2021 TDDW Abstract Book

2021 Taiwan Digestive Disease Week, TDDW Abstract Book INDEX Chairman’s Lecture ...................................................................... 1 Special Lecture (I) (II)

Colon Cancer: The Roles of Gut Microbiota .........................................................2 Surveillance Endoscopy for Patients with Low-risk Precancerous Conditions after H. pylori Eradication......................................................................................3 (III) Emerging Trends of Inflammatory Bowel Disease in Asia ....................................4 (IV) From Innovation to Clinical Practice: Co-creation Model and Case Study ...........5 (V) Update Surgical Strategy toward Pancreatic Cancer in Japan .............................6 (VI) Clinical Application of High Resolution Esophageal Manometry: What is New in Chicago 4.0 ...........................................................................................................7 (VIII) The Role of Olaparib in Management of Patients with Germline BRCA-mutated Metastatic Pancreatic Cancer ...............................................................................8

Prof. Teh-Hong Wang Memorial Lecture .................................... 9 GEST-KASID Symposium .......................................................... 11 Prof. Juei-Low Sung’s Research Foundation 34th Annual Academic Meeting ............................................................. 17 Symposium (I) (II)

Third Space Endoscopy – 2021 Update .............................................................21 How to Expand and Optimize Surgical Criteria of Locally Advanced Pancreatic Cancer ..............................................................................................26 (III) Transforming Science to Standard Practice in Gastroenterology .......................31 (IV) NASH Symposium ..............................................................................................34 (V) Updates in the Treatment of Functional GI Disorder...........................................39 (VI) First Line Combination Therapy or Sequential Therapy for HCC .......................44 (VII) TAIWAN CAN HELP – Combat against Digestive Diseases on a National Scale .....................................................................................................48 (VIII) Interventional Oncology in Digestive Medicine ...................................................54 (IX) New Diagnostic Modalities in Digestive Diseases ..............................................59

(X) (XI) (XII) (XIII)

Strategies to Improve Outcome for Gastric Cancer in Taiwan ............................63 Artificial Intelligence in Colonoscopy...................................................................67 Organ-Gut Axis: Innovation to Practice ...............................................................71 Thinking the “New Normal” of Gastroenterology Practice after COVID Pandemic ............................................................................................................76 (XIV) HBV/HCC Symposiums ......................................................................................81 (XV) Interventional Oncology in HCC..........................................................................85 (XVI) Small Bowel Lymphoma .....................................................................................88

Young Investigator Award (YIA) ................................................ 92 Free Paper (I) (II) (III) (IV) (V) (VI)

HCV ..................................................................................................................100 LGI ....................................................................................................................106 HBV................................................................................................................... 111 Pancreas / Biliary ..............................................................................................117 Cirrhosis & HCC................................................................................................121 UGI....................................................................................................................127

Poster Liver ............................................................................................................................133 GI ................................................................................................................................190

2021 TDDW

Chairman’s Lecture AN INTERESTING VENTURE ON INNOVATIONS IN GASTROENTEROLOGY Xi-Zhang Lin Division of Gastroenterology, Department of Internal Medicine, National Cheng Kung University Hospital, Tainan, Taiwan College of Medicine, National Cheng Kung University, Tainan, Taiwan We are a small country but play an important role in the global science and technology. Thanks to the heritage from our society, we have a culture of smart production. Therefore, during our professional career, it is likely that we can create something new and something useful to our patients, which I would like to share with you.

Hepatoma is a terrible disease. Thanks to HBV vaccine and magic drugs of HCV, the incidence is decreasing. However, many patients still present to hospitals beyond curable treatment. Transcatheter arterial chemoembolization (TACE) is conducted as palliative measure for some of them. During recent decades, the embolization technique improved a lot but the cost of the used material and device also become very expensive, notably drug-eluting beads and the iodized oil.

As a physician in a university hospital, we take the advantages of multidisciplinary collaborations to manufacture a radiopaque and drug-eluting microsphere for hepatoma embolization. The product is unique for its radiopaque and biodegradable in human body. We have conducted clinical trials in 42 patients. Pivotal test is going to be conducted.

