their working age are associated with a higher rate of drug noncompliance. These patients should be followed up more frequently to reinforce adherence.

P.014 ELECTRONIC REMINDER SYSTEM LEADS THE QUALITY OF HEPATITIS B/C PATIENTS ON FOLLOW UP CARE

Pei-Yuan Su1, Yuan-Chi Yang2

1Division of Gastroenterology and Hepatology, Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan

2Center for Gastroenterology, Changhua Christian Hospital, Changhua, Taiwan

system to improve annual enrollment and followup rates, including prescriptions for outpatients, database management for patients with hepatitis B and C, mobile messaging service and APP.

Results: In 2019, the annual enrollment and follow-up rates had dramatically increased to 58.91% (4542/7710) and 74.45% (3107/4173), respectively. These were higher than the average data from other national medical centers in Taiwan. The efficiency of the case management was enhanced, and the monthly working hours was reduced from 37.8 to 1.6. A monthly growth in care services was apparently found from 132 to 379, it was about 2.8 times increase. Early detection can improve treatment outcomes and reduces cost of treatment.

Conclusions: Electronic follow-up reminder system is reliable and benefit for the quality of hepatitis B/C patients on follow up care.

Background: Patients with hepatitis B and C require regular follow-up to monitor disease activity and screen for the presence of hepatocellular carcinoma. Since 2010, Changhua Christian Hospital has implemented a hepatitis B and C care plan guided by the National Health Insurance Administration (NHIA), Ministry of Health and Welfare (MOHW). The rates of patient enrollment and follow-up between 2010 and 2016 were unsatisfactory. The annual enrollment and followup rates were only 14.6% and 28.8%, respectively, in 2016, falling below the three quality indicator standards established by the NHIA. The absence of insight into patient disease and the complexity of patient enrollment and follow-up procedures were identified as the main problems. Therefore, in 2017, we developed a strategy for improving and simplifying the patient enrollment process, enhancing the efficiency of the case managers involved in patient enrollment and follow-up, and increasing the rate of medical compliance. An electronic follow-up reminder system was implemented to enhance our quality of care among patients with hepatitis B and C. Thus, in 2019, the annual enrollment and follow-up rates had dramatically increased to 58.91% (4542/7710) and 74.45% (3107/4173), respectively.

Aims: To simplify the process of enrollment, improve the patients’ compliance, and enhance our quality of follow-up care among patients with hepatitis B and C.

Methods: Using an electronic follow-up reminder

蘇培元1,2 楊媛淇2

1 彰化基督教醫院胃腸肝膽科

2 彰化基督教醫院消化系中心

P.015

SERIOUS ADVERSE CLINICAL EVENTS AFTER CESSATION OF NUCLEOS(T)IDE ANALOGUES IN PATIENTS WITH CHRONIC HEPATITIS B: A SYSTEMATIC REVIEW AND META-ANALYSIS

Cheng-Hao Tseng1,2, Tzu-Haw Chen1,2, Jia-Ling Wu3, Teng-Yu Lee4, John A. Borghi5, Jaw-Town Lin1,2, Mindie H. Nguyen5, Yao-Chun Hsu1,2

1Division of Gastroenterology and Hepatology, E-DA Hospital, Kaohsiung, Taiwan

2Division of Gastroenterology and Hepatology, E-DA Cancer Hospital, Kaohsiung, Taiwan

3Department of Public Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan

4Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan

5Division of Gastroenterology and Hepatology, Stanford University Medical Center, Palo Alto, CA, USA

慢性

Background: The risk of serious clinical outcomes following cessation of nucleos(t)ide analogue (Nuc) in patients with chronic hepatitis B remains poorly characterized, especially for those treated with tenofovir or entecavir.

Aims: This systematic review and meta-analysis aimed to evaluate the existing literature that addressed this issue.

Methods: We searched PubMed, Embase, and Web of Science for Nuc stop studies that noted clinical outcomes published between January 1,

2006 and February 14, 2022. We performed metaresearch analyses to examine the relationships of reported outcomes with study designs and characteristics and also pooled studies with nonoverlapping populations to provide risk estimation for the proportions of (1) severe hepatitis flares or hepatic decompensation or (2) hepatitis flarerelated death or liver transplantation.

Results: The meta-research analysis included 46 studies of highly heterogeneous designs and characteristics. We found that reporting of safety outcomes varied widely according to outcome definition, follow-up duration, and sample size. Only nine studies prespecified safety events as the study outcome, and only three of them had an outcome definition to include manifestations of hepatic insufficiency, a follow-up duration >12 months, and a sample size >100 patients. We further pooled 14 studies with 4415 individual patients and estimated the proportion of severe hepatitis flares or decompensation at 1.23% (95% confidence interval [CI], 0.71–2.12%), with significant heterogeneity (I2 = 56%, p < 0.01), while that of hepatitis flare-related death or liver transplantation was 0.37% (95% CI, 0.21–0.68%), without significant heterogeneity (I2 = 0%, p = 1.00).

Conclusions: Current literature on the risk of serious clinical outcomes following Nuc cessation is limited, highly heterogeneous, and should be carefully interpreted.

3 國立成功大學公共衛生學院

4 臺中榮民總醫院胃腸肝膽科

5 美國史丹佛大學醫學院

P.016

WILL ANTI-HBC AND ANTI-HBS POSITIVITY INFLUENCE THE SEVERITY AND PROGNOSIS OF HBSAG-NEGATIVE HEPATOCELLULAR CARCINOMA?

COMPARATIVE OUTCOMES OF ANTI-HBC POSITIVE VERSUS ANTI-HBC NEGATIVE AND ANTIHBS POSITIVE VERSUS ANTI-HBS NEGATIVE NON-B NON-C HCC

Yen-Chung Wang, Su-Hong Wang, Hsing-Tao Kuo, Ming-Jen Sheu

Division of Hepatogastroenterology, Department of Internal Medicine, Chi Mei Medical Center, Tainan, Taiwan

Anti-HBc 以及 Anti-HBs 陽性是否會

negative Non-HBV Non-HCV (NBNC-HCC) HCC population.

Methods: 408 newly diagnosed non-B non-C HCC patients from January 2011 to May 2021 were retrospectively reviewed. 46 (27.2%) NHBcHCC and 123 (72.8%) HBc-HCC patients and 88 (52.4%) NHBs-HCC and 80 (47.6%) HBs-HCC were identified. Patient HCC diagnosis date BCLC stage and survival outcomes were analysed.

Results: There was no significant difference in BCLC stage (0-A, B, C, D) between NHBc-HCC and HBc-HCC (P = 0.787), NHBs-HCC and HBs-HCC (P = 0.209). There was no significant difference in survival outcomes between NHBcHCC and HBc-HCC (P = 0.935) and NHBs-HCC and HBs-HCC (P = 0.397)

Conclusions: Anti-HBc and Anti-HBs seropositivity in HbsAg negative NBNC-HCC patients had no significant difference in BCLC stage and survival outcomes compare with seronegative patients.

王彥中 王宿鴻 郭行道 許銘仁

奇美醫療財團法人奇美醫院胃腸肝膽科

Background: Hepatocellular carcinoma (HCC) has been extensively studied and well-established etiologies include chronic Hepatitis B Virus (HBV) infection, chronic Hepatitis C infection (HCV) and metabolic causes such as chronic alcoholism and non-alcoholic fatty liver disease. Hepatitis B is a potentially life-threatening liver infection caused by the HBV. It is a major global health problem. It can cause chronic infection and puts people at high risk of death from cirrhosis and liver cancer. Though improved HBV screening and surveillance strategies have also allowed better control of HBV viral load and earlier detection of HCC in HBV patients, the management of patients who develop subsequent clearance of HBsAg continues to be controversial.

Aims: There is lack of studies evaluating the severity and survival outcomes of HBsAgnegative/Anti-HBc-positive and Anti-HBs-positive related HCCs. To compare the presentations and outcomes of anti-HBc and anti-HBs seropositive Hepatocellular Carcinoma (HBc-HCC and HBsHCC) with anti-HBc and anti-HBs seronegative (NHBc-HCC and NHBs-HCC) patients in HBsAg

影響 HBsAg 陰性之肝細胞癌病患的嚴 重程度和預後？比較在 HBsAg 陰性之 肝細胞癌之病患在 Anti-HBc 陽性與陰 性以及 Anti-HBs 陽性與陰性

COMPARISON OF BODY WEIGHT AND LIPID PROFILES FOLLOWING TENOFOVIR DISOPROXIL FUMARATE OR ENTECAVIR SWITCHING TO TENOFOVIR ALAFENAMIDE IN

Pin-Nan Cheng1, Chun-Jen Liu2, Jyh-Jou Chen3, I-Cher Feng4, Hsing-Tao Kuo4, Pei-Lun Lee3, Ming-Lung Yu5, Yeng-Chen Chiu1, Hung-Chih Chiu1, Shih-Chieh Chien1, Pei-Jer Chen2

1Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan

2Department of Internal Medicine, National Taiwan University Hospital, Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan

3Division of Gastroenterology and Hepatology, Department of Internal medicine, Chi-Mei Medical Center, Liouying, Tainan, Taiwan

4Department of Internal Medicine, Chi-Mei Medical Center, Tainan, Taiwan

5Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan

and needs to investigate.

Methods: This was a prospective, multi-center, observational study. CHB patients from five hospitals in Taiwan treated with TDF or entecavir for at least 1 years and then switched to TAF were enrolled. Measurement of biochemical, virological, and atherosclerotic cardiovascular disease (ASCVD) risk score at baseline and then at an interval of 12 weeks or 48 weeks by items. Primary endpoint was the body weight changes following switching to TAF or entecavir. Secondary endpoints included ASCVD score changes, and changes of lipid and sugar profiles following switching to TAF.

Results: At the end of May 2022, 159 patients, including 100 males with a mean age of 56.1 years, completed a 48 weeks follow-up were enrolled for analysis. Of them, 97 and 62 patients treated with TDF or entecavir before switching to TAF, respectively. At baseline, significantly lower TG, Chol, HDL, and LDL (all p < 0.05) in TDF switch group than entecavir switch group. Figure 1 shows the BW changes during 48 weeks of TAF treatment. Following switching to TAF, significant BW gain was present from 12 weeks and maintained thereafter until 48 weeks in TDF switch group comparing with baseline BW (p < 0.01 in all timepoints). In contrast, BW remained unchanged in entecavir switch group during the first 36 weeks of observation, but significantly decreased at week 48 (p < 0.05). In TDF switch group but not entecavir switch group, all of the lipid profiles including TG (88.6 ± 48.3 vs. 104.4 ± 66.6 mg/dL, p = 0.001), Chol (160.3 ± 33.1 vs. 188.1 ± 38.9 mg/dL, p < 0.001), LDL (104.9 ± 28.9 vs. 121.9 ± 34.2 mg/dL, p < 0.001), and HDL (48.2 ± 11.7 vs. 58.2 ± 13.2 mg/dL, p < 0.001) were significantly increased following 48week TAF treatment. The ASCVD score remained similar in both groups.

Background: Body weight (BW) and lipid profiles changes have been reported in HIV infected patients treated with tenofovir alafenamide (TAF) containing regimens. Tenofovir disoproxil fumarate (TDF) treated chronic hepatitis B (CHB) patients exhibited lower lipid profiles in phase III study.

Aims: The impact of TAF, as a new drug for CHB treatment, on BW and lipid profiles remains unclear

Conclusions: Body weight Significantly gains after switching from TDF to TAF, not from ETV to TAF. Increase of lipid profiles after switching to TAF mainly results from the lipid-lowering effect of TDF.

4 奇美醫學中心胃腸肝膽科

5 高雄醫學大學附設醫院胃腸肝膽科

P.018

EFFICACY AND SAFETY OF BULEVIRTIDE MONOTHERAPY GIVEN AT 2 MG OR 10 MG DOSE LEVEL ONCE DAILY FOR TREATMENT OF CHRONIC HEPATITIS DELTA: WEEK 48 PRIMARY ENDPOINT RESULTS FROM A PHASE 3 RANDOMIZED, MULTICENTER, PARALLEL DESIGN STUDY

Heiner Wedemeyer1, Soo Aleman2, Maurizia Brunetto3, Antje Blank4, Pietro Andreone5, Pavel Bogomolov6, Vladimir Chulanov7, Nina Mamonova7, Natalia Geyvandova8, Viacheslav Morozov9, Olga Sagalova10, Tatiana Stepanova11, Dmitry Manuilov12, Vithika Suri12, Qi An12, John F. Flaherty12, Anu Osinusi12, Julian Schulze zur Wiesch13, Markus Cornberg1, Stefan Zeuzem14, Pietro Lampertico15,16

1Clinic for Gastroenterology, Hepatology, and Endocrinology, Hannover Medical School, Hannover, Germany; 2Department of Infectious Diseases, Karolinska University Hospital/Karolinska Institute, Stockholm, Sweden; 3Hepatology Unit, Reference Center of the Tuscany Region for Chronic Liver Disease and Cancer, University Hospital of Pisa and Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy; 4Clinical Pharmacology and Pharmacoepidemiology, Heidelberg University Hospital, Heidelberg, Germany; 5Internal Medicine, University of Modena and Reggio Emilia, Modena, Italy; 6State Budgetary

Institution of Health Care of Moscow region

“Moscow Regional Research Clinical Institute after M.F. Vladimirsky,” Moscow, Russian Federation; 7FSBI National Research Medical Center for Phthisiopulmonology and Infectious Diseases of the Ministry of Health of the Russian Federation, Moscow, Russian Federation; 8Stavropol Regional Hospital, Stavropol, Russian Federation; 9LLC Medical Company “Hepatolog,” Samara, Russian Federation; 10Federal State-Funded Institution

of Higher Education “Southern Ural State Medical University of Ministry of Health of the Russian Federation,” Chelyabinsk, Russian Federation; 11LLC “Clinic of Modern Medicine,” Moscow, Russian Federation; 12Gilead Sciences, Inc., Foster City, USA; 13Hepatology Outpatient Medical Clinic, University Hospital Hamburg-Eppendorf, Hamburg, Germany; 14Department of Medicine, University Hospital Frankfurt, Frankfurt am Main, Germany; 15Foundation IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Division of Gastroenterology and Hepatology, Milan, Italy; 16CRC “A. M. and A. Migliavacca” Center for Liver Disease, Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy

Background: Bulevirtide (BLV) is a novel firstin-class entry inhibitor conditionally approved by the EMA for treating chronic hepatitis delta virus (HDV) infection (CHD). In an interim 24week (W) analysis of a Phase 3 study (MYR301; NCT03852719), BLV monotherapy at 2 or 10 mg once daily demonstrated significantly greater combined virologic/biochemical response vs control and favorable safety.

Aims: Present findings for MYR301’s W48 primary endpoint.

Methods: 150 CHD patients were randomized 1:1:1 and stratified by compensated cirrhosis status: Arm A (control), no active anti-HDV treatment for 48W followed by BLV 10 mg/d for 96W (n = 51); Arms B and C, BLV 2 (n = 49) or 10 mg/d (n = 50), respectively, for 144W. All arms then entered a 96W treatment-free follow-up. The primary endpoint was combined response (undetectable HDV RNA or decrease by ≥2 log10 IU/mL from baseline and alanine aminotransferase [ALT] normalization) at 48W. Other endpoints included viral response (undetectable HDV RNA or decrease by ≥2 log10 IU/mL from baseline), biochemical response (ALT normalization), change in HDV RNA, and change in liver stiffness measured by elastography.

Results: Baseline characteristics: mean (SD) age, 41.8 (8.4) years; 57.3% males; 82.7% White; 47.3% with compensated cirrhosis; 60% on nucleos(t)ide analogues; mean (SD) HDV RNA, 5.05 (1.35) log10 IU/mL; mean (SD) ALT, 110.9 (69.0) U/L. Combined response was achieved by 22 (44.9%) and 24 (48.0%) patients in Arms B

and C vs 1 (2.0%) in Arm A (p < .0001 for both). Viral and biochemical response rates were similar in both BLV arms and significantly greater than control at W48 (both p < .0001). No adverse events (AEs) led to BLV discontinuation; no serious AEs were attributed to BLV. Asymptomatic total serum bile salt elevations and injection-site reactions occurred more frequently with BLV 10 mg.

Conclusions: BLV treatment resulted in a significantly greater combined response vs control and was well-tolerated at 48W.

P.019 TREATMENT WITH BULEVIRTIDE IMPROVES PATIENT-REPORTED OUTCOMES IN PATIENTS WITH CHRONIC HEPATITIS DELTA (CHD): AN INTERIM EXPLORATORY ANALYSIS AT WEEK 24

Heiner Wedemeyer1, Soo Aleman2, Vladimir Chulanov3, Gudrun Hilgard4, Jenya Antonova5, Ankita Modi Kaushik5, Andrew Lloyd6, Dmitry Manuilov5, Vithika Suri5, Tram T. Tran5, Anu O. Osinusi5, Pietro Lampertico7, Viacheslav Morozov8, Olga Sagalova9, Tatiana Stepanova10, Maria Buti11

1Clinic for Gastroenterology, Hepatology, and Endocrinology, Hannover Medical School, Hannover, Germany; 2Department of Infectious Diseases, Karolinska University Hospital/Karolinska lnstitute, Stockholm, Sweden; 3Central Research Institute of Epidemiology, Moscow, Russian Federation; 4University Hospital Essen, Essen, Germany; 5Gilead Sciences, Inc., Foster City, CA, USA; 6Acaster Lloyd Consulting Ltd, London, UK; 7Foundation IRCCS Ca’ Granda Ospedale Maggiore Policlinico, CRC “a.M. and a. Migliavacca” Center for Liver Disease, University of Milan, Milan, Italy; 8Hepatolog, LLC, Samara, Russian Federation; 9Southern Ural State Medical University, Chelyabinsk, Russian Federation; 10Clinic of Modern Medicine, Moscow, Russian Federation; 11Liver Unit, University Hospital Valle Hebron, Barcelona, Spain

Background: Chronic hepatitis delta (CHD) is the most severe form of viral hepatitis. In 2020, the European Medicines Agency granted conditional marketing authorization to bulevirtide (BLV) 2 mg as the first treatment for CHD.

Aims: To report an exploratory interim analysis of health-related quality of life (HRQoL) benefits of 24 weeks of treatment with BLV 2 mg in CHD patients within an ongoing Phase 3 trial.

Methods: In MYR301 a randomized, openlabel, parallel-group, multicenter trial CHD patients were randomized (1:1:1) to, and started receiving, 1 of 3 treatments (BLV 2 or 10 mg or

delayed treatment [DT]) for a total of 3 years. (BLV 10-mg data are not reported here, as it is not a conditionally approved dosage.) DT patients received no active treatment until week (W)48. Patients completed the Hepatitis Quality of Life Questionnaire (HQLQ, including SF-36 and 15 supplemental items) at baseline and W24.

Results: At baseline, patients receiving BLV 2 mg (n = 49; mean ± SD age, 43.6 ± 9.0; BMI, 24.4 kg/m2; 61.2% male; 48% with cirrhosis) and DT (n = 51; mean ± SD age, 40.5 ± 7.5; BMI, 25.3 kg/m2; 51% male; 51% with cirrhosis) reported varying levels of HRQoL. From baseline to W24, BLV 2-mg–treated patients reported improvements in all domains of the HQLQ, notably >5-point improvements in general health, bodily pain, vitality, mental health, hepatitis-specific (HS) limitations, and HS health distress and >4-point improvements in social functioning and role functioning–emotional domains. DT patients reported >5-point improvements in mental health and HS health distress and a >4-point improvement in HS limitations.

Conclusions: Both BLV 2-mg and DT groups reported improvements from baseline to W24 in HRQoL, most notably in HS limitations, HS health distress, and mental health. More domain improvements were observed with BLV 2 mg than with the DT arm.

P.020 A WIDER DYNAMIC RANGE TO QUANTITATE HEPATITIS B VIRUS USING ALINITY M HBV ASSAY

Tai-Chung Tseng1,2,3, Chun-Jen Liu1,2, Min-Long Lai4, Shih-Rong Huang4, Jia-Horng Kao1,2,3

1Division of Gastroenterology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan

2Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan

3Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan

4Union Clinical Laboratory, Taipei, Taiwan

使用 Alinity m HBV Assay 能夠提升 B 型肝炎病毒定量的有效範圍

曾岱宗

4

Background: Serum HBV DNA level is a major viral predictor for different clinical outcomes in patients with chronic hepatitis B (CHB) infection. The linear range of traditional assay is from 20 to 1.7 x 108 IU/mL. The Alinity m HBV assay is a new in vitro polymerase chain reaction assay to quantitate HBV with the detection limits from 10 to 1.0 x 109 IU/mL.

Aims: We aimed to explore its performance in clinical samples.

Methods: A total of 137 CHB patients were enrolled retrospectively. The serum samples were collected and stored in -20℃ when the data from a current assay (Roche COBAS® AmpliPrep/ COBAS® TaqMan® HBV Test, v2.0) was available. Alinity m HBV assay was used to quantitate HBV using the stored serum samples.

Results: Among the 137 samples, 48 samples were within the dynamic range using the Roche assay. The correlation between the two assays was good with R2 = 0.917. For the 89 samples outside the dynamic range of the Roche assay, 53 and 36 were below and above the dynamic range, respectively. For the samples < 20 IU/mL, 22 (41.5%) of them could be quantified using the Alinity m HBV assay and 12 were within the range

from 10-20 IU/mL. For the samples > 1.7 x 108 IU/ mL, 34 (93.9%) of them was within the dynamic range of the Alinity m HBV assay and 23 were within the range from 1.7 x 108 IU/mL to 1.0 x 109 IU/mL.

Conclusions: Alinity m HBV assay has a wider dynamic range to quantitate HBV, which is useful in for accurately monitoring the viral replication in CHB patients.

P.021 INCIDENCE AND PREDICTIVE FACTORS OF HBSAG LOSS IN HBEAG-POSITIVE PATIENTS WHO STOP NUCLEOT(S)IDE ANALOGUE THERAPY

Chien-Wei Peng1,3, Wen-Juei Jeng1,3, Yen-Chun Liu1,3, Rong-Nan Chien1,2,3, Yun-Fan Liaw2

1Division of Gastroenterology and Hepatology, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan

2Liver Research Unit, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan

3College of Medicine, Chang Gung University, Taoyuan, Taiwan

2 林口長庚紀念醫院肝臟研究中心

3 長庚大學醫學院

Background: HBsAg loss is an ultimate goal for treatment of chronic hepatitis B patients. The Incidence and predictors of off-Nucleot(s)ide analogue (Nuc) HBsAg loss in HBeAg-negative patients were well reported but little information for HBeAg-positive patients stopping Nuc.

Aims: This study aimed to investigate the incidence and the predictive factors of HBsAg loss in HBeAg-positive patients who stop Nuc therapy.

Methods: HBeAg-positive patients who stopped Nuc therapy with > 1-year consolidation therapy after HBeAg loss in a tertiary medical center. Pretherapy age, gender, liver cirrhosis (LC), ALT, HBV genotype, HBeAg S/N ratio, HBsAg and HBV DNA levels, on-treatment response, HBsAg kinetics, and end-of-treatment (EOT) HBsAg level were analyzed. Kaplan-Meier analysis was applied for the cumulative incidence of HBsAg loss. Cox regression analysis was done for the predictors of off-Nuc HBsAg loss.

Results: Among the 295 patients enrolled, mean age was 44.7, 18.4% were cirrhotic (LC), 67% were treated by ETV and 33% by TDF, and the median EOT HBsAg level was 3 (-0.9-4.4) log10IU/mL.

E 抗原陽性之慢性 B 型肝炎病人停止

核 苷 （酸）類似物後發生表面抗原消 失之發生率與預測因子

The median follow-up duration after EOT was 3.5 (0.2-12.9) years. During a median of 3 (1.1-8.8) years of Nuc treatment, HBsAg loss occurred in one patient with 3-year cumulative incidence (CI) of 0.4%. After EOT, 9 of the 294 (3%) patients had HBsAg loss with a median time of 1.8 (0.4-9.6) years with a 1-, 2-, 3-year CI of 1.1%, 1.9% and 2.4%, respectively. Among these 9 patients, 3 had sustained remission, 2 virological relapse alone, 3 HBeAg-positive clinical relapse (CR), and 1 HBeAg-negative CR prior to HBsAg loss (P = 0.6). Multivariate Cox regression showed LC [adjusted HR (aHR): 15.6, P = 0.01] and EOT HBsAg level < 100 IU/mL [>1000 as referent, 100-999: aHR: 1.2, P = 0.88, <100: aHR: 62.8, P = 0.02] were independent predictors for HBsAg loss. Neither anti-HBe positivity at EOT, CR nor retreatment were factors for HBsAg loss. The 3-year CI of HBsAg loss is much higher in patients with EOT HBsAg < 100 IU/mL than those with EOT HBsAg 100-999, 000 IU/mL (24.5% vs. 1.2% vs. 0%, respectively, P < 0.001), higher in patients with LC than non-LC (3.5% vs. 0.6%, P = 0.04), and highest in patients with HBsAg < 100/LC, followed by HBsAg < 100/non-LC, HBsAg > 100/LC, and lowest in HBsAg > 100/non-LC (100.0% vs. 9.4% vs. 2.5% vs. 0%; P < 0.001).

Conclusions: The 3-year CI of HBsAg loss was 2.4% in HBeAg-positive patients stopping Nuc, 6 times higher than that during treatment. Those with cirrhosis or EOT HBsAg level < 100 IU/mL have higher probability to achieve off-Nuc HBsAg loss.

P.022 REAL WORLD EXPERIENCE OF TENOFOVIR TREATMENT IN PATIENTS WITH CHRONIC HEPATITIS B IN PING-TUNG COUNTY

Shi-Chi Wen1, Chieh-Yu Wang2, Hsin-Yi Shen3, Yu-Fen Chen3, Yi-Ting Chen3

1Division of Gastroenterology, Department of Internal Medicine, Pao-Chien Hospital, Pingtung, Taiwan

2Case Manager, Nursing Department, PaoChien Hospital, Pingtung, Taiwan

3Endoscopy Room, Nursing Department, PaoChien Hospital, Pingtung, Taiwan

3

Background: Nucleos(t)ide analogue (NUC) treatment can reduce risk of hepatocecullar carcinoma (HCC) development in chronic hepatitis B (CHB). The 1 year clinical relapse rate after cessation of entecavir (ETV) was 45% of which 25.6% occurred 6 months. The events after cessation of another preferred drug tenofovir (TDF) were investigated.

Aims: We evaluated TDF as first line monotherapy. The 3 years cumulative rates of HBV DNA negativity, ALT normalization, HBeAg seroconversion/loss, occurrence of hepatocecullar carcinoma, viral breakthrough rates, and retreatment in patients with chronic hepatitis B (CHB) in Ping-Tung County were evaluated.

Methods: We conducted a retrospective study. We consecutively enrolled total of 67 patients with compensated/decompensated chronic hepatitis B primary treated with TDF for 3.3 ± 1.6 years, followed for 8.5 ± 4.3 years which evaluated the clinical outcome by intention-to-treated analyses. Results: The total 67 patients comprised of male (77.6%) predominance which had a mean age (53.9 ± 12.4) years, HBeAg(-) 47 (70.1%), cirrhosis 15 (22.4%), HBV DNA level (5.7 ± 1.5) IU/ml by log. The rates of undetectable HBV DNA were 46.3%, 76.1%, 86.6% and 95.5% in 0.5, 1,

以惠立妥治療慢性 B 型肝炎在屏東地 區之真實世界經驗探討

2 and 3 years, respectively. The rates of ALT level normalization were 73.1%, 73.1% and 80.0% in 1, 2, and 3 years, respectively. HBeAg loss occurred in 13 (65%) subjects. The cumulative probabilities of HBeAg loss after 1, 3, and 5 years of treatment were 7.5%, 13.4% and 19.7%, respectively. Occurrence of HCC was observed in 2 (3%). The cumulative probabilities of HCC development exhibited 0%, 1.5%, 3% in 1, 2 and 3 years. Virus breakthrough (1 log increase in serum HBV DNA level from nadir) was not noted in any patients throughout the follow-up period. Retreatment rates occurred in 15 (22.7%) subjects with clinical relapse after cessation of NUC. It resulted in 13.4%, 19.4%, 20.9% in 1, 2, 3 years, respectively.

Conclusions: Long-term data on patients receiving TDF for CHB have demonstrated to provide high potency, no resistance and good tolerability to lower the incidence of HCC development and improve underlying liver function.

P.023 INCIDENCE FOR LOSS-TOFOLLOW-UP IN PATIENTS WITH CHRONIC HEPATITIS B DURING LONG-TERM NUCLEOS(T)IDE ANALOGUE THERAPY

Chung-Wei Su1,2,3, Yen-Chun Liu1,2,3, Chien-Wei Peng1,2,3, Wen-Juei Jeng1,2,3, Rong-Nan Chien1,2,3, Yun-Fan Liaw2,3

1Department of Gastroenterology and Hepatology, Linkuo Chang Gung Memorial Hospital, Taoyuan, Taiwan

2Liver Research Unit, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan, Taiwan

3College of Medicine, Chang Gung University, Taoyuan, Taiwan

2

Background: On-treatment loss-to-follow-up (LTFU) is a major safety concern in chronic hepatitis B patients receiving long-term nucleos(t) ide analogue (Nuc) treatment. However, there is limited information for the incidence of patients LTFU during Nuc therapy.

Aims: This study aims to investigate this issue by a Nuc-treated cohort with a well-established call back system.

Methods: CHB patients who were treated by Entecavir (ETV) or Tenofovir (TDF) from January 2010 to December 2021 at a tertiary medical center in Taiwan were monitored by scheduled visit with every 3 months interval during Nuc therapy. Patients who did not return for medication refill were contacted by phone call to re-arrange the schedule or confirm their refill status. Patients receiving prophylactic Nuc for chemotherapy or blockage of vertical transmission or in combination use with interferon were excluded from this analysis. Those who missed their appointment and not returned > 6 months from the last date of medication refill were defined as LTFU. Follow-up duration is defined as from start of treatment (SOT)

長期使用口服抗病毒藥物治療之慢性 B 型肝炎患者未回診盛行率

to end of treatment (EOT) or to LTFU. KaplanMeier method is applied for cumulative incidence. Baseline characteristics are compared between patients with and without LTFU.

Results: A total of 328 Nuc treated patients were enrolled. The mean age was 54.3 yearold, 71% male, 37.5% cirrhotic, 27.8% with pretherapy HBeAg positivity, 15.5% with hepatic decompensation at SOT. During a median treatment duration of 2.68 (0.01-9.68) years, 20 patients lost to follow-up. The cumulative incidence of LTFU in 1-year, 2-years, 3-years, 4-years, and 5-years were 2.13%, 3.66%, 3.96%, 4.57%, and 5.49%, respectively (Figure). These patients refused to come back for drug refill or to pick up the repeated phone call. Those who LTFU were older (65.1 vs. 53.7 year-old, P < 0.001), higher proportion of FIB-4 score >3.25 (75% vs. 39.9%, P = 0.002) and with comorbidity (80% vs. 52.6%, P = 0.017) than those adhered to on-treatment monitoring and refill schedule.

Conclusions: This study documented the incidence and characteristics of patients LTFU during Nuc treatment. Even with call-back mechanism, the incidence was alarmingly high with the increasing duration of therapies. These LTFU patients may at risk of self-discontinuation related underdiagnosed severe flare which may be catastrophic if not promptly diagnosed and timely retreated.

P.024 OUTCOMES AFTER DISCONTINUATION OF NUCLEOS(T)IDE ANALOGUES THERAPY IN NON-CIRRHOSIS

CHRONIC HEPATITIS B PATIENTS: A SINGLE CENTER STUDY

Bi-Zhen Kao1, Ming-Yao Chen2

1Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taipei Medical University-Shuang Ho Hospital, New Taipei, Taiwan

慢性 B 型肝炎無肝硬化患者根據全民 健康保險藥物給付下抗病毒口服藥停

陳明堯 衛生福利部雙和醫院胃腸肝膽內科

Background: Relapses are observed in chronic hepatitis B patients (CHB) who discontinue treatment with nucleos(t)ide analogues (NA); however, the rates of relapse vary widely among studies, and whether all patients with relapse need retreatment is unclear and predictors of relapse still remain an unmet clinical need.

Aims: To determine outcomes after discontinuation of NA therapy and to identify predictors of relapse.

Methods: A retrospective study of non-cirrhotic CHB patients who was initiated NA therapy and discontinued under TASL guideline from 2010 to 2021 at Taipei medical university-Shuang Ho hospital.

Results: Among 213 non-cirrhotic CHB patients with NA treatment, 104 patients received entecavir (ETV) and 109 patients received tenofovir (TDF); 86 patients were positive for HBV e-Antigen (HBeAg) and 127 were negative for HBeAg. The viral relapse was defined as HBV DNA level > 2000 IU/mL and clinical relapse was defined as viral relapse combined with a twofold elevation of aminotransferase level from the upper limit of normal and/or acute decompensation. The median duration of therapy was 37 months and follow-up for at least 12 months after stopping NA treatment or until retreatment. During off-NAs follow-up, viral relapse was 49.2% (median duration: 12 months), retreatment was 31.9% (median duration: 13.5 months), six patients (2.8%) experienced

藥後之預後評估：單一中心的回顧研 究 高碧珍

HBsAg loss, 15 patients (7%) experienced liver decompensation but no patient died after timely retreatment. Cumulative viral relapse rates were 14%, 26%, and 51% at 3, 6 and 12 months, respectively, whereas cumulative retreatment rates were 7%, 19%, and 45% at 3, 6 and 12 months, respectively after NA cessation. The patients with off-TDF patients experienced sooner viral relapse than off-ETV patients. (median: 9 months Vs 14 months) and required earlier retreatment (11 months Vs 17 months), p < 0.001. The probabilities of retreatment in off-TDF patients Vs off-ETV patients was 74% Vs 39% within 1 year (p < 0.001). The relapse rate and duration were no difference between positive HBeAg positive and HBeAg negative patients. HBeAg seroconversion occurred 76.3% patients with median duration of 26 months and the patients treated with TDF were higher rate of HBeAg seroconversion than those with ETV (98.7% Vs 64.8%, p < 0.001). Older age and early viral relapse < 1 year were associated with probability of retreatment.

Conclusions: Our study showed that entecavir or TDF therapy can be safely discontinued in noncirrhotic CHB patients, however we should have pay attention to early relapse. The probability of relapse was earlier in off-TDF patients but no difference in relapse rate compared with off-ETV patients. Despite half of off-NA patients experienced viral relapses and 43% had clinical relapse, 37% viral relapse patients and 26% clinical relapse patients enters inactive state without retreatment. Further research are warranted to learn longterm outcomes of discontinuation under current therapies or longer treatment duration to achieve an optimal treatment goal.

Cheng-Er Hsu1, Wen-Juei Jeng1,2, Yi-Chung Hsieh1,2, Yen-Chun Liu1,2, Rong-Nan Chien1,2

1Department of Gastroenterology and Hepatology, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan

2College of Medicine, Chang Gung University, Taoyuan, Taiwan

Background: Hepatitis B virus (HBV) core-related antigen (HBcrAg) is a novel marker, reflecting the transcriptional activity of intrahepatic covalently closed circular (ccc)DNA levels. Recent study has proposed the utility of using HBcrAg in subjects who were seronegative for both HBsAg and anti-HCV (NBNC) for prediction of HCC in HBV endemic region, but little information in known for its predictability for HCC in chronic hepatitis B (CHB) patients who achieved HBsAg seroclearance.

Aims: To investigate the predictability of HBcrAg for HCC in chronic hepatitis B (CHB) patients who achieved HBsAg seroclearance.

Methods: CHB patients in Chang Gung Memorial Hospital, Linkou branch who had achieved HBsAg seroclearance naturally or after antiviral treatment or stopping Nuc were recruited. Patients who had HCC diagnosis before HBsAg seroclearance or within 6 months after HBsAg clearance were excluded. HBcrAg is assayed in blood sample collected at the time of HBsAg clearance. Host characteristics, biochemical blood tests and HBcrAg level at time of HBsAg clearance were compared between those with and without subsequently HCC development. Cox regression analysis was performed for HCC predictors.

Results: Among 202 CHB patients enrolled, 6 patients developed HCC after HBsAg clearance during a median follow-up time of 4.1 (0.27~19.49)

P.025 HEPATITIS B VIRUS CORERELATED ANTIGEN HAS NO ROLE IN PREDICTING HEPATOCELLULAR CARCINOMA DEVELOPMENT AFTER HBSAG CLEARANCE

B 型肝炎的表面抗原消失後，抗核抗 原無法預測後續的肝癌發生

years. Higher proportion of cirrhosis was observed in the HCC arm (HCC vs. non-HCC: 83.3% vs. 31.1%, P = 0.0072) while the other parameters, including HBcrAg level (median 200 U/ml, P = 0.4525), were comparable between those with and without HCC. Cox regression showed cirrhosis is the only factor for HCC development (HR: 11.07, 95% CI: 1.27-96.74, P = 0.03).

Conclusions: In CHB patients who achieved HBsAg clearance, HBcrAg has no role in predicting HCC.

P.026

LONG-TERM OUTCOMES AFTER CESSATION OF ANTIVIRAL THERAPY IN HBEAG NEGATIVE PATIENTS

Wen-Juei Jeng1,2, Yen-Chun Liu1,2, Chien-Wei Peng1,2, Rong-Nan Chien1,2,3, Yun-Fan Liaw2,3

1Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan, Taiwan

2College of Medicine, Chang Gung University, Taoyuan, Taiwan

3Liver research unit, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan, Taiwan

E 抗原陰性慢性 B 型肝炎患者停藥後 長期預後

2 長庚大學醫學院

Background: We reported a cohort of 691 HBeAg negative chronic hepatitis B patients who had stopping Nuc (Hepatology 2018) with a median follow-up duration about 3 years. We have extended the follow-up to a median of 6.6 (Q1Q3: 5-8.2) years and to examined the long-term outcome of these patients.

Aims: To examine the long-term outcome of HBeAg negative CHB patients receiving finite therapy by APASL stopping rule.

Methods: The 691 HBeAg negative CHB patients were followed-up till Dec 2021. Virological relapse (VR) was defined as HBV DNA > 2000 IU/mL and clinical relapse (CR) as VR plus ALT > 2X ULN. Retreatment decision was made according to the Taiwan reimbursement criteria: cirrhosis with detectable HBV DNA or non-cirrhosis with CR prolonged over 3 months or CR with serum bilirubin level > 2 mg/dL or INR > 1.5 or by joint physician/patient discussion. According to the clinical outcome and management, these patients were categorized into 4 groups: A: no CR and no retreatment(retx); B: no CR but retx; C: CR and no-retx; D: CR and retx.

Results: During a median of 6.6 years follow-up of this observational cohort, 180 (26%) were group

3 林口長庚紀念醫院肝臟研究中心

A, 27 (4%) were group B, 103 (15%) were group C and 381 (55%) were group D. The cumulative VR, CR, retreatment rate are listed in table. The annual HBsAg decline in group A-D was: -0.304, -0.144, -0.277, -0.205 log10 IU/mL, respectively. Among the 691 patients, 343 (49.6%) achieved HBsAg < 100 IU/mL (group A-D: 72.8%, 38.5%, 56.3%, 37.8%, respectively) and 112 (16.2%) achieved HBsAg loss by the end of follow-up. The 5 and 10-year cumulative HBsAg loss rate are: group A: 27%, 57%; group B: 0%, 6%; group C: 13%, 38%; group D: 3%, 11%, respectively. Among the retreatment group (N=407), 251 patients (61.7%) had completed additional course of finite therapy with a 10-year cumulative HBsAg loss rate (from the first EOT) of 15%, > 2 times higher than 6% in those still under continued treatment. The incidence of HCC and liver related mortality was very low, mostly occurs in cirrhotic patients (10year HCC: LC vs. non-LC: 11% vs. 2%; 10-year liver related mortality: LC vs. non-LC: 6% vs. 0%).

Conclusions: The finite therapy does much increase the functional cure rate, especially in those remain untreated. The HBsAg loss rate accelerated along with follow-up time, especially after year 3.

P.027

LIVER INJURY CAUSED BY SARSCOV-2 DELTA AND OMICRONVARIANT IN TAIWAN

Tyng-Yuan Jang, Chia-Yen Dai

Division of Hepatobiliary, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan

Delta 和 Omicron 新冠肺炎感染對肝 指數影響

戴嘉言 高雄醫學大學附設中和紀念醫院肝膽胰內科

Background: Recently, the Omicron variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has emerged and spread globally. Aims: We aimed to compare the liver injury of the patients with Delta variant and Omicron variant.

Methods: An outbreak of coronavirus disease 2019 (COVID-19) caused by the Delta variant occurred in Southern Taiwan in June 2021 and has been eliminated. However, the Omicron variant out broke in Taiwan in April 2022. We compared the clinical characteristics of the patients with Delta variant and Omicron variant.

Results: There were no differences of age (59.9 vs 57.1 years, P=0.96), male gender (63.6 vs 60.0 %, P=1.00), diabetes ratio (27.3 vs 35.7 %, P=1.00), body mass index (25.0 vs 26.0 kg/ m2, P=1.00), pneumonia ratio (18.2 vs 40.0 %, P=0.40) between the Delta and Omicron variant. There were also no differences in serum levels of aspartate aminotransferase (AST) (40.1 vs 25.8 IU/L, P=0.24) and alanine aminotransferase (ALT) (26.3 vs 27.2 IU/L, P=0.64) between the two groups. Among the patients, all patients were symptomatic. The most common symptoms were upper respiratory tract infection symptoms (60.0%) (supplementary table 1). Six patients developed pneumonia without mechanical ventilator support requirement during admission (40.0%). Remdesivir, Paxlovid or Molnupiravir were prescribed to patients according to their clinical conditions.

Conclusions: There were about one-fifth of patients who suffered from a liver injury in the study. There was no difference in liver injury between Delta and Omicron variants in our study.

IMPACT OF COEXISTENCE OF FATTY LIVER DISEASE IN PATIENTS WITH BREAST CANCER

Cheng-Chi Lee, Jen-Chieh Huang, Jeng-Shiann Shin, Chi-Hung Chen, Hung-Yao Chen-Cheng, Shih-Chi Ho

Division of Gastroenterology & Hepatology, Department of Internal Medicine, Cheng

Ching General Hospital Chung Kang Branch, Taichung, Taiwan

P.029

PAN-GENOTYPIC

AGENTS FOR UNDETERMINED OR MIXED-GENOTYPE HEPATITIS C INFECTION: A REAL-WORLD MULTI-CENTER EFFECTIVENESS ANALYSIS

Pei-Yuan Su1, Yang-Yuan Chen1,2, Jun-Hung Lai3, Hung-Ming Chen4, Chih-Ta Yao5, Hsu-Heng Yen1

1Division of Gastroenterology and Hepatology, Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan

Background: Fatty liver disease is one of the most common chronic liver diseases in the world. Breast cancer is the most common cancer among women worldwide and in Taiwan. An increasing incidence of breast cancer is noted in recent years by epidemiological studies. During the follow up using ultrasonography, many women with breast cancer were found to have fatty liver.

Aims: The aim of this study was to investigate the association between fatty liver and breast cancer.

Methods: From January 2001 to June 2020, 561 patients were diagnosed with tissue-proven breast cancer at the Cheng-Chin general hospital Chung-Gang branch. Ultrasonography was performed using a 3.5mHz transducer. Patients were evaluated on the basis of age, BMI, clinical variables, coexistence of viral hepatitis, survival time, stage and use of hormone therapy. Data were statistically analyzed using the chi-squared test & student’s t-test. Analysis of survival was performed using the Kaplan-Meier method.

Results: Demographic data including average age, BMI, clinical laboratory data, coexistence of viral hepatitis, use of hormone therapy and severity of fatty liver are summarized in table 1 and table 2. The severity of fatty liver disease in patients with breast cancer did not influence the prognosis (figure 1). But poorer prognosis was noted among breast cancer patients with fatty liver treated with tamoxifen and coexistence of viral hepatitis in the subgroup analysis (figure 2).

Conclusions: The survival was not influenced by the severity of fatty liver in patients with breast cancer.

2Division of Gastroenterology, Department of Internal Medicine, Yuanlin Christian Hospital, Changhua, Taiwan

3Division of Gastroenterology, Department of Internal Medicine, Erhlin Christian Hospital, Changhua, Taiwan

4Division of Gastroenterology, Department of Internal Medicine, Yunlin Christian Hospital, Yunlin, Taiwan

5Division of Gastroenterology, Department of Internal Medicine, Lukang Christian Hospital, Changhua, Taiwan

5

Background: Although the pan-genotypic directacting antiviral regimen was approved for treating chronic hepatitis C infection regardless of the hepatitis C virus (HCV) genotype, real-world data on its effectiveness against mixed-genotype or genotype-undetermined HCV infection are scarce. Aims: We evaluated the real-world safety and efficacy of two pan-genotypic regimens for HCVinfected patients with mixed or undetermined HCV genotypes from the five hospitals in the Changhua

脂肪肝的存在對乳癌患者的影響 李政祺 黃仁杰 辛政憲 陳季宏 陳鄭弘堯 何士奇 澄清綜合醫院中港分院胃腸肝膽科

DIRECTACTING ANTIVIRAL

Christian Care System that commenced treatment between August 2018 and December 2020.

Methods: This retrospective study evaluated the efficacy and safety of the pan-genotypic directacting antiviral (DAA) treatment in adults with HCV infection. The primary endpoint was the sustained virological response (SVR) observed 12 weeks after completing the treatment.

Results: Altogether, 2446 HCV-infected patients received the pan-genotypic DAA regimen, 37 (1.5%) patients had mixed-genotype HCV infections and 110 (4.5%) patients had undetermined HCV genotypes. The mean age was 63 years and 55.8% of our participants were males. Nine (6.1%) patients had end-stage renal disease and three (2%) had co-existing hepatomas. We lost one patient to follow during the treatment and four died; however, none of these losses were due to treatment-related side effects. The rates of SVR12 for mixed-genotype and genotype-undetermined infections were 97.1% and 96.2%, respectively, by per-protocol analyses, and 91.9% and 92.7% respectively, by intention-to-treat population analyses. Laboratory adverse events with grades ≥3 included anemia (2.5%), thrombocytopenia (2.5%), and jaundice (0.7%).

Conclusions: Pan-genotypic DAAs are effective and well-tolerated for mixed-genotype or genotypeundetermined HCV infection real-world settings.

P.030

SAFETY AND EFFECTIVENESS USING 8 WEEKS OF GLECAPREVIR/PIBRENTASVIR IN HCV-INFECTED TREATMENT-NAIVE PATIENTS WITH COMPENSATED CIRRHOSIS: THE CREST STUDY

Cornberg M1, Ahumada A2, Aghemo A3, Andreoni M4, Bhagat A5, Butrymowicz I5, Carmiel M6, Chodick G7,8, Conway B9, Fang Y5, Gasbarrini A10, Hüppe D11, Jorquera Plaza F12, Lampertico P13,14, Manzano Alonso ML15, Myles L16, Persico M17, Ramji A18, Sarrazin C19, Villa E20, Weil C7,8, Uriz Otano JI21,22

1Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany; 2Liver Unit, Hospital General Universitario Gregorio Marañón, Madrid, Spain; 3Department of Biomedical Sciences, Humanitas University, and Department of Gastroenterology, Humanitas Research Hospital IRCCS, Rozzano, Italy; 4University of Tor Vergata, Rome, Italy; 5AbbVie Inc., North Chicago, IL, USA; 6Liver Unit, Galilee Medical Center, Nahariya, Israel. The Azrieli Faculty of Medicine, BarIlan University, Zefat, Israel; 7Maccabitech, Maccabi Healthcare Services, Tel-Aviv, Israel; 8Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel; 9Vancouver Infectious Diseases Center and Simon Fraser University, Vancouver, Canada; 10Internal Medicine and Gastroenterology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy; 11Gastroenterologische Gemeinschaftspraxis Herne, Herne, Germany; 12Aparato Digestivo, Complejo Asistencial Universitario de León, León, Spain; 13Foundation IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Division of Gastroenterology and Endoscopy, Milan, Italy; 14CRC “A. M. and A. Migliavacca” Center for Liver Disease, Department of Pathophysiology and Transplantation, University of Milan, Milan, Italy; 15Liver Unit, Hospital Universitario 12 De Octubre, Madrid, Spain; 16Barrie GI Associates, Barrie, Ontario, Canada; 17Dipartimento di Medicina Clinica Medica, Epatologica e

Lungodegenza, AOU OO. RR. San Giovanni di Dio Ruggi e D’Aragona, Salerno, Italy; 18University of British Columbia, Vancouver, BC, Canada; 19Department of Internal Medicine and Livercenter, St. Josefs-Hospital Wiesbaden and Viral Hepatitis Research Group, Goethe-University Hospital Frankfurt, Frankfurt, Germany; 20UC Gastroenterologia, Dipartimento di SpecialitàMediche, Azienda Ospedaliera Universitaria di Modena, Modena, Italy; 21Navarra Institute for Health Research (IdiSNA), Pamplona, Spain; 22Department of Gastroenterology, Liver Unit, Complejo Hospitalario de Navarra, Pamplona, Spain

Background: Glecaprevir/pibrentasvir (G/P), a direct-acting antiviral combination approved for the treatment of chronic hepatitis C genotypes (GT) 1–6 in patients with or without compensated cirrhosis (CC), has treatment as short as 8 weeks in most cases.

Aims: To further corroborate registrational trial findings in real-world cohorts, this study investigated effectiveness and safety of 8-week G/P therapy in treatment-naïve (TN), CC patients, with an emphasis on those with advanced liver disease (platelets < 150,000 /µl, FibroScan > 20 kPa, or both platelets < 150,000 /µl and FibroScan > 20 kPa) and patients with GT3 infection.

Methods: CREST is an ongoing, noninterventional, multicenter, observational study. Data were collected from 5 countries (Canada, Germany, Israel, Italy, Spain) for TN, CC patients (with documented Child-Pugh A cirrhosis). In this interim analysis, safety and laboratory abnormalities were assessed on the full analysis set (FAS); effectiveness was reported as sustained virologic response at post-treatment week 12 (SVR12) in the modified analysis set (MAS), excluding patients lost to follow-up and those who discontinued G/P for reasons other than virologic failure.

Results: Of 386 patients receiving ≥1 dose of G/P, 26.2% (101/386) had GT3, 45.7% (166/363) had platelets < 150,000 /µl, 13.4% (45/335) had FibroScan > 20 kPa and 8.2% (27/331) had platelets < 150,000 /µl and FibroScan > 20 kPa. Overall, 26.9% (104/386) of patients experienced an adverse event (AE): 1.3% (n=5) were serious and 0.3% (n = 1) of AEs resulted in drug discontinuation. The most frequent AEs (> 5%) were fatigue (9.8%) and headache (6.2%).

Of patients with documented laboratory values during treatment (N=370), one patient (0.3%) had an aspartate aminotransferase > 5x upper limit of normal. Of patients in the MAS with data available, 99.1% (322/325) reached SVR12. In subgroups of interest, MAS SVR12 rates in patients with GT3, patients with platelets <150,000 /µl, patients with FibroScan > 20 kPa or both, platelets <150,000/ µl and FibroScan > 20 kPa, were 97.5% (78/80), 99.3% (143/144), 100.0% (39/39) and 100.0% (24/24), respectively.

Conclusions: In this real-world cohort, 8-week G/P therapy was well-tolerated. SVR12 rates were similar to clinical trials, supporting 8-week treatment in TN, CC patients, including those with signs of advanced liver disease and GT3 patients. Additional efficacy data in the overall study population will be presented at the meeting.

P.031 SHORTER DURATION HEPATITIS C VIRUS

TREATMENT

IS ASSOCIATED WITH BETTER PERSISTENCE TO PRESCRIPTION FILLS IN PEOPLE WHO INJECT DRUGS

Anthony Martinez1, Wei-Han Cheng2, Steven E Marx2, Shivaji Manthena2, Emmanuel Thomas3

1Department of Medicine, University at Buffalo, State University of New York, Buffalo, New York, USA

2AbbVie Inc., Mettawa, Illinois, USA

3Sylvester Comprehensive Cancer Center, Miller School of Medicine, University of Miami, Miami, Florida, USA

Background: A large portion of global hepatitis C virus (HCV) burden is attributable to injection drug use, yet people who inject drugs (PWID) often face many treatment adherence challenges. Simplifying treatment may support efforts to achieve HCV elimination in this population.

Aims: To understand how shorter durations affect medication persistence in PWID, which may impact rates of achieving sustained virologic response and HCV cure.

Methods: This retrospective study assessed treatment persistence using data from the Symphony Health Solutions administrative claims database collected between 08/2017 and 11/2020. Patients ≥12 years of age with a written and authorized 8- or 12-wk prescription for a direct-acting antiviral (DAA) were included. The date of the first prescription fill was the index date; eligible patients recorded a claim during the 6-months pre-index and 3-months post-index and had a diagnosis of illicit drug use within 6 months before a diagnosis of chronic HCV. Patients with acute HCV, hepatic failure or decompensation, or prior HCV treatment were excluded. Patients had a DAA prescription for 28 days that had 1 refill in the 8-wk group and 2 refills in the 12wk group. Patients completing their refills were deemed persistent; the percentage of persistent patients was compared between groups by chisquare test. Propensity score matching was used to match 8-wk and 12-wk groups 1:1 by baseline characteristics (ie, age, gender, region, index year, insurance type, and comorbidities) and probability

of persistence between groups was estimated by logistic regression analysis.

Results: This study enrolled 7203 PWID (8wk: N=4002; 12-wk: N=3201). Mean patient age was 43 and 48 years for 8- and 12-wk groups, respectively. More patients prescribed an 8-week DAA were female (8-wk: 46% vs. 12-week: 40 %) and Medicaid-insured (8-wk: 78% vs. 12-wk: 65%). All patients had mental/behavioral disorders due to psychoactive substance abuse at baseline. Overall, patients receiving 8-wk vs 12-wk DAA had significantly greater refill persistence (88% vs 64%, p<0.05). Similar percentages of patients missed their first refill (8-wk: 12% vs 12-wk: 11%), whereas 25% of patients receiving 12-wk DAA missed their second refill. Propensity-matched results demonstrate similar persistence findings (8-wk: 88% vs 12-wk: 62%, p<0.05). Patients prescribed 8-wk vs 12-wk DAA were more likely to be persistent (odds ratio [95% confidence interval]: 4.3 [3.8, 5.0]).

Conclusions: Patients treated with 8-wk DAA had significantly greater refill persistence than those prescribed 12-wk DAA treatment, highlighting the benefit of shorter-treatment duration in an HCVinfected PWID population.

P.032 OUTCOMES OF HEPATITIS C VIRUS-RELATED HEPATOCELLULAR CARCINOMA IN DIRECT-ACTING ANTIVIRAL ERA

Kuo-Hsuan Huang1, Tsung-Hui Hu1, Chao-Hung Hung1, Kuo-Chin Chang1, Chih-Chi Wang2, Yueh-Wei Liu2, Ming-Chao Tsai1

1Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan

2Division of General Surgery, Department of Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan

型肝炎導致之肝細胞癌於 DAA 世代

2 高雄長庚紀念醫院一般外科

Background: It remains controversial whether hepatocellular carcinoma (HCC) recurrence in hepatitis C virus (HCV)-infected patients can be suppressed by the elimination of the virus using direct-acting antivirals (DAAs).

Aims: This study aimed to evaluate the sustained inhibitory effect on HCC recurrence following radical treatment in different era of HCV treatment (non-DAA (2001-2014) and DAA (2015-2019)).

Methods: This single center retrospective study included 708 radical resection cases of hepatitis C virus (HCV)-related HCC (HCV-HCC) in early stage (BCLC stage 0/A) between 2001 and 2019 at Kaohsiung Chang Gung Memorial Hospital. Regarding to the timing of surgery, patients were classified into the non-DAA era group (2001-2014, n = 425) and the DAA era group (2015-2019, n = 283). Recurrence free survival (RFS) following radical resection in each group was analyzed using the Kaplan Meier method and log rank test. A Cox proportional hazards model was used to analyze the factors that affected RFS and OS.

Results: In non-DAA era, 111 patients (26.1%)

were treated by interferon, while in DAA era, 134 patients (47.3%) received DAAs treatment (p < 0.05). The cumulative incidence of HCC recurrence was significantly lower in the DAA era than in nonDAA era (p < 0.001), but there was no statistically significant difference in OS. After excluding 29 patients who received antiviral therapy after HCC recurrence, recurrence rate was significantly lower in the antiviral therapy group (interferon-based or DAA) than in the non-antiviral therapy group (p < 0.001). In multivariate analysis, antiviral therapy was independently associated with reduced HCC recurrence (HR: 1.71; p < 0.001).

Conclusions: In HCV related early-stage HCC, antiviral treatment is associated with lower risk of HCC recurrence. Furthermore, with the use of DAA therapy, an increasing of proportion of HCVrelated HCC have been successfully treated, resulting a significant reduction in the risk of HCC recurrence in the DAA era than in non-DAA era.

P.033 HEPATITIS C VIRUS REINFECTION INCIDENCE IN PATIENTS WITH END STAGE RENAL DISEASE ON

MAINTAIN HEMODIALYSIS

FOLLOWING ACHIEVING 12 WEEKS

SUSTAINED VIRAL RESPONSE BY DIRECT-ACTING ANTIVIRALS

Kuang-Chen Huang, Li-Wei Chen, Jia-Jang Chang, Chun-Yu Chen

Keelung Chang Gung Memorial Hospital, Keelung, Taiwan

C 型肝炎併有末期腎臟疾病洗腎患者

達到 SVR12 後的再感染率

黃冠程

基隆長庚紀念醫院胃腸肝膽科系

Background: Patients with end stage renal disease (ESRD) on maintain dialysis have higher prevalence of hepatitis C virus (HCV) infection than normal people. Although direct-acting antivirals (DAAs) have a high HCV eradicated rate in patients with ESRD, HCV reinfection following achieving 12 weeks sustain viral response (SVR12) after DAAs should be surveyed.

Aims: This study aimed to evaluate the HCV reinfection rate within 3 years after achieved SVR12 in ESRD patients with maintenance hemodialysis.

Methods: In this retrospective study, maintenance hemodialysis patients with hepatitis C infection in the Keelung Chang Gung Memorial hospital were included from March 2019 to December 2021. Patients who were treated with 12 weeks DAAs were included in this study. After achieved SVR12, they received additional 3 years HCV RNA and genotype follow up measurements.

Results: Total 41 patients were included (21, 51% females). Table 1 revealed the demographic data. Three patients did not complete treatment and not achieve SVR12. Among the left 38 patients, all achieved SVR12. However, HCV RNA was detected in 4 patients within 3 years after achieving SVR12. The incidence of HCV reinfection after SVR12 was 3.5% [4/(38*3)*100%] person-year in patients with maintenance hemodialysis in our hospital. Two of these 4 patients got a different genotype of HCV (from genotype 1b into 2). Three out of these 4 patients received re-treatment with

Maviret. All of three patients achieved SVR12 later. Conclusions: Patients with maintain hemodialysis and HCV infection got a high eradicated rate of HCV post DAAs (total 92.7%, 38/41; complete drug therapy 100%, 38/38). The incidence of HCV reinfection after SVR12 was 3.5% person-year in patients with maintenance hemodialysis in our hospital.

陳立偉 張家昌 陳俊宇

HEPATITIS C MICRO-ELIMINATION THROUGH RETRIEVAL OF PATIENTS LOST TO FOLLOW-UP PLAN

Cheng-Jen Chen, Yung-Hsin Huang, Chao-Wei Hsu, Yi-Cheng Chen, Ming-Ling Chang, Chun-Yen Lin, Yi-Hsien Shen, Rong-Nan Chien

Division of Hepato-Gastroenterology, Department of Internal Medicine, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan

經由失聯病患叫回計劃達成 C 型肝炎 微消除

lived in Taoyaun City or had tested positive for antiHCV Ab at the department of internal medicine department had an increased rate of successful call back. There were 563 patients (44.1%) returning to our GU. Of them, 354 patients (62.9%) were positive for HCV viremia. 323 patients (91.2%) received the DAAs treatment.

Conclusions: Call back system can expand our reach to those unaware or ignoring chronic HCV infection patients and link them to treatment.

林口長庚紀念醫院胃腸肝膽科

Background: World Health Organization sets up an ambitious and attainable goal to eliminate hepatitis C (HCV) by 2030. The previous diagnosed HCV patients lost to follow-up were considered as an important target group for HCV elimination.

Aims: We conducted a call back program to retrieve the lost to follow-up HCV patients and link them to care in our hospital. By analyzing and comparing our result with that from other studies, we wish to improve our retrieval strategy and provide our experience to the general communities.

Methods: A list of the patients with a medical record showing seropositive for antibody to HCV (anti-HCV Ab) from 2004 to 2017 was retrieved by the department of intelligent technology of our hospital. Three dedicated staff members reviewed the patients’ electronic medical records (EMRs) and recruited the patient lost follow-up to the call back program. The staff members contacted the qualified patients by telephone and inquired about their opinions for treating their chronic HCV infection. Referrals to our gastroenterology unit (GU) were arranged for the patients who would like to continue their chronic HCV care in our hospital.

Results: There were 31275 anti-HCV positive patients. We included 11934 patients (38.2%) into the call back system and contacted them by telephone. Based on the response to our call, we ascertained 1277 eligible cases (10.7%) for retrieval. The patients who were younger (<55),

陳正仁 黃永信 許朝偉 陳益程 張明鈴 林俊彥 沈一嫻 簡榮南

P.035

EFFECT ON FIBROSIS AND ASSOCIATED BIOMARKERS OF CHRONIC HEPATITIS C AFTER DIRECT-ANTIVIRAL AGENTS’ THERAPY: A HOSPITAL STUDY

Hung-Ting Chung1, Jui-Ting Hu1,2, Hsin-Yi Chen1, Chia-Long Lee1,3, Chih-Sheng Hung1,2, Sien-Sing Yang1,2

1Division of Digestive Medicine, Cathay General Hospital Medical Center, Taipei, Taiwan

2School of medicine, College of Medicine, Fu-Jen Catholic University, New Taipei City, Taiwan

3School of medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan

口服抗病毒藥物對 C 型肝炎患者之肝 纖維化及相關肝功能之影響：單一醫 學中心之研究

鍾鴻鼎1 胡瑞庭1,2 陳信宜1 李嘉龍1,3 洪志聖1,2

楊賢馨1,2

1 國泰綜合醫院消化內科

2 輔仁大學醫學院醫學系

3 臺北醫學大學醫學院醫學系

Background: Chronic hepatitis C virus (HCV) infection represents a liver disease with gradual progression towards cirrhosis and hepatocellular carcinoma (HCC). In Taiwan, Chronic hepatitis C infection affects more than half a million people. Direct-acting antiviral agents (DAAs) is a main current treatment for the HCV patient.

Aims: The present study investigated the temporal effect of post-DAAs therapy on the noninvasive index values (liver function test and fibrosis score) and BMI (Body Mass Index) of patients with CHC. The laboratory tests and fibroscan tests at baseline, end of therapy (EOT), 12 weeks, 24 weeks and 1 year to about 4~5 years after therapy were performed and collected.

Methods: We retrospectively enrolled consecutive patients with CHC who had received DAAs from 2016 to 2017. A total of 106 consecutive patients were enrolled. The biochemical markers (AST, ALT, total bilirubin) and fibrosis score (measured in kilopascals (kPa)) was documented. The median level of post-treatment was compared with pre-

treatment level using paired t-test with EXCEL. A two-sided P value of < 0.05 was considered statistically significant.

Results: A total of 106 patients were included in our study from 2016 to 2017. In patients received DAA therapy who achieved SVR12, the median AST (72.7 U/L), ALT (94.0 U/L) level after therapy decreased significantly (post-DAA 1 year: AST: 32.7 U/L, ALT: 29.3U/L, 4~5 years: AST: 39.1 U/L, ALT: 32.9 U/L, P < 0.05) and sustainably compared with pre-treatment level but not total bilirubin. The mean fibrosis score decreased significantly from 17.3 (kPa) before treatment to 15 (kPa) after finish of treatment and to 9.2 (kPa) after 4~5 years after therapy (P < 0.05). Decrease of the percentage of cirrhosis (F4) and severe fibrosis (F3) stage was noted (Pre-treat: F4:42%, F3:35%, EOT: F4:36%, F3:24%, 4~5 years after DAA: F4:14%, F3:17%).

No significant change was found before and after DAA therapy in BMI (pre-DAA therapy: 24.9 kg/m2, 1 year after DAA: 24.3 kg/m2, P > 0.05), however.

Conclusions: In conclusion, our study showed sustained decrease in liver function test (AST, ALT) and improvement of fibrosis score after DAA therapy However, no significant causal relationship (decrease or increase) regarding BMI value before and after DAA treatment was found.

P.036

HIGHER HEPATOCELLULAR CARCINOMA RISK IN DIRECTACTING ANTIVIRAL AGENTS TREATED CHRONIC HEPATITIS C WITH HIGHER ALPHAFETOPROTEIN

Yen-Chun Liu1,2, Wei-Ting Chen1,2, Cheng-Er Hsu1,2, Ya-Ting Cheng1,2, Chung-Wei Su1,2, Chia-Hung Tai1,2, Yi-Cheng Chen1,2, Yi-Chung Hsieh1,2, Wei Teng1,2, Wen-Juei Jeng1,2, Chun-Yen Lin1,2

1Department of Gastroenterology and Hepatology, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan

2Chang Gung University, Taoyuan, Taiwan

C 型肝炎口服抗病毒藥使用前甲

without ACLD.

Results: Among 1596 enrolled patients with median follow-up duration of 29 (0.3-73) months, the mean age was 62 years old, 40% patients were male, 67% were HCV genotype 1 and 58% had ACLD. The optimal cut-off value of pretherapy AFP for HCC prediction was 6 ng/mL. Multivariate cox regression showed male [adjusted hazard ratio (aHR): 2.38 (1.48-3.84), P < 0.01] and AFP ≥ 6 ng/mL [aHR: 2.44 (1.32-4.53), P < 0.01] were predictors for HCC occurrence while ACLD showed borderline significant [aHR: 2.78 (0.977.96), P = 0.06]. The 4-year cumulative and annual HCC incidences was highest in ACLD patients with AFP ≥ 6 ng/mL (11.8% and 4.2%) followed by non-ACLD with AFP ≥ 6 ng/mL (2.9% and 2.1%), ACLD with AFP < 6 ng/mL (2.87% and 1.2%), and then non-ACLD with AFP < 6 ng/mL (0.2% and 0.08%) (Log-rank P < 0.001) (Figure). The sensitivity and negative predictive value (NPV) of AFP ≥ 6 ng/mL for HCC occurrence were both good in patients with and without ACLD (ACLD: sensitivity 78%, NPV 97%; non-ACLD: sensitivity 75%, NPV 99.8%), while the AUROCs in patients with non-ACLD showed numerically better than ACLD patients (0.88 vs. 0.68, P = 0.22).

Background: Alpha fetoprotein (AFP) has been reported as a biomarker for hepatocellular carcinoma (HCC) surveillance. It is unknown whether AFP is useful to stratify HCC risk of the non-advanced chronic liver disease (ACLD) population among chronic hepatitis C(CHC) patients achieving sustained virological response (SVR).

Aims: The study aimed to investigate the possibility of utilizing AFP for HCC risk stratification in CHCSVR patients with and without ACLD.

Methods: CHC patients achieved SVR by directacting antiviral agents (DAA) without HCC history before starting DAA in Chang Gung Memorial Hospital, Linkou branch, were enrolled. The ACLD was defined as LSM > 10 kPa and/or FIB-4 > 3.25 and/or ultrasound signs of cirrhosis before the start of DAA therapy. The optimal cutoff of AFP was estimated by Youden Index. The cumulative HCC incidences were calculated by Kaplan-Meier Method. Cox regression was applied to find the predictors for HCC occurrence, and predictabilities of AFP were compared between patients with and

Conclusions: CHC patients with ACLD and pretherapy AFP ≥ 6 ng/mL had the highest HCC risks while those with non-ACLD and AFP < 6 ng/mL were the least likely for HCC. Non-ACLD patients with AFP ≥ 6 ng/mL are still at high risk of HCC and warrant regular HCC surveillance.

P.037

FACTORS ASSOCIATED WITH TREATMENT FAILURE OF DIRECTACTING ANTIVIRAL DRUGS FOR CHRONIC HEPATITIS C: REALWORLD DATA OF A MEDICAL CENTER IN TAIWAN

Pin-Yi Wang, Chun-Chi Yang, Hsing-Tao Kuo, Ming-Jen Sheu

Department of Internal Medicine, Chi Mei Medical Center, Tainan, Taiwan

EOT but detectable thereafter). We calculated the cure rate of hepatitis C. We also reviewed these DAA treatment failure patients about their viral genotype and other characteristics, including liver cirrhosis (defined by FIB-4 score or image) and resistance-associated substitutions.

Background: Hepatitis C virus causes chronic hepatitis and progression to chronic liver disease and cirrhosis. With the advent of new directacting antiviral (DAA) therapies, the HCV cure rates remain more than 95%. The various factors, which may result in the failure of DAA therapy, are not exactly known. According to recent reports, genotype 3 infection seemed to have higher treatment failure rate compare to other genotype. Liver cirrhosis was also a risk factor of treatment failure. DAA treatment schedule was affordable since 2017 in Taiwan. Although DAA drugs are associated with high cure rate (>95%), few cases of treatment failure was not fully explained.

Aims: We reviewed DAA treatment failure patients in a single medical center in Taiwan, to analyze factors which possible influence DAA treatment failure.

Methods: We conducted a study in a single medical center in Taiwan about DAA treatment patients during the recent 5 years (from 2017 January to 2021 December). Including criteria were (1) anti-HCV antibody seropositive and detectable HCV viral load, (2) DAA naive patients, (3) treatment completed in our hospital. Among these patients, we excluded (1) no medical compliance, (2) expired or loss follow up. They were treated with affordable DAAs in our hospital, including Viekira, Harvoni, Maviret, or Epclusa. Patients with liver decompensation were treated with combination therapy (DAA plus ribavirin). We defined DAA treatment failure as (1) no reached SVR12, and (2) relapse (HCV-RNA suppressed at

Results: Totally, 1975 patients in our hospital recieved DAA treatment during 2017 January to 2021 December. 67 patients were excluded according to the above criteria. 1860 patients accomplished DAA treatment with sustained virological response at 12 weeks (SVR 12). The cure rate was 97.5%. 48 patients had treatment failure. Of these patients, mean age was 59 years, 58% (n = 28) were male, the average ALT level was 71.5 U/L, the average bilirubin level was 0.83 mg/dL. 8 patients had coinfection with hepatitis B, and 7 patients had coinfecion with HIV. Their genotype was predominantly genotype 2 (n = 23, 23/48 = 54%), second most was genotype 1 (n = 11, 11/48 = 23%), and genotype 6 was ranked the third (n = 10, 21%). Genotype 3 accounted for 6% (n = 3, 3/48 = 6%). Among genotype 6 infection patients, 40% had coinfection with HIV (n = 4, 4/10 = 40%), 20% used to be drug abuser (n = 2, 2/10 = 20%), and none of them was the same person. 31% (n = 15, 15/48 = 31%) had liver cirrhosis. Resistance-associated substitutions was available only in 12 patients.

Conclusions: DAA treatment had high cure rate. The factors influenced treatment failure could be viral genotype, underlying liver cirrhosis or other factors, such as resistance-associated substitutions.

C 肝病毒藥物治療失敗相關因

楊畯棋 郭行道 許銘仁

P.038

THE

BENEFITS AND SUSTAINABILITY OF SUSTAINED VIROLOGIC RESPONS (SVR) AFTER HCV ERADICATION

AMONG UREMIC PATIENTS ON MAINTENANCE HEMODIALYSIS

Yu-Ju Wei1,2,3, Chung-Feng Huang1,5, Chia-Yen Dai1,5, Jee-Fu Huang1,5, Yi-Wen Chiu4,5, Shang-Jyh Hwang4,5, Wan-Long Chuang1,5, Ming-Lung Yu1,5

1Division of Hepatobiliary, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan

2Department of Internal Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung, Taiwan

3Graduate Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan

4Division of Nephrology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan

5Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan

to maintain hemoglobin concentration.

Aims: The aim of this study is to evaluate the impact of HCV eradication on anemia, nutrition status and the sustainability of sustained virologic respons (SVR) after HCV eradication in hemodialysis patients.

Methods: We included 93 uremia patients with SVR12 from the 18 hemodialysis centers of the outreach onsite treatment program of HCV. Serum hemoglobin and albumin were evaluated in 12, 24, and 48 months after DAA therapy course. HCV RNA was determined at post-treatment week 24 and 48 among patients who achieved SVR12. EPO consumption was recorded before and after treatment.

2 高雄市立大同醫院內科部

3 國立中山大學生物醫學研究所

4 高雄醫學大學附設中和紀念醫院腎臟內科

Background: HCV infection frequently leads to liver complications and non-liver complications. Some HCV infected special populations including uremia patients were not treated due to side effects and lower efficacy of interferon. In the DAA era, more patients were cured of hepatitis C virus (HCV) infection, and long-term outcome of virologic response in uremia population was unknown. Uremia patients are almost anemic and require regular erythropoietin (EPO) administration

Results: Among 93 HCV infected uremia patients with SVR12, the baseline hemoglobin was 10.05 ± 1.27 (g/dL), the mean erythropoietin (EPO) consumption per month was 16538.17 ± 9750 (U) and the mean albumin was 3.74 ± 0.25 (g/dL). The hemoglobin (g/dL) was 10.42 ± 1.37 (P = 0.61), 10.35 ± 1.35 (P = 0.42), and 10.47 ± 1.29 (P = 0.72) in 3, 6, 12 months after DAA treatment. The dose of EPO increased to 16581.40 ± 11779.81 (U) after DAA treatment 6 months (M6). The Albumin (g/dL) increased in 3, 6, 12 months after DAA treatment: 3.81 ± 0.32 (P = 0.02), 3.8 ± 0.25 (P = 0.01), 3.98 ± 0.39 (P = 0.00), respectively. Age (P = 0.05), BMI (P = 0.02) and liver fibrosis stage (P = 0.03) was associated with albumin improvement one year after DAA treatment in univariate analysis. In multivariate analysis, liver fibrosis stage (F0-F2) was associated with albumin improvement after DAA treatment with SVR. HbA1c (P = 0.04) and age (P = 0.01) were associated with change of albumin level in univariate analysis, but only age was associated with change of albumin in multivariate analysis. The rate of undetectable HCV RNA was 100% (91/91), and 100% (78/78), respectively at post-treatment week 24 and 48.

Conclusions: No patients experienced HCV RNA reappearance during follow up. The albumin level, but not EPO consumption, significantly improved after HCV eradication in uremia patients on hemodialysis.

5 高雄醫學大學醫學院

EFFECTIVENESS OF REPEATED HEPATITIS C IN-HOSPITAL CALL-BACK PROGRAM IN LOW PREVALENCE REGION OF TAIWAN

Chen-Ta Chi1,2, I-Cheng Lee1, Keng-Hsin Lan1, Chi-Jen Chu1, Chien-Wei Su1, Ming-Chih Hou1, Yi-Hsiang Huang1,2

1Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan

2Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan

respectively after sending the first call-back letter. As compared with the 444 patients with successful call-back, remote anti-HCV testing, longer distance from hospital, and non-internal medicine outpatient department patients were associated with call-back failure. For the second call-back, the call back rate, HCV RNA test rate, HCV RNApositive rate, and DAAs implementation rate were 5.0% (68/1363), 92.6% (63/68), 44.4% (28/63), and 85.7% (24/28), respectively. The distribution of HCV genotypes (GT) for GT1a/1b/2/3/6 was 7.0%/47.4%/33.5%/1.7%/3.5%, and 6.9% of them were unclassified. Only one patient did not achieve sustained virological response by DAAs. Independent factors associated with detectable HCV RNA were age ≤ 50 years old (OR, 1.834; p = 0.032; 95% CI, 1.053 – 3.195) and anti-HCV testing date within 2 years (OR, 2.099; p = 0.001; 95% CI, 1.351 – 3.260). Of the 27 patients with age ≤ 50 years old and anti-HCV test date within 2 years, the HCV RNA positive rate was 74.1%.

Background: The implementation of direct-acting antivirals (DAAs) has dramatically decreased the viremic patients with hepatitis C virus (HCV) infection. However, it is estimated that significant portion of HCV-infected patients still unaware their disease with a gap linking to treat. Callback program is one strategy to achieve microelimination in hospital, but its effectiveness is varied due to a low call-back rate. Whether repeated call-back program works for patients who did not respond to initial call deserves exploration.

Aims: To access the index of care cascade in a repeated call-back program, and explore the features of responders.

Methods: From September 2013 to December 2019, 4938 anti-HCV antibody-positive patients in Taipei Veterans General Hospital (a tertiary medical center in North Taiwan) were retrospectively enrolled into the in-hospital call-back program. After exclusion, 2501 patients were eligible for call-back. For patients who didn’t come back by the first call, we resend the call-back letter one year later. The features of patients with successful call-back and predictors of HCV viremia were also investigated.

Results: The call-back rate, HCV RNA test rate, HCV RNA-positive rate, and DAAs implementation rate were 17.8% (444/2501), 70.5% (313/444), 52.7% (165/313), and 90.3% (149/165),

Conclusions: In-hospital call-back program can repeat once, even though the call-back rate was suboptimal by the second call-back. Prioritization by age and anti-HCV test date is cost-effectiveness for a call-back program.

2 國立陽明交通大學臨床醫學研究所

P.040

PCSK9 INHIBITION AMELIORATES OXIDATIVE STRESS AND HYPERLIPIDEMIA IN BILIARY CIRRHOTIC RATS

Ching-Chih Chang1,2, Hui-Chun Huang1,2, Shao-Jung Hsu1,2, Chiao-Lin Chuang1,2, Ming-Chih Hou1,2, Fa-Yauh Lee1,2

1Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan

2Faculty of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan

PCSK9 抑制可改善肝硬化大鼠氧化壓 力及高血脂症

hepatic inflammation, intrahepatic angiogenesis, liver fibrosis and free cholesterol accumulation in the liver of BDL rats.

Conclusions: PCSK9 inhibition by alirocumab treatment ameliorates hyperlipidemia and systemic oxidative stress in biliary cirrhotic rats. However, it does not affect the plasma level of ox-LDL, intrahepatic inflammation and fibrosis. In addition, PCSK9 inhibition has a neutral effect on abnormal angiogenesis and hepatic encephalopathy in biliary cirrhotic rats.

2 國立陽明交通大學醫學院醫學系

Background: Hyperlipidemia and oxidative stress with elevated oxidized low-density lipoprotein (oxLDL) exacerbate hepatic inflammation and fibrosis. The plasma level of low density lipoprotein (LDL) is controlled by proprotein convertase subtilisin/kexin 9 (PCSK9). Alirocumab is a monoclonal antibody that decreases LDL via inhibiting PCSK9 function. Apart from lipid-lowering effects, alirocumab exerts anti-inflammation, anti-angiogenesis and anti-oxidant effects.

Aims: This study aims to investigate the impact of alirocumab treatment on common bile duct ligation (BDL)-induced biliary cirrhotic rats.

Methods: After a 4-week treatment of alirocumab, the hemodynamic data, blood biochemistry, ox-LDL level, oxidative stress markers, severity of hepatic encephalopathy and abnormal angiogenesis of BDL rats were measured and compared to the control group.

Results: BDL rats presented cirrhotic pictures and elevated ammonia, total cholesterol, LDL and oxLDL levels compared to control group. Alirocumab decreased plasma levels of total cholesterol, LDL, and oxidative stress markers; however, it did not affect the hemodynamics, liver and renal biochemistry, and the plasma levels of ammonia and ox-LDL. The motor activities, portal-systemic collaterals and mesenteric vascular density were not significantly different between alirocumabtreated and control groups. Also, it did not affect

P.041

THERAPEUTIC PREFERENCE WITH CURATIVE INTENT FOR LEFT LATERAL SEGMENT

HEPATOCELLULAR CARCINOMA UNDER THE ERA OF MINIMAL INVASIVE SURGERY

Tsung-Han Wu, Yu-Chao Wang, Hao-Chien Hung, Jin-Chiao Lee, Chih-Hsien Cheng, Chen-Fang Lee, Ting-Jung Wu, Hong-Shiue Chou, Kun-Ming Chan, Wei-Chen Lee, Hou-Ju Lee

Department of General Surgery, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan 左側葉肝細胞癌以微創手術切除與射

）的治療成果比較

Background: Hepatocellular carcinoma (HCC) occurring at the left lateral segment (LLS) is relatively susceptible to treatment with curative intent in terms of tumor location. However, outcomes might vary depending on the selection of treatment modalities.

Aims: This study aimed to analyze patients who had undergone curative therapy for early HCC at LLS.

Methods: A retrospective analysis of 179 patients who underwent curative therapy for early HCC at LLS was performed. Patients were grouped based on treatment modalities, including radiofrequency ablation (RFA) and liver resection (LR). The longterm outcomes of the two groups were compared. Additionally, the impact of the LR approach on patient outcomes was analyzed.

Results: Among these patients, 60 received RFA and 119 underwent LR as primary treatment with curative intent. During follow-up, a significantly higher incidence of HCC recurrence was observed in the RFA group (37/60, 61.7%) than in the LR group (45/119, 37.8%) (p = 0.0025). The median time of HCC recurrence was 10.8 (range: 1.160.9 months) and 17.6 (range: 2.4-94.8 months) months in the RFA and LR groups, respectively. In addition, multivariate analysis showed that liver cirrhosis, multiple tumors, and RFA treatment were significant risk factors for HCC recurrence. The 1-,

2-, and 5-year overall survival rates in the RFA and LR groups were 96.4%, 92.2%, and 71.5% versus 97.3%, 93.6%, and 87.7%, respectively. (p = 0.047). Moreover, outcomes related to LR were comparable between laparoscopic and conventional open methods. (p = 0.506)

Conclusions: Early HCC at LLS had satisfactory outcomes after curative therapy, in which LR seems to have a superior outcome, as compared to RFA treatment. Moreover, laparoscopic LR could be considered a preferential option in the era of minimally invasive surgery.

P.042

MACHINE LEARNING ALGORITHM FOR PREDICTING FATTY LIVER DISEASE IN A TAIWANESE POPULATION

Pei-Yuan Su, Yang-Yuan Chen, Shun-Sheng Wu, Hsu-Heng Yen

Division of Gastroenterology and Hepatology, Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan

Conclusions: The xgBoost model has the best overall prediction ability for diagnosing FLD in the Taiwanese population. The use of machine learning algorithms provides considerable benefits for screening candidate with FLD.

Background: The rising incidence of fatty liver disease (FLD) poses a health challenge and is expected to be the leading cause of liver-related morbidity and mortality worldwide in the near future. Early case identification is crucial for disease intervention.

Aims: Compare the prediction result of machine learning model and the fatty liver index.

Methods: A retrospective cross-sectional study was performed on 31930 Taiwanese subjects (25544 training and 6386 testing sets) who received health checkups and abdominal ultrasounds in Changhua Christian hospital from Jan 2009 to Jan 2019. Clinical and laboratory factors were included for analysis by different types of machine learning algorithms. The performance of machine learning algorithms was compared with the fatty liver index (FLI).

Results: Totally 6658/25544 (26.1%) and 1647/6386 (25.8%) subjects had ultrasoundproven of moderate to severe fatty liver disease in the training and testing sets, respectively. Five machine learning-based models were examined and demonstrated good performance in predicting FLD. Among these models, the xgBoost model revealed the highest area under the receiver operating characteristic (AUROC) (0.882), accuracy (0.833), F1 score (0.829), sensitivity (0.833), and specificity (0.683) compared with neural network, logistic regression, random Forest and support vector machine learning models. The xgBoost, neural network, and logistic regression models had a significantly higher AUROC compared with FLI. Body mass index was the most important feature to predict FLD according to the feature ranking scores.

陳洋源 吳順生 顏旭亨

P.043

THE HEPATIC HETEROGENEITY RELATED TO THE PROGNOSIS OF HEPATOCELLULAR CARCINOMA AFTER HEPATIC RESECTION

Hsuan-Hwai Lin, Tien-Yu Huang, Peng-Jen Chen, Yu-Lueng Shih, Wei-Kuo Chang, Tsai-Yuan Hsieh

Division of Gastroenterology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan

Kaplan-Meier survival curve showed a longer disease-free survival in patients with heterogenous enhancement (Fig. 1, Log-rank test, p < 0.001). The Cox proportional-hazards model was used to adjust the gender and AST, the disease-free survival of patients with heterogeneity of liver parenchymal enhancement was still significantly longer than the other (OR: 2.86, 95% CI: 1.40–5.86, p = 0.004).

Conclusions: The early-stage HCC patients who had undergone resection as the initial treatment modality with heterogeneity of liver parenchymal enhancement associate a longer disease-free survival.

Background: The young hepatocellular carcinoma (HCC) patients presented with a better liver function and less heterogeneity of liver parenchyma, but had more advanced cancer stage compared with old HCC patients. Whether the heterogeneity of liver parenchymal enhancement related to cancer progression is still unclear.

Aims: The aim of this study to define the role of heterogeneity of liver parenchymal enhancement on computed tomography (CT) in the disease-free survival of patients with early-stage HCC after hepatic resection.

Methods: We retrospectively reviewed the medical records of the patients who had earlystage HCCs, and undergone resection as the initial HCC treatment modality. The heterogeneity of liver parenchymal enhancement was estimated using standard deviation (SD) of the enhanced values of CT scan. SD > 5.6 was heterogenous enhancement, and SD ≦ 5.6 was homogeneous enhancement.

Results: 47 patients were heterogenous enhancement and 101 patients were homogeneous enhancement. The clinical characteristics, liver function reserve, and severity of liver fibrosis of these two groups were not different, except gender and AST. There was higher proportion of man with homogeneous than heterogenous enhancement (72.8% vs. 61.2%, p = 0.029). The patients with homogeneous enhancement had lower AST than the other (46.5 ± 40.2 U/L vs. 87.5 ± 104.1 U/L, p = 0.01), but there was no difference in ALT. The

肝實質異質性與肝細胞癌經肝切除術 後之預後相關

林煊淮 黃天祐 陳鵬仁 施宇隆 張維國 謝財源 三軍總醫院內科部胃腸科

P.044

Wei-Fan Hsu1,2,3, Hung-Wei Wang1,4, Shih-Chao Hsu5, Te-Hong Chen5, Chien-Hung Lin6, Ying-Chun Lin7, Yu-Wei Chang8, Yu-Min Liao9, Hsueh-Chou Lai1,3, Cheng-Yuan Peng1,4

1Center for Digestive Medicine, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan

2Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan

3School of Chinese Medicine, China Medical University, Taichung, Taiwan

4School of Medicine, China Medical University, Taichung, Taiwan

5Department of Surgery, China Medical University Hospital, Taichung, Taiwan

6Department of Radiology, China Medical University Hospital, Taichung, Taiwan

7Department of Radiation Oncology, China Medical University Hospital, Taichung, Taiwan

8Department of Pathology, China Medical University Hospital, Taichung, Taiwan

9Division of Hematology and Oncology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan

reserve and tumor burden. The albumin–bilirubin (ALBI) grade is an objective and reproducible model for evaluating overall survival (OS) in patients with HCC. However, the original ALBI grade was established among patients of Child classes A to C. HCC patients with Child class C or poor performance status (The Barcelona Clinic Liver Cancer [BCLC] stage D) usually receive hospice care. Therefore, modified cutoffs for ALBI grade for stratifying OS in patients with HCC who receive therapeutic intervention are pertinent for accurate prognostication.

Aims: This study aims to find a modified cutoff for ALBI grade in patients with early, intermediate, and advanced HCC.

Methods: This study retrospectively enrolled 2116 patients with early, intermediate, or advanced HCC at China Medical University Hospital from January 2012 to October 2020 after excluding those receiving liver transplantation, hospice care, or those with BCLC stage D. Demographic data, clinical features, and comorbidities were recorded at baseline. We modified ALBI grade according to OS stratified by splitting linear predictors of ALBI scores at different percentiles.

2 中國醫藥大學生物醫學研究所

3 中國醫藥大學中醫學系

4 中國醫藥大學醫學系

5 中國醫藥大學附設醫院一般外科

6 中國醫藥大學附設醫院醫學影像部

7 中國醫藥大學附設醫院放射腫瘤科

8 中國醫藥大學附設醫院病理部

9 中國醫藥大學附設醫院血液腫瘤科

Background: The prognosis of hepatocellular carcinoma (HCC) depends on liver functional

Results: Of the 2116 patients, 968 (45.7%), 590 (27.9%), and 558 (26.4%) had BCLC stages A, B and C, respectively. According to OS, we stratified enrolled patients into three groups by splitting linear cutoffs of ALBI scores at the 25th and 80th percentiles optimized through multivariable Cox regression analysis. The modified ALBI (mALBI) grade was as follows: ALBI score ≤ -3.02 for mALBI grade 1, ALBI score more than -3.02 to ≤ -2.08 for mALBI grade 2, and ALBI score > -2.08 for mALBI grade 3. The original ALBI grade and mALBI grade were independent predictors of OS in all enrolled patients and those receiving trans-arterial chemoembolization (n = 799). In patients receiving curative therapies (radiofrequency ablation and operation, n = 1042), mALBI grade (grade 2 vs. 1 and grade 3 vs. 2) was an independent predictor of OS. The original ALBI grade 2 vs. 1 was an independent predictor of OS, whereas ALBI grade 3 vs. 2 did not reach statistical significance (P = 0.085). In patients receiving systemic therapy (n = 159), the original ALBI grade 3 vs. 2 and mALBI grade 3 vs. 2 were independent predictors of OS but ALBI grade 2 vs. 1 (P = 0.057) and mALBI grade 2 vs. 1 (P = 0.309) did not reach statistical significance.

MODIFIED CUTOFFS FOR ALBI GRADE FOR PATIENTS WITH EARLY, INTERMEDIATE, OR ADVANCED HEPATOCELLULAR CARCINOMA

Conclusions: The mALBI grade could stratify patients with early, intermediate, or advanced HCC into three groups. The mALBI could be applied to all enrolled patients, those receiving curative therapy, TACE, or with Child class A. However, external validation of the mALBI grade is warranted.

P.045 MINIMALLY INVASIVE SURGERY VERSUS PERCUTANEOUS RADIOFREQUENCY ABLATION FOR EARLY-STAGE HEPATOCELLULAR CARCINOMA: RESULTS FROM A HIGH-VOLUME LIVER SURGERY CENTER IN EAST ASIA

Yi-Hao Yen1, Yueh-Wei Liu2, Chih-Chi Wang2, Kwong-Ming Kee1, Tsung-Hui Hu1

1Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung

Chang Gung Memorial Hospital and Chang

Gung University College of Medicine, Kaohsiung, Taiwan

2Liver Transplantation Center and Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan

Background: The outcomes of minimally invasive surgery (MIS) vs. percutaneous radiofrequency ablation (RFA) in treating early-stage hepatocellular carcinoma (HCC) remain inconclusive.

Aims: This study thus aimed to compare the outcomes of both treatments for early-stage HCCs.

Methods: This retrospective study consecutively enrolled patients with newly diagnosed earlystage HCCs treated with MIS or percutaneous RFA between 2011 and 2018. Outcomes were compared between the MIS and RFA groups both before and after 1:1 propensity score matching (PSM).

Results: A total of 119 and 481 patients underwent MIS and percutaneous RFA, respectively. Patients undergoing percutaneous RFA exhibited older age (p=0.007) and higher rates of Child–Pugh class B (p<0.001) and multifocal disease (p<0.001). The median overall survival (OS) was 73.7 months in the MIS group, which was significantly higher than that for the RFA group of 65.1 months (p=0.003). 50% HCC recurrence after MIS was not reached. The mean recurrence-free survival (RFS) was 49.6 months for the MIS group, which

比較微創手術以及經皮射頻燒融術治 療早期肝癌

was significantly higher than the RFA group of 41.3 months (p<0.001). On multivariate analysis, age ≥65 (HR: 1.61; 95% CI: 1.13–2.31, p=0.009), RFA (HR: 2.21; 95% CI: 1.14–4.29, p=0.019), and Child–Pugh class B (HR: 2.03; 95% CI: 1.29–3.21, p=0.002) remained risk factors for OS, and RFA (HR: 2.18; 95% CI: 1.42–3.35; p<0.001) remained a risk factor for RFS. After PSM, 103 patients were included in each group. No significant difference in OS was identified (p=0.198), but RFS was higher in the MIS group than the RFA group (p=0.003). Severe postoperative complications occurred at the same rate (1%) in both groups (p>0.99).

Conclusions: After PSM, severe postoperative complication and OS rates were found to be comparable between the MIS and RFA groups, but RFS was higher in the MIS group than the RFA group, suggesting that MIS may have better outcomes for patients with early-stage HCC.

P.046 RISK FACTOR FOR EARLY RECURRENT HEPATOCELLULAR CARCINOMA AFTER HEPATECTOMY

Yu-Lun Chen1, Hsiang-Lin Lee1,2,5, Li-Chuan Ting1,3,4, Lu-Huan Chou3,4, Yi-Hui Sung3,4, Su-Chin Tsao2,3,4

1Department of Surgery, Chung Shan Medical University Hospital, Taichung, Taiwan

2Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan

3Department of Nursing, Chung Shan Medical University Hospital, Taichung, Taiwan

4Department of Nursing, Chung Shan Medical University, Taichung, Taiwan

5School of Medicine, Chung Shan Medical University, Taichung, Taiwan

4

5

Background: Hepatocellular carcinoma (HCC) is a major cause of death in Taiwan and hepatectomy is one of the choice for curative treatment. Early recurrence of HCC still had more worse prognosis. Aims: This study was reviewed the risk factor for early recurrent HCC after hepatectomy.

Methods: This study is a retrospective research which enrolled 68 patients underwent curative resection for HCC. 22 patients had the recurrence of HCC after resection. Analysis method was used the Cox proportional hazards regression analysis to assess the risk factor.

Results: Mean age was 61.0 years. Univariate analysis showed the rate of recurrence is 5.32 times normal, tumor sizes increased by 1 cm, 4-fold increased risk of recurrence, recurrence rate in patients with vascular invasion is 2.7 times to patients without vascular invasion, in late stage higher than early stage by 7.5 times and tumor recurrence rate is 5.61 times in patients who

had more intraoperative blood loss. Multivariate analysis showed independent predictors for worse prognosis which were preoperative platelet count less than 100,000/μL and preoperative HCV RNA level than 50-100 million.

Conclusions: Our results suggest that closely follow-up is mandatory for patients who present with a large tumor burden, vascular invasion, late cancer stage, lower preoperative platelet count, higher the HCV-RNA level and the amount of blood loss.

P.047 RETHINKING OF THE SURVIVAL OUTCOME AS THE QUALITY INDICATOR IN CANCER CARE FOR HEPATOCELLULAR CARCINOMA

Yu-Min Lin1,2, Lee-Won Chong1,2, Hung-Chuen Chang1,2, Yu-Hwa Liu1, Cheuk-Kay Sun1,2, Kou-Ching Yang1

1Division of Gastroenterology and Hepatology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan

2School of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan

Background: The Taiwan government provides “stage-specific” but not “treatment-specific” survival feedback to the hospitals to assure the quality of cancer care.

Aims: This study aims to understand the fiveyear overall survival (5-year OS) of hepatocellular carcinoma (HCC) with different treatment allocations in different medical facilities (medical centers and non-center hospitals).

Methods: We acquire the key information about HCC including the number of cases, tumor stage, treatment options, and medical facilities from “CANCER REGISTRY ANNUAL REPORT, 2017, TAIWAN”. The management of HCC is allocated to surgical resection (SR) and non-surgical treatment (non-SR). We compare the distributions of age, gender, tumor stages, and treatment allocations in different medical facilities. A linear equation for estimating the treatment-specific 5-year OS is made as: C = (Ax + By) / (A + B). We define the coefficient, constant and variable as: Coefficient A = Number of HCCs with SR; Coefficient B = Number of HCCs with non-SR; Constant C = 5-year OS of HCCs in all cases (provided by Health Promotion Administration); Variable x = 5-year OS of HCCs allocated to SR; Variable y = 5-year OS of HCCs allocated to non-SR. The treatment-specific 5-y OS (SR and non-SR) among different medical facilities can be estimated by giving the reported

data of A, B, and C.

Results: In 2017, a total of 8644 new HCC cases were diagnosed in Taiwan. Among 8644 HCCs, 5075 (58.7%) and 3569 (41.3%) were treated in medical centers and non-center hospitals respectively. The age, gender, and tumor stage distribution of HCCs revealed no significant difference between medical centers and noncenter hospitals. The treatments allocated to SR were 32.7% and 21.0% in medical centers and non-center hospitals respectively (p<0.01, chisquared test). The estimations of the treatmentspecific (SR vs. non-SR) 5-year OS of the medical center, non-center hospital, and the index hospital were illustrated in the figure. There is a gap in treatment-specific 5-year OS between medical centers and non-center hospitals. There is a point intersection for the medical center and the index hospital suggests they may have different stagespecific 5-year OS but similar treatment-specific 5-year OS.

Conclusions: Our results suggest OS as a quality indicator for cancer care should be interpreted with caution because survival is greatly affected by the allocation of treatments especially when there are multiple options. Evaluating the treatment-specific survival rate is essential to assure the quality of cancer care.

P.048 A COMPARISON OF LIVER BIOCHEMICAL TEST, METABOLIC PROFILES AND HISTOLOGIC FEATURES BETWEEN SUBJECTS WITH LEAN, OBESE AND DIABETES IN METABOLIC ASSOCIATED FATTY LIVER DISEASE

Xiu-Wei Li, Li-Wei Chen, Liang-Che Chang, Mi-Sio Huang

Keelung Chang Gung Memorial Hospital and University, Keelung, Taiwan

比較精瘦型、肥胖型及糖尿病代謝相 關性脂肪肝病之生化、代謝鹼驗及組 織學特性差異

李修維 陳立偉 張良慈 黃密修 基隆長庚紀念醫院

Background: Metabolic associated fatty liver disease (MAFLD) is diagnosed in patients with hepatic steatosis. It has the following three metabolic dysregulation conditions: lean (body mass index, BMI less than 23 kg/m2), obese and diabetes mellitus (DM). The aim of this study was to compare the characteristics of demographic data, liver biochemical test, metabolic profiles and histology between these three metabolic conditions based on data from patients receiving liver biopsy for abnormal liver biochemistry test. Aims: The aim of this study was to compare the characteristics of demographic data, liver biochemical test, metabolic profiles and histology between these three metabolic conditions based on data from patients receiving liver biopsy for abnormal liver biochemistry test

Methods: From Jan 2006 t0 Nov 2021, total 170 consecutive patients whose histological finding revealing steatosis were included in Keelung Chang Gung memorial hospital. Those patients were divided into three groups: lean, obese and DM.

Results: Among the 170 patients, 18 (10.6%) were lean, 122 (71.8%) were obese and 30 (17.6%) were DM. Subjects in the lean group were older (60.4 vs. 55.1 y/o), higher values in TG, AST, ALK-P and total bilirubin than those in the obese group. But subjects in the lean group have less HTN, lower values of fasting glucose and glycohemoglobin (HBA1C). An increasing trend of steatosis score

(1.44, 1.52, 1.73) or fat score (29.17, 33.43, 39.23) was found among subjects in the lean, obese and DM group. The mean hepatic fibrosis scores were higher in the lean group (1.61 ± 1.53) and DM group (1.53 ± 1.33) than obese group (1.17 ± 1.37). However, when comparing the hepatic fibrosis score among the three groups by one-way ANOVA, there was no statistical difference (P = 0.25) after adjustment of age, gender and BMI.

Conclusions: Subjects in the lean or DM group are older, higher mean values of AST or ALT than those in obese group. Although the mean values of hepatic fibrosis scores in lean and DM group were higher than the value in obese group, there was no statistical differences in this study.