Iodized oil (Lipiodol) is a conventional material for transcatheter arterial embolization. The oil comes from poppy seeds oil, of which is scarce. Its supply is not stable in many countries besides the souring price. I initiated to produce a new iodized fatty acids ethyl esters (same with Lipiodol, but different in each proportions) when I took sabbatical at Food Industry Research and Development Institute (FIRDI). The

starting raw material (sunflower oil) is common but refined technology is advanced. Under the help from Industrial Technology and Research Institute (ITRI), the new iodized oil is permitted to conduct phase I/ II clinical trials from US FDA and TFDA. Endoscopic mucosal resection and submucosal dissection are two new therapies. The major concern of these technology is safety. To improve the safety, we designed an alginate-based hydrogel to get excellent mucosal lifting. We went through IRB and clinical trial process to recruit 12 patients to conduct ESD. Moreover, our thermosensitive hydrogels will serve drug delivery for other treatment goals.

GI bleeding is a major challenge for gastroenterologists. The widely accepted endoscopic therapeutic methods are local injection, clipping and electric coagulations. For large area bleeding or difficult to approach bleeders, there is an emerging therapy — hemostasis by powder spray. We used redesigned formula for hemostasis powder and delivery system. The new system becomes more effective and easy to manipulate. The clinical trials are under processing; we try to add an effective tool to stop difficult bleedings.

Innovations come from new combination of known facts, experience and professional knowledge. It begins with the empathy for patients’ suffering and remain resilient to keep improving outcomes of our practice. If our professional career is focus on the cure or palliation of patients’ suffering, it is really an interesting innovational venture.

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2021 TDDW

Special Lecture (I) COLON CANCER: THE ROLES OF GUT MICROBIOTA Jun Yu Department of Medicine & Therapeutics, The Chinese University of Hong Kong, Hong Kong, China Cancer is a major disease burden globally.

The gut microbiome and its role in carcinogenesis is a rapidly evolving research field. Mounting evidence has suggested that the gut microbiota is implicated in a variety of cancers especially in the colorectal cancer (CRC). In this connection, detailed and holistic investigations into the gut metagenome in translational research in CRC pathogenesis, diagnosis and response to therapies are imperative. This lecture aims to provide the latest overview and discoveries of the

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gut microbiota in colorectal neoplasia, including relevant mechanisms in microbiota (pathogen or probiotics)-related carcinogenesis, the potential of utilizing the microbiota as CRC biomarkers, the prospect for modulating the microbiota for CRC prevention or treatment, and the effect of gut microbiome on the therapeutic efficacy of drug through causing drug degradation. These scientific findings will pave the way to clinically translate the use of gut microbiota for CRC in the near future.

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Special Lecture (II) SURVEILLANCE ENDOSCOPY FOR PATIENTS WITH LOW-RISK PRECANCEROUS CONDITIONS AFTER H. PYLORI ERADICATION Takuji Gotoda Division of Gastroenterology and Hepatology, Department of Medicine, Nihon University School of Medicine, Tokyo, Japan I have been in trouble because TDDW gave me a lecture title with no correct answer. In my personal opinion, I don’t think there is a need for surveillance endoscopy for patients with low-risk precancerous conditions after H. pylori eradication.

However, this policy should be decided based on the understanding of the government financial situation and the citizen of each country.

Helicobacter pylori (H. pylori) was declared a human carcinogen in 1994. It is well known that the evidence has now accumulated to show that at least 95% of gastric cancers are etiologically related to H. pylori. A meta-analysis published in 1999 reported that the risk of gastric cancer with H. pylori infection had an odds ratio of 2.04 (95% confidence interval [CI], 1.65–2.45). Similarly, a 2007 study in nine European countries reported that the risk of gastric cancer with H. pylori infection had an odds ratio of 2.6 (95% CI, 1.7–3.9).

Gastric cancer is the second most common cause of death from cancer worldwide, and especially in Eastern Asia countries such as China, Japan and Korea. Thus, the need for efficient, costeffective and practical nationwide mass screening systems for gastric cancer in Eastern Asia remains controversial. In Japan, however, there has been a progressive increase H. pylori naïve and H. pylori eradicated subjects, consequently, the number of gastric cancer deaths has begun to decline in recent years. In near future, selective screening or target screening should be considered even in countries with frequent gastric cancer.