P.049 CURATIVE RADIOFREQUENCY ABLATION (RFA) IN TREATMENT OF INTERMEDIATE HEPATOCELLULAR CARCINOMA (HCC) PATIENTS AFTER TRANSCATHETER ARTERIAL CHEMOEMBOLIZATION (TACE) DOWNSTAGING

Yuan-Jie Ding1, Te-Sheng Chang1,2, Chien-Heng Shen1, Liang-Mou Kuo2,3, Sheng-Lung Hsu2,4, Yi-Hsing Chen1,2, Yung-Yu Hsieh1,2, Hui-Ling Huang5, Sheng-Nan Lu1,6

1Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chiayi Chang Gung Memorial Hospital, Chiayi, Taiwan

2College of Medicine, Chang Gung University, Taoyuan, Taiwan

3Department of General Surgery, Chiayi Chang Gung Memorial Hospital, Chiayi, Taiwan

4Department of Diagnostic Radiology, Chiayi Chang Gung Memorial Hospital, Chiayi, Taiwan

5Department of cancer, Chiayi Chung Gung Memorial Hospital, Chiayi, Taiwan

6Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung

Chang Gung Memorial Hospital, Kaohsiung, Taiwan

3 嘉義長庚紀念醫院一般外科

4 嘉義長庚紀念醫院放射診斷科

5 嘉義長庚紀念醫院癌症中心

6 高雄長庚紀念醫院胃腸肝膽科

Background: TACE is the main treatment modality in patients with intermediate stage HCC who have not undergone surgical resection or liver transplantation. The response to TACE of patients with intermediate stage is variable. There is no

established protocol of sequential therapies for those who received few TACEs.

Aims: To elucidate survival benefit of sequential curative treatment after transcatheter arterial chemoembolization (TACE) for TACE suitable Barcelona Clinics Liver Cancer (BCLC) stage B hepatocellular carcinoma (HCC) cases, we retrospectively analyzed HCC patients in a regional hospital.

Methods: During July 2017 to July 2020, a total of 787 treatment-naïve patients with HCC were registered and underwent their initial treatment, and 78 (9.9%) suitable for TACE BCLC stage B patients were enrolled to this analysis.

Results: Their initial treatment modalities were TACE only (n = 66, 84.6%) or TACE combined with other treatments within 2 months (n = 12, 15.4%). The median survival of TACE only group (n = 66) were 38 months. Treatment response of 52 (78.8%) out of 66 patients with available pre- and post- TACEs CT or MRI for comparison after 2 or 3 consecutive TACEs were evaluated. Treatment response was divided into 5 groups as follows: complete response (n = 13, 25%, Group (Gr)1), incomplete response without new growth tumor (n = 27, 52.0%, Gr2), incomplete response with oligo intrahepatic recurrence (n = 2, 3.8% Gr 3), disease progression but not stage progression (n = 4, 7.7%, Gr 4), and stage progression (n = 6, 11.5%, Gr 5). Among 27 patients of Gr 2, 13 further treated by RFA (Gr2a), 9 by TACE (Gr2b) and 5 by others (Gr2c). The median survival of Gr2a was significantly better than that of Gr2b (45.2 Vs 27.4 months, p = 0.025). Nine of Gr2a (69%, 9/13) achieved complete response, but none of Gr 2b (p = 0.001).

Conclusions: For TACE suitable BCLC stage B HCC patients, integration of curative treatment modalities in adequate timing gains survival benefit.

P.050 PERFORMANCE OF AGILE 3+ SCORE IN ADVANCED LIVER FIBROSIS ASSESSMENT IN PATIENTS WITH NON-ALCOHOLIC FATTY LIVER DISEASE

Yi-Cheng Chen1,3,5, Li-Wei Chen2,3,4, Tsung-Hsing Chen1,3, Chao-Wei Hsu1,3, Dar-In Tai1,3

1Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Taoyuan, Taiwan

2Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Keelung, Taiwan

3Chang Gung University, College of Medicine, Taoyuan, Taiwan

4Community Medicine Research Center, Chang Gung Memorial Hospital, Keelung, Taiwan

5School of Medicine, National Tsing Hua University, Hsinchu, Taiwan

3 長庚大學

4 基隆長庚機構醫院社區醫學研究中心

5 國立清華大學

Background: The stage of liver fibrosis is an important factor to predict disease prognosis in patients with nonalcoholic fatty liver disease (NAFLD). Fibrosis 4 index (FIB-4) and liver stiffness measurement (LSM) by vibration-controlled transient elastography (VCTE) are currently widely used non-invasive procedures in the assessment of advanced liver fibrosis (fibrosis score >=3) with moderate ability. Agile3+ score, a novel VCTEbased scoring system, has been developed to rule in NAFLD patients with advanced liver fibrosis.

Aims: To investigate the performance of Agile3+ score in assessing advanced liver fibrosis in NAFLD patients.

Methods: Patients with suspected NAFLD who received liver biopsy, LSM by VCTE and routine liver biochemistries were retrospectively

reviewed from 2010 January to 2022 May in Chang Gung Memorial Hospital, Linkou and Keelung branches. Those with hepatitis B/C viral infection, HIV infection, alcoholic, autoimmune or drug-associated liver diseases were excluded. Pathological parameters of steatosis, ballooning, lobular inflammation, NAFLD activity score (NAS) and fibrosis stage were recorded. Agile3+ was computed using a formula composing of LSM (kPa), aspartate aminotransferase (AST), alanine aminotransferase (ALT), platelet count (10^9/L), diabetes status, age and gender to generate a score between 0 and 1. Cut-off values for at least 85% sensitivity and 90% specificity were derived to rule out and rule in advanced liver fibrosis, respectively for LSM, FIB-4 and Agile3+ score. Receiver operating characteristic (ROC) analysis and pairwise comparison using DeLong test were performed.

Results: A total of 214 patients with biopsy-proved NAFLD were included. The median (IQR) age was 49 (36-59) years and males were 128 (59.8%). There were 57 (26.6%) diabetes and 55 (25.7%) advanced fibrosis (F ≥ 3). The cut-off values with at least 85% sensitivity to rule out advanced fibrosis for LSM, FIB-4 and Agile3+ were 8.5 kPa, 1.03, and 0.26, respectively. The corresponding negative predictive value (NPV) were, 94%, 92.4% and 94.2%. The cut-off values with at least 90% specificity to rule in advanced fibrosis for LSM, FIB-4 and Agile3+ were 10.5 kPa, 1.84, and 0.35, respectively. The corresponding positive predictive value (PPV) were, 71.2%, 65.1% and 74.6%. The area under ROC of Agile3+ was 92.8% (95% CI: 0.891-0.966), significantly greater than that of FIB4 (82.1%, p < 0.001) whereas comparable with that of LSM (90.7%, p = 0.281).

Conclusions: The performance of Agile3+ in advanced liver fibrosis was significantly better than FIB-4, while similar to LSM by VCTE. Agile3+ score <0.26 and >0.34 had a NPV of 94.2% and a PPV of 74.6% in advanced liver fibrosis.

P.051

A COMPARISON OF LENVATINIB VERSUS SORAFENIB IN THE REAL-WORLD FIRST-LINE THERAPY OF UNRESECTABLE HEPATOCELLULAR CARCINOMA IN A TAIWANESE POPULATION

Chi-Yu Lee1, Tsang-En Wang1,2,3, Shih-Ting Huang1, Chia-Yuan Liu1,2,3, Ming-Jen Chen1,2,3, Horng-Yuan Wang1,2,3, Ching-Wei Chang1,2,3

1Division of Gastroenterology, Department of Internal Medicine, MacKay Memorial Hospital, Taipei, Taiwan

2MacKay Medicine, Nursing and Management College, Taipei, Taiwan

3Department of Medicine, MacKay Medical College, New Taipei, Taiwan Lenvatinib

Background: Currently, systemic therapy including tyrosine kinase inhibitor (TKI) or immunotherapeutic agents are recommended for first-line treatment in patients with unresectable hepatocellular carcinoma (HCC). In the REFLECT study, Lenvatinib has been shown to be noninferior to sorafenib in terms of overall survival (OS) time in patients with unresectable HCC as primary treatment.

Aims: This retrospective study was to compare the effectiveness of lenvatinib and sorafenib in the Taiwanese patients with unresectable HCC in our real-world experience.

Methods: We retrospectively reviewed the medical records of patients with unresectable HCC who received lenvatinib or sorafenib as the first-line therapy from July 2020 to March 2022. Patients’ baseline general data and OS were collected. We used Pearson’s Chi-square test and independent t-test for statistical comparisons. Statistical significance was set at p<0.05. Survival analysis was carried out using the Kaplan-Meier

method for univariate analysis and comparisons were subsequently performed with the log-rank test.

Results: A total of 30 patients with lenvatinib and 85 patients with sorafenib were enrolled. The characteristics of these cases are shown in table 1. The median age of the two groups was 66.7 and 65.66, respectively. Both groups were male predominant (66.7% and 72.9%, respectively). The prevalence of chronic HBV infection, HCV infection and alcoholic liver disease was 43.3%, 36.7%, 6.7 in the lenvatinib group and 58.8%, 24.7%, 8.2% in the sorafenib group. Most patients belonged to Child-Pugh score A. The proportion of patients with BCLC stage C in two groups was 56.7% and 78.8%, respectively. Fourteen cases (46.7%) and 4 cases (13.3%) in the lenvatinib group, and 39 cases (45.9%) and 36 cases (42.4%) in the sorafenib group, had portal vein thrombosis and extrahepatic spread, respectively. The average of total bilirubin and alpha-fetoprotein are not significantly different in two groups. The therapeutic durations of the lenvatinib group and the sorafenib group were 5.04 ± 3.95 and 6.83 ± 5.43 months, respectively. The median OS (95% CI) of the lenvatinib group and the sorafenib group was 13.65 months (10.65-16.65) and 17.1 months (15.08-19.13), respectively. Patients with sorafenib seemed to have longer OS, compared to patients with lenvatinib, but there was no significant difference between two groups (p = 0.588).

Conclusions: In our real-world data, there was no significant difference in OS between HCC patients with lenvatinib and sorafenib. Therefore, sorafenib or lenvatinib as first-line therapy for unresectable HCC might be selected based on individualized treatment goals. More sample size and subgroup analysis are needed for further analysis.

P.052 ROLE OF TUMOR BURDEN ON ALBI GRADE MIGRATION TO TRANSARTERIAL CHEMOEMBOLIZATION IN INTERMEDIATE STAGE

HEPATOCELLULAR CARCINOMA: CRITERIA FOR UNSUITABLE CASES SELECTION

Chen-Ta Chi1,2, I-Cheng Lee1, Rheun-Chuan Lee3, Ya-Wen Hung1, Chien-Wei Su1, Ming-Chih Hou1, Yee Chao4, Yi-Hsiang Huang1,2

1Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan

2Institute of Clinical Medicine, National Yang

Ming Chiao Tung University, Taipei, Taiwan

3Department of Radiology, Taipei Veterans General Hospital, Taipei, Taiwan

4Cancer Center, Taipei Veterans General Hospital, Taipei, Taiwan

Background: BCLC-B hepatocellular carcinoma (HCC) encompasses heterogeneous populations with varied tumor burden and liver reserve resulting in diverse clinical outcomes to Transarterial chemoembolization (TACE). TACE is the standard of care for intermediate stage HCC. Liver function deterioration would happen after TACE in patients with high tumor burden.

Aims: We aimed to identify unsuitable cases who were at risk of ALBI grade migration by TACE.

Methods: From October 2007 to January 2017, consecutive 531 treatment-naïve BCLC-B HCC patients undergoing TACE as the initial treatment with evaluable image studies in Taipei Veterans

General Hospital were retrospectively reviewed. Incidences of TACE-related ALBI-grade migration in acute and chronic phases, progression-free survival (PFS), and overall survival (OS) were investigated. Factors associated with ALBI-grade migration were also analyzed.

Results: There were 129 (24.3%) patients experienced acute ALBI-grade migration after TACE, and 85 (65.9%) out of the 129 patients had chronic ALBI-grade migration. Incidences of acute ALBI-grade migration were 13.9%, 29.0% for patients within or beyond up-to-7 criteria (p < 0.001) and 20.0%, 36.2% for patients within or beyond up-to-11 criteria (p < 0.001), respectively. HBV infection, tumor size plus tumor number criteria were risk factors associated with acute ALBI-grade migration. Bilobar tumor involvement was the risk factor of chronic ALBI-grade migration in patients with acute ALBI-grade migration. Upto eleven (p = 0.007) performed better than up-toseven (p = 0.146) to differentiate risk of dynamic ALBI score changes. In addition, patients with ALBI-grade migration in acute or chronic phases had significantly poorer PFS than patients without ALBI-grade migration.

Conclusions: Overall, tumor burden beyond up-to-eleven criteria was consistently associated with acute and chronic ALBI-grade migration, suggesting that up-to-eleven is an appropriate parameter to select TACE-unsuitable HCC patients who are at risk of liver function deterioration.

P.053 QUANTIFICATIONS OF HEPATIC STEATOSIS WITH ATTENUATION IMAGING ASSESS ASSOCIATION TO TRADITIONAL FACTORS

Hao-Yu Wu1, Tzu-Chan Hong2, Jyh-Ming Liou2, Chun-Jen Liu1

1Division of Gastroenterology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan

2Division of Gastroenterology, Department of Internal Medicine, National Taiwan University Hospital Cancer Center, Taipei, Taiwan

影像衰減超音波下脂肪肝嚴重度與風 險因子之相關性

吳浩宇1 洪子瞻2 劉志銘2 劉俊人1

2 國立臺灣大學醫學院附設醫院癌醫中心分院肝膽

Background: Non-alcoholic fatty liver disease (NAFLD) has become increasingly prevalent in Asian population. The common associated factors including metabolic factors such as type 2 diabetes, obesity, and dyslipidemia are well reported. Other diseases such as breast cancer, gallbladder polyps, gallstone disease and pancreatic steatosis also correlated with NAFLD occurrence in previous studies. However, there are low accuracy and intra/ interobserver variability in NAFLD evaluation via traditional ultrasonography. Attenuation imaging (ATI), which assesses the acoustic characteristics of beam attenuation in hepatic parenchyma, has a better performance in the detection and quantification of liver steatosis. Therefore, the purpose of this study was to investigate the correlation between previous association and risk factors and the severity of NAFLD through ATI.

Aims: The aim of this study is to establish the relationship between the quantitative severity of fatty liver and traditional associations such as breast cancer, gallbladder polyp, gallstone, and fatty infiltration of pancreas in our population.

Methods: A total of 268 subjects with abdominal sonography and ATI measurement were retrospectively collected from December 2021 to June 2022 of National Taiwan University Cancer Center. We measured hepatic steatosis by ATI and severity of hepatic fibrosis by shock wave

elastography (SWE) using standard protocol from Cannon i800 manufacturer. Grade of fatty liver were defined by ATI measurement (dB/cm/MHz; >0.62, mild; >0.72, moderate; and >0.84, severe). Grade of liver stiffness were defined by SWE measurement (kPa, >5,8, mild; >7.5, moderate; and >9.8, severe). Mann-Whitney U test and Spearman correlation were used to evaluate the significant factors associated with the fatty liver severity.

Results: Among our cohort, 51.5% patients were male. The severity grades of fatty liver were 45.9% for no fatty liver, 18.2% for mild and 18.8% for moderate and 17.1% of severe fatty liver. Median ATI for male patients were 0.675 dB/cm/MHz and for female were 0.670 dB/cm/MHz. The grade of fatty liver showed no concordant relationship between ATI and SWE with Spearman correlation coefficient (-0.07, p = 0.27). In our cohort, patients with a history of breast cancer were found to be correlated with higher mean ATI (0.78 vs. 0.66 dB/ cm/MHz, p = 0.001). Sonography finding of fatty infiltration of pancreas was noted to be related to higher measurement ATI level (0.71 vs. 0.66 dB/ cm/MHz, p = 0.012). Nevertheless, previously reported clinical factors including gallbladder polyp or gallstone were not associated with the severity of fatty liver (mean ATI 0.67 vs 0.67 dB/cm/MHz for GB polyp; and 0.66 vs 0.67 dB/cm/MHz for GB stone occurrence).

Conclusions: Based on the ultrasonography, the incidence of NAFLD increased in population with breast cancer. Sonographically, fatty infiltration of pancreas was associated with more severe hepatic steatosis but not gallbladder polyp or gallstone which showed positive correlation in previous qualitative studies. The elevated level of fatty liver was not associated with increased stiffness which may reflect merely steatosis without hepatitis will not contribute to the fibrosis of liver.

P.054

Yan-Ting Lin1, Li-Tong Liu1, Chien-Hao Huang1,2, Rong-Nan Chien1,2

1Division of Hepatology, Department of Gastroenterology and Hepatology, ChangGung Memorial Hospital, Linkou Medical Center, Taoyuan, Taiwan

2College of Medicine, Chang-Gung University, Taoyuan, Taiwan

新模型預測肝細胞癌病患預後

Background: Currently, physicians use the Barcelona Clinic Liver Cancer classification (BCLC) stage, Neutrophil-Lymphocyte Ratio (NLR) and the Albumin-Bilirubin (ALBI) score to predict the outcome of patients with hepatocellular carcinoma (HCC). Some newly developed models did not demonstrate a superior prediction ability. Aims: We aimed to develop a novel model to better predict the outcome of patients with HCC than the conventional HCC models.

Methods: We prospectively enrolled 298 patients who suffered from HCC in a medical center. By using univariate and multivariate logistic analysis, a novel model was built.

Results: The demographic table disclosed no significant difference in age, gender, white blood cell count, platelet count, and other liver biochemistry (AST, ALT, total bilirubin) but significant difference in hemoglobin, prothrombin time, segment percentage, and lymphocyte percentage of the white blood cell in the survival group and mortality group. We made a novel model from these three factors to predict the prognosis (For one-year mortality prediction, the formula = 3.012 + 0.974 (BCLC) - 0.184 (Hemoglobin) - 0.992 (Albumin)). AUROC was 83.6%.

Conclusions: Compared with conventional prognosis predictors (ALBI score, N/L ratio, and BCLC classification), the new model had a better prediction rate. The AUC (area under the curve) was 83.6%.

A NOVEL MODEL TO PREDICT THE PROGNOSIS OF PATIENTS WITH HEPATOCELLULAR CARCINOMA

P.055

RISK FACTORS OF RECURRENCE AFTER SINGLE-SESSION WITH COMPLETE RADIOFREQUENCY ABLATION OF HEPATOCELLULAR CARCINOMA – A PRELIMINARY REPORT

Yi-Hsuan Wong1, Sheng-Wei Cheng2, Li-Wei Wu3, Shih-Ping Huang1, Hua-Chen Fang1, Ming-Shun Wu1,4

1Division of Gastroenterology, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan

2Division of Gastroenterology, Department of Internal Medicine, Taiwan Adventist Hospital, Taipei, Taiwan

3Department of Internal Medicine, National Taiwan University Cancer Center, Taipei, Taiwan

4Division of Gastroenterology and Hepatology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan

RFA. Three different groups were identified, no recurrent (Group I), local recurrent (Group II) and distant recurrent (Group III). We investigated the risk of recurrence with pretreatment factors by using nonparametric statistics, including age, gender, type of RFA needle, BCLC stage, ChildPugh class, White blood cell count, AST, ALT, AFP, hepatitis status, neutrophil/lymphocyte ratio (NLR), tumor number, tumor size and ALBI score. Results: AFP > 7 ng/ml was significantly associated with a higher recurrence rate after complete ablation. There were no significant differences in age, gender, type of RFA needle, BCLC stage, Child-Pugh class, White blood cell count, AST, ALT, hepatitis status, NLR, tumor number, tumor size and ALBI score. The overall recurrent rate (local vs. distant recurrent) were 18.8% (9.4% vs. 9.4%), 32.9% (12.9 % vs. 20.0%), 34.1% (0 vs. 34.1), 36.5% (0 vs. 36.5%) at 1, 2, 3, 5 years, respectively. For small tumors (smaller than 3 cm), the overall recurrent rates were 10.6 %, 12.9 %, 14.1% and 15.3% at 1, 2, 3, 5 years, respectively. For large tumors (more than 3 cm), the overall recurrence rates were 8.2% and 20% and 21.2% and 22.4% at 1, 2, 3, 5 years, respectively.

Conclusions: After single-session RFA with complete ablation, the >3 cm tumor and AFP >7 ng/ml is associated with higher recurrent rate in this study.

1 臺北市立萬芳醫院—委託財團法人臺北醫學大學 辦理內科部消化內科

2 基督復臨安息日會醫療財團法人臺安醫院內科部 消化內科

3 國立臺灣大學醫學院附設醫院癌醫中心內科部

4 臺北醫學大學醫學院醫學系內科學科消化內科

Background: Radiofrequency ablation (RFA) is a minimally invasive treatment for hepatocellular carcinoma (HCC). The higher rate of complete ablation and fewer rate of local recurrent indicate the more meticulous techniques. After a singlesession of RFA with complete ablation, the baseline characters with incidence of recurrence in the following years were observed.

Aims: To analyse the risk factors of recurrence after single-session with complete radiofrequency ablation of hepatocellular carcinoma.

Methods: From May 2015 to May 2022, 85 HCC patients with 157 tumors were successfully treated with complete ablation by single-session

肝癌於單次完全燒灼成功後的復發風 險分析

P.056

PREDICTORS OF SURVIVAL OUTCOMES

PATIENTS

UNRESECTABLE HEPATOCELLULAR CARCINOMA TREATED WITH 1ST LINE SYSTEMIC THERAPY WITH LENVATINIB: ONE SINGLE CENTER REAL-WORLD EXPERIENCE

Hung-Wei Wang, Hsueh-Chou Lai, Po-Heng Chuang, Wei-Fan Hsu, Cheng-Yuan Peng

Center for Digestive Medicine, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan

reached. According to multivariate Cox regression analyses, neutrophil-lymphocyte ratio (NLR) ≤ 5.8 (hazard ratio [HR]: 0.239, 95% CI: 0.063–0.909; p = 0.036) was a prognostic factor of PFS in an albumin-bilirubin (ALBI)-based model. ALBI grade 1/2a plus NLR ≤ 5.8 is an independent predictor of PFS (HR: 0.300, 95% CI: 0.119–0.754; p = 0.010) and OS (HR: 0.166, 95% CI: 0.028–0.993; p = 0.049) in an ALBI-NLR combination model.

Conclusions: Our real-world data for 1st line systemic therapy with lenvatinib demonstrate its promising efficacy. A combination of ALBI grade and NLR may be used to stratify patients with unresectable HCC undergoing systemic treatment with lenvatinib.

Background: In the REFLECT study, lenvatinib demonstrated non-inferiority to sorafenib for survival benefit in patients with advanced hepatocellular carcinoma (HCC).

Aims: This study aimed to explore the effectiveness of lenvatinib in the real-world setting and investigate the predictors of survival outcomes.

Methods: We retrospectively evaluated 38 patients with HCC who received 1st line systemic therapy with lenvatinib from January 2020 to December 2021 at China Medical University Hospital. Baseline patient characteristics, treatment response and survival outcomes were reviewed and analyzed for predictors of progression-free survival (PFS) and overall survival (OS) by univariate and multivariate Cox regression analyses. Kaplan–Meier analysis was used to compare the survival outcomes among subgroups.

Results: In this cohort, patients who belonged to BCLC stage B and C were 42.1% and 57.9%, respectively. Objective response rate (ORR) and disease control rate (DCR) were 36.8% and 89.5%, respectively. Median PFS was 8 months (95% CI: 4.5–11.5) and median OS was not reached during the median follow-up of 12.5 months. Median PFS for those with ORR and DCR groups were 13 and 8 months, respectively and median OS were both not

IN

WITH

針對無法切除之肝癌患者接受樂衛瑪 為第一線全身性治療之存活預測因 子：單一中心的真實世界經驗

王鴻偉 賴學洲 莊伯恒 許偉帆 彭成元

中國醫藥大學附設醫院內科部消化醫學中心

P.057 LENVATINIB PLUS PEMBROLIZUMAB FOR PATIENTS WITH UNRESECTABLE HEPATOCELLULAR CARCINOMA AS 1ST LINE SYSTEMIC COMBINATION THERAPY: ONE SINGLE CENTER REAL-WORLD EXPERIENCE

Hung-Wei Wang, Hsueh-Chou Lai, Po-Heng Chuang, Wei-Fan Hsu, Cheng-Yuan Peng

Center for Digestive Medicine, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan

Notably, patients receiving combination therapy had significantly higher ORR than those receiving lenvatinib alone (ORR: 35.9%). During the median follow-up of 12 months, the 6-month PFS rate was 64.3% and one-year survival rate was 83.9%. Patients receiving combination therapy had numerically longer PFS than those receiving lenvatinib alone (median PFS: 10 and 7 months, respectively). The median OS for patients receiving lenvatinib with/without pembrolizumab were both not reached. The treatment related adverse events (TRAEs) in any grade were hypertension (42.9%), pruritus (35.7%), proteinuria (28.6%), fatigue (28.6%), and palmar-plantar erythrodysesthesia (21.4%). No grade 3/4 TRAEs were reported in this cohort.

Conclusions: Our real-world data demonstrate lenvatinib combined with pembrolizumab showed significantly higher ORR and numerically longer PFS than lenvatinib alone in patients with unresectable HCC. No life-threatening TRAEs were reported in our cohort.

Background: According to the REFLECT study, lenvatinib is regarded as the first-line therapy for patients with unresectable hepatocellular carcinoma (HCC). However, the treatment efficacy for the combination of lenvatinib plus pembrolizumab as the 1st line systemic therapy remains unclear.

Aims: This study aimed to explore the effectiveness of lenvatinib plus pembrolizumab combination therapy in the real-world setting.

Methods: We retrospectively enrolled 14 patients with HCC who received 1st line systemic therapy with lenvatinib plus pembrolizumab from January 2020 to December 2021 at China Medical University Hospital. Baseline patient characteristics, treatment response and survival outcomes were reviewed. Progression-free survival (PFS), overall survival (OS), objective response rate (ORR), and disease control rate (DCR) were calculated to assess the antitumor response. We also enrolled another cohort using lenvatinib alone (n = 39) for further comparison.

Results: In this cohort, patients who belonged to BCLC stage C were 85.7% and all of them were classified as Child-Pugh class A. Objective response rate (ORR) and disease control rate (DCR) were 71.4% and 92.9%, respectively.

針對無法切除之肝癌患者接受樂衛瑪 與吉舒達為第一線全身性合併治療： 單一中心的真實世界經驗

王鴻偉 賴學洲 莊伯恒 許偉帆 彭成元 中國醫藥大學附設醫院內科部消化醫學中心

P.058 ASSESSMENT OF LENVATINIBBASED COMBINATION TREATMENT FOR PATIENTS WITH UNRESECTABLE HEPATOCELLULAR CARCINOMA: A MEDICAL CENTER EXPERIENCE

Chia-Chien Kang1, Tsang-En Wang1,2,3, Shen-Yung Wang1,2,3, Yen-Po Chen1,2,3, Si-Hsuan Chen1,2,3, Shih-Ting Huang1, Chia-Yuan Liu1,2,3, Ming-Jen Chen1,2,3, Horng-Yuan Wang1,2,3, Ching-Wei Chang1,2,3

1Division of Gastroenterology, Department of Internal Medicine, MacKay Memorial Hospital, Taipei, Taiwan

2MacKay Medicine, Nursing and Management College, Taipei, Taiwan

3Department of Medicine, MacKay Medical College, New Taipei, Taiwan

was considered as the combine treatment group. The treatment outcomes and overall survival were evaluated.

Results: A total of 23 patients with unresectable HCC who received lenvatinib were enrolled. The lenvatinib only group enrolled 15 patients and the combine treatment group enrolled 8 patients were compared (Table 1); The mean age of the patients at the time of starting lenvatinib was 67.27 ± 10.04 and 67.88 ± 5.16 years old, respectively, and male predominance. The proportion of patients positive for HCV Ab and HBsAg were 73.3% and 87.53%, respectively. The proportion of patients with Child-Pugh score A were 73.3% and 87.5%, respectively. In the lenvatinib only group, patient proportion with BCLS stage A, B and C were 0%, 26.7% and 66.7%. In the combine treatment group, patient proportion with BCLC stage A, B and C each were 25%. The lenvatinib therapeutic duration in two groups were 5 ± 3.86 and 7.38 ± 5.43 months. The above characteristics between two groups had no statistical significance. The median overall survival of the lenvatinib only group and the combine treatment group was 12.48 (8.77–16.18) and 12.75 (8.93–16.57) months, respectively, and the difference was nonsignificant (p = 0.368)(figure 1).

Background: Lenvatinib is one of the standard first-line treatments for advanced hepatocellular carcinoma (HCC). The efficacy of lenvatinibbased combination treatment for patients with unresectable HCC remains unclear.

Aims: The aim of this study was to compare the outcomes of patients with unresectable HCC who received lenvatinib only to lenvatinib combined treatment.

Methods: The medical records of patients with HCC who received lenvatinib from 2020 to 2022 in the MacKay Memorial Hospital were reviewed retrospectively. These patients were divided into two groups, lenvatinib only group and combine treatment group. The patient received lenvatinib combined with any of operation, radiofrequency ablation therapy(RFA), transcatheter arterial embolization(TAE), transarterial chemoembolization (TACE), radiotherapy (RT), or immunotherapy

Conclusions: Although HCC patients with lenvatinib-based combination treatment had longer median overall survival, there’s no statistical significance compared to HCC patients with lenvatinib only. The study disclosed the realworld data in a medical center, further prospective studies are needed to validate these results.

P.059 ULTRASOUND TIME-FREQUENCY ENTROPY IMAGING OF HEPATIC STEATOSIS

Hao-Tsai Cheng1,2,3, Shu-Wei Huang1, Tsung-Hsing Chen2,3, Chang-Mu Sung2,3, Sen-Yung Hsieh2, Po-Hsiang Tsui4

1Division of Gastroenterology and Hepatology, Department of Internal Medicine, New Taipei Municipal Tucheng Hospital, Tucheng, New Taipei City, Taiwan

2Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University, Taoyuan, Taiwan

3Graduate Institute of Clinical Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan

4Department of Medical Imaging and Radiological Sciences, Chang Gung University, Taoyuan, Taiwan

肝臟脂肪浸潤之超音波時頻熵成像

1 新北市立土城醫院（委託長庚醫療財團法人興建 經營）胃腸肝膽科

2 林口長庚紀念醫院胃腸肝膽科系

3 長庚大學臨床醫學研究所

4 長庚大學醫學影像暨放射科學系

Background: The excessive accumulation of fat droplets in hepatocyte may progress to hepatic steatosis, which is the major cause of nonalcoholic fatty liver disease. Acoustically, hepatic steatosis results in the effect of attenuation, which further induces the downshift of ultrasound frequency as the key diagnostic clue. Considering the mechanism of ultrasound energy absorption is frequency-dependent, the information analysis of the overall spectrum may be more sensitive to reflecting acoustic attenuation.

Aims: This study proposed a time-frequency entropy (TFE) to measure the complexity of the spectrum for the assessment of hepatic steatosis.

Methods: In this study, a total of 132 participants scheduled for performing liver biopsies or partial liver resections were enrolled for ultrasound examinations by using a clinical ultrasound

system and Fibroscan, which is the typical tool for clinical evaluations of hepatic steatosis. For each subject, the short-time Fourier transform of each backscattered signal in the image data was performed to obtain the spectrums as a function of time, which were used to estimate information entropy values for TFE imaging. The controlled attenuation parameter (CAP) was also measured by Fibroscan. The diagnostic performances of TFE imaging and CAP in diagnosing the steatosis grade (G0: normal; G1: mild; G2: moderate; G3: severe) were evaluated by the receiver operating characteristic (ROC) curve analysis. The statistical significance of the diagnostic performance was identified by the p-value obtained from DeLong test.

Results: With increasing the steatosis grade from G0 to G3, the CAP increased, representing the increase in the effect of attenuation. Concurrently, the TFE value decreased, meaning that the attenuation due to hepatic steatosis reduces the complexity of the signal spectrum. Fig. 1 shows the ROC curves obtained from using TFE and CAP in the assessment of hepatic steatosis. Compared to CAP, ultrasound TFE provided an improved diagnostic performance in detecting early grades of hepatic steatosis.

Conclusions: Ultrasound TFE imaging may have great potential to be a new analysis method providing new physical insights for the diagnosis of hepatic steatosis.

P.060 COMPARISON OF RADIOFREQUENCY ABLATION AND TRANSARTERIAL CHEMOEMBOLIZATION FOR HEPATOCELLULAR CARCINOMA WITHIN MILAN CRITERIA: PROGNOSTIC ROLE

OF TUMOR BURDEN SCORE

Shu-Yein Ho1, Jia-I Liao2, Yi-Hsiang Huang2, Chien-Wei Su2, Ming-Chih Hou2, Teh-Ia Huo3

1Division of Gastroenterology and Hepatology, Min-Sheng General Hospital, Taoyuan, Taiwan

2Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan

3Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan

2 臺北榮民總醫院胃腸肝膽科

3 臺北榮民總醫院醫學研究部

Background: The diameter of tumor and nodules indicate tumor burden in hepatocellular carcinoma (HCC). Tumor burden score (TBS) was recently proposed to assess the extent of tumor involvement.

Aims: We aimed to evaluate the prognostic impact of TBS on HCC patients within Milan criteria undergoing radiofrequency ablation (RFA) versus trans-arterial chemoembolization (TACE).

Methods: A total of 546 patients undergoing RFA and 337 patients undergoing TACE were analyzed. The multivariate Cox proportional hazards model was used to determine independent prognostic predictors in different patient cohort.

Results: TACE group had significantly higher TBS compared with RFA group. RFA group had better long-term survival than the TACE group in patients within Milan criteria in univariate survival analysis.

In the Cox model, serum α-fetoprotein (AFP) > 20 ng/mL (hazard ratio [HR]: 1.435, 95% confidence interval [CI]: 1.221-1.687, p < 0.001), performance status 1-2 (HR: 1.565, 95% CI: 1.304-1.878, p <

0.001), medium TBS (HR: 1.372, 95% CI: 1.1561.630, p < 0.001), high TBS (HR: 1.512, 95% CI: 1.181-1.937, p < 0.001), albumin-bilirubin (ALBI) grade 2 (HR: 1.611, 95% CI: 1.355-1.916, p < 0.001), and ALBI grade 3 (HR:2.297, 95% CI: 1.555-3.394, p < 0.001) were independent prognostic predictors linked with mortality. Overall, TACE was not an independent prognostic factor; among patients with low TBS, TACE was independently associated with decreased survival compared with RFA (HR: 1.372, 95% CI: 1.0251.836, p = 0.034).

Conclusions: TACE may provide similar longterm survival compared with RFA for HCC patients within Milan criteria, with the exception that among patients with low TBS, RFA is associated with better outcome compared with TACE.

P.061

DAILY ASPIRIN REDUCED THE INCIDENCE OF HEPATOCELLULAR CARCINOMA AND OVERALL MORTALITY IN CIRRHOTIC PATIENTS

Chern-Horng Lee1, Chiu-Yi Hsu2, Tzung-Hai Yen3, Tsung-Han Wu4, Ming-Chin Yu4, Sen-Yung Hsieh5,6

1Department of General and Geriatric Medicine, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan

2Center for Big Data Analytics and Statistics, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan

3Department of Nephrology, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan

4Department of General Surgery, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan

5Department of Gastroenterology and Hepatology, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan

6College of Medicine, Chang Gung University, Taoyuan, Taiwan

肝硬化患者每日服用阿斯匹靈可以降

aspirin for at least 84 days were defined as the therapy group, whereas those without treatment were controls. A 1:2 propensity score matching by age, sex, comorbidities, drugs, and major clinical laboratory tests with covariate assessment was used.

Results: Multivariate regression analyses revealed that daily aspirin use was independently associated with a reduced risk of HCC (three-year HR: 0.567; 95% CI: 0.371-0.869; P = 0.0091; fiveyear HR: 0.629, 95% CI: 0.449-0.882; P = 0.0072). inversely correlated with the treatment duration [3-12 months: HR: 0·88 (95% CI: 0.576-1.344); 12-36 months: HR: 0.56 (0.311-0.996); and ≥ 36 months: HR: 0.37 (0.178-0.764)]. Overall mortality rates were significantly lower among aspirin users compared with untreated controls [three-year HR: 0.43 (0.33-0.57); five-year HR: 0.51 (0.42-0.63)]. The similar result was validated by NHI cohort using PSM method and HCC incidence reduced inverse with correlated with aspirin dose duration interval dependent. Consistent results were obtained when the laboratory data were included in the propensity score for matching.

Conclusions: Long-term aspirin use significantly reduced the incidence of HCC, inversely correlated with the treatment duration and overall mortality in cirrhotic patient.

1 林口長庚紀念醫院高齡醫學科暨一般內科

2 林口長庚紀念醫院巨量資料及統計中心

3 林口長庚紀念醫院腎臟內科

4 林口長庚紀念醫院一般外科

5 林口長庚紀念醫院胃腸肝膽內科

6 長庚大學醫學院

Background: Cirrhosis is the primary risk factor for hepatocellular carcinoma (HCC) and gastrointestinal bleeding.

Aims: We aim to assess the efficacy and safety of daily aspirin on HCC occurrence, and overall survival in patients with cirrhosis.

Methods: 35898 eligible cases were enrolled for analyses from an initial 40603 cirrhotic patients without tumor in CGRD. Validation was confirmed by 4902 cirrhotic patient with aspirin, 9804 cirrhotic patient without aspirin from NHI between 2004 and 2017. Patients continuously treated with

低肝癌發生及死亡率

P.062

COMBINATION OF SYSTEMIC IMMUNE-INFLAMMATION INDEX AND ALBUMIN-BILIRUBIN SCORE PREDICT PROGNOSIS OF SEQUENTIAL THERAPY WITH SORAFENIB AND REGORAFENIB IN UNRESECTABLE HEPATOCELLULAR CARCINOMA

Tai-An Cheng1, Wei Teng1,2,3, Po-Ting Lin1,2,3, Chen-Chun Lin1,2,3, Chun-Yen Lin1,2,3, Shi-Ming Lin1,2,3

1Department of Internal Medicine, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan, Taiwan

2Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan, Taiwan

3College of Medicine, Chang Gung University, Taoyuan, Taiwan

ALBI ）以用於預測

retrospectively enrolled for analysis. Treatment response was evaluated by modified Response Evaluation Criteria in Solid Tumors (mRECIST) criteria. The pre-treatment host factors, tumor status, biochemistry markers and inflammatory index (NLR, PLR, MLR, SII, SIRI, ILIS) were collected, which were evaluated by Area under the receiver operating characteristic curve (AUROC) for performance of predicting PFS and OS. Progression-free survival (PFS) and overall survival (OS) were assessed using the Kaplan–Meier survival curves. The Cox regression model was used to identify independent predictors of PFS and OS. Statistical analysis was done by the SAS software, version 9.4 (SAS institute, Inc., Cary, NC, USA).

2 長庚醫療財團法人林口長庚紀念醫院肝膽腸胃科

3 長庚大學醫學院

Background: Sequential therapy with sorafenib and regorafenib had shown promising results to improve outcomes for unresectable hepatocellular carcinoma (uHCC) patients. Although there have been several reports regarding the efficacy of sequential therapy in real-world, the role of specific inflammation markers for predicting the prognosis are still unclear.

Aims: This study aimed to investigate prognostic value of systemic inflammatory markers in HCC patients receiving sorafenib-regorafenib sequential therapy.

Methods: A total of 122 uHCC patients who received sorafenib–regorafenib sequential therapy from August 2016 to August 2021 were

Results: Among the 122 patients, the median age was 66 years old and 84% were male gender. Regorafenib was used as the second and third lines of therapy in 97 (80%) and 25 (20%) patients respectively. Most patients were ChildPugh A (96%), ABLI grade II (52%) and BCLC stage C (73%) at baseline. The median duration of Regorafenib treatment was 4.1 months (IQR: 2.6-8.0). The overall response rate (ORR) and disease control rate (DCR) was 7.4% and 46.7%, respectively, while the median OS and PFS were 15.9 (95% CI: 11.4-20.4) and 3.4 (95% CI: 3.0-3.8) months respectively. Multivariate Cox regression analysis showed that baseline ALBI grade I and systemic inflammatory index (SII) < 330 were independent factors associated with good OS (hazard ratio [HR] = 0.655, p = 0.031 & HR = 0.570, p = 0.039) and PFS (HR = 0.725, p = 0.040 & HR = 0.341, p = 0.016). We further stratified our patients into 3 risks group (A: SII ≤ 330 & ALBI grade I, B: SII > 330 or ALBI grade II/III, C: SII > 330 & ALBI grade II/III). The combination of SII ≤ 330 & ALBI grade I showed the best OS (A vs. B vs. C = NR vs. 17.9 vs. 7.5 months, log-rank P = 0.003) and PFS (A vs. B vs. C = NR vs. 3.7 vs. 2.9 months, log-rank P = 0.001) than other two groups.

Conclusions: This study was a retrospective cohort study in a real-world setting, investigating the survival benefit and efficacy of regorafenib therapy. The combination of ALBI grade and SII level at the initiation of regorafenib therapy can be used to stratify patients by their survival probability from receiving sequential therapy.

P.063

MAC-2 BINDING PROTEIN GLYCOSYLATION ISOMER IS A POTENTIAL BIOMARKER TO PREDICT BACTERIAL INFECTION IN CIRRHOTIC PATIENTS

Pei-Shan Wu1,2,3, Yun-Cheng Hsieh1,2, Kuei-Chuan Lee1,2, Yi-Hsiang Huang1,2, Han-Chieh Lin1,2, Ming-Chih Hou1,2,3

1Division of Gastroenterology and hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan

2Department of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan

3Endoscopy Center for Diagnosis and Treatment, Taipei Veterans General Hospital, Taipei, Taiwan MAC-2

who did not. On multivariate Cox regression analysis, age [Hazar ratio (HR) = 1.04, p = 0.034] and M2BPGi (HR = 1.11, p = 0.016) are potential predictors for overall bacterial infection events at first year of follow-up. Furthermore, the cumulative incidence is significant higher in patients with plasma M2BPGi ≥ 6.23 C.O.I than those with M2BPGi < 6.23 C.O.I. (43% vs. 7%, p < 0 .001) However, M2BPGi did not predict mortality and other cirrhosis-related outcomes.

Conclusions: Plasma M2BPGi levels might have a potential role in predicting development of bacterial infection for cirrhotic patients, which may help to identify cirrhotic patients who are at risk of developing bacterial infection.

Background: Mac-2-binding protein glycosylation isomer (M2BPGi) is a novel plasma biomarker for liver fibrosis, but less is known about its role in cirrhosis-related clinical outcomes.

Aims: We aimed to investigate the role of M2BPGi in predicting prognosis of cirrhotic patients.

Methods: A total of 149 patients with the diagnosis of liver cirrhosis and received regular follow-up in Taipei Veterans general hospital were retrospectively enrolled. Twenty-two healthy adults were enrolled as healthy control. Patients were followed for at least one year and the cirrhosis-related clinical outcomes were recorded. Cox proportional hazards regression models were used to identify predictors for clinical outcomes.

Results: Plasma M2BPGi levels were higher in cirrhotic patients than healthy subjects (7.22 ± 4.49 vs. 0.78 ± 0.29 C.O.I, p < 0.001). In cirrhotic patients, patients who developed bacterial infection events, acute kidney injury, hepatic encephalopathy, received liver transplant or died had higher plasma levels of M2BPGi than those

P.064

SIMILAR EFFICACY AND SAFETY BETWEEN LENVATINIB VERSUS ATEZOLIZUMAB PLUS BEVACIZUMAB AS THE FIRST-LINE TREATMENT FOR UNRESECTABLE HEPATOCELLULAR CARCINOMA

Chung-Wei Su1,2, Wei Teng1,2, Po-Ting Lin1,2, Wen-Juei Jeng1,2, Kuei-An Chen2,3, Yi-Chung Hsieh1,2, Wei-Ting Chen1,2, Ming-Mo Hou2,4, Chia-Hsun Hsieh2,5, Chen-Chun Lin1,2, Chun-Yen Lin1,2, Hsi-Ming Lin1,2

1Department of Gastroenterology and Hepatology, Linkuo Chang Gung Memorial Hospital, Taoyuan, Taiwan

2College of Medicine, Chang Gung University, Taoyuan, Taiwan

3Department of Medical Imaging and Intervention, Linkuo Chang Gung Memorial Hospital, Taoyuan, Taiwan

4Department of Medical Oncology, Linkuo Chang Gung Memorial Hospital, Taoyuan, Taiwan

5Department of Medical Oncology, Tucheng Composite Municipal Hospital, New Taipei City, Taiwan

received lenvatinib (n = 46) and atezolizumab plus bevacizumab (n = 46) as first-line systemic therapy for unresectable HCC in a tertiary medical center. Objective response rate (ORR), progression free survival (PFS), and overall survival (OS) were evaluated according to modified Response Evaluation Criteria in Solid Tumors (mRECIST). Pretreatment age, gender, etiology, biochemistry and Barcelona Clinic Liver Cancer (BCLC) stages were analyzed. Propensity score matching (PSM) with 1:1 was performed for baseline clinical features balance. Cox regression analysis was applied for predictors of PFS.

Results: A total of 92 patients with a median age of 63.8 year-old, 78.3% male, 85.9% viral hepatitis infected, 67.4% BCLC stage C were enrolled. The median treatment and follow up duration were 4.7 months and 9.4 months, respectively. During the follow-up period, tumor progression and mortality were observed in 59 patients and 33 patients respectively. There was no significant difference in ORR (26.1% vs. 40.0%, P = 0.1226), PFS (5.9 vs. 5.3 months, P = 0.4066) (figure), and OS (not reached vs. not reached, P = 0.7128) between lenvatinib and atezolizumab plus bevacizumab groups. After PSM, the results of survival and response rate were also comparable between these two groups. Subgroup analysis suggested that using lenvatinib was not inferior to atezolizumab plus bevacizumab in regards of PFS, including those with elder, Child-Pugh class B, beyond up-to-seven, or portal vein invasion VP4 patients. Among the lenvatinib treated patients, multivariate regression analysis showed patients elder than 65 year-old was an independent predictor associated with shorter PFS (adjust HR: 2.085 [0.914-4.753], P = 0.0213). The incidence rates of treatment related adverse events were similar between two groups (76 vs. 63%, P = 0.1740). Both of two regimens had similarly few impact on liver function by comparison of baseline, 3rd month, and 6th month albumin-bilirubin index and Child-Pugh score.

Background: Lenvatinib and atezolizumab plus bevacizumab are the two mainstay first-line therapy for unresectable Hepatocellular carcinoma (HCC).

Aims: Real-world study comparison of efficacy and safety between these two regimens is limited, so we aimed to investigate these issues in a realworld cohort.

Methods: We retrospectively reviewed patients

Conclusions: The efficacy and safety of lenvatinib are similar to atezolizumab plus bevacizumab as a primary systemic therapy for unresectable HCC.

4 林口長庚紀念醫院腫瘤科

5 新北市立土城醫院腫瘤科

P.065

REAL-LIFECLINICAL EXPERIENCE OF LENVATINIB PLUS PEMBROLIZUMAB IN PATIENTS WITH UNRESECTABLE HEPATOCELLULAR CARCINOMA

Yuan-Hung Kuo, Ming-Chao Tsai, Chao-Hung Hung, Sheng-Nan Lu, Tsung-Hui Hu, Yi-Hao Yen, Chien-Hung Chen, Jing-Houng Wang

Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan

無法切除肝癌病人使用樂衛瑪合併吉 舒達現實生活的臨床經驗

郭垣宏

長庚醫療財團法人高雄長庚紀念醫院胃腸肝膽科系

Background: Lenvatinib combined with pembrolizumab has been reported to have survival benefits in an early phase study for unresectable hepatocellularcarcinoma (uHCC), but the application of this combo is still uncommon in daily clinical practice.

Aims: This study was attempted to evaluate the efficacy and safety of lenvatinib plus pembrolizumab for patients with uHCC in realworld.

Methods: Twenty-nine consecutive patients who received lenvatinib plus pembrolizumab for uHCC were retrospectively enrolled. Treatment response was assessed according to the criteria of Response Evaluation Criteria in Solid Tumors version 1.1 (RECIST v1.1). Treatment-related adverse events(TRAE) and clinical outcomes of study patients were obtained from electronic medical records.

Results: All the enrolled 29 patients were ChildPugh class A, and 27 (93.7%) were in Barcelona Clinical Liver Cancer stage C. The median age was 61 (range: 32–84). There were 17 (58.6%) for the first-line systemic treatment, and 12 (41.4%) for the later-line treatment following atezolizumab plus bevacizumab or sorafenib-based sequential therapies. At median follow-up of 8.1 months, the objective response rate and disease control rate

were 30.8% and 69.2% for the first-line group, as well as 0% and 30% for the later-line group, respectively. Additionally, the progression-free survival was 9.4 months versus 4.9 months, and the overall survival was not estimated yet versus 10.9 months for the first-line group and later-line group, respectively. Overall, 51.7% of patients experienced TRAEs and 10.3% experienced Grade 3 or above TRAEs.

Conclusions: Lenvatinib plus pembrolizumab seemed to achieve a promising treatment response and encouraging survival outcomes with acceptable toxicity in uHCC patients under the first-line setting. However, the treatment outcome of the later-line group was suboptimal in real-life practice.

蔡明釗 洪肇宏 盧勝男 胡琮輝 顏毅豪 陳建宏 王景弘

P.066

THE NEWEST 1,25(OH)2D3 ANALOG, MART 11, COULD REPRESS HEP3B

HEPATOCELLULAR CARCINOMA CELL LINE GROWTH AND IS MORE POTENT THAN 1,25(OH)2D3

Li-Wei Chen1, Kun-Chun Chiang2, Ya-Hui Hsu3

1Division of Hepato-Gastroenterology, Department of Internal Medicine, Keelung Chang Gung Memorial Hospital, Keelung, Taiwan

2Department of General surgery, Min Sheng General Hospital, Taoyuan, Taiwan

3Graduate Institute of Clinical Medical Sciences, College of Medicine, Chang Gung University, Taoyuan, Taiwan

obviously attenuated F-actin synthesis of Hep3B cells more than 1,25(OH)2D3. MART-11 increased E-cadherin, decreased N-cadherin expression of Hep3B cells. The EMT-related transcriptional factors, Slug, Snail and twist were all repressed by MART-11 and 1,25(OH)2D3 in hep3B cells.

Conclusions: MART-11 could repress Hep3B cell growth and metastasis. MART-11 obviously is more potent than 1,25(OH)2D3. Hence, MART-11 deserves further investigation for HCC treatment.

陳立偉1 江坤俊2 許雅惠3

1 基隆長庚紀念醫院胃腸肝膽科

2 敏盛綜合醫院一般外科

3 長庚大學臨床醫學研究所

Background: Vitamin D is one kind of pleotropic hormone. Because of the anti-cancer effect of vitamin D, it has been widely studied in the past decades for cancer treatments. A newest vitamin D analog, 19-nor-2β- (3-hydroxypropyl)1,25(OH)2D3 (MART-11), was studied for the treatment of hepatocellular carcinoma (HCC).

Aims: This study aimed to evaluate the effect of MART-11 on HCC growth and metastasis.

Methods: Hep3B cell line was used in this study. To investigate the anti-proliferative effect (by BrdU combined with MTT [3-(4,5-dimethylthiazolyl-2)-2, 5-diphenyltetrazolium bromide] assay) , cell cycle control (by CDK inhibitors), apoptosis induction (by flow cytometry with cell double stained by PI and anexin V), anti-invasion and migration effect (by using 24-well Transwell chamber with 8 mm pore filter), of 1α,25(OH)2D3 and MART-11 on HCC.

Results: Under 10-7 and 10-8 M, both MART-11 and 1,25(OH)2D3 could inhibit Hep3B cell growth, induce a cell cycle arrest at G1 phase, inhibit migration and invasion of Hep3B cells . MART11 is more potent than 1,25(OH)2D3. MART-11

最新一代維他命 D 類似物（ MART11）抑制肝癌 Hep3B 細胞株的生長且 療效勝於傳統維他命 D

P.067 ASSOCIATION OF SERUM FERRITIN, URIC ACID LEVELS AND HEPATIC FIBROSIS IN LEAN SUBJECTS WITH METABOLIC ASSOCIATED FATTY LIVER DISEASE IN THE KEELUNG COMMUNITY

Cheng-Han Xie1, Li-Wei Chen1,2, Chih-Lang Lin1,2, Cheng-Hung Chien1,2, Rong-Nan Chien1,2

1Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital and University at Keelung, Keelung, Taiwan

2Community Medicine Research Center, Chang Gung Memorial Hospital and University at Keelung, Keelung, Taiwan

divided into two groups of lean MAFLD subjects and lean healthy subjects. Positive correlation of serum ferritin and uric acid concentrations with liver fibrosis were observed no matter using fibrosis-4 (FIB4), NAFLD fibrosis score (NFS) or AST to Platelet Ratio Index (APRI) as references. Univariate logistic regression analysis showed age [OR = 1.20 (1.04-1.38), P = 0.012], uric acid [OR = 6.33 (1.29-31.13), P = 0.023] were associated with advanced liver fibrosis (FIB4 > 2.67). After adjusting for potential confounders, only uric acid level was statistically significance in predicting the advanced liver fibrosis [OR = 6.94 (1.11-42.94), P = 0.038] in the lean MAFLD group. Conclusions: In this community-based study, we found the elevated serum uric acid level is an independent factor associated with advanced liver histology in lean MAFLD subjects in the Keelung community.

2 基隆長庚紀念醫院社區醫學研究中心

Background: Elevated serum ferritin or serum uric acid level is common in patients with nonalcoholic fatty liver disease (NAFLD) in previous studies. The association between serum ferritin, serum uric acid level and hepatic fibrosis showed inconsistent results from previous studies.

Aims: The aim of this study is to access serum ferritin level, serum uric acid level and its association with liver fibrosis in lean metabolic associated fatty liver disease (MAFLD) subjects in the Keelung community.

Methods: A cross-sectional study was performed from a community screening examination for metabolic syndrome from December 2018 to September 2019 in Keelung Chang Gung memorial hospital. The subjects’ demographics, blood biochemistry and abdominal ultrasonography were collected. The Fibrosis-4 (FIB-4) score was used to evaluate liver fibrosis. The abdominal ultrasonography and fatty liver index were used to evaluate liver steatosis. Subjects with lean MAFLD was defined as body mass index (BMI) < 23 Kg/ m2 and hepatic steatosis following MAFLD criteria.

Results: A total of 211 lean subjects were included in this study. The lean subjects were further

P.068

URSODEOXYCHOLIC ACID MODULATE FARNESOID X RECEPTOR AND NF-KAPPA B SIGNALING IN HEPATOCYTE

Chi-Yi Peng1, Yi-Jun Liao2, Cheng-Hung Lai1, Su-Peng Ho1, Yen-Chun Peng3

1Department of Veterinary Medicine, National Chung Hsing University, Taichung, Taiwan

2Division of Gastroenterology, Taichung

Veterans General Hospital, Taichung, Taiwan

3Division of gastroenterology, Taichung

Veterans General Hospital, Chiayi Branch, Chiayi, Taiwan

Ursodeoxycholic Acid 對於法尼醇 X 受體與 NF-kappa B 訊息路徑在肝細 胞的調控

1 國立中興大學獸醫系

2 臺中榮民總醫院胃腸科

3 臺中榮民總醫院嘉義分院胃腸科

Background: Ursodeoxycholic acid (UA) is a bile acid as a conjugate with taurine. It prevents the synthesis and absorption of cholesterol. Clinically, it is lead to the dissolution of gallstones. It has a role as a human metabolite and a mouse metabolite. farnesoid X receptor (FXR) has a positive role in hepatic carcinogenesis, and NF-kappa B regulates inflammation and carcinogenesis.

Aims: The aim of the present study is to demonstrated the role of UA in the interaction of FXR and NF-kappa B.

Methods: HepG2 cell line and LPS treatment was used for the reaction of UA. Western blots of NFkappa B components including p65, P-p65, and FXR were expressed after LPS and UA treatment. NF-kappa associated signaling COX-2, TNF-alpha and IL-6 were determined by RT-PCR.

Results: Wester blots showed UA treated LPS stimulated HepG2 cell showed upregulation of FXR and downregulation of NF-kB/p65. The NFkappa B signaling COX-2, TNF-alpha and IL-6 were also decreased by RT-PCR by UA treating.

Conclusions: UA could upregulate FXR and downregulation of NF-kappa B signaling COX-2, TNF-alpha and IL-6. There is possible role of UA in hepatic carcinogenesis.

P.069

PIVKA-II PREDICTS

HEPATOCELLULAR CARCINOMA DEVELOPMENT IN CHRONIC B RELATED LIVER CIRRHOSIS PATIENT LONG-TERN EFFECT OF ANTIVIRAL TREATMENT

Kuo-Chin Chang1, Tsung-Hui Hu1, Sherry Yueh-Hsia Chiu1,2, Ming-Tsung Lin1, Chao-Hung Hung1, Jing-Houng Wang1

1Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan

2Department of Health Care Management, College of Management; and Healthy Aging Research Center, Chang Gung University, Taoyuan, Taiwan

PIVKA-II 是經長期抗病毒治療慢性 B

Background: Chronic hepatitis B virus (HBV)related liver cirrhosis (LC) patients have the high risk for hepatocellular carcinoma (HCC) even undergoing long-term nucleos(t)ide analog (NUCs) therapy.

Aims: Protein induced by vitamin K absence or antagonist-II (PIVKA-II) is currently used to as a predict risk factors for the development of hepatocellular carcinoma CHB patients were receiving NUCs in CHB-treated patients, but the PIVKA-II in LC patients long-term NUCs-treated is still unclear.

Methods: This retrospective study was conducted in 1108 NUC-treated cirrhosis They received NUC therapy from April 1999 to February 2015 and all patients were diagnosed the virus was complete suppressed. The baseline biomarkers and followed results were collected by hospital.

Results: Among the 1108 patients, 219 of 1108 developed HCC within a median follow-up of 6.85 years. Patients with older age, DM, lower platelet count, AFP ≥ 20 ng/mL, FIB-4 ≥ 3.25, APRI ≥ 1.25,

or PIVKA-II > 40 were tended to have significant risk of HCC. Univariate and adjusted-multivariable models revealed low PLT count, AFP ≥ 20 ng/ mL, DM, FIB-4 ≥ 3.25 as risk factors of HCC development. PIVIKA-II level resulted in risk of HCC development treatment with the adjusted hazard ratios (aHRs) of 1.00, 1.46, 2.11 and 2.47 under stepwise selection multivariable models, respectively.

Conclusions: After adjustment for potential confounding factors, patients with CHB related LC with PIVIKA-II > 25 levels had significant risk of HCC development even under long-term effective NUC antiviral therapy.

P.070 CASE SERIES OF IDIOPATHIC MESENTERIC PHLEBOSCLEROSIS FROM A SINGLE COMMUNITY HOSPITAL IN SOUTHERN TAIWAN

Yoen-Young Chuah, Lian-Feng Lin, Seng-Howe Nguang, Chia-Jung Kuo, Yi-Chun Chan, Chun-Fong Lin, Lin-Suei Jhang

Division of Gastroenterology and Hepatology, Department of Internal Medicine, Ping Tung Christian Hospital, Pingtung, Taiwan

自發性腸系膜靜脈硬化自南部單一社 區醫院的案例系列

Background: Ischemic colitis is usually caused by arterial obstruction secondary to arteriosclerosis or thrombosis. However, mesenteric venous abnormalities may also attribute to the cause of ischemic colitis that eventually lead to fibrosis and calcification of mesenteric veins with features of mucosa thickening of colon that result in decreased motility and luminal stenosis. Idiopathic mesenteric phlebo-sclerosis (IMP) is a special form of ischemic colitis with calcifications along the wall of colon as the peculiar features in radiography as well as bluish discoloration of mucosa in colonoscopy.

Aims: To retrospectively review the clinical characteristics, comorbidity and drug exposure of idiopathic mesenteric phlebosclerosis cases encountered in our hospital.

Methods: Three cases of idiopathic mesenteric phlebosclerosis encountered in our hospital in the past 15 years of this rare entity of ischemic colitis were retrospectively reviewed and analyzed.

Results: All the three cases were females with average age of 57 years-old when first diagnosed with idiopathic mesenteric phlebosclerosis. All three cases had abdominal pain. Two cases had bloody stool passage. One case was diagnosed by sigmoidoscopy by bluish discoloration of mucosa and the other two cases were diagnosed on KUB and CT of abdomen by peculiar calcification of mesenteric veins. It took average about 6.7 years (4 to 11 years) to reach the diagnosis of idiopathic mesenteric phlebosclerosis radiographically

after patients first encounter with their relevant clinical presentation according present study. One patient had history of non- B non-C liver cirrhosis and primary sclerosing cholangitis and the other one patient had long-term exposure to chinese medicine of geniposide. One patient died of decompensated liver.

Conclusions: Due to the rarity of Idiopathic mesenteric phlebosclerosis, it is easily underdiagnosed clinically. Further education may help to increase the alertness of this disease among physicians.

P.071

THE COMBINATION OF FIB-4 AND NEUTROPHIL-TO-LYMPHOCYTE RATIO FOR PREDICTING RECURRENCE-FREE SURVIVAL OF PATIENTS UNDERGOING CURATIVE RADIOFREQUENCY ABLATION FOR HEPATOCELLULAR CARCINOMA

Chien-Wen Whang1, Che-Wei Chang2, Hung-Wei Wang2

1Division of Gastroenterology, Department of Internal Medicine, Cheng-Hsin General Hospital, Taipei, Taiwan

2Center for Digestive Medicine, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan

黃建文1 張哲維2 王鴻偉2

1 振興醫療財團法人振興醫院內科部胃腸科 2 中國醫藥大學附設醫院內科部消化醫學中心

Background: Radiofrequency ablation (RFA) is one of curative treatment for early stage of hepatocellular carcinoma (HCC). The prognostic value of the combination of FIB-4 and neutrophillymphocyte ratio (NLR) after curative RFA isn’t discussed.

Aims: We aim to explore the prognostic values of baseline FIB-4, albumin-bilirubin (ALBI) score and NLR in patients with HCC after RFA.

Methods: Total 25 patients with HCC receiving RFA were enrolled retrospectively and were confirmed complete ablation by CT or MRI study. We evaluated the prognostic values of FIB-4, ALBI and NLR for recurrence free survival (RFS). Area under the receiver operating characteristic curve (AUROC) was used to evaluate the performance of FIB-4, ALBI and NLR in predicting RFS and compared by DeLong test.

Results: In this cohort, their baseline median age was 66 years and 15 (60%) were male. Total 12 patients (48%) had recurrent HCCs during a median follow-up period of 24 months. An optimal cut-off value for NLR in predicting RFS was 3 by

結合 FIB-4 和 Neutrophil-tolymphocyte Ratio 對於肝癌患者接受

根除性腫瘤射頻消融術後可預測肝癌 無復發生存率

Youden index. The AUROC of NLR (AUROC: 0.644) was numerically higher for RFS than those of FIB-4 and ALBI (AUROC: 0.487 and 0.494, respectively). The combination of FIB-4 (cutoff value: 3.25) and NLR (cut-off value: 3) could be used to stratify patients by the probability of RFS (log-rank test, P = 0.044). Multivariable Cox proportional hazards model showed that male gender (hazard ratio (HR): 7.330, 95% confidence interval (CI): 1.554-34.58, P = 0.012), the combination of FIB-4 (>3.25) and NLR (≥3) (HR: 9.553, 95% CI: 2.051-44.49, P = 0.004) were both significant predictors of RFS.

Conclusions: The combination of FIB-4 (>3.25) and NLR (≥3) is an independent poor prognostic factor affecting the RFS of patients with earlystage HCC after complete ablation. Further study is warranted.

FATTY LIVER DISEASE

Yang-Sheng Lin1,2,3, Wei-Chen Lin2,3, Ching-Wei Chang2,3, Ming-Jen Chen2,3

1Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan

2Division of Gastroenterology and Hepatology, Department of Internal Medicine, MacKay Memorial Hospital, Taipei, Taiwan

3MacKay Medical College, Taipei, Taiwan

林揚笙1,2,3

2,3

Background: Acoustic radiation force impulse (ARFI) is an ultrasound-based elastography method to access the hepatic fibrosis of liver disease. Evidence has shown that ARFI exerted a satisfactory diagnostic performance in nonalcoholic fatty liver disease (NAFLD) with advanced liver fibrosis (F ≥ 3). However, the clinical value of ARFI to determine significant fibrosis (F ≥ 2) in NAFLD remains uncertain.

Aims: To evaluate the significant hepatic fibrosis of ARFI in NAFLD.

Methods: We enrolled consecutive patients with NAFLD identified by ultrasound. Significant liver fibrosis was determined using ARFI with a cut-off value of 1.45 m/s. Liver biopsies were taken from segment 5/8 of the liver and reviewed by the same pathologist. The histological checklist was from the NASH-CRN with few additional comments. The diagnostic odds ratio (OR) performed using STATA software.

Results: 23 patients underwent ARFI and followed by liver biopsy were included. In comparison with significant hepatic fibrosis (F ≥ 2) with advanced hepatic fibrosis (F ≥ 3) the diagnostic OR was 1.5 (CI= 0.27 to 8.45, p value = 0.645).

Conclusions: ARFI failed to differentiate significant hepatic fibrosis from advanced hepatic

P.072 USING ACOUSTIC RADIATION FORCE IMPULSE ELASTOGRAPHY TO EVALUATE LIVER FIBROSIS IN NON-ALCOHOLIC

使用聲輻射力脈衝彈性成像評估非酒 精性脂肪肝的肝纖維化

2 馬偕紀念醫院腸胃肝膽科

fibrosis in the present study. Probably, the small sample size leading to lack of statistic power. However, ARFI is still a preferable non-invasive screening tool for in NAFLD under daily practice.

P.073 INCIDENCE OF HELICOBACTER PYLORI INFECTION ALONG WITH CIRRHOSIS

Zubin Pradeep Sharma, Divya Sharma

Department of Gastroenterology and Pathology, Aditya Hospital & Gastro Center, Sriganganagar, Rajasthan, India

Background: H. pylori infection is one of the main causes of peptic lesions among cirrhotics. Peptic lesions may manifest as upper GI bleed apart from variceal bleed in cirrhotics. Oxygen free radicals cause gastric inflammation and are not normal in patients of chronic liver disease.

Aims: Documentation of incidence of H. pylori infection along with cirrhosis

Methods: 50 cirrhosis patients were taken into consideration for this documentation, while doing endoscopy, antral biopsy was taken as well as rapid urease test was carried out.

Results: 19 percent were positive for Rapid Urease Test while 81 percent were negative. 58 percent reported esophageal varices, 12 percent reported gastric varices, 78 percent reported portal gastropathy, 22 percent reported duodenal ulcer (10 percent tested Rapid Urease Test +) 14 percent reported antral erosions (6 percent tested Rapid Urease Test +).

Conclusion: There was preponderance of Cirrhotic patients who tested negative for Rapid Urease Test whereas patients who had concomitant peptic ulcer disease, reported a higher H. pylori infection (positive test).

P.074

SURVIVAL EVIDENCE OF LOCAL CONTROL FOR COLORECTAL CANCER LIVER METASTASES BY HEPATECTOMY AND/OR RADIOFREQUENCY ABLATION

Shu-Hsien Lin1, Yueh-Wei Liu2, Hong Hwa Chen3, Wang-Hseng Hu3, Yao-Hsu Yang4, Chao-Hung Hung1

1Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang

Gung University College of Medicine, Kaohsiung, Taiwan

2Liver Transplant Center, Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, and Chang Gung University College of Medicine, Kaohsiung, Taiwan

3Department of Colorectal Surgery, Kaohsiung

Chang Gung Memorial Hospital and Chang

Gung University College of Medicine, Kaohsiung, Taiwan

4Department of Traditional Chinese Medicine, Chiayi Chang Gung Memorial Hospital, Chiayi, Taiwan

肝切除和射頻消融術局部控制大腸直 腸癌肝轉移的生存證據

林淑賢

1 高雄長庚紀念醫院胃腸肝膽科系

2 高雄長庚紀念醫院一般外科肝臟移植中心

3 高雄長庚紀念醫院大腸直腸肛門外科

4 嘉義長庚紀念醫院中醫科

Background: Hepatectomy and/or local ablation therapy has been recommended for colorectal cancer liver metastases (CRLM) if curative-intent treatment is possible. However, there is no direct evidence to prove their survival benefits in addition to systemic therapy.

Aims: This study aimed to evaluate the survival evidence of hepatectomy and/or radiofrequency ablation (RFA) therapy in patients with CRLM from a large multi-institutional database in Taiwan.

Methods: A total of 20,251 patients with colorectal cancer and 4,521 of them with CRLM were screened for eligibility from 2004 to 2017. Finally, 2,612 patients (637 hepatectomy, 93 RFA, 92 hepatectomy combined RFA and 1,790

non-aggressive local therapy) were enrolled. Frequency matching analysis was used to adjust for baseline differences to compare the overall survival between patients with hepatectomy and/ or RFA and those without.

Results: Kaplan-Meier curves showed that hepatectomy, RFA and both significantly associated with better overall survival (OR) compared to those without aggressive local therapy (p < 0.001). Multivariate Cox’s regression analysis showed that male gender (hazard ratio (HR) 0.89; 95% confidence interval (CI), 0.810.97; p = 0.011), old age (≥60 years) (HR, 1.20; 95% CI, 1.09-1.32; p<0.001), high CEA level (>5 ng/ml) (HR, 2.14; 95% CI, 1.89-2.42; p < 0.001), primary right side colon cancer (HR, 1.35; 95% CI, 1.22-1.51; p < 0.001), extrahepatic metastasis (HR, 1.46; 95% CI, 1.33-1.60; p < 0.001), systemic therapy (HR, 0.7; 95% CI, 0.62-0.79; p < 0.001) and aggressive local therapy (hepatectomy vs. non-local therapy HR, 0.22; 95% CI, 0.20-0.26; p < 0.001; RFA vs. non-local therapy HR, 0.29; 95% CI, 0.29-0.41; p < 0.001) were independent factors associated with OS. In the frequency matching analysis, patients receiving hepatectomy and/or RFA resulted in better OR than those who did not receive aggressive local therapy (p < 0.001).

Conclusions: Aggressive local control by hepatectomy and/or RFA in patients with CRLM has survival benefits in addition to systemic therapy.

P.075 RISK OF HEPATIC EVENTS IN IMMUNE CHECKPOINT INHIBITORTREATED CANCER PATIENTS

Yi-Ping Hung1,3, Pei-Chang Lee2,3,4, Yen-Hwa Chang5, Muh-Hwa Yang1,2,3, Chao-Hua Chiu3,6, Ming-Huang Chen1,3, Keng-Hsin Lan3,4, I-Cheng Lee3,4, Ming-Chih Hou3,4, Yee Chao1,3, Yi-Hsiang Huang1,2,3

1Department of Oncology, Taipei Veterans General Hospital, Taipei, Taiwan

2Institute of Clinical Medicine, National Yang

Ming Chiao Tung University, Taipei, Taiwan

3Faculty of Medicine, National Yang Ming Chiao Tung University School of Medicine, Taipei, Taiwan

4Department of Internal Medicine, Division of Gastroenterology and Hepatology, Taipei Veterans General Hospital, Taipei, Taiwan

5Department of Urology, Taipei Veterans General Hospital, Taipei, Taiwan

6Department of Chest Medicine, Taipei

Veterans General Hospital, Taipei, Taiwan

patients experienced ICI therapy. Four hepaticassociated outcomes were defined: hepatitis flare, immune-related hepatitis (irHepatitis), and HBV reactivation. We further analyze virological data and antiviral therapy in these patients. Risk factors of events were determined through cox proportional hazard regression model.

Results: 1283 cancer patients were eligible for analyze and 283 (22.1%) were HBsAg positive. There were 190 HCC patients and 1093 nonHCC cancer patients. Hepatitis flare events were significantly more prevalent in HCC patients than non-HCC patients. HCC and baseline HBV > 40 U/L were independent risk factors, while ICI cycle > 4 was independent protective factor. There were no differences between HCC and non-HCC patients in irHepatitis risk. ALT > 40 U/L was independent risk factor, while ICI cycles > 4 was independent protective factor for irHepatitis. Seven patients (2.5%) experienced HBV reactivation and four of them then experienced decompensated hepatitis. All of them were HBsAg positive at baseline. None of them received NUC prophylaxis. NUC prophylaxis significantly reduce the risk for HBV reactivation in HBsAg positive patients. HCC is the only risk factor for HBV reactivation.

Conclusions: HBV reactivation is a rare but critical issue in HBsAg positive cancer patients under ICI therapy. Decompensation is common in reactivation patients. NUC prophylaxis minimizes the risk, even in high baseline HBV DNA patients.

Background: Significant advances have been made in immune checkpoint inhibitor (ICI). Rare but severe adverse effects, especially hepatotoxicity, remains critical challenging issues. Chronic hepatitis B patients were handled with more care for the concerns of hepatitis B virus (HBV) reactivation and fulminant hepatitis.

Aims: We would like to find out the risk of hepatic events in cancer patients under ICI therapy.

Methods: This is a single-institute retrospective cohort study in Taipei Veterans General Hospital from May 2014 to August 2020 focusing on cancer

5 臺北榮民總醫院泌尿部

6 臺北榮民總醫院胸腔部

P.076

A REAL-WORLD SINGLECENTER EXPERIENCE OF SEQUENTIAL SORAFENIBREGORAFENIB THERAPY FOR PATIENTS WITH UNRESECTABLE HEPATOCELLULAR CARCINOMA

Shou-Wu Lee1,2,3, Teng-Yu Lee1,2, Sheng-Shun Yang1,2,3, Yen-Chun Peng1,3, Chun-Fang Tung1,3, Chi-Sen Chang1,2

1Division of Gastroenterology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan

2Department of Internal Medicine, Chung Shan Medical University, Taichung, Taiwan

3Department of Internal Medicine, Yang Ming University, Taipei, Taiwan

單一中心針對中晚期肝細胞腫瘤病患

療之經驗分享

Background: Sorafenib (Sora) and Regorafenib (Rego) were the first approved 1nd-line and 2ndline effective systemic therapy to unresectable hepatocellular carcinoma (uHCC) respectively.

Aims: The aim of the study was to determine the real-world one-center outcomes of the patients with uHCC who received sequential Sora-Rego treatment.

Methods: Data on patients with BCLC stage B or C HCC who were receiving Sora-Rego as the sequential treatment from June 2019 to March 2022 was collected. All patients belonged to ChildPugh class A. The patients with combining other tyrosin kinase therapy or immunotherapy were excluded.

Results: A total of 54 patients were enrolled, and 16 (29.6%) and 38 cases (70.4%) were BCLC stage B and C respectively. The average therapeutic duration of Sora was 9.88 ± 6.49 months, and Rego was 7.64 ± 6.83 months. The overall survival of these patients was 20.75 ± 10.22 months. The survival rates of 1-year,

2-year and 3-year were 90.4%, 42.2% and 14.3% respectively. The regression analysis of patients’ overall survival showed a significant poor outcome in the patients with AFP > 400 ng/ml while comparing with those with AFP < 400 ng/ml (HR: 0.305, 95% CI: 0.143-0.649, P = 0.021).

Conclusions: The sequential Sora-Rego treatment provided acceptable efficacy to the patients with uHCC. The patients with higher AFP had a poor outcome.

Section：GI

P.077

EARLY ENDOSCOPY FOR UPPER GASTROINTESTINAL BLEEDING IN ACUTE CORONARY SYNDROME PATIENTS: A RANDOMIZED CONTROLLED TRIAL

Kuei-Chang Kuo1, Chen-Shuan Chung1,2, Chieh-Chang Chen3, Kuan-Chih Chen1, Yu-Jen Fang3, Wen-Feng Hsu4, Yen-Nien Chen4, Wei-Chuang Tseng1, Cheng-Kuan Lin1, Tzong-Hsi Lee1, Hsiu-Po Wang4, Yen-Wen Wu5

1Division of Gastroenterology and Hepatology, Department of Internal Medicine, Far Eastern Memorial Hospital, New Taipei City, Taiwan

2College of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan

3Department Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Yunlin Branch, Yunlin, Taiwan

4Department Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan

5Division of Cardiology, Department of Internal Medicine, Far Eastern Memorial Hospital, New Taipei City, Taiwan

safety of early endoscopy (EE) to those in the pharmacological therapy alone in the patients with acute UGIB after recent ACS.

Methods: We randomly assigned the patients with recent ACS presenting the symptoms of acute UGIB to the EE and the non-EE groups. The proton pump inhibitor (PPI) therapy was applied to all the patients. The endoscopy was performed on the patients in the EE group within 24 hours after the onset of bleeding. In non-EE group, the endoscopy was performed 2 weeks after enrollment. The data regarding the efficacy and the safety of EE were collected and analyzed.

3 國立臺灣大學醫學院附設醫院雲林分院內科部

4 國立臺灣大學醫學院附設醫院內科部

Background: Acute upper gastrointestinal bleeding (UGIB) is common in the patients with acute coronary syndrome (ACS), especially with the use of the dual antiplatelet therapy (DAPT). However, the endoscopic hemostasis may be associated with high risks of cardiopulmonary events. There is no adequate evidence supporting the optimal timing and the safety of the UGI endoscopy among patients with ACS.

Aims: We aimed to compare the efficacy and the

Results: We terminated the trial early because the UGIB rate was lower than expected. Forty-three patients were included and randomly assigned to EE (22 patients) groups and non-EE (21 patients) groups. The background characteristics, medications, laboratory findings before intervention, cardiac function, proportion of patients underwent coronary artery catheterization, and status of discontinuing DAPT were not different statistically between the two groups. The rate of failure bleeding control (intention-to-treat [ITT] 4.55% vs. 23.81%, p < 0.001; per-protocol [PP] 0% vs. 4.55%, p = 0.058) and the rate of rebleeding within 3 days (ITT 4.55% vs. 28.57%, p = 0.033; PP 0% vs. 21.05%, p = 0.027) were lower in the EE group. The mortality and the complication rates were not different between the two groups, but male patients had higher risk of both the minor (odds ratio [OR] 3.50, 95% confidence interval [CI] 1.15–10.63) and the major complications (OR 4.25, 95% CI 1.43–12.63) after EE. In the multivariate analysis, the amount of blood transfusion was lower in the EE group (OR 0.13, 95% CI 0.02–0.98). A higher risk of coronary artery stent re-thrombosis within 6 months was noted in the patients who discontinued the DAPT therapy for the UGIB (OR 5.25, 95% CI 1.21–22.74).

Conclusions: In patients with recent ACS, EE for acute UGIB has a higher rate of bleeding control, lower rate of rebleeding within 3 days, and lower needs for blood transfusion. Higher complications rate was noticed in male patients after EE. Further study with larger sample size is needed.

5 亞東紀念醫院心臟血管內科

SMALL INTESTINE BACTERIAL OVERGROWTH PREDICTS ACUTE CHOLANGITIS IN BILIARY ATRESIA PATIENTS

Jia-Feng Wu1, Peng-Huei Tseng2, Wen-Ming Hsu3, Mei-Hwei Chang1

1Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan

2Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan

3Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan

小腸細菌過度增長會增加膽道閉鎖病

(hazard ratio = 6.50, P < 0.001). The prediction persisted after adjusting the gender and liver cirrhosis status in multivariate models.

Conclusions: The prevalence of SIBO in BA patients is 22.73% in this study. The presence of SIBO is correlated with serum ALT levels and predictive of acute cholangitis in BA patients.

Background: Biliary atresia (BA) is the leading cause of pediatric liver transplantation in the world. Acute cholangitis is common in BA patients and predicts ominous outcomes.

Aims: We investigated the relationship between small intestine bacterial overgrowth (SIBO) and acute cholangitis in BA patients.

Methods: There are 66 BA patients with native liver (32 males) recruited into this prospective study at the mean age of 12.85 years. Hydrogen and methane-based breath testing (HMBT) was applied to detect SIBO in this cohort and they were followed prospectively for a mean time of 1.62 years after HMBT in our institute.

Results: There are 15 (22.73%) subjects detected to have SIBO by HMBT. BA subjects with SIBO were noted to have higher serum alanine aminotransferase (ALT) levels than in others without SIBO (P = 0.03). Sixteen (24.24%) BA patients of the whole cohort were diagnosed to have acute cholangitis during the follow-up. The risk of acute cholangitis is significantly higher in BA patients with SIBO than in others without SIBO (60% vs. 13.73%, P < 0.001). The logistic regression analysis demonstrated that BA subjects with SIBO have a higher risk of acute cholangitis than others without SIBO (Odds ratio = 9.43, P = 0.001). Cox’s proportional hazard analysis further confirmed the phenomena in survival analysis

P.079

ALDOLASE B MODULATES CELL RENEWAL AND SUSCEPTIBILITY TO 5-FLUOROURACIL BY INCREASING LACTATE AND CARCINOEMBRYONIC ANTIGEN LEVELS IN COLORECTAL CANCER

Wey-Ran Lin1,2,3, Yu-De Chu2, Chau-Ting Yeh1,2,3

1Department of Hepatology and Gastroenterology, Linkou Chang Gung

Memorial Hospital, Taoyuan, Taiwan

2Liver Research Center, Linkou Chang Gung

Memorial Hospital, Taoyuan, Taiwan

3College of Medicine, Chang Gung University, Taoyuan, Taiwan

and aerobic glycolysis activities for patients with CRC. Cell-based assays showed that increased ALDOB expression impacted on cell proliferation, susceptibility to 5-FU, bioenergetic alterations, and CEACAM6 expression in CRC cells. The increased ALDOB expression was associated with metabolic reprogramming and thus enhanced lactate secretion, promoted cell proliferation and elevated CEACAM6 expression. CEACAM6 was finally identified as a downstream effector of ALDOB-mediated lactate secretion in modulating cell proliferation and susceptibility to 5-FU.

Conclusions: ALDOB-mediated downstream pathway, composed of ALDOB, secretory lactate, and CEACAM6, were identified to play a crucial role in modulating CRC cell proliferation and susceptibility to 5-FU.

醛縮

酶 B 通過增加結直腸癌中的乳酸 和癌胚抗原水平來調節細胞生長和對 5- 氟尿嘧啶的敏感性

林蔚然1,2,3 朱育德2 葉昭廷1,2,3

1 林口長庚紀念醫院胃腸肝膽科

2 林口長庚紀念醫院肝臟研究中心

3 長庚大學醫學院

Background: Aldolase B (ALDOB), a glycolytic pathway involving enzyme, has been implicated as a potential biomarker of clinical outcomes for patients with colorectal cancer (CRC). Also, it has been associated with bioenergetic alterations in CRC. However, the links between ALDOB and cell behaviors related to bioenergetic alterations remain unclear.

Aims: Herein, the roles of ALDOB in modulating CRC cell behaviors and bioenergetic homeostasis, and the potential crosstalk of them were investigated.

Methods: Surgically resected frozen and paraffinembedded tissues were retrieved for Western blot analysis and immunohistochemical (IHC) staining. The ratio of tumorous/nontumorous intensities derived from western blots or IHC were used to stratify patient subgroups. Kaplan-Meyer analysis was used for survival analysis. Cell-based assays were performed to understand the role of ALDOB in CRC cells.

Results: ALDOB was found to be elevated in CRC. ALDOB expression was associated with clinical outcomes, tissue oxidative phosphorylation

P.080

COMPARISON OF ENDOSCOPIC RESECTION AND CHEMO(RADIO) THERAPY FOR ESOPHAGEAL NEOPLASMS IN PATIENTS WITH SYNCHRONOUS HEAD AND NECK CANCER AND SUPERFICIAL ESOPHAGEAL SQUAMOUS CELL NEOPLASMS

Bo-Huan Chen1,4, Chung-Wei Liu3, Yung-Kuan Tsou1,4, Chi-Ju Yeh2,4, Cheng-Han Lee1,4, Cheng-Tang Chiu1,4

1Department of Gastroenterology and Hepatology, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan

2Department of Pathology, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan

3Department of Internal Medicine, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan

4College of Medicine, Chang Gung University, Taoyuan, Taiwan

對於食道鱗狀上皮病變之頭頸癌病人

their ESCN. Patient characteristics (including age, gender, Charlson comorbidity index score, ECOG performance status) and tumor characteristics (including location and clinical stage) were compared between the two groups. The main outcome comparison was overall survival (OS). The secondary outcomes were treatment-related complications.

Results: There were no differences in patient and tumor characteristics between groups, except for a significantly higher rate of ECOG performance score ≤ 1 in the ER group (100% vs 84.6%, p = 0.041). Patients in the CCRT/C-T group were more frequently hospitalized due to treatment-related complications (0 vs. 15.4%, p = 0.041). There were no treatment-related deaths in the ER group, but there were 2 patients in the CCRT/C-T group (0 vs 7.7%, p = 0.211). However, esophageal stricture related to treatment occurred more frequently in the ER group (23.3% vs. 0, p = 0.012). The 1-year, 3-year and 5-year OS rates of ER group and CCRT/C-T group were 83.3%, 66.1%, 48.4% and 69.2%, 30.8% and 30.8%, respectively. Univariate analysis revealed that Charlson comorbidity index score, ECOG performance status, clinical stage of HNC (marginal significance), CCRT/R-T for ESCN, and disease progression in HNC were prognostic indicators of OS. In multivariate analysis, Charlson comorbidity index score and disease progression in HNC remained indicators of poor OS.

Conclusions: HNC but not ESCN is a prognostic factor in patients with synchronous HNC/superficial ESCN. Endoscopic resection is the recommended approach for ESCN in these patients. due to better overall survival, lower complications and lower disease progression rate.

Background: Treatment options for patients with resectable thoracic esophageal squamous neoplasm (ESCN) and synchronous head and neck cancer (HNC) are unclear. Little has been reported about the effects but no enough data for compare endoscopic (ER) and chemo(radio) therapy (CRT/C-T) on early HNC patients.

Aims: This study aims to report the outcomes of endoscopic resection (ER) for ESCN in patients with synchronous HNC/superficial ESCN by comparing the outcomes of chemoradiotherapy or chemotherapy (CRT/C-T).

Methods: This retrospective single-center study included 56 patients with synchronous HNC/ superficial ESCN who received ER (ER group, n = 30) or CRT/C-T (CRT/C-T group, n = 26) for

P.081

THE

DIAGNOSTIC POWER OF FECAL IMMUNOCHEMICAL TEST FOR ADVANCED COLORECTAL NEOPLASM IN PEOPLE YOUNGER THAN 50

Jen-Hao Yeh1,2, Wen-Lung Wang1, Cheng-Hao Tseng1,3, Ching-Tai Lee1, Yi-Chia Lee4

1Division of Gastroenterology and Hepatology, Department of Internal Medicine, E-DA Hospital, Kaohsiung, Taiwan

2Division of Gastroenterology and Hepatology, Department of Internal Medicine, E-DA Dachang Hospital, Kaohsiung, Taiwan

3Division of Gastroenterology and Hepatology, Department of Internal Medicine, E-DA Cancer Hospital, Kaohsiung, Taiwan

4Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan

exams (426196 of which were for people aged < 50) were included. The FIT positive rate was 3.3% for young age group and 7.3% for average risk group, respectively. People who had positive FIT in the young age group had significantly high risk of ACRN (Odds ratio [OR]: 2.54, 95% confidence interval [CI]: 1.44-4.46), and CRC (OR: 3.98, 95% CI: 2.12-7.47) than those of people in the averagerisk group regardless of FIT results. Furthermore, for people with positive FIT, the risk of ACRN was comparable between 40-49 age group and 50-59 age group (OR: 0.68, 95% CI: 0.30-1.55). The sensitivity of FIT for ACRN ranged from 18% to 32.1%, and specificity ranged from 95.0% to 97.3% at cut-off of 20 ug blood/g feces.

Conclusions: FIT may be a useful tool for CRC screening in people aged 40-49.

2 義大大昌醫院胃腸肝膽科

3 義大癌治療醫院胃腸肝膽科

4 台大醫院胃腸肝膽科

Background: The incidence of early onset colorectal cancer is increasing worldwide. Current guidelines recommend earlier screening shifting the age of earlier screening at 45-years rather than 50-years. However, the diagnostic efficacy of fecal immunochemical test (FIT) for younger population is less clear.

Aims: To investigate the diagnostic efficacy of FIT in people aged < 50 by a systematic review.

Methods: We searched the PubMed, Embase, and Cochrane Library databases from inception to May 2022. The primary outcome was the detection rate of advanced colorectal neoplasm (ACRN), and the secondary outcomes included rate of colorectal cancer (CRC) and other colorectal neoplasms. The outcomes were compared between people aged < 50 (young age group) with FIT and people aged ≥ 50 (average-risk group).

Results: Ten studies consisted of 664159 FIT

P.082

SLCO1B1/SLCO1B3 MUTATIONS IN TAIWANESE PATIENTS WITH ROTOR SYNDROME

Ya-Yuan Cheng1, Kai-Chi Chang2, Pei-Lung Chen3,4, Chun-Yan Yeung5, Bang-Yu Liou2, Huey-Ling Chen2,6,7

1School of Medicine, National Taiwan University College of Medicine, Taipei, Taiwan

2Department of Pediatrics, National Taiwan University Children’s Hospital, National Taiwan University College of Medicine, Taipei, Taiwan

3Department of Medical Genetics and 4

Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan

4Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan

5Department of Pediatric Gastroenterology, Hepatology and Nutrition, MacKay Children’s Hospital, Taipei, Taiwan

6Department of Medical Education and Bioethics, National Taiwan, University College of Medicine, Taipei, Taiwan

7Hepatitis Research Center, National Taiwan University Hospital, National Taiwan University, Taipei, Taiwan

台灣黃疸病患診斷羅托症候群之

is lacking. We aimed to analyze the clinical manifestations of the Rotor syndrome patients in Taiwan and report their genetic diagnosis.

Aims: The aims of this study are to analyze the genetic mutations of SLCO1B1/SLCO1B3 of the Rotor syndrome patients in Taiwan, and to present the clinical manifestations and laboratory data.

Methods: Five cases of Rotor syndrome, age from 5 to 30 years old, were analyzed. The medical records, lab data, the image of abdominal sonography, the reports of hepatobiliary scan (DISIDA), and liver pathology were collected. Genetic analyses were performed using panelbased next generation sequencing using peripheral blood WBC DNA. Sanger sequencing was used for confirmation of the mutations found in the panel.

Results: All patients presented with conjugated hyperbilirubinemia. Two of the cases had medical history of prolong neonatal jaundice. In the genetic analyses, homozygous for the c.1738C>T (p.R580X) in SLCO1B1 and LINE-1 insertion in SLCO1B3, and homozygous for another haplotype c.757C>T (p.R580X) in SLCO1B1 and c.1747+1G>A in SLCO1B3 were found in four of our subjects. We also reported, as far as we know, the first case of compound heterozygous genotype of Rotor syndrome, with c.1738C>T (p.R580X) in SLCO1B1 linked with LINE-1 insertion in SLCO1B3 and c.757C>T (p.R580X) in SLCO1B1 linked with c.1747+1G>A in SLCO1B3.

國立臺灣大學醫學院醫學系

2 台大兒童醫院小兒部

3 台大醫院基因醫學部

台大醫院內科部

5 馬偕兒童醫院兒童腸胃科

6 國立臺灣大學醫學院醫學教育暨生醫倫理研究所

7 台大醫院肝炎研究中心

Background: Rotor syndrome was first reported in patients with jaundice in 1948. Patients with Rotor syndrome have mild hyperbilirubinemia, nearly normal liver profiles and a benign clinical course. Mutations in both SLCO1B1 and SLCO1B3 were found to cause Rotor syndrome in 2012. The genetic mutations varied among the cases reported from different countries. Some common mutations were found in the cases from the neighboring geographic regions. Data from Taiwanese patients

Conclusions: All Taiwanese patients with Rotor syndrome had initial presentation of jaundice without physical discomfort when seeking medical care. Genetic analysis confirmed the diagnosis of Rotor syndrome with mutations in SLCO1B1 and SLCO1B3 genes, including one common mutation also found in other patients in East Asia, suggesting a founder effect.

2

P.083

PRELOADED PANCREATIC DUCT STENT-ASSIST METHOD INCREASES THE SUCCESS RATE OF NEEDLE KNIFE SPHINCTEROTOMY IN DIFFICULT BILIARY CANNULATION PATIENTS

Mu-Hsien Lee1, Chi-Huan Wu1, Cheng-Hui Lin1,2, Yung-Kuan Tsou1,2, Kai-Feng Sung1, Nai-Jen Liu1,2

1Department of Gastroenterology & Hepatology, Chang Gung Medical Foundation

Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan

2College of Medicine, Chang Gung University, Taoyuan, Taiwan

插入的病人執行針刀膽管切口術的成

inserted into PD for guiding the orientation of the bile duct. However, to insert of a PD stent or not depended on the operator’s experience. The results were compared between the NKS success and failure groups. Logistic regression analysis was performed to identify factors associated with the outcomes of NKS.

Background: Needle-knife sphincterotomy (NKS) is a frequently used salvage procedure when conventional deep biliary cannulation fails, but it is not always successful. Identifying the bile duct is important when performing NKS, especially in such cases of the disorientated axis of the bile duct, like periampullary diverticulum or surgically altered anatomy. We thought that when pancreatic duct (PD) rather than bile duct is cannulated in patients with difficult biliary cannulation, placing a PD stent before NKS may increase the NKS success rate because to PD stent can guide the route of precut.

Aims: To investigate whether PD stents before NKS increase the success rate of NKS in difficult biliary cannulation patients.

Methods: This was a retrospective study. Between January 2017 and December 2021, 222 patients with difficult biliary cannulation undergoing NKS at our center were included in the study. NKS was performed when conventional biliary cannulation methods failed. In case of difficult biliary cannulation, and when PD was cannulated, a plastic stent (Boston Scientific Corporation Advanix™, 4Fr, 3cm or 7cm) was

Results: Following NKS, deep biliary cannulation failed in 24 patients (10.8%, NKS failure group) and succeeded in 198 patients (89.2%, NKS success group). A total of 90 patients received PD stents placement before NKS. In univariate analysis, factors to predict NKS failure included the presence of periampullary diverticulum (45.8% vs 20.2 % OR: 3.108, 95% CI: 1.281-7.544, p = 0.012), bleeding during NKS (37.5% vs 6.1%, OR: 9.300, 95% CI: 3.381-25.58, p < 0.001), and surgically altered anatomy (8.3% vs. 1.0%, OR: 8.909, 95% CI:0.995-66.42, p = 0.053 (marginal significance)); and inserting a PD stent was the only predictor of NKS success (42.9% vs. 20.9%, odds ratio [OR]: 0.35, 95% confidence interval [CI]: 0.126-0.975, p = 0.045). Using the three negative predictors as subgroups, we found that inserting a PD stent before NKS increases the NKS successful rate in patients with periampullary diverticulum patients (88.9% vs 66.7%, p = 0.005) but not in patients with surgically altered anatomy and bleeding during NPS. On multivariate analysis, a PD stent before NKS increase was still the factor associated with the success rate of NKS (OR: 0.331, 95% CI: 0.105-0.942, p = 0.049).

Conclusions: PD stent placement before NKS can increase the success rate of NPS in difficult biliary cannulation patients, especially in patients with periampullary diverticulum.

P.084

CLINICAL MANIFESTATIONS, RISK FACTORS, AND PROGNOSTIC FACTORS OF CYTOMEGALOVIRUS INFECTION IN IBD PATIENT

Ching-Reigh Hsieh, Puo-Hsien Le, Chia-Jung Kuo, Cheng-Tang Chiu

Department of Gastroenterology and Hepatology, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan

first case described in 1961. Obstacles faced by gastroenterologists originated from differentiation between UC flare and CMV colitis, in that both of which shared similar clinical presentations. Furthermore, despite punch-out ulcers usually considered as common findings of CMV colitis, there were no definitive or reliable endoscopic features that can distinguish between the two scenarios. Given the importance of CMV in exacerbating clinical course of inflammatory bowel disease (IBD) including increased risk of colectomy, inpatient mortality, length of stay and hospital charges, full elucidation of characteristic in IBD-CMV patients foreshadowed correct clinical judgement in deciding treatment strategy and improve patient quality of care.

Background: Cytomegalovirus (CMV), a double stranded DNA virus in Herpesviridae family, has been regarded as an opportunistic pathogen among immunocompromised patients. Among general populations, seroprevalence of 40-100% adults were infected by CMV at the age of 40. The majorities of CMV infection were asymptomatic with the small minorities (~10%) manifested as mononucleosis-like syndrome, characterized by malaise, protracted fever or mild liver dysfunction. Following CMV primary infection, latent stage transformation of virus was established for life. Despite worldwide distribution, prevalence of CMV prevailed in less industrialized countries or areas with lower socioeconomic conditions. The most notable risk factor for symptoms from CMV was immunosuppression status such as leukopenia, solid organ transplantation, AIDS and use of immunomodulating drugs. Immunomodulator use in inflammatory bowel disease (IBD) was related to asymptomatic or self-limited reactivation of latent CMV infection. A clear demarcation should be made between CMV infection, indicating detectable in serology or viral DNA and CMV disease, manifesting as colitis or extraintestinal end-organ damage as hepatitis, esophagitis, pneumonia, encephalitis or retinitis. While CMV infection rarely contributed to serious tissue damage, CMV colitis in patients with IBD is associated with adverse outcomes documented in growing body of literature. Numerous efforts have been undertaken regarding the role of CMV in inflammatory bowel disease (IBD) since the prevalence of CMV infection among hospitalized UC and CD patients escalated over time, with the

Aims: The aim of this retrospective study shed light on analyzing the clinical features of CMV infection in hospitalized IBD patients in a medical center in Taiwan. In view of the preceding purposes, major topic of interest included patient characteristics, clinical presentations, risk factors, outcomes and prognoses, and factors related to IBD patients with CMV involvement.

Methods: The Institutional Review Board did not require signed informed consent from individual patients to review medical records from the electronic medical record system, in retrospective studies. The study protocol conformed to the ethical guidelines of the 1975 Declaration of Helsinki, as reflected in a prior approval by the institution’s human research committee. In this retrospective cohort study, we enrolled inflammatory bowel disease (IBD) patients from the pathology database at the Linkou Chang Gung Memorial Hospital, who underwent small intestine CMV immunohistochemistry (IHC) staining between January, 2000 and March, 2022. Diagnosis of CMV enteritis was made primarily on positive CMV IHC staining of the enteric tissue, with or without viral inclusion bodies, using hematoxylin and eosin staining. CMV IHC was performed using monoclonal antibodies directed against the CMV pp65 antigen (Novocastra™ lyophilized mouse monoclonal antibody; Leica Microsystems, Wetzlar, Germany). The IBD patients were further separated into two groups (CMV and non-CMV) according to the pathological results. The medical records of eligible patients reviewed for data on age, sex, patient source (inpatient, outpatient), admission date, diagnostic date, recurrence date, death or last follow-up , underlying disease

(hypertension, diabetes mellitus, liver cirrhosis, coronary artery diseases, end stage renal disease, autoimmune diseases, cancer), medication history, major clinical presentation, baseline IBD complication (including stricture, perforation, abscess, fistula, IBD surgery), baseline medication (IBD medication, antibiotic type, opioid, transamin, anti-diarrhea agents), treatment and therapeutic IBD duration, outcomes (steroid dose change, hospitalization times, clinical remission, CDAI change, Mayo score change, BMI change, stricture, perforation, abscess, fistula, colon cancer, IBD surgery, overall IBD complications, death), total white blood cell count, absolute neutrophil count, absolute lymphocyte count, platelet count, hemoglobin (Hb), creatinine (Cr), aspartate aminotransferase, alanine aminotransferase, bilirubin, albumin, C-reactive protein (CRP) levels, CMV pp65 antigenemia, CMV DNA (226 bp segment on glycoprotein B gene, Light-Mix® Kit human cytomegalovirus; TIB Molbiol, Berlin, Germany), and CMV serology. Numerical data are presented as mean ± standard deviation or median (interquartile range), while categorical data are expressed as absolute numbers and percent-ages. Independent t-tests and Mann–Whitney U tests were used to compare continuous variables, while χ 2 and Fisher’s exact tests were used for categorical variables. Logistic regression models were used to identify the independent risk factors for overall IBD complications. Statistical significance was set at P < 0.05. The results are presented as odds ratios (ORs), 95% confidence intervals (CIs), and p-values. All statistical calculations were performed using the SPSS statistical software, version 22.0 (Armonk, NY: IBM Corp.).