H. pylori is a common chronic infection that has been confirmed to be significantly associated with gastric cancer. In other words, the gastric mucosa with severe atrophy and/or intestinal metaplasia

is at high risk for gastric cancer. Therefore, the high-risk population is basically an elderly person, in addition, male, smoking, high-salt diet and family history have been reported as risk factors.

Conversely, even those infected with H. pylori are at low risk for those who received H. pylori eradication therapy at a young age. When it comes to the need for surveillance endoscopy for such subjects, the answer is “no”. However, unfortunately, it is not clear what time the “point of no-return” is. Therefore, once again, each country must consider when and not a surveillance endoscope for the low-risk group is necessary for their respective circumstances.

Finally, the definitions of surveillance and screening are given. I hope it will be helpful to everyone. “Surveillance” systematically collects, analyzes, and interprets the data necessary for planning, implementing, and evaluating disease control by continuously monitoring the outbreak status and transition of diseases, and promptly obtains the results. Moreover, it is regularly returned and is used for the purpose of disease prevention and management. “Screening” is conducted as a public health activity for the population. The benefit is defined as the mortality reduction effect.

Screening by risk stratification may be cost-effective.

However, it is difficult to control the examinee, and it is uncertain whether an appropriate intervention will be made. For example, the HPV test, which is a carcinogenic risk of cervical cancer, is being introduced, but it has been reported that the accuracy control is difficult and the consultation rate is low. Verification of whether or not it will proceed as planned (surveillance) and appropriate measures to proceed is required.

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Special Lecture (III) EMERGING TRENDS OF INFLAMMATORY BOWEL DISEASE IN ASIA Min-Hu Chen President, Chinese Society of Gastroenterology Division of Gastroenterology and Hepatology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China Inflammatory bowel disease (IBD) was not common in Asia a couple decades ago. The incidence of IBD is increasing rapidly in recent years. A population-based epidemiologic study in Asia showed that the incidence of IBD varied from 0.60 to 3.44 per 100 000. From 2013 to 2018, the hospitalization rates for Crohn’s disease (CD) and ulcerative colitis (UC) in China increased from 2.20 (95% CI: 2.17–2.22) to 3.62 (3.59– 3.65) per 100,000 inhabitants (P<0.0001) with an annual percentage of change (APC) of 10.68 (6.00–15.36)% and from 6.24 (6.20–6.28) to 8.29 (8.23–8.33) per 100,000 inhabitants (P<0.0001) with an APC of 5.73 (2.32–9.15)%, respectively.

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UC is more prevalent than CD, but CD incidence is rapidly increasing. Stricture and penetrating CD are common in Asia. These epidemiologic changes may relate to increased contact with the westernization of diet, improved hygiene, increasing antibiotics use, or changes in the gut microbiota. Results from a population-based case control study showed breast-feeding, having pets, sharing bed in the childhood were protective of IBD, suggesting that environment plays an important role in etiology. Research in Asia, an area of rapidly changing IBD epidemiology, may lead to the discovery of critical etiologic factors that lead to the development of IBD.

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Special Lecture (IV) FROM INNOVATION TO CLINICAL PRACTICE: CO-CREATION MODEL AND CASE STUDY Chii-Wann Lin Biomedical Technology and Device Research Laboratories (BDL), Industrial Technology Research Institute (ITRI), Hsinchu, Taiwan Taiwan has been well recognized for the excellence in healthcare services and biomedical innovations. The practice of “co-creation” model in healthcare can further enhance innovation and outcome value with inputs from various stakeholders. To realize the ideation of unmet needs with Invent, refine, and test cycle of medical products (e.g. device and drug) design and development, ITRI has adopted “open innovation system platform” (OISP) to response to the emerging needs of technical integration. We will highlight co-creation projects and share with you about our learned experiences in the implementation processes of iPMx molecular diagnostic system for

SARS-Cov-2, Open Ventilator project, fiber optical coherent tomography system (f-OCT), and ImageGuided Radiofrequency Ablation (iRFA). These efforts align with the technology roadmap of ITRI’s 2030 and BTC 2020 data driven precision health goal for both smart med-tech and health-tech with the integration of ICT enabling technologies. With the support from MOEA DOIT, ITRI has worked with academic/industrial partners to establish a “Taiwan Integrated Biomedical Industrial Center (TIBIC)” to facilitate effective translational research of medical/healthcare products with co-creation mindset for the development of ecosystem.