Results: 118 inflammatory bowel disease (IBD) patients diagnosed with 49 CD and 69 UC were enrolled in our study with 41 patients having CMV infection and the rest in non-CMV group. In the CMV group, the mean age was 45.3 years and males were predominant (68.3%). There were no significant differences between IBD with CMV and control in age, gender, body weight or BMI. The major comorbidities included hypertension, diabetic mellitus and cancer. With regard to underlying diseases, hypertension was the only parameter shown to be higher in IBD with CMV positive patients (26.8%) (P = 0.021). Most importantly, older age was noted in CMV group in UC (P = 0.008). The major clinical symptoms

of IBD with CMV infection comprised of bloody stool (75.6%), diarrhea (68.3%) and abdominal pain (61%). Minor patient presented with fever (17.1%). Notably, 90.9% (10/11) patients of CD presented with baseline IBD complications in CMV group while 55.3% (21/38) was noted in control (P = 0.038). However, no differences in overall IBD complication have been noted following anti-viral treatment between CMV group and control. In consideration of medication usage of IBD patients with CMV, medications used at time of admission included 5-ASA, oral prednisolone, azathioprine and biological agents. They were 27.3%, 54.5%, 36.4%, 36.4% in CD patients, and 3.3%, 53.3%, 20%, 20% in UC patients, respectively. Notably, 3 patients (27.3%) used 5-ASA as inflammatory modulatory agents in CD with CMV while none was noted in control (P = 0.009). Furthermore, antibiotics usage in 7 patients (63.6%) of CD with CMV was noted in comparison to control (23.7%) (P = 0.025). Similarly, mesalazine enema usage in UC patients was 40% in CMV positive group whereas 17.9% in CMV negative group (P = 0.042). Hydrocortisone usage rate was disclosed 20% (6/30) in CMV positive group relative to 2.6% (1/39) in control. Hypoalbuminemia (3 g/dL) was noted in CMV group in UC. In terms of virology test, higher CMV-IgG and CMV-PCR level were noted in CMV-IBD patients, 96.6% and 45.5% respectively (P = 0.008) (P = 0.003). However, only 12.9% patients developed CMV-IgM and 8.3% patients had CMV pp65 antigenemia. In consideration of tissue sampling, diagnosis of CMV infection in IBD patients relied primarily on immunohistochemistry staining of colonoscopic biopsy. Besides, CMV inclusion bodies were also examined by H&E staining. In this study, the mean time to diagnosis [from admission (or first visit to the outpatient clinic) to diagnosis of CMV colitis was diagnosis revealed approximately 1.3 months. Of note, 33 patients of 42 (78.6%) underwent antiviral therapy of either oral valganciclovir or intravenous ganciclovir with a variable duration range (intravenous: 8-48 days, oral: 6-119 days). 10 patients (90.9%) of CD with CMV exhibited IBD complications compared to control (55.3%) (P = 0.038). A nonsignificant in BMI change was detected in co-infected patients relative to CMV controls (P = 0.075). However, concomitant infection of CMV and Clostridium difficile somehow contributed to higher biopsy negative rates (100%) compared to IBD patient with CMV infection alone (45%) (P = 0.022).

There was no significant increase of CMV group in hospitalization times, CDAI change or Mayo score change, BMI change, IBD complication rate, IBD surgery rate, colon cancer risk and death rate. CMV PCR status (OR, 12; 95% CI, 1.177136.283; P = 0.036), diarrhea (OR, 0.449; 95% CI, 0.208-0.97; P = 0.042) and biological failure (OR, 2.9; 95% CI, 1.274-6.67; P = 0.011) were three independent prognostic factors for overall IBD complications.

Conclusions: To sum up, older age and hypoalbuminemia were risk factors for UC with CMV infection. Bloody stool, diarrhea and abdominal pain were most common clinical symptoms. Besides, coinfection of CMV and Clostridium difficile did not contribute to exacerbated overall IBD complications or mortality rate. Diarrhea and biological failure are poor prognostic factors for overall IBD complications. Identification of IBD with CMV involvement and early administration of anti-viral treatment even in either high-grade or low-grade but severe CMV disease guarantees better clinical outcome. Physicians should take these characteristics into consideration for early acknowledgement of potentially risky cases and ultimately improve quality of care in clinical practice.

P.085 COMPARISON OF CONTINUOUS VERSUS ON-DEMAND PROTON PUMP INHIBITOR THERAPY ON THE SYMPTOM CONTROL IN PATIENTS WITH BARRETT’S ESOPHAGUS (COBE TRIAL)

Sung-Shuo Kao1, Deng-Chyan Wu2, Seng-Kee Chuah3, Chang-Bih Shie4, Feng-Woei Tsay1, Wen-Chih Chen1, Chao-Hung Kuo2, Kun-Feng Tsai4, Sheng-Yeh Tang4, Li-Fu Kuo4, Wen-Wei Huang4, I-Ting Wu4, Ping-I Hsu4

1Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan

2Division of Gastroenterology, Department of Internal Medicine Kaohsiung Medical University Hospital, Kaohsiung, Taiwan

3Division of Hepatogastroenterology, Department of Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan

4Division of Digestive Medicine, Department of Medicine, Tainan Municipal An Nan Hospital, China Medical University, Tainan, Taiwan

1 高雄榮民總醫院內科部胃腸肝膽科

2 高雄醫學大學附設醫院內科部胃腸科

3 高雄長庚紀念醫院內科部胃腸肝膽科

4 臺南市立安南醫院—委託中國醫藥大學興建經營 內科部消化內科

Background: No universally accepted guideline exists regarding the duration of proton pump inhibitor (PPI) therapy for Barrett’s esophagus, and whether continuous PPI therapy is superior to ondemand therapy for symptom control of patients with Barrett’s esophagus remains unclear.

Aims: To compare the efficacies of on-demand and continuous PPI therapy in the symptom control of patients with Barrett’s esophagus.

Methods: Consecutive symptomatic adult patients who had Barrett’s esophagus proven by esophageal biopsy were randomly assigned to receive either on-demand or continuous esomeprazole (40 mg q.d.) maintenance therapy for 40 weeks following an initial treatment with esomeprazole 40 mg daily for 8 weeks and completed daily symptom questionnaires at each visit. A follow-up endoscopy was conducted at the end of 48 weeks. The primary outcome was the total number of symptomatic days within the 40week maintenance therapy period. The secondary outcome measure was the total amount of PPI consumed during the 40-week maintenance therapy period.

Results: From February 2010 to December 2021, 235 eligible patients were randomly assigned to receive either on-demand (n = 119) or continuous (n =116) esomeprazole therapy. The two treatment groups had a comparable total number of symptom days (27.7 ± 41.5 vs 24.3 ± 47.7; P = 0.570) in the maintenance therapy period. However, the on-demand group took fewer numbers of esomeprazole tablets compared to the continuous group (230.6 ± 96.5 vs 330.0 ± 15.6; P < 0.001). At the end of week 48, the frequencies of erosive esophagitis were 10.6% and 6.7%, respectively. There was no significant difference in the frequency of erosive esophagitis between the on-demand and continuous groups (95% confidence interval: -3.9% - 11.8%; P = 0.301).

Conclusions: On-demand PPI therapy reduces the total amount of PPI used while achieving similar symptom relief compared to continuous PPI therapy in patients with Barrett’s esophagus. It is a cost-effective way for the long-term symptom control of Barrett’s esophagus.

TESTS PERFORMANCE WITHIN TAIWAN COLORECTAL CANCER SCREENING PROGRAM

Wen-Feng Hsu1,3, Chiu-Wen Su1,3, Yi-Chia Lee1,3, Li-Ju Lin2,3, Shu-Li Chia2,3, Ming-Shiang Wu1, Han-Mo Chiu1,3

1Department of Internal Medicine, National Taiwan University Cancer Center, Taipei, Taiwan

2Health Promotion Administration, Ministry of Health and Welfare, Taipei, Taiwan

3Taiwan Colorectal Cancer Screening Program

Background: Our previous analysis revealed that HM-JACK, one of the two fecal immunochemical tests (FITs) kits used in the Taiwan Colorectal Cancer Screening Program, had lower performance than the other (OC-SENSOR) (Gastroenterology 2014;147:1317-1326). Positivity rate affects not only the detection of significant neoplasm but also the required colonoscopy capacity hence affecting both the effectiveness and the cost-effectiveness of the screening program. Accordingly, the screening program launched a stepwise renewal plan by replacing the HM-JACK kit with the HMJACKarc kit in 2015.

Aims: To evaluate the performance of the new HM-JACKarc kit since its implementation.

Methods: Subjects who received FITs within Taiwan Colorectal Cancer Screening Program from 2015 to 2021 were included in this analysis. The seasonal variation in average fecal hemoglobin concentrations (FHbCs) of HM-JACK, HMJACKarc, and OC-Sensor FIT kits were calculated, and their positivity rate, the detection rate, and the positive predictive value (PPV) for CRC were also calculated and compared.

Results: A total of 8,995,263 subjects underwent FIT screening from 2015 to 2021 in the screening

P.086 DIMINISHING THE DISCREPANCY OF FECAL IMMUNOCHEMICAL

program. Of them, 6,005,751 (67.1%), 1,615,884 (18.0%), and 1,333,628 (14.9%) underwent FIT screening with OC-Sensor, HM-JACK, and HMJACKarc kits, respectively. The average FHbC of HM-JACK fluctuated with the season and was lowest (24.91 μg/g) in summer and highest (39.32 μg/g) in the winter season (p < 0.001). In contrast, the average FHbCs of the OC-SENSOR and HM-JACKarc were rather constant in different seasons. The positivity rates of OC-Sensor, HMJACK, and HM-JACKarc tests were 7.06%, 8.22%, and 5.07%, respectively, by using the cutoff of 20 μg/g, 30 μg/g, and 30 μg/g. The detection rate for CRC by HM-JACKarc (0.22%) was similar to that by OC-Sensor (0.19%) and HM-JACK (0.20%). In the summer season, however, the detection rate of HM-JACK for CRC decreased by 0.18%, but not with HM-JACKarc and OC-Sensor kits. The PPV for CRC significantly improved by replacing HMJACK with HM-JACKarc [3.5%, 95% CI = 3.3%3.6%, and 5.9%, 95% CI = 5.7%-6.1%], and it was even higher than that of OC-SENSOR (3.7%, 95% CI = 3.6%-3.7%).

Conclusions: The seasonal variation by HMJACK kits in positivity rate and detection rate for CRC was diminished by the kit renewal plan, and the PPV to detect CRC was also improved. Whether it can improve the effectiveness and cost-effectiveness of the entire screening program needs further exploration and sophisticated analysis considering the population demographics.

P.087 SURVIVAL ANALYSES OF COLORECTAL CARCINOGENESIS RESULTING FROM INTESTINAL BACTEROIDES RELEVANT METABOLOMICS

Kuang-Tsu Yang1,2,3,4, Ping-I Hsu5, Yau-Huei Wei6,7,8, Chun-Ying Wu8,9,10,11,12, Yao-Tsung Yeh13,14,15, Yao-Shen Chen8,16, Jin-Shuen Chen17,18, Tsi-shu Huang19, Yen-Hsiu Yeh20, Tsai-Kun Li20,21,22, Hsin-Bai Zou23, Cheng-Chih Richard Hsu23, Wun-Long Jheng24,25, Wayne Huey-Herng Hsu8,26, Cheng-Hsiu Hsieh27, Chun-Yu Lin28,29, Chia-Chi Yen30,31,32, Ming-Hong Tai4, Kuang-Hung Cheng4,33,34,35, Deng-Chyang Wu36, Huei-Kang Sytwu37,38

1Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Municipal Min-Sheng Hospital, Kaohsiung, Taiwan; 2Department of Medicine, National Taiwan University, Taipei, Taiwan; 3Division of Family Medicine, Department of Community Medicine, Kaohsiung Municipal Min-Sheng Hospital, Kaohsiung, Taiwan; 4Institute of Biomedical Science, National Sun Yat-Sen University, Kaohsiung, Taiwan; 5Division of Gastroenterology & Hepatology, Department of Internal Medicine, An Nan Hospital, China Medical University, Tainan, Taiwan; 6Department of Medicine, Mackay Medical College, New Taipei City, Taiwan; 7Center for Mitochondrial Medicine and Free Radical Research, Changhua Christian Hospital, Changhua, Taiwan; 8School of Medicine, College of Medicine, National Yang Ming

Chiao Tung University, Taipei, Taiwan; 9Division of Gastroenterology and Hepatology, Fu-Jen Catholic University Hospital, FuJen Catholic University, New Taipei City, Taiwan; 10Division of Translational Research, Taipei Veterans General Hospital, Taipei, Taiwan; 11Department of Public Health, China Medical University, Taichung, Taiwan; 12Taiwan Microbiota Consortium, Taipei, Taiwan; 13Aging and Disease Prevention Research Center, Fooyin University,

Kaohsiung, Taiwan; 14Department of Medical Laboratory Sciences and Biotechnology, Fooyin University, Kaohsiung, Taiwan; 15Institute of Biotechnology and Chemical Engineering, I-Shou University, Kaohsiung, Taiwan; 16Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan; 17Division of Nephrology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan; 18Faculty of Medicine, School of Medicine, National Defense Medicine, Taipei, Taiwan; 19Division of Microbiology, Department of Pathology and Laboratory Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan; 20Department and Graduate Institute of Microbiology, College of Medicine, National Taiwan University, Taipei, Taiwan; 21Centers for Genomic and Precision Medicine, National Taiwan University, Taipei, Taiwan; 22Center for Biotechnology, National Taiwan University, Taipei, Taiwan; 23Department of Chemistry, National Taiwan University, Taipei, Taiwan; 24Institute of Artificial Intelligence in healthcare, International Academia of Biomedical Innovation Technology; 25Medical 3D Printing Center, National Defense Medical Center Tri-Service General Hospital, Taipei, Taiwan; 26Division of Endocrinology and Metabolism, Department of Internal Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; 27Division of Colorectal Surgery, Department of Surgery, Kaohsiung Municipal Min-Sheng Hospital, Kaohsiung, Taiwan;

28Division of Infectious Disease, Department of Internal Medicine, Kaohsiung Municipal Min-Sheng Hospital, Kaohsiung, Taiwan;

29Associate Dean, Kaohsiung Municipal

Min-Sheng Hospital, Kaohsiung, Taiwan;

30Superintendent’s Office, Kaohsiung

Municipal Min-Sheng Hospital, Kaohsiung, Taiwan; 31Department of Nutrition, Institute of Biomedical Nutrition, Hung-Kuang University, Taichung, Taiwan; 32Department of Business Management, National Sun

Yat-Sen University, Kaohsiung, Taiwan; 33National Institute of Cancer Research,

National Health Research Institutes, Tainan, Taiwan; 34Regenerative Medicine and Cell Therapy Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan; 35Department of Medical Laboratory Science and Biotechnology, Kaohsiung Medical University, Kaohsiung, Taiwan; 36Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; 37Vice President Office, National Health Research Institutes, Taiwan; 38Academia Sinica, Academician, Taiwan

癌變過程之生存分析

楊光祖1,2,3,4 許秉毅5 魏耀揮6,7,8 吳俊穎8,9,10,11,12

葉耀宗13,14,15 陳垚生8,16 陳金順17,18 黃采菽19

葉彥秀20 李財坤20,21,22 鄒欣蓓23 徐丞志23

鄭文隆24,25 許惠恒8,26 謝政修27 林俊祐28,29

顏家祺30,31,32 戴明泓4 鄭光宏4,33,34,35 吳登強36 司徒惠康37,38

1 高雄市立民生醫院內科部胃腸肝膽科；2 國立臺 灣大學醫學系；3 高雄市立民生醫院社區醫療部家 庭醫學科；4 國立中山大學生物醫學研究所；5 臺 南市立安南醫院內科部胃腸肝膽科；6 馬偕醫學院 醫學系；7 彰化基督教醫院粒線體醫學及自由基研 究中心；8 國立陽明交通大學醫學院醫學系；9 輔 仁大學附設醫院胃腸肝膽科；10 臺北榮民總醫院 轉譯研究科；11 中國醫藥大學公共衛生部；12 台灣 微菌聯盟；13 輔英科技大學老化及疾病預防研究 中心；14 輔英科技大學醫學檢驗生物技術系；15 義 守大學化學工程學系；16 高雄榮民總醫院內科部； 17 高雄榮民總醫院內科部腎臟科；18 國防醫學院醫 學系；19 高雄榮民總醫院病理檢驗部及微生物科； 20 國立臺灣大學醫學院微生物所；21 國立臺灣大學 基因體暨精準醫學研究中心；22 國立臺灣大學生

物科技研究所；23 國立臺灣大學化學系；24 國際創 新生醫技術研究院人工智慧健康照護機構；25 三 軍總醫院3D 醫學列印中心；26 臺北榮總內科部內

分泌暨新陳代謝科；27 高雄市立民生醫院外科部

大腸直腸外科；28 高雄市立民生醫院內科部感染 科；29 高雄市立民生醫院副院長；30 高雄市立民生 醫院院長；31 弘光科技大學營養系暨營養醫學研 究所；32 國立中山大學企業管理學系；33 國家衛生 研究院腫瘤研究部；34 高雄醫學大學再生醫學及 細胞治療研究中心；35 高雄醫學大學醫學檢驗科 學暨生物科技部；36 高雄醫學大學附設醫院；37 國 家衛生研究院；38 中央研究院院士

腸道擬桿菌相關代謝組學引起結直腸

Background: Intestinal microbiota play important roles in colorectal carcinoma (CRC) development. Short chain fatty acids (SCFAs), especially butyric acid/propionic acid/ acetic acid were also investigated in CRC signaling pathways. However, the interplay between CRC-related microbiome and SCFA in metabolomics viewpoints was less discussed and undetermined.

Aims: Using biomedical informatics to explore the interlink between CRC, SCFAs, and intestinal microbiota.

Methods: We used GMrepo website tool to analyze the microbiota abundance. HMDB for metabolomics evaluation and GEPIA2 was deployed for CRC overall survival analyses. Finally, GeneMania for relevant genomics were studied.

Results: After data identification and search, we found that bacteroides was strongly prevalent in worldwide human beings with CRC vs normal ones (Table 1). GutMEGA datasets was retrieved for the top ten experiments of bacteroides from CRC/ Normal poopulations (Table 2). HMDB showed the detailed relevant enzymes and transporters for SCFAs (Table 3). GEPIA2 revealed SCFAsassociated gene markers for CRC overall survival analyses (Figure 1a, 1b, 1c). As genomic networks and functions, the detailed content were involved in Figure 2.

Conclusions: Through biomedical informatics, we discovered that the potentially relevant gene markers adjusting CRC survival. Further detailed mechanisms should be documented.

VESICAL EZRIN ACTIVATES FIBROBLASTS TO EXACERBATE CANCER METASTASIS THROUGH STAT3 AND YAP-1 SIGNALING PATHWAYS

Yu-Ting Chang1,2, Hsuan-Yu Peng1, Chun-Mei Hu3, Sui-Chih Tien3, Yi-Ing Chen3, Yung-Ming Jeng4, Ming-Chu Chang1,2

1Department of Internal Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan

2Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan

3Genomics Research Center, Academia Sinica, Taipei, Taiwan

4Department of Pathology, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan

Background: Cancer-associated fibroblasts, a major component of the tumor microenvironment in pancreatic ductal adenocarcinoma (PDAC), play an important role in tumorigenesis, metastasis, and chemoresistance of PDAC. The tumor-derived small extracellular vesicles (sEVs) as mediators in cell-to-cell communication between cancer cells and fibroblasts are critical in cancer progression and metastasis.

Aims: We aimed to investigate whether PDAC cell-derived sEVs are involved in the activation of fibroblasts and to explore the underlying mechanisms that exacerbate PDAC progression and metastasis attributed to the crosstalk between fibroblasts and PDAC cells through sEVs.

Methods: Small EVs (exosomes) were isolated and characterized from PDAC patient-derived cell lines and controls. The activation of fibroblasts by the PDAC cell-derived sEVs and the crosstalk between the activated fibroblasts and PDAC were determined by proliferation, invasion, or migration assays. The activated fibroblasts to exacerbate PDAC metastasis was demonstrated in the PDAC animal model.

Results: We report that PDAC cell-derived sEV Ezrin (sEV-EZR) can activate fibroblasts with increased migration ability and high expressions of α-SMA, PDGFRB and the extracellular matrix. Reciprocally, the sEV-EZR activated fibroblasts

P.088 PANCREATIC CANCER-DERIVED SMALL EXTRACELLULAR

enhance the PDAC cell proliferation, invasion, and metastasis to liver in animal models. Fibroblasts treated with PDAC cells-derived sEVs with EZR knockdown were found to reduce the metastatic ability of PDAC. We demonstrate that PDAC cellderived sEV-EZR modulates STAT3 and YAP-1 signaling pathways to induce fibroblast activation and the activated fibroblasts promote PDAC cell proliferation, invasion, and liver metastasis. Inhibition of STAT3 and YAP-1 signaling pathways by either gene knockdown or inhibitor can abrogate sEV-EZR-induced effects.

Conclusion: This study suggests that targeting the interaction between PDAC cell-derived sEVEZR and fibroblasts may be a potential therapeutic strategy for PDAC.

P.089 INVESTIGATION OF ESOPHAGOGASTRODUO-

FOR GASTROINTESTINAL BLEEDING IN CARDIOVASCULAR DISEASE PATIENTS: A NATIONWIDE-BASED RETROSPECTIVE STUDY

Chao-Feng Chang1, Wu-Chien Chien2, Chi-Hsiang Chung2, Hsuan-Hwai Lin1, Tien-Yu Huang1, Peng-Jen Chen1, Wei-Kuo Chang1, Hsin-Hung Huang3

1Division of Gastroenterology and Hepatology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan

2Department of Medical Research, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan

3Division of Gastroenterology, Department of Internal Medicine, Cheng Hsin General Hospital, Taipei, Taiwan

Background: Performing esophagogastroduodenoscopy (EGD) in recent happened peri-coronary artery disease (CAD) accident settings is always a dilemma.

Aims: The peri-procedural complication is a great concern, and we would like to use a national large population to analyze the CAD recurrence, mortality and associated parameters in those patients with CAD receiving EGD or not.

Methods: This study used the Taiwan National Health Insurance Research Database to identify patients with CAD and gastrointestinal bleeding who had received EGD or not between 2000 and 2013.

Results: The final population included in this study was 15147 individuals, with 3801 individuals having received EGD (study cohort group) and 11346 individuals not having received EGD

DENOSCOPY

出血的影響：回溯性研究

(comparison cohort group). We initially performed a sensitivity test CAD recurrence-related factors using multivariable Cox regression during the tracking period. A relatively earlier EGD intervention within one week demonstrated a lower risk of CAD recurrence (adjusted HR = 0.707). Although there were no significant differences in the overall tracking period, the adjusted HR of CAD recurrence was still lower in patients in the EGD group. Furthermore, our findings revealed that there was no remarkably short interval to CAD recurrence in the study group.

Conclusions: CAD recurrence is always an issue in recent episodes of peri-CAD accident settings while receiving EGD. No more risk in comparison of normal population in our study, and waiting period may be not requirable.

Shenq-jie Wong1,2, Hsiu-Po Wang1, Chia-Tung Shun1, Chien-Chuan Chen1, Ming-Lun Han1, Jiann-Hwa Chen1,3, Chung-Tsui Huang4, Tsu-Yao Cheng1

1Division of Gastroenterology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan

2Division of Gastroenterology, Department of Internal Medicine, En Chu Kong Hospital, Taipei, Taiwan

3Division of Gastroenterology, Department of Internal Medicine, Taipei Tzu Chi Hospital, Taipei, Taiwan

4Division of Gastroenterology, Department of Internal Medicine, Far Eastern Memorial Hospital, Taipei, Taiwan

Background: The small endoscopic ultrasound (EUS)-suspected gastric gastrointestinal stromal tumors (GISTs), gastric subepithelial tumors at the muscularis propria layer on EUS, are detected frequently. Under current National Comprehensive Cancer Network (NCCN) guidelines, the management of small GISTs with size less than 2 cm remains controversial. Tissue sampling via bite-on-bite forceps biopsy or EUS-guided tissue sampling yield variable results.

Aims: This study aimed to analyze clinicopathologic features of the small EUS-suspected gastric GISTs

2 cm or less in size and to evaluate the efficacy

P.090 TISSUE DIAGNOSIS NECESSARY FOR SMALL ENDOSCOPIC ULTRASOUND-SUSPECTED GASTRIC GASTROINTESTINAL STROMAL TUMORS 2 CM OR LESS IN SIZE: A PROSPECTIVE STUDY FOCUSING ON THE ENDOSCOPIC INCISIONAL BIOPSY

and safety of the endoscopic incisional biopsy (EIB) for these small tumors.

Methods: This prospective study investigated 70 patients with small EUS-suspected gastric GISTs 2 cm or less in size in two stages. Firstly, 30 patients were recruited for the efficacy and safety evaluation of the EIB. Secondly, 40 patients were randomly assigned to receive either EIB or the biteon-bite biopsy for comparison of the diagnostic yield, procedure time, and adverse event rate.

Results: Combining two study stages, leiomyoma (74%) was diagnosed histologically to outnumber GIST (26%) with a diagnostic rate of 94% for patients receiving EIB. KIT exon 11 mutations (50%) and PDGFRA exon 12 mutations (16%) were detected in the small gastric GISTs. In the direct comparison, the diagnostic yield of EIB and the bite-on-bite biopsy was 85% and 50%, respectively (P = 0.018). There was no statistically significant difference of the mean procedure time or adverse event rate between these two groups.

Conclusions: Leiomyoma is more common than expected among these small tumors. Tissue diagnosis with an effective and safe sampling technique, such as EIB, is necessary for making further clinical decisions.

P.091 CHARACTERISTICS OF ENDOSCOPIC FINDINGS IN PATIENTS WITH PRIMARY BILIARY CHOLANGITIS: ONE-CENTER EXPERIENCE IN TAIWAN

Pei-Tzu Chen, Hsuan-Hwai Lin, Tien-Yu Huang, Peng-Jen Chen, Wei-Kuo Chang, Tsai-Yuan Hsieh, Hsuan-Wei Chen

Division of Gastroenterology and Hepatology, Department of Internal Medicine, Tri-Service General Hospital, Taipei, Taiwan

Background: Patients with cirrhosis are suggested to receive endoscopic screen for esophageal varices and portal hypertension. However, the endoscopy result of patients with PBC is rarely reported, which is attributed to that they do not routinely undergo endoscopic screening. Furthermore, although it is widely discussed that bile acids have a relationship with increased colon polyp by inducing colonic epithelium cell damage, there are only few studies discussed colonic findings in PBC patients. The issues of PBC patients’ endoscopic characteristics are still unclear.

Aims: Our study aims to evaluate the esophagogastroduodenoscopy (EGD) and colonoscopy findings in the primary biliary cholangitis (PBC) patients, which was assumed to be related to cholestasis condition.

Methods: The retrospective study was conducted at the Tri-Service General Hospital, Taiwan, and comprised data of patients aged >20 years diagnosed with primary biliary cholangitis between January 2000 and December 2018 after approval from the institutional review board. Endoscopic findings including esophagogastroduodenoscopy (EGD) and colonoscopy were recorded for each patient who received endoscopic examinations.

Results: We collected 28 EGD scopic findings retrieved from the PBC group and 64 ones retrieved from the control group in this retrospective cohort study. Among the 28 PBC patients who underwent

林煊淮 黃天祐 陳鵬仁 張維國 謝財源 陳宣位

EGD, 13 (46.4%) patients had EV. F1 EV predominated with 35.7% (10/28). 6 patients were found GV, and 8 patients were found duodenal ulcer. Patients with PBC presented more often with colon polyps (50% vs. 14%; p < 0.001), the locations were as follows: A-colon (2 vs 2), T-colon (1 vs 1), S-colon (1 vs 5), rectum (3 vs 0), cecum and rectum (0 vs 1). Tubular adenoma with mild dysplasia (2 vs 4), tubular adenoma with low grade dysplasia (0 vs 1), tubular adenoma with moderate dysplasia (0 vs 1), villous tubular adenoma with moderate dysplasia (1 vs 0), hyperplastic polyp (2 vs 2) and chronic colitis (0 vs 1).

Conclusions: PBC patients have higher incidence rate of EV, grade F1, GVs and duodenal ulcers noted on EGD. There were more colon polyps seen on PBC patients’ colonscopic findings. The finding above supported rationale of endoscopic examination in PBC patients.

P.092 ANTI-REFLUX MUCOSAL ABLATION: A MEDICAL CENTER BRIEF REPORT

Yu-Chi Li1, Chih-Chien Yao1, Seng-Kee Chuah1,2, Wei-Chen Tai1,2

1Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan

2College of Medicine, Chang Gung University, Taoyuan, Taiwan

抗逆流黏膜燒灼術：單一醫學中心簡 短報告

Background: Gastroesophageal reflux disease (GERD) is one of the most commonly encountered gastrointestinal diseases in outpatient clinics. Proton pump inhibitors (PPIs) are the cornerstone of the treatment of GERD. However, approximately one-third of patients have suboptimal response to PPIs. Anti-reflux surgery was not favored for refractory GERD treatment due to high risk of complication. Therefore, minimally invasive endoscopic antireflux therapies are gaining popularity for the management of PPI-dependent and PPI-refractory GERD. Anti-reflux mucosal ablation (ARMA) was new endoscopic treatment for refractory GERD and it was first described in 202

Aims: We aimed the efficacy and safety of ARMA for treating patients with refractory GERD in in the Kaohsiung Chang Gung Memorial Hospital.

Methods: Patients was diagnosed Gastroesophageal reflux disease (GERD) by endoscopy and failure of PPIs treatment for 8 weeks. Besides, the hiatal hernia was found by endoscopy and Hill’s classification was grade I or II. All the patients had received the 24pH monitor and high resolution manometry (HRM) survey before ARMA. We enrolled these cases between Aug. 2021 and June 2022. The ARMA device we used HybridAPC® needle and ERBE VIO® 300 D coagulation machine. We used Forced APC mode with 100W for ablation of the gastric cardia mucosa surrounding about 270 degrees to induce

scar formation. We will evaluate the efficacy and safety (ex: DeMeester score, acid exposure time, clinical symptom etc) after treatment.

Results: Total 5 patients were enrolled into this study (males/female: 3/2, mean age: 43.4 years old). All patients’ gastroesophageal reflux disease is classified by Los Angeles classification system grade A. Hiatal hernia was graded by Hill’s classification (2 patients grade II, 2 patients grade III, and one patient grade I).24 hours pH monitor showed that there are 4 patients c/w acid reflux disease and one patient was alkaline reflux disease. 4 patients’ clinical symptom got improved after ARMA treatment except one patient still had GERD symptom. However, there are 4 patients’ DeMesster score elevated after ARMA treatment. There was no emergent complication after ARMA treatment.

Conclusions: ARMA is a safe treatment of choice for refractory GERD in this Taiwanese brief report. In efficacy, the GERD symptom got improved after ARMA. It needs more patient numbers and long term follow up reports to clarify the efficacy of ARMA

P.093 PATIENT PERCEPTION ON UNIVERSAL PREPROCEDURE SCREENING OF SARS-COV-2: A SINGLE CENTER EXPERIENCE IN NORTHERN TAIWAN

I-Fang Tsai1, Jing-Yi Ma1, Cheng-Shuan Chung1,2,3

1Ultrasonography and Endoscopy Center, Far Eastern Memorial Hospital, New Taipei City, Taiwan

2Division of Gastroenterology and Hepatology, Department of Internal Medicine, Far Eastern Memorial Hospital, New Taipei City, Taiwan

3College of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan

受檢者對常規性

術前篩 檢之看法：以台灣北部單一中心經驗 為例

3

Background: To reduce the risk of Severe Acute Respiratory Syndrome Coronavirus-2 (SARSCoV-2) infection among patients and health care workers (HCWs), universal preprocedural screening is one of the most important preventive measures for Coronavirus Disease 2019 (COVID-19) control. However, awareness and acceptance of patients to SARS-CoV-2 screening prior to endoscopic examination were seldom investigated.

Aims: This study aimed to understand patient perceptions upon preprocedural screening for SARS-CoV-2 infection.

Methods: This prospective study was conducted in Ultrasonography and Endoscopy Center of Far Eastern Memorial Hospital which is located in region with largest COVID-19 positive cases in Taiwan between 7th March and 22nd April, 2022. Patients who underwent the aerosol generating procedures, including 13C urea breathing test, esophagogastroduodenoscopy, transnasal endoscopy and bronchoscopy, were requested to receive self-paid rapid antigen test (RAT) for SARS-CoV-2 within 3 days of procedures. They

SARS-COV-2

were provided questionnaire about the acceptance to preprocedural screening and the data was analyzed using X2 test.

Results: Total 1,861 questionnaires were sent out and 1,815 were received with effective recovery of 97.5%. 1697 (93.5%) patients agreed this policy about preprocedure screening. Among them, 1624 (89.5%) patients thought that the screening would not affect their willingness to take the procedures. The screening had no effect on their willingneness to take the procedures (p = 0.000). There were 188 (10.4%) patients responding to the perceived barriers from this policy. The cost for RAT was the most common barriers (72.9%), followed by inconvenient access (14.4%), inadequate environment for screening (10.1%) and uncomfortable transnasal swab (2.6%). During study period, there was no procedurerelated SARS-CoV-2 infection among patients and HCWs.

Conclusions: Using RAT would be the ideal preprocedure screening tool which is patient well-accepted to reduce the risk of SARSCoV-2 transmission. Facing the COVID-19 pandemic, coexisting with SARS-CoV-2 would become the trend. Due to the expense of RAT and inconvenience concerned by patients, we suggested the home RAT for SARS-CoV-2 as the universal preprocedural screening method in the future.

NORTHERN TAIWAN

Min-Kai Liao1, Hsi-Chang Lee1, Chang-Hung Huang2, Kuan-Yang Chen3, Chih-Lin Lin1, Tsung-Jung Lin1

1Department of Gastroenterology, Renai

Branch, Taipei City Hospital, Taipei, Taiwan

2Department of Gastroenterology, Zhongxing Branch, Taipei City Hospital, Taipei, Taiwan

3Department of Gastroenterology, Yangming Branch, Taipei City Hospital, Taipei, Taiwan

Background: The main reason for H. pylori treatment failure is bacterial resistance to antibiotics. The study of antibiotics resistance rates of H. pylori may be beneficial in clinical regimen decision. Primary antibiotics resistance rates may variate over time. It’s essential to survey recent bacterial resistance rate of H. pylori for every hospital.

Aims: To investigate the trend of primary antibiotic resistant rate of H. pylori from a regional hospital in northern Taiwan.

Methods: We retrospectively analyzed patients with H. pylori infection who visited our hospital between March 2013 and May 2014 (group A, 175 patients); and between March 2019 to May 2022(group B, 225 patients). The presence of H. pylori was defined as: (1) positive results of both rapid urease test and histology examination; or (2) a positive result of culture. In cultureproved positive cases, antibiotics resistance rate were analyzed by amoxicillin, metronidazole, clarithromycin, levofloxacin, and tetracycline individually. The differences between two groups were examined with chi-squared test.

Results: In group A, 124/175 (70.8%) patients

P.094

THE TREND OF PRIMARY ANTIBIOTICS RESISTANCE RATES OF HELICOBACTER PYLORI: STUDY FROM ONE REGIONAL HOSPITAL IN

were positive with H. pylori culture. Rates of primary bacterial resistance: amoxicillin, 0% (0/124); metronidazole, 37.9% (47/124); clarithromycin, 15.3% (19/124); levofloxacin, 16.9% (21/124); tetracycline, 0.8% (1/124) respectively. In group B, 197/225 (87.5%) patients positive with H. pylori culture. Primary antibiotics resistance rate were listed as the following: amoxicillin, 1.5% (3/197); metronidazole, 35.0% (69/197); clarithromycin, 16.8% (33/197); levofloxacin, 24.4% (48/197); tetracycline, 0% (0/197) respectively.

Conclusions: In our study, the primary resistance rate of amoxicillin, metronidazole, and tetracycline remained at a similar level in two separate periods with interval more than 5 years. However, clarithromycin resistance rate kept the trend of increasing (15.3% to 16.8%). Levofloxacin resistance rate also went up to a high level (16.9% to 24.4%). This data will help us to choose the regimen of Helicobacter pylori eradication clinically.

TRIAGE POLICY TO POSTPONE ENDOSCOPY FOR PATIENTS WITH LOW-RISK VARICES IS SAFE DURING THE COVID-19 PANDEMIC

Yu-Jen Chen1,2, Ming-Chih Hou1,2

1Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan

2School of Medicine, National Yang-Ming

Chiao-Tung University, Taipei, Taiwan

在 COVID-19 流行期間使用分類策略 延後低風險靜脈曲張病人接受內視鏡 是安全的

陳宥任1,2 侯明志1,2

2 國立陽明交通大學醫學系

Background: During the COVID-19 pandemic, most of the endoscopic services were electively postponed or suspended.

Aims: We aimed to assess the safety of a triage policy in patients receiving esophageal variceal ligation during the COVID-19 pandemic.

Methods: Triage policy of endoscopic variceal ligation (EVL) was implemented in our hospital during the lockdown period from 15th May 2021 to 26th July 2021. We compared the clinical characteristics and outcomes with those receiving endoscopy due to esophageal varices from 17th May 2020 to 28th July 2020.

Results: Of the 124 patients receiving EVL, more patients experienced esophageal variceal bleeding (EVB) during the lockdown period (9/32, 28.1% vs. 8/92, 8.7%, p = 0.006), with a higher percentage of EVB in the referred cases (7/9, 77.8% vs. 2/14, 14.2%, p = 0.007). During the lockdown period, 23 patients whose endoscopies were postponed by triage policy due to low-risk or eradicated varices did not experience EVB. Child-Pughs class C was independent factor predictive of EVB (relative risk 7.674, P=0.004), entering the program of prophylactic EVL was the protective factor of EVB (relative risk 0.158, p = 0.004).

Conclusions: Entrance into the prophylaxis program does not only decrease risk of EVB but also fosters comprehensive triage to postpone endoscopy during the lockdown period.

P.095

1 臺北榮民總醫院胃腸肝膽科

P.096

THE USEFULNESS OF LOCALIZATION BY USING LUGOL CHROMOENDOSCOPY TO ASSIST EXCISION OF OROPHARYNGEAL SQUAMOUS CELL CARCINOMA IN SITU/DYSPLASIA THROUGH COLLABORATION BETWEEN GI AND ENT DOCTORS

Szu-Chia Liao1, Wan-Tzu Lin1, Ying-Cheng Lin1, Hui-Chun Chang1, Sheng-Shun Yang1,2, Ching-Ping Wang3,4

1Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taiwan

2School of Medicine, National Yang-Ming Chiao Tung University, Taiwan

3Department of Otolaryngology-Head and Neck Surgery, Taichung Veterans General Hospital, Taichung, Taiwan

4Department of Speech Language Pathology and Audiology, Chung Shan Medical University, Taichung, Taiwan

使用內視鏡併碘染色定位切除早期口 咽癌病人之成果：與耳鼻與喉科合作 模式

廖思嘉

1 臺中榮民總醫院胃腸肝膽科

2 國立陽明交通大學醫學系

3 臺中榮民總醫院耳鼻喉科

4 中山醫學大學醫學系語言治療與聽力學系

Background: More and more study reported there is a higher chance of having second primary cancer for esophageal and oropharyngeal cancer patients. If the patients receive mucosal excision for oropharyngeal cancer, they can avoid total laryngectomy or radiotherapy. The larynx is preserved and the recovery time is shortened. They will avoid suffering from swallowing problem or oropharyngeal stricture.

Aims: Therefore, we want to evaluate the efficacy for oropharyngeal cancer under the guidance of Lugol chromoendoscopy through collaboration between GI and ENT doctors.

Methods: Patients’ outcomes were reviewed between Jan. 2021 and Apr. 2022 in Taichung

Veterans General Hospital. Oropharyngeal tumors were removed by local excisions via endoscopic submucosal dissection (ESD) or excision using CO2 laser. We underwent Lugol chromoendoscopy–guidance during the procedure to delineate the tumor margin.

Results: Five patients underwent Lugol chromoendoscopy-guided excision for their oropharyngeal cancer, including SCC (n = 3), SCC in situ (n = 1), and high-grade dysplasia (n = 1). Lugol-guided excision was successfully in 5/5 with margin free in 5/5 (100%) and median hospital stay of 6 days (range 2-9 days). Oral intake could be achieved after discharge (5/5). Life quality questionnaire in cancer patients using EROTC version 3 were recorded. The median scores were 28 (range 23-39) for QLQ-STQ22, 33.5 (range 28-44) for QLQ-C30 overall, 5.5 (range 3-7) for QLQ-C30 global health status, and 5.5 (range 3-6) for QLQ-C30 quality of life. There was no procedure-related adverse event.

Conclusions: Through collaboration between GI and ENT doctors, using Lugol chromoendoscopy during excision of oropharyngeal cancer can be a safe and efficient method. It can result in high technical success with tumor margin free in cases. These patients can eat immediately after discharge and have better quality of life compared with other treatment modality, eg. laryngectomy or CCRT.

P.097

EFFICACY

AND SAFETY OF SEVENDAY NON-BISMUTH CONCOMITANT QUADRUPLE THERAPIES FOR FIRST-LINE ANTI-HELICOBACTER PYLORI TREATMENT IN THE ELDERLY

Te-Ling Ma1, Wei-Chen Tai2,3, Chih-Chien Yao2, Chih-Ming Liang2,3, Seng-Kee Chuah2,3

1Department of Internal Medicine, Fu Jen Catholic University Hospital, New Taipei City, Taiwan

2Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan

3College of Medicine, Chang Gung University, Taoyuan, Taiwan

and control groups were 84.0% (95% confidence interval [CI]: 76.4% to 89.9%) and 85.9% (95% CI: 81.3% to 89.7%) (P = 0.624) in intention-totreat analysis; 88.2% (95% CI: 81.0% to 93.4%) and 94.2% (95% CI: 90.6% to 96.7%) (P = 0.044) in per-protocol (PP) analysis. The adverse event rates were 10.9% in the elderly group and 12.8% in the control group (P = 0.607). The compliances were 100% in both groups. Multivariate analysis reveals that metronidazole resistance (odd ratio [OR], 95% CI: 6.870 [1.182-39.919], P = 0.032) and dual resistance (OR, 95% CI: 7.188 [1.32638.952], P = 0.022) were independent factors for failure of eradication.

Conclusions: The efficacy of non-bismuth concomitant quadruple therapy was lower in Taiwanese elderly cohort (<90%) for the firstline anti-H. pylori in PP analysis. Metronidazole resistance alone and dual resistance to metronidazole and clarithromycin were independent factors for failure of eradication.

2 高雄長庚紀念醫院肝膽腸胃內科

3 長庚大學醫學院

Background: Background: Aging may affect the efficacies of Helicobacter pylori (H. pylori) eradications.

Aims: The aim of our study is to compare the efficacies and safety of 7-Day Non-bismuth concomitant quadruple therapy for first-line antiH. pylori treatment in elderly.

Methods: We retrospectively analyzed a cohort with prospectively collected data from January 2013 to December 2019 at Chang Gung Memorial Hospital in Kaohsiung. There were 408 patients treated with 7 day’s concomitant therapy as first line H. pylori eradication regimen in naive infected subjects aged twenty or older. We divided the patients into elderly group (aged ≥ 60) and control group (aged < 60). Six patients were lost during follow-up in elderly group and 25 in the control group, resulting in 117 for aged ≥ 60 group and 258 in the control group. The patients were asked to performed urea breath tests eight weeks later.

Results: The eradication rates for the elderly

七日非鉍劑聯合四聯療法在老年人一 線抗幽門螺桿菌治療中的療效和安全

P.098

PRECISE DELIVERY OF TRANEXAMIC ACID TO ENHANCE ENDOSCOPIC HEMOSTASIS FOR PEPTIC ULCER BLEEDING: A PILOT STUDY

Hsueh-Chien Chiang, Er-Hsiang Yang, Ming-Tsung Hsieh, Chiao-Hsiung Chuang, I-Cheng Shih, Xi-Zhang Lin, Po-Jun Chen

Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan

casese) following block randomization procedures with a 1:1 allocation ratio. In the extra-therapy group, we sprayed 1.25gm tranexamic acid powder via the endoscopy to the peptic ulcer after the standard endoscopic treatment. Both groups then received a 3-day continuous high-dose (8 mg/h) PPI infusion, followed by oral PPI according to the Rockall scores. A second-look EGD is performed 2-3 days after the initial endoscopy. All patients will be monitored for 28 days after the first EGD. The success rate of endoscopic treatment, recurrent bleeding from a peptic ulcer, ulcer healing status on second-look EGD, length of hospitalization, bleeding-related mortality, and adverse events from tranexamic acid were analyzed.

Background: Peptic ulcer bleeding is a common emergency for patients who need therapeutic endoscopy, with a risk of mortality. Standard treatment includes proton pump inhibitor (PPI) and endoscopic therapy. Standard endoscopic hemostasis is highly effective, with overall success rates of 85%–95% in stopping hemorrhage. However, 5%–15% of the patients still experience persistent ulcer bleeding or recurrent bleeding after the initial endoscopic hemostasis. Tranexamic acid is a well-known antifibrinolytic agent, which reduces bleeding by inhibiting clot breakdown by inhibiting the degradation of fibrin by plasmin. The local use of tranexamic acid may enhance the hemostasis effect of standard endoscopic treatment.

Aims: We propose to investigate the effectiveness and safety when using tranexamic acid locally under endoscopic guidance in patients with peptic ulcer bleeding after standard endoscopic therapy.

Methods: This study is a randomized controlled trial, and sixty cases will be enrolled. Patients with peptic ulcer bleeding at National Cheng-Kung University Hospital were enrolled. We applied standard endoscopic therapy to the bleeding peptic ulcer by local injection of diluted epinephrine in combination with either heater probe coagulation, hemoclipping, and/or rubber band ligation. We then assigned the patient to either a standard-therapy group (30 cases) or an extra-therapy group (30

Results: This is an interim report. From 2022/3/25 to 2022/7/01, a total of 21 patients with peptic ulcer bleeding were enrolled, including 11 patients in the extra-therapy group and 10 in the standard therapy group. Baseline characteristics were balanced in these two groups. One patient in each group had persistent ulcer bleeding after standard endoscopic treatment, and the patient in the extratherapy group had stopped bleeding after the tranexamic acid powder spray. The successful rate of endoscopic hemostasis is 100% in the extra-therapy group, and 90% in the standardtherapy group. Two patients in each group had recurrent ulcer bleeding within 28 days, and one of each required emergent TAE and operation. The recurrent bleeding rate is 18.2% in the extratherapy group, and 20% in the standard-therapy group. There was no bleeding-related mortality or adverse events from tranexamic acid in the study period. There was no statistical difference in the length of hospitalization or the ulcer healing status on second-look EGD between the two groups.

Conclusions: Delivery of tranexamic acid powder via endoscopy for peptic ulcer bleeding is a safe procedure. The successful hemostasis rate is slightly higher and the rebleeding rate is slightly lower with this procedure. This trial will be continued (NCT05248321).

經內視鏡投予傳明酸於消化性潰瘍以 增強止血效果的前導性研究

楊貳翔 謝名宗 莊喬雄 史易正 林錫璋 陳柏潤 國立成功大學醫學院附設醫院消化內科

P.099

IS CT GRADING SYSTEM BETTER THAN ENDOSCOPIC GRADE IN PREDICTING THE OUTCOME AFTER CORROSIVE INJURY?

Shu-Wei Huang1, Hao-Tsai Cheng1,2,3, Ming-Yao Su1, Chang-Mu Sung2,3, Tsung-Hsing Chen2,3, Sen-Yung Hsieh2

1Division of Gastroenterology and Hepatology, Department of Internal Medicine, New Taipei Municipal TuCheng Hospital, New Taipei City, Taiwan

2Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University, Taoyuan, Taiwan

3Graduate Institute of Clinical Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan

黃書偉1 鄭浩材1,2,3 蘇銘堯1 宋昌穆2,3 陳聰興2,3 謝森永2

1 新北市立土城醫院（委託長庚醫療財團法人興建 經營）胃腸肝膽科

2 林口長庚紀念醫院胃腸肝膽科系

3 長庚大學臨床醫學研究所

Background: Ingestion of caustic substances may induce an extensive spectrum of injuries to aerodigestive tract including extensive necrosis and perforation of the esophagus and stomach. There were patients refuse to receive adequate endoscopic survey due to fears of aerodigestive tract perforation. In recent years, computed tomography (CT) is a noninvasive, safe, and accurate method to visualize upper gastrointestinal tract.

Aims: The aim of this study was to test the utility of two kinds of CT grading system and compared with endoscopy to predict the outcome of patients with caustic ingestion.

Methods: This is a retrospective study from 46 patients (>17 years of age), who admitted to Chang Gung Memorial Hospital, Tao-Yuan Branch between January 2014 and November 2019 for treatment of caustic condition. These caustic patients all received CT within 72 hours and

endoscopy within 24 hours after caustic ingestion. The degree of esophageal damage was graded using a scoring system based on the extensive of esophageal/gastric wall edema and the damage in adjacent tissue as seen on thoracoabdominal CT scans. Two kinds of CT are classified by Ryu and St. Louis. The presence of esophageal / gastric stricture was established by endoscopy and clinical symptoms. All patients were followed up for at least 1 month after treatment.

Results: There were 13 males and 33 females included in the study, with an average age of 46 ± 19.293 years. Fifteen patients were admitted in ICU and one died during admission. In CT finding, grade III was most common caustic injury (n = 34, 73.9%) in Ryu CT grade and grade II was most common caustic injury (n = 36, 78.3%) in St. Louis CT grade. In ICU admission, EGD grade is better than Ryn and St. Louis CT grade (AUROC 0.742: 0.66: 0660). In GI complication, EGD is also better than Ryn and St. Louis CT grade (AUROC 0.808: 0.649: 0723).

Conclusions: A noninvasive method by using CT to assess degree of upper gastrointesinal damage in caustic patients who visit the emergency department is useful in estimating occurrence of complications. In our study, EGD still has the role to predict the outcome in corrosive injury patients.