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2021 TDDW

Special Lecture (V) UPDATE SURGICAL STRATEGY TOWARD PANCREATIC CANCER IN JAPAN Akio Saiura Department of Hepatobiliary-Pancreatic Surgery, Juntendo University Graduate School of Medicine, Tokyo, Japan Pancreatic ductal adenocarcinoma (PDAC) is still one of the most devastating disease, with a 5-year survival rate of less than 10%. Surgical resection is the only treatment for potential cure, however, more than 80% of patients with PDAC are deemed unresectable at the time of diagnosis.

PDAC starts to metastasize systemically from an early stage, and can be assumed to be a systemic disease. For patients with resectable PDAC, a strategy of upfront surgery and adjuvant chemotherapy is the standard approach, with a 5-year survival rate after resection of 10-20%.

Neoadjuvant therapy (NAT) including neoadjuvant chemotherapy (NAC) or neoadjuvant chemoradiotherapy (NAC-RT) is widely used for resectable (R-PDAC) and borderline resectable PDAC (BR-PDAC). For unresectable PDAC (URPDAC), improvement of prognosis was reported with the advent of gemcitabine (GEM), and a

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higher response rate and improvement of overall survival were shown by administration of strong anticancer agents, such as gemcitabine plus nab-paclitaxel (GnP) and FOLFIRINOX. In the last decade, downstaging surgery or conversion surgery (CS) in patients with initially UR-PDAC who responded to systemic chemotherapy is increasingly reported. To date, there are no robust data which indicate the clear benefit of CS and no consensus of the indication and optimal timing of CS for UR-PDAC. Due to the development of systemic chemotherapy, systemic chemotherapy is given to patients who cannot be resected or are difficult to resect, and resection is performed after obtaining a certain response. Conversion surgery for UR-PDAC is being increasingly reported after the introduction of more effective systemic chemotherapy regimens.

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Special Lecture (VI) CLINICAL APPLICATION OF HIGH RESOLUTION ESOPHAGEAL MANOMETRY: WHAT IS NEW IN CHICAGO 4.0 John Pandolfino President, American Neurogastroenterology and Motility Society Division of Gastroenterology and Hepatology, Northwestern University Feinberg School of Medicine, Chicago, IL, USA The goal of any diagnostic scheme is to objectively classify patients with similar symptoms into appropriate clinical categories that ultimately direct specific therapies. Classification schemes for esophageal motility disorders were developed initially using conventional manometry which displayed the data in a line tracing format. While conventional manometry set the basis for the diagnosis of esophageal motility disorders, the large axial spacing between recording sites leaves large portions of the esophagus unevaluated and vulnerable to movement artifact. On the other hand, the continuous spatiotemporal representations of pressure through the entire esophagus recorded with high resolution manometry offers greater detail and improved accuracy for many of the most important measurements of esophageal motor function. This technology has evolved into the Chicago Classification 4.0, which was

recently updated to assess the restrictive protocol and flaws around defining disease based on the integrated relaxation pressure (IRP). The addition of upright position and provocative swallows can help clarify borderline cases and the use of esophagram and FLIP can help provide a conclusive diagnosis of obstruction. Last, the criteria for ineffective esophageal motility was also revised to provide a grouping that has a higher level of clinical significance. A more recent evolution of manometric technique, FLIP Panometry will also be discussed during this lecture as it represents a new modality that leverages an assessment of secondary peristalsis to classify motility disorders.

The unique application of this approach during the initial endoscopy provides a more efficient screening assessment for disease and may also describe variants not explained by manometry.