電腦斷層是否比胃鏡更能預測腐蝕性 食道患者的預後？

P.100 EXPLORATION OF ESOPHAGEAL HYPERVIGILANCE AND VISCERAL ANXIETY STATUS IN PATIENTS WITH SYMPTOMATIC GERD: A SINGLE-CENTER STUDY IN TAIWAN

Ming-Wun Wong1, Shu-Wei Liang1, Jui-Sheng Hung1, Tso-Tsai Liu1, Chih-Hsun Yi1, Wei-Yi Lei1, Lin Lin1, Jen-Hung Wang2, Chien-Lin Chen1

1Division of Gastroenterology, Department of Internal Medicine, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan

2Department of Medical Research, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan

探討食道警覺及內臟焦慮狀態在胃食

道逆流症患者之臨床應用：台灣單一

翁銘彣1 梁書瑋1 洪睿勝1 劉作財1 易志勳1 雷尉毅

1 佛教慈濟醫療財團法人花蓮慈濟醫院內科部肝膽 腸胃科

2 佛教慈濟醫療財團法人花蓮慈濟醫院研究醫學部

Background: The esophageal hypervigilance and anxiety scale (EHAS) is a valuable cognitiveaffective evaluation of visceral sensitivity, which has been demonstrated to associate with gastroesophageal reflux disease (GERD) symptom severity and psychological burden. However, the normative references of EHAS were lacking.

Aims: To obtain normative values for EHAS in the setting of patients who underwent esophagogastroduodenoscopy (EGD) without GERD symptoms and investigate potential clinical factors contributing level of EHAS in symptomatic patients. Patients scheduled EGD with or without GERD symptoms were prospectively enrolled for assessing patient-reported outcomes, including EHAS and GERD questionnaire (GERDQ).

Methods: Patients without GERD symptom had GERDQ ≤8 were classified as controls. Upper limit of EHAS in controls was defined as the 95th percentile of normative values. Potential factors influencing the level of EHAS were identified via

generalized linear model.

Results: We enrolled 534 patients, aged 20–84 years (mean, 52.78), of whom 54.2% were female; 110 had GERD symptoms, and 418 were controls. Patients with GERD symptoms had higher EHAS levels than controls (28.7 vs. 10.2, P < 0.001). On generalized linear model GERDQ scores and female gender positively correlated with EHAS (GERDQ, β = 2.254, P < 0.001; female, β = 3.828, P = 0.001). The 95th percentile for EHAS in control was 36 overall, 36 for men and 36.8 for women.

Conclusions: Patients’ GERD symptom severity and female gender positively correlate with the level of EHAS. In the setting of pre-EGD assessment, normative references of EHAS may help detect potential cognitive-affective comorbidity for GERD patients.

P.101 EXPERIENCE OF ENDOSCOPIC ULTRASOUND-GUIDED (EUS-FNA) MEDIASTINAL LESION BIOPSY: A TERTIARY HOSPITAL REPORT

Shih-Hua Chen, Yen-Chih Lin, Hsu-Heng Yen

Division of Hepatobiliary Gastroenterology, Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan

內視鏡超音波導引針對縱膈腔病灶切 片實際經驗

P.102 NEW SURVEILLANCE METHODS OF POST PER-ORAL ENDOSCOPIC MYOTOMY (POEM) REFLUX, ONE SINGLE MEDICAL HOSPITAL EXPERIENCE

Tony Kuo, Yung-Kuan Tsou, Cheng-Han Lee

Department of hepatology and Gastroenterology, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan

陳世華

林彥至 顏旭亨 彰化基督教醫院胃腸肝膽科

Background: EUS-FNA is a useful technique for pancreatic neoplasm biopsy. Previous reports demonstrate the safety and efficacy of EUS-FNA biopsy for mediastinal lesion.

Aims: Assess safety and outcome of EUS-FNA for mediastinal lesion biopsy in our hospital.

Methods: We retrospectively reviewed the patient records who received EUS-FNA for mediastinal lesion in Changhua Christian Hospital. The primary aim of the study was the diagnostic yield of EUSFNA and the second end point was to evaluate the complication orate of the procedure.

Results: All the EUS-guided procedure was performed under sedation. FNA was performed while the mediastinal lesion was identified by EUS. A total of 9 patients received EUS-FNA during the study period and tissue sampling were performed smoothly. Overall, a diagnosis rate was 77.7% and the complication rate was 0% made in the present study.

Conclusions: EUS-FNA is a safe and minimal invasive technique for mediastinal lesion biopsy.

鄒永寬 李承翰

Background: Per-Oral Endoscopic Myotomy (POEM) is a less invasive treatment compared to Heller myotomy for patients with achalasia. However, post –operative reflux occurred very commonly in POEM due to no fundoplication during the procedure and hard to distinguish with poor response to the procedure due to food stasis in the esophagus also induced the esophagitis syndrome.

Aims: The objectives of this study were to (1) identify patients with post-POEM reflux using Eckardt score, esophagography, endoscopic evaluations, and high resolution impedance manometry (HRIM) (2) investigated risk factors associated with post-POEM reflux and esophagitis to optimize patient selection for POEM and identify those who will benefit from a proactive approach to post-operative reflux management.

Methods: A retrospective review of a prospectively collected database of patients who underwent POEM between September 2020 and June 2022 at a single institution was performed. Demographics along with pre-POEM and post-POEM variables were obtained. Univariate analyses were performed, using p values ≤ 0.05 for statistical significance.

Results: 15 patients were included, with a mean follow-up of 84 days. Mean age was 54.4 (21.71); 60% were female. All of patients underwent esophagography and HRIM testing after POEM, and total 7 patients (46%) suffered from new gastric esophagus reflux symptom after POEM, and all of 7 (100%) patients post-operative endoscopy revealed reflux esophagitis without evidence

透過新的方法來評估經口內視鏡食道 括約肌切開術，單一醫學中心經驗 郭偉亮

林口長庚紀念醫院胃腸肝膽科

of restenosis. Post–operative esophagography revealed new onset of reflux episode compared with pre-operative esophagography with 2 (13%) patients and only 1 patient with symptom. 7 (46%) patients noted new reflux episode noted by HIRM compared with pre-POEM esophagography and HRIM and all of 7 patients suffered from symptom and compatible with endoscopy. Only higher preoperative Eckardt score was significantly associated with endoscopic evidence of esophagitis post-POEM.

Conclusions: Reflux is common after POEM and some episodes are not only related to acid regurgitation but also related to esophagus motility disorder. HIRM is consider a new and convenient method to detect the post-operative reflux. This population warrants close surveillance.

P.103 THE NARROW BAND IMAGE

ENDOSCOPY IMAGES

ASSOCIATED WITH THE PRESENTATIONS OF GASTRIC PRECANCEROUS LESIONS IN PATIENTS WITH MAINTENANCE USE OF PROTON PUMP INHIBITORS

Yu-Ching Tsai1,2, Hsiao-Bai Yang3,5, Wei-Lun Chang2, Hsin-Yu Kuo2,4, Chung-Tai Wu2,4, Meng-Ying Lin2, Erh-Siang Yang2, Ming-Tsung Hsieh2, Chun-Te Lee2, Yu-Ting Yu3, Hsiu-Chi Cheng1,2

1Department of Internal Medicine, Tainan Hospital, Ministry of Health and Welfare, Executive Yuan, Tainan, Taiwan

2Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan

3Department of Pathology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan

4Institute of Clinical Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan

5Department of Pathology, Ton Yen General Hospital, Hsinchu, Taiwan

Background: Chronic use of proton pump inhibitors (PPI) was considered associated with increased risks of gastric mucosal atrophy and gastric cancer (GCA). If non-biopsy endoscopic

(NBI)

WERE

surveillance could be used to predict the presentations of gastric precancerous lesions is of interest.

Aims: This study aims to assess if NBI endoscopy could be used to predict the presentations of gastric precancerous lesions in longterm-PPI users.

Methods: We arranged panendoscopy for patients with PPI treatment≥6 months and performed topographic biopsies according to the updated Sydney system protocols. The NBI endoscopic images and the presence of gastric precancerous lesions were compared. We also performed backtracking comparison for the pathology/ endoscope images with each patient’s last endoscopy/image studies. Associations between progression/regression of the image/pathology results were assessed.

Results: We enrolled 73 patients. The presence of precancerous lesions were Operative Link on Gastritis Assessment (OLGA) stage III/IV 48% (n = 32/67); Corpus-predominant Gastritis Index (CGI) 21% (n = 15/70); and the high risk IM (Operative Link on Gastric Intestinal Metaplasia (OLGIM) stage III/IV + corpus IM) 36% (n = 26/72). The endoscopic Kimula-Takemoto classification and high risk endoscopic grading of gastric intestinal metaplasia (EGGIM) (EGGIM antrum >2/corpus ≥1) were associated with OLGA stage III/IV (p = 0.048) and high risk IM (OR: 11.4, 95% CI: 3.338.9, p < 0.001). The NBI endoscopic corpus mucosal pattern with groove type and dilated subepithelial capillaries was associated with high corpus inflammation (p < 0.001) and the presence of CGI (OR: 3.6, 95% CI: 0.9-14.1, p = 0.05). With the backward comparison of the previous studies, the progression/regression of the endoscopy and the pathology had moderate association for high risk EGGIM/ OLGIM III/IV/corpus IM (Pearson’s R = 0.614, p < 0.001) and NBI corpus inflammation/ CGI (Pearson’s R = 0.396, p = 0.003); but not Kimula-Takemoto classification/OLGA III/IV (Pearson’s R = 0.165, p = 0.221).

Conclusions: The NBI endoscopy images were associated with the presentations of gastric precancerous lesions in PPI3 maintenance users that deserved further detail studies.

P.104 STANDARD BIOPSY FORCEPS FOR HISTOPATHOLOGIC DIAGNOSIS OF SMALL SUBEPITHELIAL LESIONS IN THE UPPER

GASTROINTESTINAL TRACT – A SINGLE CENTER EXPERIENCE

Chun-Jung Lin, Cheng-Yu Lin, Sheng-Fu Wang, Chen-Ming Hsu

Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan, Taiwan

病灶的組織病理學診斷 單一中心的 經驗報告

Background: Subepithelial lesions (SELs) are usually detected incidentally by endoscopy in asymptomatic patients. Recently many minimally invasive procedures were developed for accurate diagnosis either in endoscopic resection methods (e.g. ESD, STER) or in EUS-guided fine needle biopsy (FNB) other than EUS imaging. However most small SELs (<1 cm) are still a challenge to endoscopist for selection of best strategy spectrum between follow-up and resection.

Aims: To evaluate the efficacy and safety of standard forceps biopsy on small SELs in upper gastrointestinal tract (UGI) after EUS or without EUS.

Methods: We retrospectively reviewed the clinicopathology data of patients receiving forceps biopsy of UGI small SELs (EUS measurement or clinical assessment) by one endoscopist (CJ Lin) between January 2019 and May 2022. After biopsy forceps stripping of mucosal layer, SELs were exposed for further biopsy or snare resection. Disposable clips are applied for deep ulcers or for hemostasis on demand.

Results: A total of 43 patients (mean age 58.3 years, 36-77years) with SELs in esophagus (18 lesions), stomach (21), duodenum (4) were analysis for imaging pictures and report. The diagnosis yield of our biopsy series was 86% (37/43) with mean size 5.91 ± 1.84mm. The mean procedure time was 8.19 minutes (esophagus 4.93 ± 2.32 min vs. stomach 11.91 ± 5.48 min).

以標準生檢鉗對上消化道小型上皮下

林淳榮 林正佑 王昇富 許振銘 林口長庚紀念醫院胃腸肝膽科

Additional snare resections were performed over 8 gastric lesions. Immediate complication included gastric hemorrhage in 11.6% (5/43), all treated by disposable clips smoothly without recurrence.

Conclusions: Forceps biopsy technique is a simple, safe and high-yield histopathologic diagnostic method for patients with small (<1cm) upper gastrointestinal SELs. But for gastric SELs, snare resection and clip hemostasis are supplemental for this longer procedure.

P.105 INCREASED GLYCATED HEMOGLOBIN BUT DECREASED CHOLESTEROL AFTER A LOSS OF HELICOBACTER PYLORI INFECTION: A COMMUNITY-BASED LONGITUDINAL METABOLIC PARAMETERS FOLLOW-UP STUDY

Li-Wei Chen1,2, Cheng-Hung Chien1,2, Chih-Lang Lin1,2, Rong-Nan Chien2,3

1Division of Hepato-Gastroenterology, Department of Internal Medicine, Keelung Chang Gung Memorial Hospital, Keelung, Taiwan

2Community Medicine Research Center, Keelung Chang Gung Memorial Hospital, Keelung, Taiwan

3Division of Hepato-Gastroenterology, Department of Internal Medicine, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan

陳立偉1,2 錢政弘1,2 林志郎1,2 簡榮南2,3

1 基隆長庚紀念醫院胃腸肝膽科 2

Background: Helicobacter pylori (H. pylori) infection is the most common chronic bacterial infection in humans. H. pylori infection induces local inflammation in the stomach and a systemic immune reaction in the whole body. Elevated levels of inflammatory cytokines, such as interleukin 1, 8, 17, tumor necrosis factor α (TNF-α), and lowered levels of leptin are involved in these inflammatory reactions. A leptin deficiency and high levels of inflammatory cytokines are the critical mechanisms for insulin resistance (IR) and metabolic syndrome (MetS).

Aims: This study aimed to evaluate the impact of H. pylori infection on metabolic parameters in a longitudinal follow-up manner.

Methods: From August 2013 to August 2019, a com-munity-based prospective study of H. pylori and MetS was performed in the northeastern region of Taiwan. A total of 1865 subjects were

胃幽門螺旋桿菌消失增加糖化血色素 但是減少膽固醇：一個社群的長期追 蹤研究

divided into four groups according to the serial results of urea breath test (UBT): new H. pylori infection (group 1, n = 41), null H. pylori infection (group 2, n = 897), loss of H. pylori infection (group 3, n = 369), and persistent H. pylori infection (group 4, n = 558).

Results: When comparing the subjects between groups 1 and 2, HBA1c was associated with a new H. pylori infection (adjust odds ratio, aOR = 1.338, 95% CI: 1.034 1.731, P < 0.027, adjusting the confounding factors of age and gender). Body mass index (BMI) was associated with a loss of H. pylori when comparing subjects between groups 3 and 4 (aOR = 1.068, 95% CI: 1.027 1.109, P < 0.001). Elevated HBA1c and highdensity lipoprotein (HDL) levels but lower values of cholesterol and white blood cells (WBCs) were found during serial analyses within group 3 (loss of H. pylori infection).

Conclusions: HBA1c was associated with a new H. pylori infection. BMI was associated with H. pylori loss. Increased HBA1c and HDL values but decreased values of cholesterol and WBC were associated with a loss of H. pylori infection.

P.106 METABOLIC RISK FACTORS PREDICT IMPROVEMENT IN INSULIN RESISTANCE AFTER HELICOBACTER PYLORI ERADICATION

Tzu-Chan Hong1, Jyh-Ming Liou1,2, Ming-Shiang Wu2

1Department of Internal Medicine, National Taiwan University Cancer Center, Taipei, Taiwan

2Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan

2 國立臺灣大學醫學院附設醫院內科部

Background: Insulin resistance (IR) is associated with diabetic risks and cardiovascular morbidities. The improvement of IR was noted in a proportion of patients 1 year after H. pylori eradication therapy. It is still unclear who will benefit from H. pylori eradication therapy in terms of IR improvement and whether the improvement is due to host factors or caused by the change in fecal microbiota.

Aims: We aim to investigate the predictors of insulin resistance improvement and its association with gut microbiota.

Methods: The prediction model was derived from a randomized controlled trial initially aim to investigate eradication regimens. Homeostasis Model Assessment-Insulin Resistance index (HOMA-IR) was used as indicator of insulin resistance from baseline and 1 year after eradication. Multivariate logistic regression with multiple iteration steps were used to construct the model with best AUROC. The model was external validated in two other randomize controlled trials of 1st and 2nd line H. pylori eradication. The baseline, 1-year stool samples were collected, compared, and tested for alpha-diversity (Choa1, ACE for richness, Simpson and Shannon for richness and evenness tested by T-test/ANOVA), beta-diversity (tested with PERMANOVA and PERMDISP for centroid and dispersion variance) and Firmicutes to Bacteroides (F/B) ratio (tested by T-test and

代謝症候群風險因子用於預測經幽門 螺旋桿菌除菌後之胰島素阻抗改善

內科部

ANOVA).

Results: The derivation cohort consists of a total of 825 patients with 196 patients whose HOMA-IR improved 1 year after H. pylori eradication therapy. Patients with HOMA-IR improvement were tested significantly higher in baseline HOMA-IR (mean 5.80 vs 1.48, p < 0.001), percentage of diagnosis of metabolic syndrome (mean 40.8% vs 25.3%, p < 0.001). The improvements were not associated with age, gender, smoking alcohol use, H. pylori treatment regimens or endoscopic conditions. Multivariate logistic regression with iterations were used to construct prediction models from baseline

HOMA-IR (OR: 1.55, 95% CI: 1.43-1.68) and body mass index (BMI) with odds ratio (OR) 0.90 (95% CI: 0.85-0.96). The coefficient formula of this model was 0.83 - 0.1*(Baseline BMI) + 0.44*(Baseline HOMA-IR). The model has a sensitivity of 0.71, specificity of 0.91, positive predictive value (PPV) of 0.70 and negative predictive value (NPV) of 0.91 with its AUROC 0.85 (0.82-0.88). Similar specificity, NPV and AUROC were noted in external validation groups. Stool microbiota from baseline or 1 year after eradication were tested separately without difference in alpha diversity, beta diversity or F/B ratio. However, both decrease in alpha diversity and change in beta diversity were noted comparing baseline and 1 year after eradication in groups with or without HOMA-IR improvement. Conclusions: H. pylori eradication is associated with improvement of insulin resistance in terms of HOMA-IR especially in sub-population predicted by baseline higher HOMA-IR and lower BMI in our validated prediction model.

P.107 DECLINING TRENDS OF PREVALENCE OF HELICOBACTER PYLORI INFECTION AND INCIDENCE OF GASTRIC CANCER IN

TAIWAN – AN UPDATED CROSSSECTIONAL SURVEY AND METAANALYSIS

Mei-Jyh Chen1, Ming-Jong Bair2, Po-Yueh Chen3, Yu-Jen Fang4, Yao-Chun Hsu5, Yi-Chia Lee1, Ming-Shiang Wu1, Jyh-Ming Liou1,6

1Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan

2Division of Gastroenterology, Department of Internal Medicine, Taitung Mackay Memorial Hospital, Taitung, Taiwan

3Division of Gastroenterology and Hepatology, Department of Internal medicine, Chia-Yi Christian Hospital, Chiayi, Taiwan

4Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Yun-Lin Branch, Yunlin, Taiwan

5Department of Internal Medicine, E-DA Hospital and I-Shou University, Kaohsiung, Taiwan

6Department of Internal Medicine, National Taiwan University Cancer Center, Taipei, Taiwan

Background: Recent studies showed that the prevalence rates of H. pylori infection have declined in many countries; however, in real world, the direct impact of reduced H. pylori prevalence

on incidence and mortality of gastric cancer is still uncertain.

Aims: We aimed to assess the latest prevalence and secular trend of H. pylori infection and its association with the incidence and mortality of gastric cancer in Taiwan.

Methods: Adults naïve to Helicobacter pylori eradication received 13C-urea breath test (13C-UBT), H. pylori stool antigen test, and serology test during 2019-2020 in this prospective screening program. Children and adolescent aged between 7 and 19 years received 13C-UBT for H. pylori screening. We also conducted a systematic review and meta-analysis to assess the secular trend of prevalence of H. pylori from 1990 to 2020 in Taiwan. The secular trends of age-standardized incidence and mortality of gastric cancer were obtained from the Taiwan Cancer Registry.

Results: A total of 1,494 participants were enrolled, including 294 children or adolescents and 1,200 adults. The overall prevalence of active H. pylori infection by 13C-UBT was 26.6% (397/1,494), which was 30.8% in adults and 9.5% in adolescents/children. The age-standardized prevalence of active H. pylori infection was 32.3% in adults after adjustment of the population structure in Taiwan. Of the 29 studies including 38,597 subjects eligible for the meta-analysis, the pooled prevalence of H. pylori infection decreased from 63.8% (95% CI: 55.9%-71%) in 1990-2000 to 28.2% (95% CI: 21.8%-35.6%) in 2016-2020. The age-standardized incidence and mortality of gastric cancer have also declined from 15.2 and 10.75 per 100,000, respectively, in 1999 to 9.29 and 5.4 per 100,000, respectively, in 2019.

Conclusions: The prevalence of H. pylori infection has declined in Taiwan, which correlates with the declining trends of age-standardized incidence and mortality of gastric cancer in Taiwan.

P.108 RADIATION EXPOSURE IN INFLAMMATORY BOWEL DISEASE: A RETROSPECTIVE STUDY

Chen-Ta Yang, Siou-Ping Huang, Yang-Yuan Chen, Hsu-Heng Yen

Division of Gastroenterology, Changhua Christian Hospital, Changhua, Taiwan

Background: Inflammatory bowel disease (IBD) is a chronic, fluctuating, and relapsing disease that might complicate with fistula or stricture of the bowel. CT scan is essential for diagnosis and evaluation of the extent of disease and complications. However, increased CT scan will increase the radiation dose and might increase the risks of development of cancer.

Aims: The aim of this study is to evaluate the radiation exposure in an IBD cohort.

Methods: From January 2010 to December 2020, 144 patients diagnosed after Jan 2010 in Changhua Christian Hospital were retrospectively reviewed. Three of them was excluded due to cancer diagnosed before diagnosis of IBD. During follow up of IBD, we evaluated the demographic, clinical, and radiological data. The type and number of each radiological image were listed and the cumulative effective dose (CED) was calculated for each patient.

Results: Among 141 IBD patients, including 50 patients of CD and 101 patients of UC. During a median follow-up duration of 5 years, the median CED was 4.9 (IQR: 0.7–19.1) for IBD, 21.3 (IQR: 12.1–33.3) for CD, 2.1 (IQR: 0–5.6) for UC (Table 1). The percentage of CED > 50 mSv was higher among patients with CD than with UC (8.0% vs. 1.1%) (Table 1 and Figure 1). CED exposure is associated with cancer development among these IBD patients (p = 0.012). Risk factors associated with high radiation exposure (CED > 50 mSv) included age at diagnosis (p = 0.024) and Crohn’s disease (p = 0.073) (Table 2).

Conclusions: Conclusions: The study found Crohn’s disease is associated with higher radiation exposure. Either MRE or intestinal ultrasound are still underutilized in our cohort.

發炎性腸道疾病的輻射暴露（回溯性 研究）

楊承達 黃秀萍 陳洋源 顏旭亨 彰化基督教醫院胃腸肝膽內科

SEQUENCE BIOLOGIC THERAPIES IN PATIENTS WITH INFLAMMATORY BOWEL DISEASE

Wei-Chen Lin1, Chen-Wang Chang1, Ming-Jen Chen1, Tzu-Chi Hsu2, Horng-Yuan Wang1

1Division of Gastroenterology, Department of Internal Medicine, Mackay Memorial Hospital, Taipei, Taiwan

2Division of Colon and Rectal Surgery, Mackay Memorial Hospital, Taipei, Taiwan 發炎性腸炎患者之序列性生物製劑治

biologic prescription, steroid-free rate was 47.5% and 22.5% in UC and CD patients respectively. Thirteen patients (14.9%) discontinued their first biologic agent, the most common cause was secondary non-response 5/13 (38.5%), followed by the patient’s preference 4/13 (30.8%). 21 CD patients and 27 UC patients received 2nd course of biologic agent. Three UC patients (11.1%) and 10 CD patients (37%) had switching of biologics. The non-response rate to 2nd biologic agent rate were 0% in UC and 30% in CD. A comparison of the periods of 2011-2017, 2018-2019 and 20202021 revealed an increasing VDZ use in IBD (2.9%, 36.7% and 50%). The VDZ as the first line of biologic agent was more commonly prescribed in CD than UC during 2020-2021, 62.5% VS 50%.

Background: Data on real-life patterns of biologic use for inflammatory bowel disease (IBD) in Asia are scarce. In Taiwan, Adalimumab (ADA) is the first reimbursed biologic available for moderate to severe CD on 2011. For UC, Golimumab (GOL) and ADA is available on 2016. The health insurance included coverage of Vedolizumab (VDZ) and Infliximab (IFX) for IBD in the 2017. With an increasing range of biologics available and limited treatment period of insurance coverage, sequencing of such therapies is becoming more frequent.

Aims: We aimed to examine the patterns of biologic use and the factors associated with switching of biologics in Taiwanese IBD patients. Methods: Using retrospective medical electronic data, we collected data on patients who were diagnosed with IBD and exposed to biologics between 2011 and 2021 in Mackay memorial hospital, Taiwan. Patients receiving at least one dose of biologic agent with closely follow-up were included.

Results: n total, we identified 87 biologic-naïve IBD patients, including 40 patients with Crohn’s disease (CD) and 47 patients with ulcerative colitis (UC). The average [standard deviation] age (year): 44.0 [15.1] in UC and 35.0 [15.0] in CD; median disease duration to biologic use (years): 4.7 in UC and 4.1 in CD. The most common prescribed first line biologics were ADA, followed by the VEZ and IFX, 68.9%, 26.9%, 2.3% respectively. After

Conclusions: In real-world clinical practice settings, VDZ as first-line biological therapy is emerging in this study and especially in the CD patients. The switching of biologics was common in CD patients.

P.110

PROMOTE COLONOSCOPY IN MOBILE HOSPITAL HEALTH CHECK

Wen-Wei Huang, I-Ting Wu, Sheng-Yeh Tang, Li-Fu Kuo, Kung-Feng Tsai, Chang-Pi Shih, Ping-I Hsu

Division of Gastroenterology and Hepatology, Department of Internal Medicine, An Nan Hospital, China Medical University, Tainan, Taiwan

P.111

TO EVALUATE THE EFFICACY AND SAFETY OF MULTI-BAND MUCOSECTOMY FOR REMOVAL OF RECTAL SUBEPITHELIAL TUMORS – EXPERIENCES OF A TERTIARY CENTER IN NORTHERN TAIWAN

Chun-Min Chen, Ning-Hsuan Chin, Chen-Shuan Chung, Cheng-Kuan Lin, Kuan-Chih Chen

Division of Gastroenterology and Hepatology, Department of Internal Medicine, Far Eastern Memorial Hospital, New Taipei City, Taiwan

探討多環黏膜切除術應用於移除直腸

Background: Biennial fecal immunochemical test (FIT) has been performed in Taiwan for years to prevent or treat colon cancer earlier. Though FIT itself is an easy test and most people can do it by themselves, confirmation with colonoscopy when FIT is positive is sometimes not as convenient as we think, especially in the countries or small towns, where medical resources are less.

Aims: Try to increase the colonoscopy confirmation rate among FIT positive population.

Methods: On the second stage day of the mobile hospital health check held by a rural district health station, one doctor and one nurse from our hospital joined them to explain the FIT result and booked the colonoscopy time directly. We also brought GI Klean powder to them and instructed how to use it, as well as diet control at the same time. For the elders, who have no family to bring them to the hospital, we arranged a car to pick them up and send them back after the colonoscopy.

Results: From 2018 to 2022, we performed 517 colonoscopies from these countries. Among them, 284 people (54.9%) had at least one adenomatous polyp and 15 (2.9%) had cancer. 248 people (48.0%) came to and back from our hospital by booked vehicle.

Conclusions: To increase the participation rate of confirmation colonoscopy, we can do more than just an exam in the hospital. Eliminating the traffic barrier is a good step.

陳駿敏 金寧煊 鍾承軒 林政寬 陳冠至

醫療財團法人徐元智先生醫藥基金會亞東紀念醫 院肝膽胃腸科

Background: Although endoscopic submucosal dissection has high complete and en-bloc resection rates for rectal subepithelial tumors (SETs), an increased risk of complications including perforation and bleeding is concerned. Recently, multi-band mucosectomy (MBM) has shown highly effective and safe for treatment of selected SETs; however, the data of this technique for rectal SETs is still limited.

Aims: We aimed to evaluate the efficacy and safety of MBM for removal of rectal SETs at a tertiary hospital in northern Taiwan.

Methods: We collected clinical data from the consecutive patients who received MBM for removal of rectal SETs between September 2020 and April 2022 at Far Eastern Memorial Hospital. All of these patients received lower gastrointestinal (GI) endoscopic ultrasound (EUS) using Olympus miniature Probe UM-DP20-25R for SETs evaluation before the procedure. The primary outcomes were en bloc resection rate and pathologic complete resection rate. The secondary outcomes were operation time and adverse events (AEs). The MBM was performed with Duette MBM kit (Cook Medical, Limerick, Ireland), which allowed removal of SETs with no need for submucosal injection or repeated endoscope withdrawal.

Results: The MBM for removal of rectal SETs was performed in seven patients (5 female and

增加行動醫院糞便篩檢陽性追蹤率

黃文威 吳奕霆 湯昇曄 郭立夫 蔡坤峰 施長碧 許秉毅

臺南市立安南醫院—委託中國醫藥大學興建經營 內科部消化內科

黏膜下腫瘤的療效及安全性 台灣北 部單一醫學中心經驗

2 male) during the study period. Among of them, five patients (71.4%) underwent this procedure in outpatient department. The mean ± SD age was 46.7 ± 12.1 years old. The mean ± SD operation time and tumor size were 12.2 ± 1.6 minutes and 5.6 ± 2 millimeter (mm) respectively. The en bloc resection rate and pathologic complete resection rate were both 100%. All of these tumors originated from submucosal layer and the majority of pathological diagnosis of these lesions was neuroendocrine (NET) (6/7, 85.7%), and one case was lipoma (1/7, 14.3%). All the grading of NETs was grade 1. EUS assessment before the MBM did not show any pararectal lymph node metastases in all patients. All the mucosal defects were closed by hemoclips successfully after the procedure, and the mean ± SD number of hemoclips usage was 3.8 ± 1. The only complication was delayed bleeding, which occurred in only one case with final diagnosis of lipoma (28.5%). Hemostasis was achieved easily by another endoscopic procedure with additional hemoclipping and cograsper coagulation. No massive bleeding, perforation, infection, abdominal pain, and other AEs were observed.

Conclusions: This study demonstrated MBM as an efficient and safe treatment for removal of rectal SETs. The en bloc resection rate and pathologic complete resection rate both achieved 100%. Besides, the procedure time was short and can be done at outpatient department setting. The complication rate was only 28.5% (only one case with bleeding, which was easily controlled). Further studies are needed to elucidate the maximal size for resection and long-term outcome follow-up.

P.112 PATIENT PERCEPTION AND ACCEPTANCE OF COLONOSCOPY IN PATIENTS WITH INFLAMMATORY BOWEL DISEASE

Tien-Yu Huang1,2,3, Bao-Chung Chen1,3, Jung-Chun Lin1, Hsuan-Hwai Lin1, Peng-Jen Chen1, Yu-Lueng Shih1, Wei-Kuo Chang1,3, Tsai-Yuan Hsieh1,3

1Division of Gastroenterology, Department of Internal Medicine, Tri-Service General Hospital, National Defense General Hospital, Taipei, Taiwan

2Taiwan Society of Inflammatory Bowel Disease

3Taiwan Association for the Study of Small Intestinal Disease

黃天祐1,2,3 陳保中1,3 林榮鈞1 林煊淮1 陳鵬仁1

施宇隆1 張維國

Background: Inflammatory bowel disease (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), is an idiopathic chronic gut inflammation. The incidence and prevalence of IBD have been increasing in Taiwan in the past decades. Colonoscopy is the mainstay for the diagnosis and management of IBD in patients. However, the required testing frequency and the procedure are challenging for both physicians and patients.

Aims: To analyze patient perception about colonoscopy among those with IBD and compare the frequency between physician’s recommendation and patient’s tendency to undergo examination.

Methods: This prospective questionnaire study enrolled 72 patients with IBD (33 CD and 39 UC) from Tri-Service General Hospital, from July 2020 to May 2021. The clinical characteristics, including, sex, age, disease duration, types of disease, and habits, were analyzed. In the questionnaire, the patient’s perception about four components

發炎性腸道疾病病人對於大腸鏡檢查 的認知與接受度：一醫學中心的前瞻 性研究

associated with the procedure (embarrassment, pain, use of bowel cleansing agent, and stress) were assessed.

Results: The mean age of the enrolled 72 patients was 45.3 years, and male: female ratio was 1.8 (M: 63.9%; F: 36.1%). The mean age at diagnosis was 39.7 years, and the mean duration of the disease was 5.3 years. The need for a “bowel cleansing” was the most uncomfortable part of the colonoscopy procedure, with the requirement of drinking too much water being the major concern for the participants. The “pain” component was also a major concern correlated with the reluctance to undergo a colonoscopy. When a comparison was made between patients and physicians regarding their readiness to perform and experience colonoscopy, respectively, the one-year interval of frequency was similar for both parties. Male patients were more compliant to receiving colonoscopies within shorter timeframes as compared to female patients.

Conclusions: Bowel cleansing was the most uncomfortable part of the colonoscopy procedure for patients with IBD. The one-year interval was the most acceptable option for colonoscopy scheduling for those with IBD.

P.113 A RANDOMIZED CONTROLLED TRIAL COMPARING LEFT COLON MUCUS PRODUCTION BY WATER VERSUS SALINE INFUSION DURING WATER EXCHANGE COLONOSCOPY

Chi-Liang Cheng1, I-Chia Su2, Yen-Lin Kuo1, Nai-Jen Liu3, Jau-Min Lien2, Chia-Pei Tang4, Yu-Hsi Hsieh4, Felix W. Leung5,6

1Division of Gastroenterology, Evergreen General Hospital, Taoyuan, Taiwan

2Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taipei Medical University Hospital, Taipei, Taiwan

3Department of Gastroenterology and Hepatology, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan

4Division of Gastroenterology, Department of Internal Medicine, Dalin Tzu Chi Hospital, Chiayi, Taiwan

5Division of Gastroenterology, Department of Medicine, Sepulveda Ambulatory Care Center, Veterans Affairs Greater Los Angeles Healthcare System, North Hills, CA, USA

6David Geffen School of Medicine at UCLA, Los Angeles, CA, USA

2 臺北醫學大學附設醫院胃腸肝膽科

3 林口長庚紀念醫院胃腸肝膽系

4 大林慈濟醫院胃腸肝膽科

5Division of Gastroenterology, Department of Medicine, Sepulveda Ambulatory Care Center, Veterans Affairs Greater Los Angeles Healthcare System, North Hills, CA, USA

6 美國加州大學洛杉磯分校醫學院

Background: Despite human limitations, water exchange (WE) increases adenoma detection rate (ADR) compared with gas insufflation. Artificial intelligence (AI) overcomes human limitations to increase ADR but is limited by false positives (e.g.,

比較使用蒸餾水與生理食鹽水進行換 水大腸鏡檢查對左側大腸黏液生成的

bubbles, debris, mucus). WE insertion salvage cleaning reduces false positives. Thus, AI and WE complement the weaknesses of each other. However, WE also increases left colon mucus, a potential source of false positives that can diminish the benefit of WE.

Aims: To test the hypothesis that saline produces a dose-related inhibition of left colon mucus production.

Methods: Patients were randomly assigned to CO2 insufflation, WE with water, 25% saline, or 50% saline. The primary outcome was the mean left colon mucus scale (LCMS) score obtained by blinded observers: score 0: no visible mucus; score 1: clear mucus; score 2: mildly opaque mucus in thin strands; score 3: moderately opaque mucus in thick clumps covering one side of the surface; score 4: more opaque mucus in thick clumps covering more views of the lumen.

Results: Among 296 patients, baseline demographics and procedural data were similar. The mean LCMS score was highest in the WE water group, followed by 25% saline, 50% saline and CO2 group in decreasing order (1.4 ± 0.84 for WE water, 0.7 ± 0.63 for WE 25% saline, 0.5 ± 0.50 for WE 50% saline, 0.2 ± 0.38 for CO2; overall P < 0.0001), with a kappa value of 0.636 for the interobserver agreement (P < 0.0001). More patients who underwent WE with water required additional cleansing for mucus than those who underwent WE with 50% saline (6.7% vs. 0%, P = 0.032). Water filling was the only predictor of moderate mucus production (odds ratio, 33.3; 95% confidence interval, 7.2 - 153.2).

Conclusions: In a randomized trial, we found that the use of 50% saline significantly inhibited left colon mucus production compared to waterinfused WE. Since mucus is defined as false positive in AI studies, the reduction of WE-induced mucus production by saline opens a new avenue of research into the complementary relationship between AI and WE.

P.114 IMPACT OF PHYSICAL ACTIVITY ON THE RISK OF METACHRONOUS COLORECTAL NEOPLASM

Wei-Yuan Chang1, Hsuan-Ho Lin2, Wen-Feng Hsu3, Li-Chun Chang3, Ming-Shiang Wu3, Han-Mo Chiu3

1Department of Internal Medicine, National Taiwan University Cancer Center, Taipei, Taiwan

2Department of Internal Medicine, Saint Paul’s Hospital, Taoyuan, Taiwan

3Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan

運動習慣對異時性大腸直腸腫瘤生成 的影響

Background: Exercise is associated with a lower risk of colorectal neoplasm but its association with metachronous advanced colorectal neoplasm development after polypectomy remains unclear. Aims: We aimed to investigate associations between subjects’ exercise habits and the risk of metachronous advanced colorectal neoplasm.

Methods: This study analyzed subjects older than 40 years who received screening colonoscopy with polypectomy and surveillance colonoscopy between January 2009 and December 2016. All participants completed a standard questionnaire containing exercise habits before surveillance colonoscopy. Subjects’ exercise habits were quantified as weekly exercise amounts (METday/week) and dichotomized (active/sedentary exercise habit) using averages as the cut-off point. The associations between incidence of metachronous advanced colorectal neoplasm and exercise habits were evaluated using KaplanMeier analysis and Cox regression models.

Results: A total of 1820 subjects comprised the study cohort and 86 (4.73%) of them developed metachronous advanced colorectal neoplasm during surveillance period. An active exercise habit after polypectomy was associated with a lower risk of metachronous advanced colorectal neoplasm [adjusted hazard ratio (aHR) = 0.57, 95% CI =

0.35-0.91]. Furthermore, this protective effect from exercise was specific for subjects having advanced neoplasm at screening colonoscopy [aHR = 0.32, 95% CI = 0.11-0.94].

Conclusions: An active exercise habit after polypectomy, a surrogate for a more active lifestyle, is associated with a lower risk for developing metachronous advanced colorectal neoplasm. A positive lifestyle modification, such as maintaining/ establishing an active exercise habit, should be advised after polypectomy, especially for those with advanced colorectal neoplasm during screening.

P.115 COMPARISON OF DRYING EFFECTIVENESS IN ENDOSCOPE REPROCESSING USING MANUAL FORCED AIR VERSUS AUTOMATED ENDOSCOPE REPROCESSOR

I-Hua Lee1, Cheng-Shuan Chung1,2, Chun-Hsing Liao3, Mai-Yu Wu3, Ming-Hui Liang3

1Ultrasonography and Endoscopy Center, Far Eastern Memorial Hospital, New Taipei City, Taiwan

2Division of Gastroenterology and Hepatology, Department of Internal Medicine, Far Eastern Memorial Hospital, New Taipei City, Taiwan

3Infecion Control Center, Far Eastern Memorial Hospital, New Taipei City, Taiwan

內視鏡乾燥方式比較：手工強制空氣 及自動清洗機空氣灌注

3 亞東紀念醫院感染管制中心

Background: Improper reprocessing of flexible endoscopes which can lead to iatrogenic infection is ranking top ten medical technology hazards. According to recommendations from several international societies of infection control, dyring of endoscopes which can reduce the risk of biofilm formation and microbial contamination is one of the most important steps in endoscope reprocessing. However, methods of drying are inconsistent between international guidelines.

Aims: The aim of this study was to compare the efficacy for drying of endoscope by manual forced air purge and air purge by automated endoscope reprocessor (AER).

Methods: Five duodenoscopes was connected to the appropriate hookup and underwent a full programmed cycle in the same AER. Endoscope drying with manual forced air (pressure 35 psi) using manufacturer supplied adapters with 30 seconds each for suction channel and air/water channel ports were carried out. Among those using AER drying, air purge was performed for 10 minutes. Efficacy of drying was evaluated by Inspection of working channels from the inlet, upper 1/3, middle 1/3, and lower 1/3 part with a

SpyGlass cholangioscope. Residual liquids were divided into large (diameter more than the corner of endoscopic screen) and small droplets. The number of droplets was counted for comparative analysis.

Results: There were more large droplets retained in the inlet of working channel (p = 0.0001) whereas more retention of small droplets in the upper 1/3 (p < 0.0001), middle 1/3 (p < 0.0001) and lower 1/3 part (p = 0.0001) in the endoscopes of AER group as compared to manual forced air group. In terms of service life, there were more large droplets found in endoscopes used more than 3 years in the AER group (p = 0.015) while no statistically significance in manual forced air group. Comparing endoscopes with scratches in the lining of working channels and those without, a greater number of small droplets were noticed in endoscopes with scratches in the AER group (p = 0.032) but not in the manual forced air group.

Conclusions: We have found more water droplets remained in the endoscope channels after drying with AER as compared to manual forced air. The negative impacts of older service life and scratches in working channels on drying efficacy were noticed in endoscopes drying by AER rather than manual forced air purge. Manual forced air drying of the channels appears to be highly effective in eliminating moisture of endoscope channels.

P.116 THE POTENTIAL GENOMIC CARCINOGENIC SIGNATURE ASSOCIATED WITH NLRP FAMILY IN COLORECTAL CANCER INFILTRATED WITH MACROPHAGE

Kuang-Tsu Yang1,2,3,4, Chieh Hsu5, Ping-I Hsu6, Shi-Ping Luh7, Cheng-Hsiu Hsieh8, Tien-Ching Lin1, Shuei-Cheng Kang1, Ming-Yi Li9, Chun-Yu Lin10,11, Chia-Chi Yen12,13,14, Ming-Hong Tai4, Tsung-Hui Hu15, Chia-Hung Tu16, Yen-Hsiu Yeh17, Tsai-Kun Li17,18,19

1Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Municipal Min-Sheng Hospital, Kaohsiung, Taiwan; 2Department of Medicine, National Taiwan University, Taipei, Taiwan; 3Division of Family Medicine, Department of Community Medicine, Kaohsiung Municipal Min-Sheng Hospital, Kaohsiung, Taiwan; 4Institute of Biomedical Science, National Sun Yat-Sen University, Kaohsiung, Taiwan; 5Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan;

6Division of Gastroenterology and Hepatology, Department of Internal Medicine, An Nan Hospital, China Medical University, Tainan, Taiwan; 7Division of Thoracic Surgery, Department of Surgery, Kaohsiung Municipal Min-Sheng Hospital, Kaohsiung, Taiwan; 8Division of Colorectal Surgery, Department of Surgery, Kaohsiung Municipal Min-Sheng Hospital, Kaohsiung, Taiwan; 9Division of Cardiology, Department of Internal Medicine, Kaohsiung Municipal Min-Sheng Hospital, Kaohsiung, Taiwan; 10Division of Infectious Disease, Department of Internal Medicine, Kaohsiung Municipal Min-Sheng Hospital, Kaohsiung, Taiwan; 11Associate Dean, Kaohsiung Municipal Min-Sheng Hospital, Kaohsiung, Taiwan; 12Superintendent’s Office, Kaohsiung Municipal Min-Sheng Hospital, Kaohsiung, Taiwan; 13Department of Nutrition, Institute of Biomedical Nutrition, Hung-Kuang University, Taichung, Taiwan; 14Department of Business Management,

National Sun Yat-Sen University, Kaohsiung, Taiwan; 15Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan; 16Division of Hepatology and Gastroenterology, Department of Internal Medicine, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan; 17Department and Graduate Institute of Microbiology, College of Medicine, National Taiwan University, Taipei, Taiwan; 18Centers for Genomic and Precision Medicine, National Taiwan University, Taipei, Taiwan; 19Center for Biotechnology, National Taiwan University, Taipei, Taiwan

巨噬細胞浸潤的結直腸癌中與 NLRP 家族相關的潛在基因體致癌特徵

楊光祖1,2,3,4 許傑5 許秉毅6 陸希平7 謝政修8

林典慶1 康水成1 李明義9 林俊祐10,11 顏家祺12,13,14

戴明泓4 胡琮輝15 凃佳宏16 葉彥秀17 李財坤17,18,19

1 高雄市立民生醫院內科部肝膽腸胃科；2 國立臺 灣大學醫學系；3 高雄市立民生醫院社區醫療部家 庭醫學科；4 國立中山大學生物醫學研究所；5 台 大醫院內科部肝膽腸胃科；6 臺南市立安南醫院— 委託中國醫藥大學興建經營內科部胃腸肝膽科；7 高雄市立民生醫院外科部胸腔外科；8 高雄市立民

生醫院外科部大腸直腸科；9 高雄市立民生醫院內

科部心臟血管內科；10 高雄市立民生醫院內科部

感染科；11 高雄市立民生醫院副院長；12 高雄市

立民生醫院院長辦公室；13 弘光科技大學營養系

暨營養醫學研究所；14 國立中山大學企業管理學

系；15 高雄長庚紀念醫院胃腸肝膽科系；16 台大 醫院內科部胃腸肝膽科；17 台大醫學院微生物學

科暨研究所；18 國立臺灣大學基因體暨精準醫學

研究中心；19 國立臺灣大學生物科技研究所

Background: Colorectal cancer (CRC) is nowadays the most prevalent in most Asia countries. As the precision medicine era comes, plenty of biomarkers in genomics and immunomics were investigated in CRC. Nucleotide-binding oligomerization domain, Leucine rich Repeat and Pyrin domain containing (NLRP) family was considered potential in the carcinogenic development of CRC. However, its specific role in CRC is still unaddressed. No robust conclusion of NLRP in tumor microenvironment (TME) was

announced. Therefore, we conducted this pilot study to analyze the transcriptional characteristics of NLRP family in CRC.

Aims: We conducted this pilot study to analyze the transcriptional characteristics of NLRP family in CRC.

Methods: NLRP family were surveyed via TIMER 2.0. 5-year survival of CRC patients were documented. The protein-protein interaction (PPI) network was downloaded from STRING database and protein/RNA expressions were retrieved from HPA. We then investigated the genomic relationship of NLRP using GeneMania.

Results: In Table 1, only NLRP3 from NLRP family expresses most relevant in CRC patients with macrophage infiltration in TME (Z-score 2.154 in EPIC and 2.59 in MCP COUNTER). In EPIC, 5-year survival of CRC patient revealed a better outcome under low gene expression with high macrophage infiltration (hazard ratio, HR: 0.135, p = 0.0177) and a worse outcome under high gene expression with high macrophage (HR: 8.25, p = 0.0482). In MCP-COUNTER, the statistical significance was not reached but there is a similar trend (Fig. 1). Fig. 2 revealed NLRP3 associated with numerous genes in proteomics and prominent protein expression in liver, gastrointestinal tract, and other organs. Fig. 3 described NLRP family and NLRP3 networks detailedly.

Conclusions: We firstly demonstrated that NLRP3 is strongly associated with CRC carcinogenesis infiltrated with macrophage. Moreover, NLRP3 is correlated with APC/EGFR/KRAS/TP53 regarding ERBB signaling, cell adhesion, cellular protein localization, T cell activation, cellular response to peptide, and ubiquitin-like protein ligase binding.

P.117

Kuang-Tsu Yang1,2,3,4, Chun-Yu Lin5, Tian-Huei Chu4, Yen-Hsiu Yeh6, Tsai-Kun Li6,7,8, Hsin-Bai Zou9, Chia-Hung Tu10, Wei-Chih Sun11, Ping-I Hsu12, Hsien-Chung Yu11, Chao-Wen Hsu13,14, Ming-Yi Li15, Hsin-Tai Wang16, Cheng-Hsiu Hsieh16, Shi-Ping Luh17, Tien-Ching Lin1, Shuei-Cheng Kang1, Chia-Chi Yen18, Cheng-Chih Richard Hsu19,20, Ming-Hong Tai4, Tsung-Hui Hu4,21

1Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Municipal Min-Sheng Hospital, Kaohsiung, Taiwan; 2Department of Medicine, National Taiwan University, Taipei, Taiwan; 3Division of Family Medicine, Department of Community Medicine, Kaohsiung Municipal Min-Sheng Hospital, Kaohsiung, Taiwan; 4Institute of Biomedical Science, National Sun Yat-Sen University, Kaohsiung, Taiwan; 5Division of Infectious Disease, Department of Internal Medicine, Kaohsiung Municipal Min-Sheng Hospital, Kaohsiung, Taiwan; 6Department and Graduate Institute of Microbiology, College of Medicine, National Taiwan University, Taipei, Taiwan; 7Centers for Genomic and Precision Medicine, National Taiwan University, Taipei, Taiwan; 8Center for Biotechnology, National Taiwan University, Taipei, Taiwan; 9Department of Chemistry, National Taiwan University, Taipei, Taiwan; 10Division of Hepatology and Gastroenterology, Department of Internal Medicine, National Taiwan University Hospital and College of Medicine, Taipei, Taiwan; 11Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan; 12Division of Gastroenterology and Hepatology, Department of Internal Medicine, An

Nan Hospital, China Medical University, Tainan, Taiwan; 13Division of Colorectal Surgery, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan; 14School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; 15Division of Cardiology, Department of Internal Medicine, Kaohsiung Municipal Min-Sheng Hospital, Kaohsiung, Taiwan; 16Division of Colorectal Surgery, Kaohsiung Municipal Min-Sheng Hospital, Kaohsiung, Taiwan; 17Division of Thoracic Surgery, Kaohsiung Municipal Min-Sheng Hospital, Kaohsiung, Taiwan; 18Superintendent’s Office, Kaohsiung Municipal Min-Sheng Hospital, Kaohsiung, Taiwan; 19Department of Chemistry, National Taiwan University, Taipei, Taiwan; 20Center for Artifical Intelligence and Advanced Robotics, National Taiwan University, Taipei, Taiwan; 21Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan

的生存中：從真實世界的大數據到實 驗室分子生物學

9 凃佳宏10 孫煒智11 許秉毅12 余憲忠11

許詔文13,14 李明義15 王心泰16 謝政修16 陸希平17

林典慶1 康水成1 顏家祺18 徐丞志19,20 戴明泓4

胡琮輝4,21

1 高雄市立民生醫院內科部肝膽腸胃科；2 國立臺 灣大學醫學系；3 高雄市立民生醫院社區醫療部家

庭醫學科；4 中山大學生醫所；5 高雄市立民生醫 院內科部感染科；6 國立臺灣大學醫學院微生物學 科暨研究所；7 國立臺灣大學基因體暨精準醫學研 究中心；8 國立臺灣大學生物科技研究所；9 國立 臺灣大學化學系；10 台大醫院內科部胃腸肝膽科； 11 高雄榮民總醫院內科部胃腸肝膽科；12 臺南市 立安南醫院—委託中國醫藥大學興建經營內科部 胃腸肝膽科；13 高雄榮民總醫院外科部大腸直腸 科；14 國立陽明交通大學醫學系；15 高雄市立民 生醫院內科部心臟血管內科；16 高雄市立民生醫 院外科部大腸直腸外科；17 高雄市立民生醫院外

VITAMIN D SYSTEM AND ACE2 GENOMICS IN COLORECTAL CANCER PATIENTS’ SURVIVAL ASSOCIATED WITH COVID-19 PANDEMIC: FROM REAL-WORLD BIG DATA TO LABORATORY MOLECULAR BIOLOGY

維生素 D 系統和 ACE2 基因體學在與 COVID-19 大流行相關的結直腸癌患者

科部胸腔外科；18 高雄市立民生醫院院長辦公室； 19 國立臺灣大學化學系；20 國立臺灣大學人工智 慧與機器人研究中心；21 高雄長庚紀念醫院胃腸 肝膽科系

Background: During 2019-2022, COVID-19 pandemic has a great impact on global health, economics, and psychosocial status of people. Previous studies revealed that vitamin D level was associated with paitents infected with COVID-19. Angiotensin-Converting Enzyme 2 (ACE2) as a potential diagnostic and prognostic biomarker influencing patients’ metabolic pathway in COVID-19 infection. On the other hand, the metabolic role of ACE2 in colorectal cancer (CRC) patients is still unaddressed via molecular biology till now.