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Special Lecture (VIII) THE ROLE OF OLAPARIB IN MANAGEMENT OF PATIENTS WITH GERMLINE BRCA-MUTATED METASTATIC PANCREATIC CANCER Talia Golan Institute of Oncology, Sheba Medical Center, Ramat Gan, Israel Pancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive solid tumors. The median overall survival (OS) in patients with stage IV disease is limited. This disease is a challenge, with patients presenting with severe debilitating symptoms at diagnosis, including weight loss, radiating abdominal pain, loss of appetite, depression and deteriorated physical activity and well-being. Furthermore, PDAC is resistant to chemotherapy, with 4-6 months of progression free survival or less with first-line combination chemotherapy therapy.

To improve the management of PDAC in an era of precision medicine, it is highly important to identify subsets of patients who can benefit from targeted treatments. In particular, BRCA 1/2 germline mutations (gBRCAm) affect up to 7% of patients with PDAC. The BRCA 1/2 proteins play a significant role in the repair of DNA double strand breaks (DSB). Tumors with homologous recombination repair (HRR) gene abnormalities such BRCA1/2 are sensitive to both platinum and poly (ADP-ribose) polymerase inhibitors (PARPi).

In the phase III POLO study (Pancreas Cancer Olaparib Ongoing), the PARPi olaparib was given as maintenance treatment following firstline platinum-based chemotherapy in gBRCAm patients with metastatic PDAC versus placebo.

Patients had to receive at least 16 weeks of firstline, platinum-based chemotherapy, without tumor progression.

154 eligible patients for the POLO trial were randomized at a 3:2 ratio to olaparib tablets, 300 mg po bid, or placebo, and continued treatment until disease progression or unacceptable toxicity.

The primary endpoint was PFS and was measured from the time of randomization, which

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was after first-line chemotherapy had been completed. Key secondary endpoints included time to second progression, objective response rate, health-related quality of life, safety and tolerability, and overall survival.

The primary endpoint (PFS) was 7.4 months in the olaparib arm, and 3.8 months in the placebo arm, with a hazard ratio of 0.53, and a p value of 0.0038. Pre-specified analyses were performed of the proportion of patients who were progressionfree at 6, 12, 18 and 24 months. From 6 months onwards, more than twice the proportion of olaparib arm patients were progression-free compared to the placebo arm, which is consistent with the hazard ratio of 0.53.

Although the secondary endpoint, OS did not demonstrate a statistically significant difference between olaparib and placebo (HR 0.83; p = 0.3487), the totality of the evidence (primary PFS and multiple key secondary endpoints) supports a clinically meaningful benefit of maintenance olaparib in patients with metastatic pancreatic cancer and a gBRCAm. At 3 years: 17.2% of patients remained on olaparib treatment vs 3.3% on placebo. 21.5% of patients in the olaparib arm remained free of subsequent cancer therapy vs 3.6% in the placebo arm (TFST: HR 0.44, nominal p < 0.0001) and 33.9% of patients receiving olaparib were alive compared with 17.8% on placebo.

These results confirm the importance of testing for BRCA and other germline mutations in all PDAC patients, which is now recommended by both ASCO and NCCN guidelines. A strategic approach with first-line platinum-based chemotherapy followed by maintenance olaparib treatment should become a new standard of care for patients with metastatic PDAC patients who have a gBRCAm.

2021 TDDW

Prof. Teh-Hong Wang Memorial Lecture CREATING NEW IDEAS BASED ON THE HISTORY – LOOKING BACK ON THE HISTORY OF JGES – Hisao Tajiri Department of Innovative Interventional Endoscopy Research, Jikei University School of Medicine, Tokyo, Japan Gastrointestinal endoscopy started with rigid gastroscope, and the early gastroscope was developed and improved mainly in Germany. This is because Germany was the most advanced country in the research and application of optics until the middle of the 20th century.

Owing to the efforts by Dr. Tatsuo Uji of the University of Tokyo, and Mr. Fukami and Mr. Sugiura of Olympus Co., a gastrocamera was introduced in 1952. In 1955, the first gastrocamera research meeting was held. According to the memoir by Dr. Uji, it was in May 1949 that he knocked on the door of Olympus Co. with an idea. It was a time when domestic industries were finally recovering from the turmoil of the post-war period, when there was bright hope for the future, and when people began to search for new paths.

Japan Gastroenterological Endoscopy Society (JGES) was established as Japan Gastrocamera Society in 1959. In 1973, the title of the society was changed to Japan Gastroenterological Endoscopy Society to focus on the gastroenterological endoscopy. The society had a membership of only 280 at the time of establishment, but it has grown to over 34,820 members in 2021.

Looking back on the research activities of JGES to date, as its academic field is based on endoscopic instruments, the presentations of research at the society have been strongly related to the development, improvement, and popularization of endoscopic instruments of the time. From 1955 to the early 1960s was the era of the gastrocamera. One of the major achievements is the establishment of the early gastric cancer

classification in 1962. In 1963, a locally-produced gastrocamera with fiberscope was introduced and widely accepted. In 1968-1972, colonoscope and duodenoscope were completed, and diagnostic studies of these organs were incorporated. The main research themes from 1980 to 1985 were the spread of pan-endoscopes, establishment of colorectal diagnostics and development of endoscopic mucosal resection (EMR). Since 1985, the electronic endoscopy and the ultrasound endoscopy have been introduced, and their widespread use has further advanced endoscopic diagnostics. After 1989, more precise diagnosis of early esophageal, gastric, and colorectal cancer, as well as early diagnosis of pancreatic cancer and endoscopic diagnosis of pancreato-biliary diseases were established. More than 20 years have passed since the development of Endoscopic Submucosal Dissection (ESD) in 1998-1999, and the technique is now widely used around the world.

In addition, image enhanced endoscopy (IEE), represented by Narrow Band Imaging (NBI), has established a new diagnostic science. In the Reiwa era (2019~), AI-aided endoscopy, endoscopybased genomic medicine, submucosal endoscopy, and endoscopic full thickness resection (EFTR) are being developed as research themes for the society.

JGES started Japan Endoscopy Database (JED) Project in 2015. 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 17 million additional data every

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2021 TDDW 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 a lot of research of AI-assisted endoscopy with JED. The current AI technology is realized to decrease the rate of missed lesions during endoscopy and to decide the accurate endoscopic treatment strategy. AI is without any doubt an attractive option and has the potential to improve the quality of endoscopy and standardize endoscopy practice. However, almost all AI-related studies have been retrospective.

Therefore, we must await the results of highquality clinical trials.

In the future, to stay innovation, what we have to do is to promote cooperation of GI endoscopists and surgeons, as well as the promotion of

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research and development in a mid- to long-term perspective with the cooperation between industry and academia. In addition to the fusion of expert human skills and machinery (robot technology), it is important to evolve the next generation technology combining AI and information systems.

As can be seen from the history of the first industrial revolution to the recent fourth industrial revolution, endoscopic instruments have been developed along with the progress of peripheral science and technology. Today’s endoscopy is not the result of the sudden appearance of something new, but rather the result of reviewing the research already done by predecessors and adding new ideas and improvements to it. Therefore, we should learn from the past to develop new ideas.

2021 TDDW

GEST-KASID Symposium APPLICATION OF ARTIFICIAL INTELLIGENCE IN THE MANAGEMENT OF INFLAMMATORY BOWEL DISEASE

DEEP-LEARNING SYSTEM FOR REAL-TIME DIFFERENTIATION BETWEEN CROHN’S DISEASE, INTESTINAL BEHÇET’S DISEASE, AND INTESTINAL TUBERCULOSIS Jae Hee Cheon Department of Internal Medicine and Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea Behçet’s disease (BD) is a chronic, recurrent, systemic inflammatory disease characterized by oral ulcers, genital ulcers, and eye inflammation. When BD patient has predominant gastrointestinal symptoms and an intestinal ulcer in the endoscope, it can be classified as “intestinal BD”. Intestinal BD is more common in East Asia than in Eastern Mediterranean countries.