Aims: To conduct a real-word big data and laboratory molecular biology networking in colorectal cancer patients.

Methods: We downloaded the prevalence of COVID-19 and CRC and the death rate of CRC. Metabolic information and pathways regarding ACE2 and vitamin D system was retrieved from HPA. STRING database showed proteomics of ACE2. Finally, we reviewed the survival of CRC patients regarding ACE2-vitamin D system associated genomic markers.

Results: As shown in Figure 1 and Figure 2, CRC prevalence is higher in Asia-Pacific region and Europe than Latin America, but COVID-19 prevalence revealed higher in Latin America and Europe than in Asia-Pacific region. Table 1 shows ACE2 metabolic summary, mainly about transport reactions. Figure 3 illustrated detailed metabolic signaling pathway of ACE2 and proteomics informatics. Figure 4 shows 5-year survival of CRC patients on the basis of vitamin D system relevant genomic markers.

Conclusions: We demonstrated that ACE2/ CYP2E1/COQ6/CYP24A1 were statistically significant associated with CRC patients’ 5-year survival.

Kuo Chia-Jung1,2,3, Puo-Hsien Le1,2,3, Cheng-Yu Lin1,2, Ming-Yao Su1,2,4, Cheng-Tang Chiu1,2,3

1Department of Gastroenterology and Hepatology, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan

2College of Medicine, Chang Gung University, Taoyuan, Taiwan

3Chang Gung Microbiota Therapy Center

4Department of Gastroenterology and Hepatology, New Taipei Municipal Tucheng Hospital, New Taipei, Taiwan

Background: The use of biologic agents had become the cornerstone of therapy for moderately to severely active IBD. Vedolizumab (VDZ), an anti-α4β7 integrin monoclonal antibody approved for the treatment of Crohn’s disease (CD) and ulcerative colitis (UC), is increasingly used as first line biologic therapy in previously bio-naïve IBD patients who require more aggressive therapy.

Aims: To evaluate the real-world outcome after failure of VZD Induction for bio-naïve IBD patients in Taiwan. And to assesses the treatment response of IBD patients who were treated with anti-TNF agent or Ustekinumab (UST) following VDZ discontinuation.

Methods: This was a single center, retrospective and observational study. Adults with moderate to severe active IBD treated with VDZ during Oct 2017 to May 2022 were enrolled. Crohn’s Disease Activity Index (CDAI) and Mayo score were measured to evaluate the efficacy of induction

P.118

THE REAL-WORLD OUTCOME AFTER FAILURE OF VEDOLIZUMAB INDUCTION FOR MODERATE TO SEVERE INFLAMMATORY BOWEL DISEASE IN TAIWAN

therapy.

Results: A total of 138 patients who received VDZ as the induction therapy were included in current study. More than half of them (78.3%, 108/138) were biologic-naive. For bio-naïve IBD patients, the primary non-response rate during VZD induction therapy was (25%, 27/108). Among the patients who had no response to VZD induction, 14 cases were diagnosed as CD and 13 cases were diagnosed as UC. Upon VDZ discontinuation, 57.1% (8/14) and 21.4% (3/14) of CD were switched to Adalimumab (ADA) and Ustekinumab (UST) as second-line therapy. The response rate and remission rate were 12.5% (1/8) and 50% (4/8) for ADA. Among the 3 CD patients who received UST as second-line therapy, all of them achieved clinical remission.

Conclusions: VDZ is a safe treatment option for moderate to severe IBD. In real-world experience, failure of VZD as first-line biologic does not decrease response rates of second-line therapy, especially for CD patient.

P.119 STERILE FECAL FILTRATE TRANSFER PROTECTS

CHEMOTHERAPY-INDUCED INTESTINAL MUCOSITIS IN A COLORECTAL CANCER MODEL

Ching-Wei Chang1,3,4,5, Yu-Jen Chen2,3,4,5, Li-Hui Li5, Jen-Shiu Chiang Chiau5, Tsang-En Wang1,3,4, Ming-Jen Chen1,3,4, Chia-Yuan Liu1,3,4,5

1Division of Gastroenterology, Department of Internal Medicine, MacKay Memorial Hospital, Taipei, Taiwan

2Department of Radiation Oncology, MacKay Memorial Hospital, Taipei, Taiwan

3Department of Medicine, MacKay Medical College, New Taipei City, Taiwan

4MacKay Junior College of Medicine, Nursing, and Management, New Taipei City, Taiwan

5Department of Medical Research, MacKay Memorial Hospital, Taipei, Taiwan

4

Background: Studies have shown that microbial flora preparations, fecal microbiota transplantation (FMT), can reduce diarrhea by changing the intestinal flora, and have anti-inflammatory and immune-regulating effects on the intestinal mucosa. Although FMT is a promising therapy, the transfer of pathogenic microbes or toxic compounds raise concern. Removal of bacteria from donor feces by micropore filtering may reduce this risk of bacterial infection, while residual components may maintain the therapeutic effects. Our previous studies find that in animal models of colorectal cancer, FMT can change the intestinal flora and eliminate chemotherapy-induced diarrhea and intestinal mucositis. However, whether sterile fecal filtrate transplantation (FFT) can ameliorate chemotherapy-induced intestinal mucositis remain

unclear.

Aims: Evaluating the effect of FFT on FOLFOX (5FU, leucovorin, and oxaliplatin)-induced intestinal mucositis in a colorectal cancer model.

Methods: BALB/c mice subcutaneously implanted with syngeneic CT26 colorectal adenocarcinoma cells were orally administered with microbiota preparations (fecal material preparation) daily during and 2 days after a 5-day injection of the FOLFOX regimen, for 7 days. FOLFOX was intraperitoneally injected into BALB/c mice to induce gut mucositis. Fecal samples were collected from healthy, untreated, and agematched BALB/c donor mice for performing FMT and FFT. Disease severity was scored by body weight, stool consistency, tumor size, and H&E staining of the intestine.

Results: FOLFOX administration had antitumor activity in colon cancer-bearing mice. It was accompanied by marked diarrhea and severe intestinal mucositis, which was histologically characterized by the shortening of villi, destruction of intestinal crypts, and the ratio of villus height/ crypt depth. Compared with FMT, administration of FFT had a similar effect of reducing the severity of diarrhea and intestinal mucositis without affecting the anti-tumor effect of FOLFOX.

Conclusions: Resembling FMT, sterile FFT can ameliorate FOLFOX-induced intestinal mucositis in colorectal cancer-bearing mice. Future studies for elucidating the anti-mucositis mechanism and safety are required.

P.120 COVID-19 AND OUTCOMES IN PATIENTS WITH CROHN’S DISEASE: A SINGLE INSTITUTE EXPERIENCE IN TAIWAN

Po-Ju Huang1, Yi-Hua Wu1, Ken-Sheng Cheng1,2, Jen-Wei Chou1,2,3

1Center for Digestive Medicine, Department of Internal Medicine, China Medical University Hospital, China Medical University Hospital, Taichung, Taiwan

2School of Medicine, China Medical University, Taichung, Taiwan

3Taiwan Association for the Study of Small Intestinal Diseases (TASSID), Taipei, Taiwan

克隆氏症患者感染 COVID-19 臨床結

Background: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), emerged in late 2019 and spread very quickly across the world. In recent three months, COVID-19 had an outbreak in Taiwan. The cumulative number of confirmed cases in 2021 is 16301. However, the cumulative number of confirmed cases from January of 2022 to June of 2022 already more than 3.6 million people. Hence, coexist with COVID-19 is future consensus in Taiwan. And, severity level of COVID-19 is widely from asymptomatic to death. Patients with Crohn’s disease usually in an immunocompromised status. Hence, the association of Crohn’s disease patients with COVID-19 is lacking in Taiwan.

Aims: The aim of this study was to investigate the clinical features, age, diagnostic method, treatments, and severity level of Crohn’s disease with COVID-19 in a teaching hospital in middle Taiwan.

Methods: We retrospectively reviewed the medical records of patients diagnosed as Crohn’s disease at our hospital. The diagnostic criteria of COVID-19 were based on the positivity of COVID-19 rapid antigen test or polymerase chain

果分析研究：中台灣一醫學中心之經

reaction (PCR) test. Clinical characteristic, and treatment outcomes of all patients with COVID-19 were analyzed.

Results: A total of 99 patients with Crohn’s disease were enrolled into this study. Finally, 9 patient suffered from COVID-19 with the prevalence of infection was 9.09%. All 9 patient diagnosed with COVID-19 after 02 May, 2022. In the diagnostic method, 4 patients were diagnosed by COVID-19 PCR test and the other 5 patients was diagnosed by COVID-19 rapid antigen test. There were 7 males and 2 females, with a maleto-female ratio of 3.5:1. All 9 Crohn’s disease patents were treated with biological agents in the diagnosis of COVID-19. The mean age was 32.33 years (range, 19-47 years). The mean body weight was 64.9 kg (range, 44.8-94.4 kg). The mean dose of COVID-19 vaccine was 2.33: 5 patients received 3 doses vaccines, 3 patients received 2 doses vaccines, no patient received 1 dose vaccine, and 1 patient did not receive any dose of vaccine. Cough (77.7%, 7/9) accounted for the major symptom of these patients. The other symptoms were fever, rhinorrhea, sore throat, headache, weakness. Only 1 patient receive antiviral treatment with Paxlovid. All these patient had mild COVID-19 with a good outcome and none of these patient need hospitalization.

Conclusions: Although Crohn’s disease is usually considered a high risk of severe COVID-19. However, all our 9 patients had good outcome and none one need hospitalization. Hence, we consider that Crohn’s disease patients under adequate therapy can reduce the severity of COVID-19.

P.121 RISK AND OUTCOMES OF CORONAVIRUS DISEASE (COVID-19) IN PATIENTS WITH ULCERATIVE COLITIS: A HOSPITAL-BASED STUDY IN CENTRAL TAIWAN

Yi-Hua Wu1, Po-Ju Huang1, Ken-Sheng Cheng1,2, Jen-Wei Chou1,2,3, Chun-Che Lin1,2,3

1Center for Digestive Medicine, Department of Internal Medicine, China Medical University Hospital, China Medical University Hospital, Taichung, Taiwan

2School of Medicine, China Medical University, Taichung, Taiwan

3Taiwan Association for the Study of Small Intestinal Diseases (TASSID), Taipei, Taiwan

Background: In 2020, the world faced the unprecedented crisis of coronavirus disease 2019 (COVID-19). Patients with ulcerative colitis (UC) remain highly concerned that either their disease or medications-namely, biologics may increase the risk of severe coronavirus-2019 (COVID-19). Besides the infection and its consequences, COVID-19 also resulted in many complications for patients with UC. However, the association of UC patients with COVID-19 is lacking in Taiwan. We therefore hypothesized that the first wave of the COVID-19 pandemic would have some effects on UC patients and performed this retrospective study.

Aims: The aim of this study was to investigate the clinical features, age, diagnostic method, treatments, and severity level of ulcerative colitis with COVID-19 in a teaching hospital in middle Taiwan.

Methods: A total of 179 consecutive patients with UC, regularly seen at the outpatient unit of the Division of Gastroenterology at the China Medical University Hospital, a tertiary referral center in

COVID-19 臨 床結果分析研究：中台灣一醫學中心

central Taiwan, were enrolled in this study from January 1980 to December 2021. We analyzed the clinical manifestations of COVID-19-positive in UC patients. The diagnostic criteria of COVID-19 were based on the positivity of COVID-19 rapid antigen test or polymerase chain reaction (PCR) test. Clinical characteristic, and treatment outcomes of all patients with COVID-19 were analyzed.

Results: A total of 179 patients with UC were enrolled into our current study. Finally, 17 patient suffered from COVID-19 with the prevalence of infection was 9.4%. The mean diagnostic age of these enrolled patients was 45.1 years (ranging from 21 years to 75 years old). Male accounted for the majority of all patients in our present study (76.4%). The mean body weight was 62.3 kg (range, 44.0-94.5 kg). In the diagnostic method, 6 patients were diagnosed by COVID-19 PCR test and the other 11 patients was diagnosed by COVID-19 rapid antigen test. There were 15 patient (15/17; 88.2%) had received covid-19 vaccine. The mean dose of COVID-19 vaccine was 2.17. There were 10 patients (10/17; 58.8%) received three doses vaccines, 2 patients (2/17; 11.7%) received two doses vaccines, 3 patient (3/17; 17.6%) received one dose vaccine, and 2 patient (2/17; 11.7%) did not receive any dose of vaccine. The most common clinical manifestations was sore throat (12/17; 70.5%) , followed by fever (11/17; 64.7%), cough (10/17; 58.8%), runny nose (6/17; 35.2%), headachea (3/17; 17.6%), abdominal pain (1/17; 5.8%), fatigue 5.8% (1/17; 5.8%), dizziness (1/17; 5.8%), asthma (1/17; 5.8%) and muscle weakness (1/17; 5.8%). There were 10 patient using biologics (10/17; 58.8%) when diagnosed with COVID-19. The most common type of biologics used by these patient was Vedolizumab (3/17; 17.6%), followed by Humira (2/17; 11,7%), Etrasimod (2/17; 11,7%), Ixekizumab (2/17; 11,7%), and Upadacitinib (1/17; 5.8%). All these patient had mild COVID-19 with a good outcome and none of these patient need hospitalization.

Conclusions: To conclude, the risk of COVID in IBD patients is not specifically higher than the general population. Although ulcerative colitis is usually considered a high risk of severe COVID-19. all our 17 patients had good outcome and none one need hospitalization. The use of biologics was not associated with an increased risk of COVID-19 in patients with UC. Furthermore, we consider that ulcerative colitis patients under adequate therapy can reduce the severity of COVID-19.

P.122 SAFETY ASSURANCE OF FMT PRODUCTS IN THE TIME OF COVID-19

Tien-En Chang1,2,5, Kuei-Chuan Lee1,5, Yi-Tsung Lin3,5, Pei-Chang Lee1,5, Yen-Po Wang1,2,5, Hui-Chun Huang1,4,5, Yi-Hsiang Huang1,5, Ming-Chih Hou1,5

1Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan

2Endoscopic Center for Diagnosis and Therapy, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan

3Division of Infectious Diseases, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan

4Division of General Medicine, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan

5National Yang Ming Chiao Tung University, School of Medicine, Taipei, Taiwan

1 臺北榮民總醫院內科部胃腸肝膽科

2 臺北榮民總醫院內科部內視鏡診斷暨治療中心

3

4 臺北榮民總醫院內科部一般內科

5 國立陽明交通大學醫學院

Background: Fecal microbiota transplantation (FMT) is widely used in the treatment of recurrent or refractory Clostridioides difficile infection (CDI). In the past, screening of fecal donors required surveillance on personal behavior, medical history, and diseases that can be transmitted by blood or fecal-oral route. Task has increased in the era of coronavirus disease-2019 (COVID-19) pandemic. To prevent fecal transmission of severe acute respiratory syndrome coronavirus 2 (SARSCoV-2) is crucial and highly recommended in the screening protocol currently. In Taiwan, only imported cases of COVID-19 were found in the first year of pandemic. Outbreak of COVID-19 in the local community occurred until the middle of 2021.

Aims: The aim of this study was to prove whether hidden carriers of SARS-CoV-2 were enrolled for stool donation.

Methods: Fecal products that collected during August 2019 to January 2022 were pooled and got nucleic acid amplification tests for SARS-CoV-2. Those specimens were collected before and during the COVID-19 pandemic in the FMT center of Taipei Veterans General Hospital.

Results: A total of 75 fecal products were tested by pooling polymerase chain reaction (PCR) to detect SARS-CoV-2. The results showed negative in all stocks. The safety of FMT products was quartered during the pandemic.

Conclusions: Our FMT center produced COVID19-free products before, and during COVID-19 outbreak in Taiwan. The pooling procedure for SARS-CoV-2 testing was cost-effective for FMT product screening.

P.123 CLINICAL OUTCOMES OF CLOSTRIDIUM INNOCUUM AND CLOSTRIDIOIDES DIFFICILE INFECTIONS IN INFLAMMATORY BOWEL DISEASE

Puo-Hsien Le1, Cheng-Tang Chiu1, Cheng-Hsun Chiu2

1Department of Gastroenterology and Hepatology, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan

2Division of Pediatric Infectious Diseases, Department of Pediatrics, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan

Background: Clostridioides difficile and Clostridium innocuum (CI) infections can lead to poor clinical outcomes in inflammatory bowel disease.

Aims: However, no study compared the impact between them.

Methods: In this retrospective cohort study, we enrolled hospitalized IBD patients with culture results for both CI and Clostridioides difficile (CD) in a medical center between October 2019 and April 2021. They were divided into the CI (CI+/CD-), control (CI-/CD-), coinfection (CI+/ CD+), and CD (CI-/CD+) groups (Figure 2). We compared the baseline characteristics and clinical outcomes of patients in Clostridium innocuum and Clostridioides difficile groups.

Results: We enrolled a total of 90 patients, including 22, 39, 13, and 16 patients in the CI, control, coinfection, and CD groups. The incidence rates of CI (CI+) and CD (CD+) were 39% (35/90) and 32% (29/90), respectively. We analyzed the differences between CI and CD groups. The CI group presented less abdominal pain than the CD group (45.5%, 81.3%, P = 0.026). Other IBD characteristics, underline medication, and clinical outcomes were similar between the 2 groups. Thirteen patients, mostly males (84.6%), had coinfection of CI and CD (medium age: 39.6 years; range: 25.7–70.2 years). Eight of them had

無毒梭菌和困難梭菌對發炎性腸道及 病預後之影響 李柏賢1 邱正堂1 邱政洵2

1 林口長庚紀念醫院胃腸肝膽科

Crohn’s disease. These patients presented with bloody stool (61.5%), diarrhea (76.9%), abdominal pan (69.2%), and fever (7.7%). In terms of medication, 38.5% used biological agents, while 46.2% underwent steroid treatment. Records showed clinical remission rate, steroid free clinical remission rate, IBD-related complications rate, and mortality rates at 61.5%, 61.5%, 30.8%, and 0%, respectively.

Conclusions: The incidence rate of CI infection was higher than that of CD infection in inpatients with IBD. Additionally, CI decreased the clinical remission rate in ulcerative colitis. Hence, we should take CI into consideration when treating patients with IBD with active inflammation and those with refractory diarrhea with or without CD infection.

P.124 COST EFFECTIVENESS ANALYSIS OF FECAL MICROBIOTA TRANSPLANTATION IN RECURRENT OR REFRACTORY CLOSTRIDIUM DIFFICILE INFECTION IN TAIWAN

Kai-Yen Lan1, Puo-Hsien Le2, Chee-Jen Chang1,3, Cheng-Tang Chiu2, Cheng-Hsun Chiu4

1Master Degree in Clinical Trials and Assessment, Department of Biomedical Sciences, Chang Gung University, Taoyuan, Taiwan

2Department of Gastroenterology and Hepatology, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan

3Graduate institute of clinical medicine, Chang Gung University, Taoyuan, Taiwan

4Division of Pediatric Infectious Diseases, Department of Pediatrics, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan

Background: Clostridium difficile Infection (CDI) is a major cause of morbidity and mortality in hospitalized patients. It also leads to acute flareup and poor clinical outcomes of patients with inflammatory bowel disease (IBD). Compared to antibiotics treatment, fecal microbiota transplantation (FMT) is a more effective and promising treatment, but the cost is also higher.

Aims: However, there is limited studies mentioned the cost-effectiveness of FMT in recurrence or refractory CDI in general population and IBD patients. We would like to analyze the issue in Taiwan.

Methods: In this comparative study, we constructed a Markov model to evaluate a 1-year horizon in overall CDI patient and CDI in patients with (IBD) from both payer perspective and societal perspective. We assumed FMT via colonoscopy compared to vancomycin and fidaxomicin as

our base-case and conducting deterministic and probabilistic sensitivity analyses to investigate the uncertainty.

Results: In our base-case results, FMT via colonoscopy is cost-effective in overall and IBD patient compared to vancomycin (NT$1,101,971.98/ QALY gained and NT$415,142.49/QALY gained in overall patient from payer and societal perspectives; NT$1,833,719.14/QALY gained and NT$1,244,778.12/QALY gained in IBD patient from payer and societal perspectives) and it is cost-effective compared to fidaxomicin in overall patient (NT$567,133.45/QALY gained and NT$483,056.07/QALY gained from payer and societal perspectives) but with only a slightly QALY gained in IBD patient (NT$12,360,976.83/QALY gained and NT$13,639,447.67/QALY gained from payer and societal perspectives).

Conclusions: FMT shows better QALY gained than antibiotics treatment in recurrent or refractory CDI in most scenarios in Taiwan.

Tzu-Chi Hsu1, Wei-Chen Lin2, Cheng-Wang Chang2, Horng-Yuan Wang2

1Division of Colon and Rectal Surgery, Department of Surgery, Taipei Mackay Memorial Hospital, Taipei, Taiwan

2Division of Gastroentology, Department of Internal Medicine, Taipei Mackay Memorial Hospital, Taipei, Taiwan

許自齊

Background: Ulcerative colitis disease is usually treated conservatively. Surgery is reserved for treating its complications.

Aims: Incidence of ulcerative colitis in Taiwan is much lower than western countries, so the experience of surgical treatment of ulcerative colitis, especially carcinoma in most physicians is relatively limited

Methods: This is a retrospective review of indications, procedures and results of surgical treatment of patients with ulcerative colitis focusing on recurrence of carcinoma of colorectum. From December 1983 to April 2022, there were 56 patients with ulcerative colitis operated by a single surgeon. 20 of them were female, with an average of 48.1 years old (16 to 82 years old) when they were operated. Initial indications for operations were 30 for intractable diseases, 12 for toxic colitis with or without megacolon, five for bowel perforation with peritonitis, four for carcinoma of colorectum, two each for second operation following colectomies, and poor results following surgery, one for severe perianal fistulous abscess.

Results: Seventeen cases of ulcerative colitis were treated with subtotal colectomies and ileorectal anastomoses, one of them succumbed to the tongue cancer a few years later, a patient was diagnosed as having carcinoma in the

P.125 LIMITED RESECTION OF COLON IS NOT GOING TO PREVENT ULCERATIVE COLITIS RELATED COLORECTAL CANCER FOLLOWING SURGICAL MANAGEMENT

部分切除大腸無法預防潰瘍性大腸炎 相關的大腸癌症

remnant colon 13 years later. Nine patients had colectomies with stomies, one patient died of sepsis with multiple organ failure, another patient died of heart failure a few years later. Twentyeight patients had restorative proctocolectomies with pouch anal anastomoses and diverting ileostomies, three of ileostomies had not been closed, eight pouches were resected because of late complications. A patient died of postoperative sepsis, a patient died of hepatoma a few years later. A patient with poor general condition was treated with a stoma for colonic obstruction and fistula died of multiple organ failure. A patient had a laparotomy with biopsy for rectal cancer with carcinomatosis. Eighteen pouches were currently functioning well.

Conclusions: Complicated ulcerative colitis should be treated surgically. Restorative proctocolectomy is not a perfect operation, but can offer a reasonable good quality of life to the patient with ulcerative colitis if the operation is successful. Physicians should be alert for the possibility of carcinoma in the patient with long standing disease. Following subtotal colectomy with ileorectal anastomosis, all Patients should be carefully followed for possibility of carcinoma in the remnant segment of colon.

IN TAIWANESE ADULTS

Ying-Cheng Lin1, Wen-Hong Wang2, Hui-Fen Lang2, Fu-Yu Kuo1, Kareen Chong1, Han-Chung Lien1,3,4

1Division of Gastroenterology & Hepatology, Department of Internal Medicine, Taichung

Veterans General Hospital, Taichung, Taiwan

2Department of Food and Nutrition, Taichung

Veterans General Hospital, Taichung, Taiwan

3School of Medicine, National Yang Ming

Chiao Tung University, Taipei, Taiwan

4Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, Taiwan

2 臺中榮民總醫院營養科

3 國立陽明交通大學醫學系

4

Background: Instruments assessing Mediterranean diet (MD) pattern in Asia countries are scarce.

Aims: We aimed to develop and validate a selfadministered Taiwanese version Mediterranean Diet Adherence Screener (T-MEDAS) by including 81 apparently healthy adults (59 hospital employees, 22 college students), and to evaluate its association with gastroesophageal reflux disease (GERD) symptoms in 1051 college students.

Methods: We translated 12 questions and developed 2 questions. Participants completed both the T-MEDAS and 3-day food record for concurrent validity, retest of the T-MEDAS for reliability, and the Chinese GERDQ for criterion validity.

Results: The T-MEDAS score was slightly higher (7.0 ± 2.0 vs. 6.0 ± 2.4, P < 0.001), well correlated (r = 0.68, P < 0.0001; ICC = 0.64, P

P.126 DEVELOPMENT AND VALIDATION OF A QUESTIONNAIRE TO MEASURE ADHERENCE TO THE MEDITERRANEAN DIET

< 0.0001), and fairly agreed with food record (κ = 0.32, 95% CI = 0.15-0.49, P < 0.0001; gross misclassification of 5.1%). The test-retest reliability showed similar results. The T-MEDAS score was inversely associated with the risk of GERD in adjusted models (adjusted odds ratio for each 1 point increase in the T-MEDAS score = 0.859, 95% CI = 0.738-1.00; P = 0.05).

Conclusions: The T-MEDAS is a valid tool for assessing MD adherence among Taiwanese adults. The T-MEDAS score was inversely correlated with the prevalence of GERD.

P.127 PROTON PUMP INHIBITORINDUCED GUT DYSBIOSIS INCREASES MORTALITY RATES FOR PATIENTS WITH CLOSTRIDIOIDES DIFFICILE INFECTION

Cheng-Yu Lin1,2, Hao-Tsai Cheng2,3, Chia-Jung Kuo1,2, Chang-Mu Sung1,2, Sen-Yung Hsieh1,2

1Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan

2College of Medicine, Chang Gung University, Taoyuan, Taiwan

3Department of Gastroenterology and Hepatology, Tu Cheng Hospital, New Taipei City, Taiwan

2

3

Background: Clostridioides difficile infection (CDI) is associated with high mortality rates among patients with chronic illnesses.

Aims: We aimed to identify avoidable risk factors to reduce the mortality rate in CDI patients.

Methods: A total of 306 patients with diarrhea and clinical suspicion of CDI were enrolled, and fecal samples were gathered from 145 patients. CDI was diagnosed by fecal positivity for the C. difficile tcdB gene. Risk factors associated with death within 180 days were identified using Cox regression analysis. The fecal microbiota was determined through bacterial 16S rRNA gene sequencing.

Results: Of the patients with diarrhea, 240 (mean age, 69.1 years) were positive for CDI, and 91 died within 180 days. Multivariate analysis revealed that male sex, high Charlson Comorbidity Index and McCabe scores, high serum C-reactive protein levels, low hematocrit levels, low absolute eosinophil counts, high neutrophil/lymphocyte

使用質子幫浦抑製劑與困難梭菌感染 患者死亡風險之關係

ratios, and daily use of proton pump inhibitors (PPIs) were independent risk factors for overall mortality. Cumulative analyses confirmed the association of duration-dependent PPI use with a high mortality rate. Fecal microbiota analyses showed associations of decreased relative abundance of Ruminococcus gnavus (P = 0.001) and Prevotella copri (P = 0.025) and increased relative abundance of Parabacteroides merdae (P = 0.001) and Clostridioides difficile (P = 0.040) with higher mortality rates in patients with CDI. Moreover, these microbiota changes were correlated with the duration of PPI use.

Conclusions: Daily PPI use was the only avoidable risk factor for death. With more extended PPI use, the mortality rate was higher in patients with CDI. Gut dysbiosis in line with daily PPI use duration were significantly associated with the death of CDI patients. Our findings provide in-depth insights into the cautious use of PPIs in chronically ill patients with CDI.

P.128

THE IMPACT OF ENDOCUFF VISION ON THE DETECTION OF COLORECTAL POLYP DURING SCREENING COLONOSCOPY: A PRELIMINARY RESULT OF PROSPECTIVE RANDOMIZED CONTROL TRIAL

Chun-Wei Chen1, Wey-Ran Lin1,2, Chia-Jung Kuo1, Chun-Jung Lin1, Wei-Pin Lin1, Chen-Ming Hsu1, Cheng-Tang Chiu1,2

1Department of Gastroenterology and Hepatology, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan

2College of Medicine, Chang Gung University, Taoyuan, Taiwan

Endocuff Vision 對於篩檢性大腸鏡瘜

Background: Adenoma detection rate (ADR) plays an important role in the quality of colonoscopy. Measures to improve colon mucosal observation are associated with higher ADR including better bowel preparation, use of sedative medication, slower withdraw time and wide-angle colonoscopy. However, attachable devices to the tip of colonoscopy created to flatten colon folds have not been consistently improved the ADR.

Aims: The aim of the study is to demonstrate the impact of Endocuff Vision (EV) on ADR during screening colonoscopy.

Methods: The study was a prospective randomized control trial and performed in Linkou Chang Gung Memorial Hospital from Sep, 2020 to Oct, 2021, patients performed screening colonoscopy were included in this study. Patients with EV were EV groups and without EV were control groups. The demography of patients, time of withdraw and insertion and the polyp characteristics including polyp pathological findings, size, location and morphology were collected. The cecal intubation rate, polyp detection rate (PDR) and ADR were also recorded. Descriptive statistics and frequency

肉偵測的影響：一個前瞻性隨機分配 試驗的初步報告

were calculated. Comparisons of continuous data were performed using the Mann-Whitney U test, and comparisons of discrete variables were conducted with the Chi-square test. Statistical significance was defined as p value < 0.05.

Results: There were 74 patients were enrolled in this study. 43 patients (58.1%) were EV group, and 31 patients were control group. The demography of patients and polyps were listed in Table 1. The polyp detection rate was 69.8% in EV group and 48.4% in case group. (p = 0.06) Compared to control group, the total detected polyps were significantly higher in EV groups (52 vs 18; p = 0.004). The cecal intubation rate was 97.6% (42/43) in EV group and 100% in case group. The patient failed to reach the cecum was due to colon cancer obstruction. The ADR was 44.2% in EV group and 29% in control group. The ADR was comparable between these two groups.

Conclusions: Our preliminary result demonstrated that the PDR and ADR were comparable with or without EV. However, more colorectal polyps could be found in EV group.

P.129

REAL WORLD EXPERIENCE WITH TOFACITINIB IN ULCERATIVE COLITIS AT A TERTIARY CENTER IN TAIWAN

Puo-Hsien Le, Chia-Jung Kuo, Cheng-Tang Chiu

Department of Gastroenterology and Hepatology, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan 捷抑炎治療潰瘍性結腸炎的台灣真實

臨床經驗

Background: Tofacitinib is a Janus kinase inhibitor recently approved for the treatment of biological experienced, moderate to severe ulcerative colitis (UC) in Taiwan. It has robust efficacy and safety data derived from OCTAVE clinical trials, but no real-world data in Taiwan.

Aims: We aim to provide the preliminary treatment outcomes at a Tertiary Center.

Methods: We prospectively collected the basic data and clinical outcomes of patients with ulcerative colitis receiving Tofacitinib induction with standard dosage during March to June 2022. The biochemical and clinical outcomes were evaluated. Results: Ten biological experienced UC patients were enrolled in this study. Male to female ratio was 50%. The average age was 42-year-old and disease duration was 7 years. Two patients failed one biologics (IFX, VDZ), five patients failed two biologics (1: IFX + VDZ, 4: ADA + VDZ), two patients failed three biologics (1: IFX + ADA + VDZ, 1: ADA + VDZ + Risakizumab) and one patient failed four biologics (IFX + ADA + VDZ + Risakizumab). The 4-week clinical remission rate was 100%, and 8-week remission rate was 83%. No significant change over CPK, LDL, HDL, TG over 8 weeks. According to side effects, only mild chest tightness and headache were noted.

Conclusions: Tofacitinib is effective and safe in biologics experienced UC patients according in the first real-world study in Taiwan.

P.130

WHICH IMMUNE CELL IS THE MOST RELEVANT TO SALMONELLAINDUCED COLORECTAL CANCER?

Kuang-Tsu Yang1,2,3,4, Smith Wun-Long Jheng5,6, Huey-Kang Sytwu7,8,9, Jui-Tzu Wang10, Renin Chang10,11,12,13, Yao-Min Hung14,15,16, James Cheng-Chung Wei17,18,19, Yao-Shen Chen20,21, Jin-Shuen Chen22,23, Muh-Yong Yen21,24,25, Shin-Jung Lee21,26, Tsi-Shu Huang27, Ching-Wai Cheng28, Ming-Yi Li29, Chun-Yu Lin30,31, Chia-Chi Yen32,33,34, Chun-Ying Wu35,36,37,38,39, Ping-I Hsu21,40, Chih-Hsin Hung41, Tsung-Hui Hu4,42, Ming-Hong Tai4, Kuang-Hung Cheng4,43,44,45

1Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Municipal Min-Sheng Hospital, Kaohsiung, Taiwan; 2Department of Medicine, National Taiwan University, Taipei, Taiwan; 3Division of Family Medicine, Department of Community Medicine, Kaohsiung Municipal Min-Sheng Hospital, Kaohsiung, Taiwan; 4Institute of Biomedical Science, National Sun Yat-Sen University, Kaohsiung, Taiwan; 5Medical 3D Printing Center, National Defense Medical Center Tri-Service General Hospital, Taipei, Taiwan; 6International Academia of Biomedical Innovation Technology; 7Academia Sinica, Taipei, Taiwan; 8National Health Research Institutes, Taipei, Taiwan; 9National Defense Medical Center Tri-Service General Hospital, Taipei, Taiwan; 10Department of Education and Research, Kahoshiung Veterans General Hospital, Kaohsiung, Taiwan; 11Department of Emergency Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan; 12Institute of Biotechnology and Chemical Engineering, I-Shou University, Kaohsiung, Taiwan; 13Department of Recreation and Sports Management, Tajen University, Pingtung, Taiwan; 14Department of Internal Medicine, Kaohsiung Municipal United Hospital, Kaohsiung, Taiwan; 15Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan; 16College of Health

and Nursing, Meiho University, Pingtung, Taiwan; 17Department of Allergy, Immunology & Rheumatology, Chung Shan Medical University Hospital, Taichung, Taiwan; 18Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan; 19Graduate Institute of Integrated Medicine, China Medical University, Taichung, Taiwan; 20Department of Administration, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan; 21Faculty of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; 22Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan; 23School of Medicine, National Defense Medical Center, Taipei, Taiwan; 24Kunming Prevention Center, Taipei City Hospital, Taipei, Taiwan; 25Division of Infectious Diseases, Cheng Hsin General Hospital, Taipei, Taiwan; 26Division of Infectious Disease, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan; 27Division of Microbiology, Department of Pathology and Laboratory Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan; 28Department of Internal Medicine, Taipei City Hospital, Ren-Ai Branch, Taipei, Taiwan; 29Division of Cardiology, Department of Internal Medicine, Kaohsiung Municipal Min-Sheng Hospital, Kaohsiung, Taiwan; 30Division of Infectious Disease, Department of Internal Medicine, Kaohsiung Municipal Min-Sheng Hospital, Kaohsiung, Taiwan; 31Associate Dean, Kaohsiung Municipal Min-Sheng Hospital, Kaohsiung, Taiwan; 32Superintendent’s Office, Kaohsiung

Municipal Min-Sheng Hospital, Kaohsiung, Taiwan; 33Department of Nutrition, Institute of Biomedical Nutrition, Hung-Kuang University, Taichung, Taiwan; 34Department of Business Management, National Sun Yat-Sen University, Kaohsiung, Taiwan; 35Institute of Biomedical Informatics and Research Center for Epidemic Prevention, National Yang Ming Chiao Tung University, Taipei, Taiwan; 36Faculty of Medicine and Institute of Clinical Medicine, National

Yang Ming Chiao Tung University, Taipei, Taiwan; 37Division of Translational Research, Taipei Veterans General Hospital, Taipei, Taiwan; 38Department of Public Health, China Medical University, Taichung, Taiwan; 39National Institute of Cancer Research and Institute of Population Health Science, National Health Research Institutes, Miaoli, Taiwan; 40Division of Gastroenterology and Hepatology, Department of Internal Medicine, An Nan Hospital, China Medical University, Tainan, Taiwan; 41Institute of Biotechnology and Chemical Engineering, I-Shou University, Kaohsiung, Taiwan; 42Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan; 43National Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan; 44Regenerative Medicine and Cell Therapy Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan; 45Department of Medical Laboratory Science and Biotechnology, Kaohsiung Medical University, Kaohsiung, Taiwan 何種免疫細胞與沙門桿菌造成的大腸

整合醫學部；20 高雄榮民總醫院副院長；21 國立 陽明交通大學醫學系；22 高雄榮民總醫院內科部； 23 國防醫學院醫學系；24 臺北市立聯合醫院昆明 院區；25 振興醫院感染科；26 高雄榮民總醫院內 科部感染科；27 高雄榮民總醫院病理暨檢驗醫學 部微生物科；28 臺北市立聯合醫院仁愛院區內科

部；29 高雄市立民生醫院內科部心臟血管內科；30 高雄市立民生醫院內科部感染科；31 高雄市立民

生醫院副院長；32 高雄市立民生醫院院長；33 弘 光科技大學營養系暨營養醫學研究所；34 國立中 山大學企業管理學系；35 國立陽明交通大學生物

醫學資訊研究所；36 國立陽明交通大學醫學系；37 臺北榮民總醫院轉譯研究科；38 中國醫藥大學公

共衛生所；39 國家衛生研究院癌症研究所及群體 健康科學研究所；40 臺南市立安南醫院—委託中

國醫藥大學興建經營內科部胃腸肝膽科；41 義守 大學生物科技及化學工程系；42 高雄長庚紀念醫

院胃腸肝膽科系；43 國家衛生研究院癌症研究所； 44 高雄醫學大學再生醫學以及細胞治療研究中心；

45 高雄醫學大學醫學檢驗生物技術學系

Background: Previous studies showed that Salmonella protein AvrA could activate STAT3 signaling pathway in colon adenocarcinoma (COAD). However, the role of immune cells in the above-carcinogenic pathways was still unaddressed.

Aims: To evaluate the role of immune cells in Salmonella related colon cancer.

Methods: We first examed the 5-year survival outcome relevant to COAD and several immune cells in TIMER. Afterwards, GeneMania and HPA were deployed to retrieve gene-gene network and RNA expression in different tissues. Finally, we got proteomic bioinformatics from STRING.

2 國立臺 灣大學醫學系；3 高雄市立民生醫院社區醫療部家

庭醫學科；4 國立中山大學生物醫學研究所；5 國

防醫學院三軍總醫院3D 醫學列印中心；6 國際創

新生醫技術研究院；7 中央研究院；8 國家衛生研 究院；9 國防醫學院三軍總醫院；10 高雄榮民總醫

院教學研究部；11 高雄榮民總醫院急診醫學部；12

義守大學生物科技及化學工程研究所；13 大仁大 學休閒與運動管理系；14 高雄市立聯合醫院內科

部；15 中山醫學大學醫學院；16 美和科技大學健

康暨護理學院；17 中山醫學大學附設醫院風濕免

疫科；18 中山醫學大學醫學系；19 中國醫藥大學

Results: Low STAT3 gene expression with high CD4+ T cell showed a worse trend of 5-year survival of COAD patients than with low CD4+ T cell infiltration. According to previous studies and our bioinformatic analyses, AvrA/IL-6/STAT3 might play a carcinogenic pathway in COAD. In RNA expression, STAT3 was more prominent than IL6. Proteomic bioinformatics analyses revealed the detailed protein-protein networks of STAT3/IL6/ CTLA4.

Conclusions: We firstly demonstrated that CD4+ T cell is a crucial role in Salmonella-induced COAD development, regarding the association with STAT3, AvrA, and IL-6.

P.131

EATING HABITS ASSOCIATED WITH MEDITERRANEAN DIET ADHERENCE IN COLLEGE STUDENTS: A CROSS-SECTIONAL STUDY

Hui-Fen Lang2, Ying Cheng Lin1, Fu-Yu Kuo1, Kareen Chong1, Wen-Hong Wang2, Han-Chung Lien1,3,4

1Division of Gastroenterology & Hepatology, Department of Internal Medicine, Taichung

Veterans General Hospital, Taichung, Taiwan

2Department of Food and Nutrition, Taichung Veterans General Hospital, Taichung, Taiwan

3School of Medicine, National Yang Ming

Chiao Tung University, Taipei, Taiwan

4Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, Taiwan

大學生的飲食習慣影響地中海飲食遵 從性：橫斷性研究

2 臺中榮民總醫院營養室

3 國立陽明交通大學醫學系

4 國立中興大學學士後醫學系

Background: Studies focusing on the relationship between lifestyle and eating habits and healthy dietary pattern are scarce in Taiwan, especially in the younger generation.

Aims: To examine clinical correlates of healthy dietary pattern in college students in Taiwan.

Methods: In a cross-sectional study, a total of 821 of 1051 (78.1%) college students completed the survey (551 female, mean age: 20.4 ± 2.7 years). Adherence to the Mediterranean diet was assessed using the 14-item Taiwanese version of Mediterranean Diet Adherence Screener (T-MEDAS). Sex and age-adjusted logistic regression was conducted to evaluate the association of lifestyle and eating habits with Mediterranean dietary pattern.

Results: In students with lower T-MEDAS score, significant trends were found to have higher percentage of irregular meal (p for trend = 0.031), eating out of home (p for trend < 0.001), nocturnal

eating (p for trend < 0.001), eating snacks (p for trend = 0.018), dining in fast-food restaurants (OR: 2.3, 95% CI: 1.5-3.6), dining in convenience stores (OR: 1.6, 95% CI: 1.1-2.4), and lower percentage of dining in vegetarian restaurants (OR: 0.4, 95% CI: 0.2-0.8). In logistic regression models, students who had T-MEADS scores in the lowest quartile remained associated with above eating habits, except for eating snacks and dining in vegetarian restaurants.

Conclusions: Our finding suggested a strong correlation between eating habits and dietary quality in Taiwanese college students.

REAL WORLD EXPERIENCE WITH USTEKINUMAB IN CROHN’S DISEASE IN TAIWAN: A MULTICENTER STUDY

Puo-Hsien Le1, Chia-Jung Kuo1, Jen-Wei Chou2, Hsu-Heng Yen3, Chen-Wang Chang4, Cheng-Tang Chiu1

1Department of Gastroenterology and Hepatology, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan

2Center for Digestive Medicine, Department of Internal medicine, China Medical University Hospital, Taichung, Taiwan

3Division of Gastroenterology, Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan

4Division of Gastroenterology and Hepatology, Mackay Memorial Hospital, Taipei, Taiwan

detail of Montreal classification was as below, A1 (2%), A2 (71%), A3 A3 (28%); L1 (28%), L2 (11%), L3 (62%); B1 (52%), B2 (23%), B3 (25%), p (23%). Baseline mean HBI, CDAI, CRP and albumin level were 6.7, 314, 14.7 mg/dL, 3.1 g/dL, respectively. Fourteen percent of patients had extraintestinal manifestations, and 34% experienced intestinal surgery. Regards to baseline medications, steroid users were 65%, and azathioprine users were 33%. The clinical symptom improved since 7 (mean, range 1-56) days. Clinical response rates were 73%, 82%, 76% and 53% in week 4, 8, 12, 24. Clinical remission rates were 24%, 49%, 47%, 52%. No severe adverse event was noted. Conclusions: Ustekinumab is effective and safe in Crohn’s disease treatment. However, we should prescript it every 8 weeks, rather than every 12 weeks after induction to maximize the therapeutic effect, especially in biological experienced cases.

1 林口長庚紀念醫院胃腸肝膽科

2 中國醫藥大學附設醫院消化內科

3 彰化基督教醫院胃腸肝膽科

4 台北馬偕紀念醫院胃腸肝膽科

Background: Ustekinumab, a monoclonal antibody to the p40 subunit of interleukin-12 and interleukin-23, is indicated for moderate to severe Crohn’s disease treatment in Taiwan. In Taiwan, it was covered by national heal insurance with 12 weeks interval after induction rather than 8 weeks. No real-world data showing its efficacy and safety in Taiwan.

Aims: We aim to provide the first real-world data in Taiwan.

Methods: In this multi-center retrospective study, we collected the basic data, laboratory and clinical outcomes of patients with Crohn’s disease receiving Ustekinumab treatment during December 2019 and April 2022 in four medical centers in Taiwan. The biochemical and clinical outcomes were evaluated.

Results: We enrolled 65 patients in this study. Men was 75%, and average age was 41.6-yearold. The average disease duration was 6.8 years and 66% patients were biologics experienced. The

喜達諾治療克隆氏症真實臨床經驗： 多中心研究

P.133

“SUGAR-SWEETENED BEVERAGES” IS AN INDEPENDENT RISK FROM PANCREATIC CANCER

Chien-Hua Chen, Chi-Chieh Yang, Kwei-Ming Chen, Yu-Tsai Liu, Chih-Sheng Wu, Yi-Jen Fang

Division of Gastroenterology, Department of Internal Medicine, Show-Show Memorial Hospital, Changhua, Taiwan

response relationship. The association of SSB intake of ≥2 servings/day with pancreatic cancer mortality among the total cohort was significant after excluding those who smoke or have diabetes (HR: 2.12, 97% CI: 1.26–3.57), are obese (HR: 1.57, 95% CI: 1.08–2.30), have hypertension (HR: 1.90, 95% CI: 1.20–3.00), and who died within 3 years after enrollment (HR: 1.67, 95% CI: 1.15–2.45). Risks remained in the sensitivity analyses, implying its independent nature.

Conclusions: We concluded frequent drinking of SSB increased pancreatic cancer in adults, with highest risk among young people.

Background: Although the link between sugarsweetened beverages (SSB) and pancreatic cancer has been suggested for its insulinstimulating connection, most epidemiological studies showed inconclusive relationship.

Aims: Whether the result about sugar-sweetened beverages (SSB) and pancreatic cancers was limited by sample size is explored.

Methods: This prospective study followed 491,929 adults, consisting of 235,427 men and 256,502 women (mean age: 39.9, standard deviation: 13.2), from a health surveillance program and there were 523 pancreatic cancer deaths between 1994 and 2017. The individual identification numbers of the cohort were matched with National Death file for mortality, and Cox models were used to assess the risk. The amount of SSB intake was recorded based on the average consumption in the month before interview by a structured questionnaire. we classified the amount of SSB intake into 4 categories: 0 - <0.5 serving/day, ≥0.5 - <1 serving per day, ≥1 - <2 servings per day, and ≥2 servings per day. One serving was defined as equivalent to 12 oz and contained 35 g added sugar. We referred to the age and the variables at cohort enrolment for the reported risks of pancreatic cancers. The cohort was divided into 3 age groups, 20-39, 40-59 and ≥60.

Results: We found young people (age < 40) had more prevalence and frequency of sugarsweetened beverages than the elderly. Those consuming 2 servings/day had a 50% increase in pancreatic cancer mortality (HR: 1.55, 95% CI: 1.08-2.24) for the total cohort, but a 3-fold increase (HR: 3.09, 95% CI: 1.44-6.62) for the young. The risk started at 1 serving every other day, with a dose-

含糖飲料與胰臟癌的關聯 陳建華 楊基滐 陳奎閔 劉裕財 吳志昇 方怡仁 秀傳紀念醫院胃腸肝膽科

P.134

THE RISK FACTORS FOR EARLY SEMS DYSFUNCTION IN DISTAL EXTRAHEPATIC MALIGNANT BILIARY OBSTRUCTION WHO CHANGED A PLASTIC STENT WITH A SEMS

Chia-Chia Lu, Chia-Changc Chen, Hsin-Ju Tsai

Division of Gastroenterology and Hepatology, Taichung Veterans General Hospital, Taichung, Taiwan

of early SEMS dysfunction were nonocclusion cholangitis and stent clogging (41% and 23%, respectively) and other reasons including tumor ingrowth, tumor overgrowth, one of them is not fully expansion of SEMS.The patients who had shorter plastic stents patency (dysfunction within 90 days) reported a significantly higher rate of early SEMS dysfunction (70.6% vs 30.7%, P = .013). The post-ERCP cholangitis is also a risk factor of early SEMS dysfunction (29.4% vs 7.69%; P = .04). Shorter plastic stents patency and postERCP cholangitis were risk factors (odds ratio, 7.52; 95% CI, 1.81-31.33; P = .006; odds ratio, 8.48; 95% CI, 1.34-53.58; P = .023) in a multiple logistic regression model.