Crohn’s disease (CD) is a chronic inflammatory bowel disease characterized by transmural inflammation and granuloma formation, affecting the gastrointestinal tract. Intestinal tuberculosis (ITB) occurs when tuberculosis bacteria enter the gastrointestinal tract. ITB diagnosis requires colonoscopy using multiple biopsies on the ulcer margins and confirmation by histology, smear, and culture. The most commonly observed area of ITB is also the ileocecal area, comprising >75% of total gastrointestinal tuberculosis. In East Asia, where intestinal BD, CD, and ITB are prevalent, their differential diagnosis can be difficult owing to limited diagnostic accuracy and limitations of clinical or endoscopic predictive models. The finding that the most commonly associated area in the gastrointestinal tract is the ileocecal area and similarity of ileocecal ulcer shapes between the diseases cause difficulty for clinicians to differentiate between the three diseases and determine the optimal treatment strategy. Accurate

diagnosis is a prerequisite because treatment strategies for these diseases are different and steroid or immunosuppressive treatments can be fatal for ITB patients.

Recently, there has been increasing interest in applying artificial intelligence to the medical field through different machine-learning models.

Machine learning is a data analysis method that learns descriptive or predictive models by iterating over models that gradually improve the performance of a specific task by itself. Deep learning is a machine-learning method comprising complex architectures of deep neural networks (DNNs). DNN research comprises a training process, which defines the network architecture and determines different weights between the neural nodes, and a test process, which evaluates DNN’s ability to predict the desired output.

Accumulation of an enormous number of digital images and medical records has become the basis for further improving the performance of the deeplearning-based model. Moreover, improvement in computing performance through improved graphic processing units made it possible to create deeplearning models in a reasonable time, which was previously impossible.

Prior to emergence of deep learning, studies focused on extracting key features from colonoscopy images, yielding an algorithm by

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2021 TDDW expert endoscopists. Currently, the automated diagnosis of various diseases using the deeplearning method has become a major research area in the gastroenterology field. However, there has been limited research differentiating the morphology of multiple colorectal ulcers of a single patient. Majority of the current work has concentrated on detecting and differentiating colorectal polyps, as it is relatively easier to obtain images through screening; traditional machinelearning methods such as support vector machine alone have demonstrated acceptable performance in detecting these polyps. Majority of studies to date designed deep-learning models and concurrent evaluation techniques that facilitated the detection

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and differentiation of a single disease entity in the endoscopic images.

Differential diagnosis of intestinal BD, CD, and ITB is clinically important because of its high prevalence in East Asia and difficulty in determining treatment strategies. Previous studies have begun to report the usefulness of deep learning for the diagnosis and differentiation of diseases through colonoscopy images; however, this is not so for the differential diagnosis of these diseases. Therefore, we investigated the usefulness of differential diagnosis through deep-learning algorithms using colonoscopic images of intestinal BD, CD, and ITB patients.

2021 TDDW

GEST-KASID Symposium APPLICATION OF ARTIFICIAL INTELLIGENCE IN THE MANAGEMENT OF INFLAMMATORY BOWEL DISEASE

APPLICATION OF ARTIFICIAL INTELLIGENCE TO IMPROVE DIAGNOSIS OF INFLAMMATORY BOWEL DISEASE Chih-Sheng Hung Department of Gastroenterology, Cathay General Hospital, Taipei, Taiwan Artificial intelligence (AI): An emerging technology in the past decades, has been applied in clinical studies to improve the medical care of patients with gastroenterological diseases. For example: detect polyps, early cancer lesions, facilitate the analysis of inflammatory lesions of bowel, liver fibrosis and medical response of medications.

From deep neurological learning and large data base input for machine learning, several clinical studies comprising inflammatory bowel

disease (IBD) patients to determine the differential diagnosis of ulcerative colitis and crohn’s disease, and to predict the response and clinical outcomes of medications used to treat IBD. AI-assisted endoscopy in IBD progress rapidly with promising technical results when tested in an experimental clinical application.

We collect and present recent advances of AI to improve diagnosis of inflammatory bowel disease.

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2021 TDDW

GEST-KASID Symposium APPLICATION OF ARTIFICIAL INTELLIGENCE IN THE MANAGEMENT OF INFLAMMATORY BOWEL DISEASE

ARTIFICIAL INTELLIGENCE FOR DISEASE RISK ASSESSMENT Yen-Nien Chen Department of Internal Medicine, National Taiwan University Cancer Center, Taipei, Taiwan Complexity of inflammatory bowel disease (IBD) etiology and heterogeneity among IBD patients make the disease course become difficult to be evaluated. Current risk stratification profiles or tools of IBD are not yet satisfactory.