Background: Endoscopic Retrograde Biliary Drainage (ERBD) is an effective treatment for malignant extrahepatic biliary stricture. Selfexpandable metallic stents (SEMS) provide longer patency and require minimal auxiliary procedures. The mean or median duration of SEMS patency of malignant biliary tract obstruction was >270 days according to previous studies. However, early (<3 months) SEMS dysfunction is still observed in clinical practice and the risk factors for their early dysfunction remain unclear.

Aims: To identify risk factors for early SEMS dysfunction in distal extrahepatic malignant biliary obstruction who changed a plastic stent with a SEMS.

Methods: A single-center retrospective study was performed on all consecutive patients who underwent SEMS to replace previous plastic stent for malignant extrahepatic biliary stricture between January 2015 and December 2021. We collected baseline demography, SEMS patency duration, SEMS types, characteristics of stricture, the effectiveness of plastic stent before SEMS, and adverse outcomes were performed. Rates and risk factors of early SEMS dysfunction were evaluated. Univariate and multivariable analyses were performed to identify factors associated with early SEMS dysfunction.

Results: In all, 56 eligible patients were identified. The mean time to SEMS dysfunction was 182 days. The rates of all and early SEMS dysfunction were 50% and 30.3%, respectively. The major causes

Conclusions: Shorter plastic stents patency before SEMS deployment and post-ERCP cholangitis are risk factors for early SEMS dysfunction in patients with malignancy distal biliary obstruction who change a plastic stent with a SEMS.

惡性遠端膽道阻塞病患併發早期金屬 支架功能障礙的危險因子

呂家嘉 陳家昌 蔡炘儒 臺中榮民總醫院胃腸肝膽科

P.135

Jiann-Hwa Chen1,2, Wei-Chih Su1, Tsung-Hsien Hsiao1, Hung-Da Chen1,2, Lung-Yuan Hsu1,2, You-Chen Chao1,2

1Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taipei, Taiwan

2School of Medicine, Tzu Chi University, Hualien, Taiwan

showed abnormal cellular findings consistent with malignancy as compared to 4 of 18 (22.2%) in the historical control group (P < 0.05). There are two true negative cases who proved to be benign strictures with the clinical course. There are three false negative patients who are two CBD and one pancreatic cancer cases after tissue proof by surgical intervention and endoscopic ultrasound guided fine needle aspiration, respectively. The overall accuracy value is 78.6%. The rate of whitish core tissue obtained is higher in the new design brush group in comparison with the historical controls.

Conclusions: CONCLUSION: The use of a new brush design for brush cytology of biliary strictures shows increased diagnostic accuracy, likely due to improved cellular yield, as evidenced by an increase in number of white tissue core obtained.

Background: Background: Indeterminate biliary stricture remains an important clinic problem regardless of emerging newly diagnostic modalities for the past ten years. Brushing cytology is a useful and easily available tool in the endoscopic retrograde cholangiopancreatography (ERCP) procedure when patients receiving concomitant biliary decompression.

Aims: AIM: To determine the utility of a newly designed brush which could improve the diagnostic yield of indeterminate biliary stricture.

Methods: METHODS: Retrospective chart review was performed in all ERCP procedures with indeterminate biliary stricture brushing between January 2014 and December 2022. A standard wireguided cytology brush was used prior to protocol implementation in July 2019, after which, a new 7.5 French wire-guided cytology brush (Infinity® ERCP sampling Device, Steris Endoscopy Co., Mentor, OH) was used for all cases. All specimens were reviewed by two experienced cytopathologists who determined whether the sample was positive or negative for malignancy.

Results: RESULTS: Fourteen new brush cases were compared to 18 historical controls. Nine of 14 (64.3%) cases in the new brush group

THE UTILITY OF A NEWLY DESIGNED CYTOLOGY BRUSH WHICH COULD IMPROVE THE DIAGNOSTIC YIELD OF INDETERMINATE BILIARY STRICTURE

特殊設計的組織細胞刷能增加不明原 因膽道阻塞的診斷率

台北慈濟醫院胃腸肝膽科 2 慈濟大學醫學院

P.136

PANCREATIC ADENOCARCINOMA IN PATIENTS BELOW 50 YEARS OLD AND ITS COMPARISON WITH GENERAL PATIENT POPULATION

Kuan-Wei Wu1,2, Shing-Ting Huang3, Tsang-En Wang1,2, Chih-Jen Chen1,2, Horng-Yuan Wang1,2, Ming-Jen Chen1,2

1Division of Gastroenterology, Department of internal medicine, MacKay Memorial Hospital, Taipei, Taiwan

2Department of Medicine, MacKay Medical College, New Taipei City, Taiwan

3Nurse Practitioner, Division of Gastroenterology, Department of Internal Medicine, MacKay Memorial Hospital, Taipei, Taiwan

Results: 32 patients had pathologic diagnoses of PAC. The mean age is 44.5 years old. 78.1% were male, significantly higher than general PAC patients. (78% vs. 51%, p = 0.001) The most common initial presentation is abdominal pain (71.8%), followed by nausea (46.9%) and jaundice (40.6%). 25% of patients smoked, and 15.6% drank heavily. No patient had any family history of PAC. Common comorbidities include diabetes mellitus (18.8%) and HBV (15.6%). The most common primary tumour site is the pancreatic head, similar to the general PAC population. Most cases were poorly differentiated, much higher than the general PAC patient population (43.7% vs 16.4%, p = 0.004). Most patients were at stage IV when diagnosed, and the rate was much higher than that of general PAC patients (71.8% vs 44.9%, p = 0.002). 10 patients (31.3%) received surgical resection, which was mildly higher than the general PAC patient group (31.3% vs 13.5%, p = 0.04). The 1-year-survival rate is 22%, and the 3-year-survival rate is 3.1%, which is lower than the general PAC patient group. Since most patients died within the first year, we compared the 1-year survival rate between different tumour variables, but we found no variable that caused significant differences.

Background: Most patients diagnosed with pancreatic adenocarcinoma (PAC) are 6080 years old. The incidence rate was low for patients less than 50 years old. However, as the global incidents of PAC have grown recently, the percentage of patients below 50 years old is also increasing. Since there were not many studies about these younger PAC patients, we share our experience here.

Aims: We share our experience with PAC in patients less than 50 years old. Their clinical features, diagnosis, treatments and prognosis were analysed and compared with general PAC patients.

Methods: We conducted a retrospective study of patients diagnosed with PAC who were below 50 years old in our hospital from 2004 to 2021. We analysed their gender, clinical manifestation, risk factors, tumour characteristics, treatments, and survival rates. Then we compared some of these variables to one study that enrolled 136100 PAC patients of all ages from the USA from 1975 to 2016.

Conclusions: Many PAC patients below 50 years old had common known risk factors like smoking, heavy alcohol abuse, diabetes mellitus and HBV infection. However, the family history of PAC seemed to be unrelated. Common symptoms are abdominal pain, nausea, jaundice, body weight loss and malaise. The most common primary tumour site is at the pancreatic head. When comparing with general PAC patients, there are several significant differences in patients below 50 years old. Firstly, it is more male predominant. In grading and staging, the tumours are more likely to be poorly differentiated and at a more advanced stage when first diagnosed. Even though slightly more patients could receive surgical resection, the survival rate was much worse. Finally, we found no tumour characteristics related to any difference in survival rate.

低於五十歲之胰臟腺癌病患與不分年 齡層之整體病患族群的比較

P.137

A WEAKLY SUPERVISED CONVOLUTION NEURAL NETWORK CAN HELP NONEXPERT PHYSICIANS

DISTINGUISHING CHOLEDOCHOLITHIASIS ON CT SCAN

Meng-Ying Lin1, Chun-Rong Huang2, Ya-Han Chang2, I-Chin Wu1, Wei-Lun Chang1

1Division of Gastroenterology and Hepatology, Department of Internal Medicine, Nation Cheng Kung University Hospital, Tainan, Taiwan

2Department of Computer Science and Engineering, National Chung Hsing University, Taichung, Taiwan

in our weakly supervised CNN was 94.5% in separated independent validation set. In the external validation cohort, the AUROCs of CNN, medical student, junior physician (seniority < 5 years) and experienced physician (seniority ≥ 5 years) were 0.894 ± 0.009, 0.625 ± 0.017, 0.767 ± 0.013 and 0.811 ± 0.014 separately. The p values were less than 0.001 no mater compared CNN with which degree of physicians.

Conclusions: A weakly supervised CNN can achieve about 90% diagnostic performance of expert and help non-expert physician interpreting choledocholithiasis on CT scan.

Background: Common bile duct stones were usually symptomatic and needed to be detected earlier. CT is a convenient modality in diagnosing choledocholithiasis with acceptable accuracy in expert. However, the diagnostic performance was poor in inexperienced doctors.

Aims: We aimed to develop an artificial intelligence system to assist physician in interpreting choledocholithiasis on CT scan.

Methods: Patients who met 2010 ASGE high probability criteria from Jan. 2018 to Aug. 2019 presented with CT scan prior to treatment were retrospectively collected. A radiologist interpretated each CT image dedicatedly and recorded the presentation of choledocholithiasis picture by picture. 57.5% of pictures were used as training cohort to develop a weakly supervised CNN. The other pictures were separated as independent validation set. After that, 180 randomly selected pictures were used for external validation.

Physicians with different seniority and the CNN interpreted the cohort at the same time.

Results: A total 268 patients were enrolled with 4244 pictures collected. The overall accuracy

助非專家醫師在電腦斷層中判讀出總 膽管結石

1 國立成功大學醫學院附設醫院內科部胃腸肝膽科

P.138

A NEW ALBI-BASED MODEL TO PREDICT SURVIVAL FOR UNRESECTABLE INTRAHEPATIC CHOLANGIOCARCINOMA UNDERGOING CHEMOTHERAPY

Chen-Ta Chi1,2, I-Cheng Lee1, Ming-Huang Chen3, Pei-Chang Lee1, Yi-Ping Hung3, Ming-Chih Hou1, Yee Chao3, Yi-Hsiang Huang1,2

1Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan

2Institute of Clinical Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan

3Department of Oncology, Taipei Veterans General Hospital, Taipei, Taiwan 一個以

was 62 years old. Most patients were within Child–Pugh class A (61.7%) and Albumin-bilirubin (ALBI) grade 2/3 (67.3%). Of them, 106 (65.4%) received gemcitabine-based regimen, while 56 (34.6%) patients received fluoropyrimidine-based regimen. The ORR was 26.0% and disease control rate (DCR) was 48.0% in the whole 123 ICC patients with evaluable images. Absence of HBV infection, gemcitabine-based regimen were the independent predictors of ORR. In general, the median OS of the 162 ICC patients was 6.1 months. Presence of cirrhosis, Albumin ≤ 3.5 g/dl, Child-Pugh B/C, ALBI grade 2/3, NLR ≧ 3, and CA 19-9 ≧ 300 U/ ml were independent risk factors associated with OS. A novel ALBI-based scoring system to predict OS was created, the patients could be classified into 4 groups. Kaplan-Meier analysis showed that the new ALBI-based model could significantly discriminate OS between contiguous group.

Conclusions: Albumin-bilirubin grade is an important factor associated with survival in unresectable ICC patients receiving chemotherapy. The new ALBI-based model can be applied to select patients who can get the best benefit from chemotherapy.

Background: Intrahepatic cholangiocarcinoma (ICC) is a highly aggressive malignancy. Gemcitabine-based and fluoropyrimidine-based chemotherapy are the mainstay treatments for Unresectable ICC, even though the survival is still far from satisfaction in real-world experience.

Aims: We aimed to assess outcomes and identify the prognostic factors for patients with unresectable ICC patients receiving gemcitabinebased or fluoropyrimidine-based chemotherapy.

Methods: From December 2006 to January 2020, consecutive 309 unresectable ICC patients were enrolled. Of them, 162 ICC patients received chemotherapy as first-line treatment were retrospectively reviewed, and 123 patients had evaluable images for tumour response evaluation. Objective response rate (ORR) and overall survival (OS) were assessed and factors associated with ORR and OS were analysed.

Results: Of the 162 ICC patients received chemotherapy as first-line therapy, the mean age

ALBI Grade 為基礎的新預測模 型用於評估無法接受手術切除的惡性

P.139

GALLBLADDER POLYPOID LESION PREVALENCE RE-EVALUATION IN SOURTHERN TAIWAN: A REALWORLD EXPERIENCE FROM HEALTH EXAMINATION CENTER OF A MEDICAL INSTITUTE

Kuang-Tsu Yang1,2,3,4, Ming-Hong Tai4, Tsung-Hui Hu5, Tian-Huei Chu4, Chih-Lin Lin6, Li-Ying Liao6, Kuan-Yang Chen6,7, Geng-Lie Li6, Chung-Kwe Wang8, Bou-Zenn Lin6, Rong Xie9, Shu-Lin Chien9, Yi-Wen Shen10, Tzu-Ying Chao10, Mei-Chen Chen11, Kuan-Chang Yu12, Jun-Ting Chen12, Shun-Yi Chen12, Chia-Hsien Tsai12, Ting-Yu Yan12, Yu-Chen Chang12, Tzung-Jiun Tsai12, Wei-Chih Sun12, Sung-Shuo Kao12, Hui-Min Wang12, Feng-Woei Tsay12, Hsien-Chung Yu12, Wei-Lun Tsai12, Kung-Hung Lin12, Yao-Chun Hsu13, Chih-Hao Lin14, Wen-Chi Chen12, Kwok-Hung Lai11,15, Jin-Shiung Cheng16, Kai-Wen Huang17, Qiong-Ling Qiu3, Yu-Feng Hsu3, Cheng-Nan Hsieh3, Wei-Zhong Lin18, Ming-Yi Li19, Tien-Ching Lin1, Shuei-Cheng Kang1, Cheng-Hsiu Hsieh20, Ta-Kuan Li21, Ming-Ren Huang22, Chun-Yu Lin23, James Cheng-Chung Wei24, Chun-Ying Wu25,26, Ping-I Hsu27,28, Chia-Chi Yen29

1Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Municipal Min-Sheng Hospital, Kaohsiung, Taiwan; 2Department of Medicine, National Taiwan University, Taipei, Taiwan; 3Division of Family Medicine, Department of Community Medicine, Kaohsiung Municipal Min-Sheng Hospital, Kaohsiung, Taiwan; 4Institute of Biomedical Science, National Sun Yat-Sen University, Kaohsiung, Taiwan; 5Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan;

6Department of Gastroenterology and Hepatology, Ren-Ai Branch, Taipei City Hospital, Taipei, Taiwan; 7Yang-Ming Branch, Taipei City Hospital, Taipei, Taiwan; 8Division

of Hepatology and Gastroenterology, KangNing Hospital, Taipei, Taiwan; 9Medical Education Centre, Kaohsiung Municipal Min-Sheng Hospital, Kaohsiung, Taiwan; 10Department of Radiology, Kaohsiung Municipal Min-Sheng Hospital, Kaohsiung, Taiwan; 11Division of Hepatology and Gastroenterology, Department of Internal Medicine, Yuan’s General Hospital, Kaohsiung, Taiwan; 12Division of Hepatology and Gastroenterology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan; 13Division of Gastroenterology and Hepatology, Department of Internal Medicine, E-DA Hospital, Kaohsiung, Taiwan; 14Division of Gastroenterology & Hepatology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; 15Airen Hospital, Kaohsiung, Taiwan; 16SyongDA Polyclinic, Kaohsiung, Taiwan; 17Centre of Mini-Invasive Interventional Oncology, National Taiwan University Hospital; 18Division of Occupational Medicine, Department of Community Medicine, Kaohsiung Municipal Min-Sheng Hospital, Kaohsiung, Taiwan; 19Division of Cardiology, Department of Internal Medicine, Kaohsiung Municipal MinSheng Hospital, Kaohsiung, Taiwan; 20Division of Colorectal Surgery, Department of Surgery, Kaohsiung Municipal Min-Sheng Hospital, Kaohsiung, Taiwan; 21Division of General Surgery, Department of Surgery, Kaohsiung Municipal Min-Sheng Hospital, Kaohsiung, Taiwan; 22Kaohsiung Municipal Min-Sheng Hospital, Kaohsiung, Taiwan; 23Division of Infectious Disease, Department of Internal Medicine, Kaohsiung Municipal Min-Sheng Hospital, Kaohsiung, Taiwan; 24Institute of Medicine of Chung Shan Medical University, Taichung, Taiwan; 25Institute of Biomedical Informatics, National Yang Ming Chiao Tung University, Taipei, Taiwan; 26Division of Translational Research, Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan; 27Department of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; 28Division of

Gastroenterology, Department of Internal Medicine, An Nan Hospital, China Medical University, Tainan, Taiwan; 29Department of Orthopaedics, Kaohsiung Municipal MinSheng Hospital, Kaohsiung, Taiwan

該是時候重新評估膽囊息肉病灶盛行

率：一份來自南部醫療機構健康檢查

楊光祖1,2,3,4 戴明泓4 胡琮輝5 儲天輝4 林志陵6

廖麗瑛6 陳冠仰6,7 李耿列6 王鐘貴8 林柏任6 謝鎔9

簡淑玲9 沈怡彣10 趙子瑩10 陳美蓁11 余冠璋12

陳俊廷12 陳順益12 蔡宗憲12 顏廷宇12 張宇辰12

蔡騌圳12 孫煒智12 高崧碩12 王惠民12 蔡峯偉12

余憲忠12 蔡維倫12 林恭弘12 許耀峻13 林志豪14

陳文誌12 黎國洪11,15 鄭錦翔16 黃凱文17 邱瓊令3

許育峯3 謝政男3 林偉中18 李明義19 林典慶1

康水成1 謝政修20 李大寬21 黃明仁22 林俊祐23

魏正宗24 吳俊穎25,26 許秉毅27,28 顏家祺29

1 高雄市立民生醫院內科部肝膽腸胃科；2 國立臺

灣大學醫學系；3 高雄市立民生醫院社區醫療部家

庭醫學科；4 國立中山大學生物醫學研究所；5 高 雄長庚紀念醫院胃腸肝膽科系；6 臺北市立聯合醫

院仁愛院區內科部肝膽腸胃科；7 臺北市立聯合醫 院陽明院區；8 康寧醫院肝膽腸胃科；9 高雄市立 民生醫院醫教中心；10 高雄市立民生醫院放射部； 11 阮綜合醫院一般內科及肝膽腸胃內科；12 高雄 榮民總醫院內科部胃腸肝膽科；13 義大醫院內科 部胃腸肝膽科；14 高雄醫學大學附設中和紀念醫

院內科部胃腸肝膽科；15 愛仁醫院；16 雄大診所； 17 台大醫院癌症微創介入治療中心；18 高雄市立

民生醫院社區醫療部職業醫學科；19 高雄市立民

生醫院內科部心臟血管內科；20 高雄市立民生醫

院外科部大腸直腸科；21 高雄市立民生醫院外科

部一般外科；22 高雄市立民生醫院；23 高雄市立

民生醫院內科部感染科；24 中山醫學大學附設醫

院醫學研究部；25 國立陽明交通大學生物醫學資

訊研究所；26 臺北榮民總醫院轉譯研究科；27 國

立陽明交通大學醫學系；28 臺南市立安南醫院胃 腸肝膽科；29

高雄市立民生醫院骨科部

Background: Globally, there is approximately 5% prevalence of gallbladder polypoid lesion (GBPL) of the in the adult population. In Taiwan and Asian countries, the prevalences are different from country to country, but near 8-10% in 1990-2010. GBPL is associated with metabolic disorder, diet type, and life style. The risk of gallbladder cancer

resulted from GBPL is also a crucial issue. We have no up-to-date prevalence data of GBPL in Taiwan recently.

Aims: To conduct a real-world approach to investigate the prevalence of general population GBPL in Southern Taiwan.

Methods: We recorded the upper abdomen sonography data from health examination center of Kaohsiung Municipal Min-Sheng Hospital (KMSH) during May 3rd 2022 to June 24th 2022. Individual information, clinical characteristics, and image data were recruited. A descriptional methodology was applied.

Results: In total, 137 individuals were enrolled. Among them, 32.1% was male. Mean age was 42.2 years old. We found that GBPL prevalence in normal population was 29.9%. After sex-based stratification, we noticed that GBPL prevalence in male gender was higher than female gender (36.4% vs 26.9%).

Conclusions: A higher prevalence of GBPL is discovered in Southern Taiwan than other countries in Asia, Europe, and Latin America. Further cooperative projects of hospital networking should be proposed.

SYSTEMATIC REVIEW AND NETWORK META-ANALYSIS: THE COMPARISONS OF DIFFERENT INSERTION TECHNIQUES FOR DIFFICULT BILIARY CANNULATION

Cheng-Che Chen1, Sz-Iuan Shiu1,2,3, Chung-Wang Ko1, Chun-Fang Tung1

1Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan

2Department of Critical Care Medicine, Taichung Veterans General Hospital, Taichung, Taiwan

3Evidence-based Practice and Policymaking Committee, Taichung Veterans General Hospital, Taichung, Taiwan

1 臺中榮民總醫院胃腸肝膽科

2 臺中榮民總醫院重症醫學部

3 臺中榮民總醫院實證醫學與決策委員會

Background: Difficult biliary cannulation would prolong ERCP manipulation and increase postERCP complications. Several cannulation techniques including guidewire or cutting-based methods have been proposed to facilitate the procedure, but the optimum choice among these approaches remains inconclusive.

Aims: We conducted a network meta-analysis to compare these tactics for difficult biliary cannulation.

Methods: Three major bibliographic databases were reviewed for enrollment of comparative trials prior to December 25, 2021. We included adults with difficult biliary cannulation and compared two or more of seven interventions including controlled group, precut papillotomy (PP), precut fistulotomy (PF), delayed precut papillotomy (dPP), delayed precut fistulotomy (dPF), transpancreatic biliary sphincterotomy (TPS), and double-guidewire technique (DGW). Our focus was on the deep cannulation rate and post-ERCP complications including pancreatitis, bleeding, perforation, and infection at follow-up periods.

Results: Seventeen studies involved a total of

2,189 participants for analysis. When compared with controlled group, TPS was significantly superior to the other techniques in cannulation efficacy (OR: 6.00, 95% CI: 1.29~27.96), and only PF was significantly associated with lower complication rate (OR: 0.61, 95% CI: 0.40~0.93). Subgroup analysis also found that PF experienced less post-ERCP pancreatitis significantly in comparison to controlled group, and there was no difference in bleeding, perforation, and infection after ERCP.

Conclusions: For difficult biliary cannulation, only TPS achieved better cannulation efficacy while PF showed lower complication rate with statistical significance especially in post-ERCP pancreatitis.

P.141

IMPACT OF PREOPERATIVE BILIARY DRAINAGE ON POSTOPERATIVE BILIARY TRACT INFECTION OF PATIENTS UNDERGOING

PANCREATICODUODENECTOMY

Min-Jung Wu1,2, Shang-Yu Wang1,2, Chun-Nan Yeh1

1Division of General Surgery, Linkou Chang

Gung Memorial Hospital, Taoyuan, Taiwan

2School of Traditional Chinese Medicine, Chang Gung University, Taoyuan, Taiwan

吳旻容1,2 王尚煜1,2 葉俊男1

1 林口長庚紀念醫院一般外科

2 長庚大學醫學院中醫學系

Background: For patients with obstructive jaundice and indicated for pancreaticoduodenectomy (PD) due to periampullary lesion, biliary drainage, either endoscopic retrograde cholangiopancreatography (ERCP) or percutaneous transhepatic cholangiography and drainage (PTCD), may be indicated preoperatively. However, the possibility of procedure-related postoperative biliary tract infection (BTI) should be concerned.

Aims: We tried to evaluate the impact on postoperative BTI from ERCP and PTCD drainage. The possible risk factors regarding postoperative BTI were also investigated. In addition, we also assess the value of postoperative biliary stent and drainage in the prevention of postoperative BTI in patients who underwent preoperative ERCP biliary drainage.

Methods: Patients, from June 2013 to March 2022, with periampullary lesions diagnosed in our institute and with PD indicated were enrolled in present work. Patients without intraoperative bile culture taken, non-neoplastic lesions, and missing drainage data (ERCP or PTCD done at other institutes) were excluded. Clinical information, including demographic data, pathologic diagnosis, methods of biliary drainage, laboratory data, results of microbiologic tests, and relevant infectious outcomes, was extracted from medical records for analysis.

Results: There were 279 patients fulfilling our

selection criteria. One-hundred-and-fifty-six from the cohort (156/279) underwent biliary drainage, either ERCP (n = 120) or PTCD (n = 36). The positive yield of intraoperative biliary culture was significantly higher in patients who underwent ERCP than PTCD (90% vs. 38.9%, p < 0.001). Although there was no statistical significance, there was a trend of higher postoperative BTI (13.3% vs. 2.8%) and BTI-related septic shock (5 vs. 0, 4.2% vs. 0%) in the group undergoing ERCP. The risk factor of postoperative BTI cannot be confirmed at present work although there was a trend of ERCP procedures related to higher postoperative BTI and a borderline p-value was observed (p = 0.05, regarding ERCP biopsy). Placement of intraoperative hepaticojejunostomy stent for patients with preoperative ERCP makes no difference in postoperative outcome.

Conclusions: ERCP in patients undergoing PD increases the positive yield of intraoperative biliary culture. PTCD may be the favorable option if preoperative biliary drainage is indicated.

EMERGING CHALLENGE OF PRIMARY LIVER CANCER – THE DISEASE BURDEN OF INTRAHEPATIC CHOLANGIOCARCINOMA IS INCREASING IN TAIWAN

Yu-Min Lin1,2, Lee-Won Chong1,2, Hung-Chuen Chang1,2, Yu-Hwa Liu1,2, Cheuk-Kay Sun1,2, Kou-Ching Yang1,2

1Division of Gastroenterology and Hepatology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan

2Division School of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan

7.39% to 10.38% with the years of diagnosis (p for trend<0.01). The proportions of advanced stages (stage III and IV) of HCC and ICC were 36.35% and 58.54% respectively (p < 0.01, chi-squared test).

Conclusions: Our reports provide several essential aspects. The incidence pattern for HCC is declining but remains unchanged for ICC. The relative proportion of ICC among primary liver tumors is increasing over the years. Early diagnosis of ICC remains difficult to achieve. Clinicians should be aware of these emerging challenges to make proper decisions in facing hepatic neoplasms.

Background: Hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (ICC) are the two major types of primary liver cancers. Recent studies suggest the incidence of primary liver cancer is declining in Taiwan; however, the epidemiological characteristics of ICC remain not clear.

Aims: This study investigated the epidemiological features to understand the disease burden of ICC in Taiwan.

Methods: We acquired data of new registered cases of primary liver cancer (including HCC and ICC) from the Taiwan Cancer Annual Reports. We evaluated key epidemiological features including age, gender, incidence, average annual percentage changes (AAPC), stage distribution and their relative proportions of primary liver cancers for the period of 2010–2019. A linear regression analysis was applied to determine the trend of disease burden. A p-value <0.05 was considered as significant.

Results: The median age at ICC diagnosis was 66 years. The male to female ratio was 56%: 44%. A stationary pattern for the ICC incidence with the years of diagnosis was observed. The AAPC was 0.25 (p for trend = 0.63). The proportion ratio of ICC among primary liver cancer increased from

THE POTENTIAL ONCOGENE CAST OF PANCREATIC ADENOCARCINOMA USING SINGLE-CELL OMICS ANALYSES

Kuang-Tsu Yang1,2,3,4, Wei-Chih Sun5,6, Kuan-Yang Chen7,8, Chih-Lin Lin7, Ping-I Hsu6,9, Huey-Kang Sytwu10, Tsung-Hui Hu11, Tsai-Kun Li12,13,14, Yen-Hsiu Yeh12, Tian-Huei Chu4, Chia-Chi Yen15, Chun-Yu Lin16, Ming-Yi Li17, Ming-Hong Tai4

1Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Municipal Min-Sheng Hospital, Kaohsiung, Taiwan; 2Department of Medicine, National Taiwan University, Taipei, Taiwan; 3Division of Family Medicine, Department of Community Medicine, Kaohsiung Municipal Min-Sheng Hospital, Kaohsiung, Taiwan; 4Institute of Biomedical Science, National Sun Yat-Sen University, Kaohsiung, Taiwan; 5Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan; 6School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan; 7Department of Gastroenterology and Hepatology, Ren-Ai Branch, Taipei City Hospital, Taipei, Taiwan; 8Yang-Ming Branch, Taipei City Hospital, Taipei, Taiwan; 9Division of Gastroenterology, Department of Internal Medicine, An Nan Hospital, China Medical University, Tainan, Taiwan; 10Taiwan National Health Research Institutes; 11Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan; 12Department and Graduate Institute of Microbiology, College of Medicine, National Taiwan University, Taipei, Taiwan; 13Centers for Genomic and Precision Medicine, National Taiwan University, Taipei, Taiwan; 14Center for Biotechnology, National Taiwan University, Taipei, Taiwan; 15Department of Orthopaedics, Kaohsiung Municipal Min-Sheng Hospital, Kaohsiung, Taiwan; 16Division of Infectious Disease, Department of Internal Medicine,

Kaohsiung Municipal Min-Sheng Hospital, Kaohsiung, Taiwan; 17Division of Cardiology, Department of Internal Medicine, Kaohsiung Municipal Min-Sheng Hospital, Kaohsiung, Taiwan 使用單細胞組學分析胰腺癌潛在致癌

基因卡斯特

楊光祖1,2,3,4 孫煒智5,6 陳冠仰7,8 林志陵7 許秉毅6,9

司徒惠康10 胡琮輝11 李財坤12,13,14 葉彥秀12

儲天輝4 顏家祺15 林俊祐16 李明義17 戴明泓4

1 高雄市立民生醫院內科部肝膽腸胃科；2 國立臺 灣大學醫學系；3 高雄市立民生醫院社區醫療部家

庭醫學科；4 國立中山大學生物醫學研究所；5 高 雄榮民總醫院內科部胃腸肝膽科；6 國立陽明交通 大學醫學系；7 臺北市立聯合醫院仁愛院區內科部 肝膽腸胃科；8 臺北市立聯合醫院陽明院區；9 台 南市立安南醫院內科部胃腸肝膽科；10 台灣國家 衛生研究院；11 高雄長庚紀念醫院胃腸肝膽科系； 12 國立臺灣大學醫學院微生物學科暨研究所；13 國立臺灣大學基因體暨精準醫學研究中心；14 國 立臺灣大學生物科技研究所；15 高雄市立立民生 醫院骨科部；16 高雄市立民生醫院內科部感染科； 17 高雄市立民生醫院內科部心臟血管內科

Background: From our previous research, we found CAST was a newly-found potential oncogene of gastrointestinal (GI) cancer and hepatocellular carcinoma (HCC). However, the relationship between single-cell omics of CAST and pancreatic adenocarcinoma (PAAD) is still unaddressed.

Aims: We used biomedical informatics to further analyze the potential oncogene of CAST role in PAAD.

Methods: STRING, HPA, and GEPIA2 were used to show the protein expression and RNA-seq of CAST. We then retrieved data from DISCO and HPA for single cell analyses and relative gene and immune cells search.

Results: Discrepancy of protein expression and RNA expression exists. CAST relevant gene such as CAPN1/CAPNS1/CAPN2/PXN/PTK2/ TLN1/CDK5R1/CAPN8/CAPNS2/ACTA1 were networked. The RNA single cell type specificity were revealed detailedly, with the top three cell is early spermatids/cardiomyocytes/urothelial cells. In pancreas single cell analyses, mixed cell types c-12, pancreatic endocrine cells c-1, and ductal cells c-2 are predominant. The feature genes related to CAST in PAAD were exhibited as a heat

map.

Conclusions: We demonstrate that CAST was a potential oncogene of PAAD in single-cell omics biomedical informatics analyses. The discrepancy of CAST expression in protein and RNA levels should be documented and investigated precisely in further researches.

P.144 ENDOSCOPIC MANAGEMENT OF CHOLEDOCHOCELE – A SINGLE CENTER EXPERIENCE

Chi-Ying Yang, Wen-Hsin Huang, Shih-Chieh Chuang, Hsing-Hung Cheng, Chun-Kai Lin, Tsung-Lin Hsieh

Division of Hepatogastroenterology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan

膽總管囊腫的內鏡治療 單一醫學中 心經驗

黃文信 莊世杰 鄭幸弘 林群凱 謝宗霖

Background: Choledochal cyst is congenital anomalies with dilatations of the extra-and/or intrahepatic biliary tree. Alonos-Lej reported the classification of choledochal cyst in 1959 and the most commonly used is adapted by Todani in 1977. Type III choledochal cyst, also known as choledochocele, is a dilatation of distal common bile duct within ampulla of Vater and is typically protruded into the duodenum. It was rare than other types, accounting for 0.5%-4% of cases. The choledochocele is subdivided into type A and type B by Sarris and Tsang in 1989. Type A choledochocele is cystic dilatation of bile duct in ampulla and is located proximal to orifice of ampulla. Type B choledochocele is located distal to orifice of ampulla and is diverticula of common channel in ampulla. In a meta-analysis study, 10.7 per cent of patients with choledochal cyst developed malignancy. The reflux of pancreatic enzyme and bile stasis promote the proliferation of epithelium of bile duct and increased the risk of malignancy. The periampullary carcinoma has been reported in patients with choledochocele. Cyst excision is the standard treatment of choledochal cyst due to the risk of biliary malignancy. For choledochocele, endoscopic management (including endoscopic sphincterotomy, endoscopic snare resection with or without balloon-catheter-assisted) and surgical resection have been reported. Although endoscopic cyst resection has been proposed, not all cyst edges can be identified, and there is still a risk of rupture during endoscopic resection. Aims: To evaluate clinical feature, endoscopic findings of choledochocele and the safety of endoscopic sphincterotomy.

中國醫藥大學附設醫院內科部消化系

Methods: A retrospective review of all patients received retrograde cholangiopancreatography (ERCP) was performed in China Medical University Hospital from January 2015 to June 2022. The diagnosis of choledochocele was made when cystic protruding ampulla of Vater by endoscopic finding and abdominal computer tomography or magnetic resonance imaging showed cystic lesion at distal CBD within ampulla of Vater. The clinical symptoms, laboratory data and cystic size of choledochocele were collected. The ERCP was performed under sedation status, in the supine position, with a duodenoscope TJF-260V (Olympus Japan Corp.).

Results: Five patients (1 female, 4 males) were diagnosed as choledochocele and the mean age at diagnosis was 58.4 years (range, 41-68 years). The five patients were all choledochocele type A. The most common clinical symptom was abdominal pain (5/5, 100%) and laboratory studies showed that four patients (4/5, 80%) had abnormal serum liver chemistry result, which aspartate aminotransferase (AST) was 45-440 U/L and alanine aminotransferase (ALT) was 55-335 U/L. Two patients had CBD stones with cholangitis at diagnosis and three patients had a history of gall stones. The mean size of choledochocele was 22 mm (range 12 -47 mm) and the mean diameter of CBD was 7.8 mm (range 6-11 mm). Endoscopic finding revealed choledochocele has the features of bulging and sunken major duodenal papilla. There was no comorbid biliary or periampullary malignancy in our series. For endoscopic management, four patients underwent endoscopic sphincterotomy, and one patient underwent endoscopic papillary balloon dilatation because of antiplatelet agent. No ERCP-related complications were observed.

Conclusions: Choledochocele can be diagnosed and management by endoscopy. The features of duodenal papilla bulging and sunken can be helpful for diagnosis during examination. Although endoscopic sphincterotomy is not cyst excision, it is a safe and effective drainage to symptom improvement. Whether it will be malignant change still need longer follow-up.

P.145

Yi-Tse Su1,2, Yung-Kuan Tsou1,2, Cheng-Hui Lin1,2, Kai-Feng Sung1,2, Nai-Jen Liu1,2, Mu-Hsien Lee1,2, Chi-Huan Wu1,2, Sheng-Fu Wang1,2

1Department of Gastroenterology and Hepatology, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan

2Department of Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan 膽總管結石與惡性膽道梗阻的引起的

Background: Acute cholangitis (AC) is usually caused by choledocholithiasis, followed by malignant biliary obstruction (MBO). It is unclear whether the clinical outcome of AC varies with different etiologies.

Aims: The aim of this study was to compare the clinical outcomes of AC caused by choledocholithiasis and MBO.

Methods: The diagnostic criteria for AC were based on the 2018 Tokyo Guidelines. Patients who underwent ERCP at our center between 2016 and 2017 were retrospectively collected from the computerized database of the Therapeutic Endoscopy Center. A total of 683 cm of patients meeting the definite diagnostic criteria of AC were identified. The exclusion criteria were: (1) the indication for ERCP was not choledocholithiasis or MBO (including previous indwelling stent dysfunction, n = 105); (2) The major papilla was not native (previous endoscopic sphincterotomy or endoscopic papillary balloon dilatation, n = 50). Medical records were reviewed. The primary outcome was 30-day mortality. Secondary outcomes were ICU admission rate, length of hospital stay (LOHS), and 30-day readmission rate.

Results: A total of 528 patients were included in

THE DIFFERENCES BETWEEN ACUTE CHOLANGITIS CAUSED BY CHOLEDOCHOLITHIASIS AND MALIGNANT BILIARY OBSTRUCTION

急性膽管炎的區別

the study; 63 in the MBO group and 465 in the choledocholithiasis group. Patient age and gender did not differ between groups. Body temperature (median, 37°C vs. 37.4°C, p = 0.002), percentage of abnormal white blood cell count (41.3% vs. 61.3%, p = 0.002), and serum creatine level (median, 0.87 mg/dL vs. 0.96 mg/dL, p = 0.019) were significantly lower in the MBO group. Platelet count (median, 218/µL vs. 196.5/µL, p = 0.034), serum total bilirubin level (median, 7.5 mg/dL vs. 3.7 mg/dL, p < 0.001), and prothrombin time (INR, 1.2 vs. 1.1, p = 0.013) were significantly higher in the MBO group. There were no differences in any organ dysfunction between groups in terms of cardiovascular, neurological, respiratory, renal, hepatic, or hematological dysfunction. The median time to ERCP was longer in MBO group (89.9 h vs. 47.4 h, p < 0.001). The proportion of time to ERCP for MBO and choledocholithiasis (<24 hours, 11.1% vs. 21.3%; 24-48 hours, 17.5% vs. 29.7%; >48 hours, 71.4% vs. 49%) was significantly different between groups (p = 0.004). The percentage of severe AC was significantly higher in the MBO group (grade III AC, 34.9% vs 22.2%, p = 0.025). The 30-day mortality rate was significantly higher in the MBO group (4.8% vs. 0.6%, p = 0.025). ICU admission rates (12.7% vs. 4.7%, p = 0.018) and 30-day readmission rates (20.6% vs. 8%, p = 0.001) were significantly higher, while LOHS was significantly longer (median, 15 days vs. 7 days, p < 0.001) in the MBO group.

Conclusions: Compared with choledocholithiasis, patients with MBO-related AC tended to be more severe and had higher 30-day mortality, but were treated with ERCP later. This might be because the clinical manifestations of systemic inflammatory responses were less pronounced in MBO patients. Therefore, clinicians should be vigilant in MBO patients with clinical suspicion of AC, and perform ERCP for biliary drainage as soon as possible.

P.146

BROKEN HANDLE CORD OF IMPACTED RETRIEVAL BASKET RESCUED BY CHOLANGIOSCOPY WITH ELECTROHYDRAULIC/LASER LITHOTRIPSY: EXPERIENCE OF A SINGLE MEDICAL CENTER AND REVIEW OF LITERATURE

Hsing-Hung Cheng, Wen-Hsin Huang, Chi-Ying Yang, Shih-Chieh Chuang, Chun-Kai Lin, Cheng-Yuan Peng

Center for Digestive Medicine, Department of Internal Medicine, China Medical University Hospital, China Medical University, Taichung, Taiwan

/ 雷 射碎石術救援：一醫學中心經驗及文 獻回顧

鄭幸弘 黃文信 楊其穎 莊世杰 林群凱 彭成元 中國醫藥大學附設醫院消化醫學中心

Background: Endoscopic retrograde cholangiopancreatography (ERCP) is the important procedure for the treatment of bile duct stones or pancreatic duct stones with high successful rate with retrieval baskets or extraction balloons. Impaction of retrieval basket occurs sometimes which could solve by mechanical lithotripsy or Soehendra lithotriptor (Cook Medical). However, on rare occasions, broken handle cord of impacted retrieval basket could occur. Such situation may need surgical intervention. Cholangioscopy (SpyGlass, Boston Scientific) with electrohydraulic/ laser lithotripsy provides a rescue treatment.

Aims: The aims of the study is to access the clinical characteristics of theses cases.

Methods: A retrospective analysis was performed between 2015 and 2022 at our hospital. We also performed a systematic literature search of PubMed, Cochrane library and Google Scholar database. Three articles describing three cases were enrolled. We reviewed the clinical condition of these patients.

Results: Six patients (3 women, 3 men, age range 35-79) underwent ERCP for CBD/MPD stones. The median size of the stones was 1.6 cm (range from 0.8 cm to 1.8 cm). Five of six patient suffered from

內視鏡逆行性膽胰管取石術併發取石 籃網斷裂後經膽管鏡親水性碎石術

CBD stone with obstructive jaundice. One of the six patient had chronic pancreatitis with distal MPD stone. All patients had relatively small size of the distal CBD/MPD compared to stone size. Five of the six patient had broken handle cord of impacted retrieval basket after using mechanical lithotripter with Soehendra lithotriptor (Cook Medical). One had broken handle cord after using mechanical lithotripter with BML lithotriptor (Olympus). One of the six patient ever been tried extracorporeal shock wave lithotripsy (ESWL) before cholangioscopy with electrohydraulic lithotripsy. There was no major post-electrohydraulic/laser lithotripsy complications in these six patients.

Conclusions: Broken handle cord of impacted retrieval basket after mechanical lithotripsy is a very rare complication during stone retraction. The situation needed surgical intervention in past decades. Now with cholangioscopy, the impacted basket-stone complex could be targeted for electrohydraulic or laser lithotripsy under direct visualization. The impacted basket and stones were then could be successfully pulled out. In such situation, broken handle cord of impacted retrieval basket occurred, cholangioscopy provided a rescue method and prevented from surgical intervention.

P.147 SEROUS CYSTIC NEOPLASMS OF PANCREAS – A DIAGNOSTIC APPROACH AND VARIABLE MANAGEMENT OPTIONS: THREE CASE REPORTS & REVIEW OF LITERATURE

Cho-Hsun Lee, Jen-Lung Chen, Yao-Sen Chen

Department of General Surgery, E-Da Hospital, Kaohsiung, Taiwan

Background: Serous cystic neoplasm (SCN) of pancreas occurs in 12-16% of pancreatic cystic neoplasms. Radiographic and clinical evidence are justifiable in the diagnosis of SCN and malignant features must be excluded. This subset of pancreatic cystic neoplasm is generally considered to be benign with rare malignant cases, and detailed discussion with patient is pertinent in clinical decision-making. This case series presents three cases of serous cystic neoplasms that had similarities in achieving their diagnosis yet differences in their management.

Aims: This case series presents three cases of serous cystic neoplasms that had similarities in achieving their diagnosis yet differences in their management.

Methods: Three adult female patients, within age 60-70 year-old, in E-Da Hospital incidentally found to have serous cystic neoplasm of pancreas based on their classic imaging characteristics. Three were all females between the age 60-70 and presented with epigastric discomfort. Tumor markers including CEA and CA-199 were all within normal limits.

Results: One patient had intermittent epigastric discomfort and incidentally discovered 7-cm cystic tumor at pancreatic head. Her tumor exhibited honey-comb like with equivocal calcifications, and the patient decided to receive regular follow up. The second patient had epigastric pain and a bout of pancreatitis before incidentally discovering serous cystic neoplasm in pancreatic head, and she was managed with repeated ERCPs and stents. Her biopsy yielded only acute and chronic inflammation. The third patient had mild epigastric discomfort and incidentally discovered 5cm tumor at pancreatic head with clear margin abutting to portal vein. The patient decided to receive pancreaticoduodenectomy due to possible

malignant risk. Of the 3 cases, only the third patient had pathologic diagnosis of microcystic serous cystadenoma. Nonoperative management and close follow up were sufficient for the first 2 patients.

Conclusion: Diagnosis of pancreatic SCN is achieved based on radiographic characteristics clinical exclusion, and demographics, however clinicians must keep in mind the malignant features that would require more aggressive management. Regular follow up may be feasible for asymptomatic patients while ERCP with stents or operation are necessary for certain cases of symptomatic patients.

P.148

THE UTILITY OF DIGITAL CHOLANGIOSCOPY (SPYGLASS DS) IN DIAGNOSIS OF BILIARY DISEASES: SINGLE TERTIARY CARE CENTER EXPERIENCE IN TAIWAN

Chia-Chang Chen1,2, Chun-Fang Tung1, Yen-Chun Peng1,3,4, Yi-Jun Liao1,2, Hsin-Ju Tsai1,2, Sz-Iuan Shiu1, Sheng-Shun Yang1,3

1Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taichung

Veterans General Hospital, Taichung, Taiwan

2Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, Taiwan

3School of Medicine, National Yang Ming

Chiao Tung University, Taipei, Taiwan

4Department of Internal Medicine, Taichung

Veterans General Hospital Chiayi Branch, Chiayi, Taiwan

使用史拜葛雷斯（ SPYGLASS DS ）

Background: Single-operator cholangioscopy system SpyGlass has gained popularity for many diagnostically and therapeutically challenging biliary and pancreatic conditions. The upgrade version of Spyglass DS (SDS) was launched in 2015. There were still few reports about the diagnostic ability of this new system in Taiwan.

Aims: We want to evaluate the diagnosis performance of SDS for indeterminate biliary strictures and filling defects in this hospital-based cohort.

Methods: This was a retrospective single-center study conducted at Taichung Veterans General Hospital. Patients who underwent SDS from November 2017 to June 2022 were identified from an electronic database and reviewed

retrospectively. Patients were included if they received SDS for indeterminate biliary strictures or filling defects. Patients were excluded if they did not receive definite surgery with a short followup time. (Less than 3 months) Their demographic data, lesion location and characteristics, SDS result and final diagnoses were reviewed. For the patients with a final diagnosis of benign disease, the mean follow-up time is 21 months.

Results: There were 30 cases (22 males and 8 females) included in the final analysis. Indications were indetermined biliary stricture (n=24) and intraductal filling lesions(n=6). The locations of lesions were distal common bile duct (n= 11), middle common bile duct to common hepatic duct (n=12) and above hilar (n=7). Visual diagnosis was made in all patients (100%), while SpyBitebiopsy were done 21 patients (70%). The final diagnosis could be stratified into benign (n=13) or malignant (n=17). Surgery was performed in 43.4% of the patients (n=13). The method for final diagnosis was either pathology (either by surgery or endoscopy, n=18) or clinical follow-up (n=12). The sensitivity, specificity and accuracy for SpyGlass DS visual diagnosis is 94.1%, 84.6% and 93.3% respectively. The sensitivity, specificity and accuracy for SpyBite histology is 58.3%, 100% and 76.2% respectively.

Conclusions: Spyglass DS effectively diagnoses indetermined biliary stricture and intraductal filling defects. The diagnosis ability of SpyBite is only moderate and needs to be improved.

GEMCITABINE PLUS NANOALBUMIN BOUND PACLITAXEL OR MODIFIED FOLFIRINOX AS SECOND-LINE CHEMOTHERAPY IN PANCREATIC CANCER PATIENTS

Hung-Yuan Yu1,2, Chun-Yang Lee1,2, Le-Gin Lin2,3, Yee Chao2,4, Chung-Pin Li1,2,5

1Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan

2School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan

3Department of Nursing, Taipei Veterans General Hospital, Taipei, Taiwan

4Division of Medical Oncology, Department of Oncology, Taipei Veterans General Hospital, Taipei, Taiwan

5Division of Clinical Skills Training, Department of Medical Education, Taipei Veterans General Hospital, Taipei, Taiwan

Nanoliposomal Irinotecan 作為胰

Gemcitabine Plus NanoAlbumin Bound Paclitaxel

Modified

Background: Nanoliposomal irinotecan (nalIRI), accompanied by 5-fluorouracil (5-FU) and leucovorin (LV), is an effective and safe therapy for patients with metastatic pancreatic cancer as second line therapy after gemcitabine-based chemotherapy failure. However, there was no enough data support the use of nanoliposomal irinotecan as an advanced line therapy after nano-albumin bound paclitaxel (nab-paclitaxel) or modified FOLFIRINOX (mFOLFIRINOX) failure.

P.149 NANOLIPOSOMAL IRINOTECAN IS AN EFFECTIVE THERAPY FOLLOWING WHETHER

Aims: To investigate the outcomes of patients with nal-IRI + 5-FU/LV regimen after disease progression with first-line chemotherapy, whether nano-albumin bound paclitaxel plus gemcitabine or mFOLFIRINOX therapy.

Methods: We retrospectively collected the baseline characteristics, treatment courses and dosage, treatment response, and progressionfree survival of patients treated with the nal-IRIbased regimen in several hospitals in Taiwan. The relationships among baseline characteristics, firstline chemotherapy regimen and outcomes were investigated.

Results: In this study, 99 patients received nabpaclitaxel and 45 patients received modified FOLFIRINOX before the nal-IRI + 5-FU/LV regimen. The median age was 62.2 years and 61.1 years, respectively; the percentage of male sex were 58.6% and 62.2%, respectively. In patients who had received nab-paclitaxel regimen and in patients who had received modified FOLFIRINOX before nal-IRI + 5FU/LV, the objective response rates of nal-IRI + 5-FU/LV were 11.7% and 5.1% and the disease control rates of nal-IRI + 5-FU/ LV were 42.9% and 41.0%. The progression-free survival of nal-IRI + 5FU/LV were 2.1 months (95% confidence interval (CI): 1.7 – 2.5 months) in patients who had received nab-paclitaxel and 2.0 months (95% confidence interval (CI): 1.2 – 2.8 months) in patients who had received mFOLFIRINOX. There was no statistically difference between the PFS (p = 0.98).

Conclusions: Nal-IRI + 5-FU/LV is an effective regimen after treatment failure with whether nab-paclitaxel or mFOLFIRINOX in patients with metastatic pancreatic cancer.