Clinical information from IBD patients include clinical data, chronicity of gastrointestinal and extraintestinal symptoms, laboratory values (such as C-reactive protein and fecal calprotectin), imaging, endoscopy, and histopathology findings.

In addition, immunophenotyping using whole genome gene expression datasets, progress of gut microbiome, and data from multi-omics analyses might play important roles on predicting the disease course. Such condition has inevitably led to vast arrays of high dimensional data that pose significant challenges with traditional statistical and computational methods. Advances in artificial intelligence (AI) provide clinicians and researchers

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chances to process, analyze, and interpret high dimensional data and large datasets. Adequate disease risk assessment is crucial for early and effective treatment intervention.

So far, there are several studies focused on predicting risk of IBD. Random forest (RF) and support vector machines (SVM), both are examples of supervised machine learning (ML), were used to deal with microarray, RNA-seq data sets and micro-RNA profiles. Gradient boosted trees and artificial neural networks were used to analyze gene expression profiles. Convolutional neural networks (CNNs) analysis of endoscopic images also applied in assessment of disease severity in IBD. These examples highlight the clinical utility, versatility, and performance of AI in disease risk assessment at the clinical, endoscopic, and histologic level.

2021 TDDW

GEST-KASID Symposium APPLICATION OF ARTIFICIAL INTELLIGENCE IN THE MANAGEMENT OF INFLAMMATORY BOWEL DISEASE

ARTIFICIAL INTELLIGENCE FOR PREDICTION OF PROGNOSIS Soo-Kyung Park Department of Internal Medicine, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea Inflammatory bowel disease (IBD), which includes ulcerative colitis (UC) and Crohn’s disease (CD), is an idiopathic condition related to a dysregulated immune response to commensal intestinal microflora in a genetically susceptible host.

Artificial intelligence, in particular, the deeplearning subtype has emerged as a breakthrough in computer technology enabled by the application of labeled big data across all the sectors. AI allows computers to identify, quantify, and interpret relationships among variables by algorithmically learning the efficient data representations, which is a formidable task for physicians. AI was considered in medical research when its ability to learn complex patterns and make predictions was noticed. In the entire field of gastroenterology, AI is mainly used in image recognition and statistical analysis of diagnosis or prediction of prognosis.

Currently, the goal of treatment of IBD has changed from the traditional clinical remission to a more specific, integrated, and complete deep remission or mucosal healing. The advent of new biologics and small molecules such as anti-TNF agents has significantly changed the treatment strategies of IBD. Clinical decisions are more difficult for not only patients but also clinicians.

At present, the action targets and predictable tolerability of novel treatment options usually serve as the driving factors for clinical decisions.

However, many difficulties remain to be solved in optimizing treatment strategies, improving

longterm prognosis, and changing the natural history of IBD. Machine learning (ML) is thus feasible because of its ability to extract information from existing medical records and digital images for predicting the progression of IBD or the efficacy of certain medications. One study applied random forest (RF) algorithms for predicting the likelihood of patients with IBD experiencing disease flares over a certain period. Corticosteroid use and hospitalizations were considered as a surrogate for IBD flares in this study. This study initially limited the predictors, including age, sex, and five other features, for the diagnosis of IBD and used these finite factors to establish models for predicting the IBD flares.

Finally, the best prediction performance was achieved by the RF longitudinal model anticipated with previous hospitalization or steroid use, and its AUC reached 0.87. Another study performed a case-cohort study utilising a paediatric cohort.

Applying machine learning to a paediatric Crohn’s disease inception cohort, they have identified protein biomarkers that can compositely predict the development of complications when assayed in the blood at time of diagnosis. Distinct proteins were selected for B2 and B3, highlighting the differential underlying biologic processes behind these complications. Protein-based models performed as well as or better than clinical feature and serology-based models at predicting Crohn’s disease complications and selected proteins were not correlated with other biomarkers of disease

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2021 TDDW activity or prognosis.

A recent study aim to predict which patients with CD need early intestinal resection within 3 years of diagnosis, according to a tree-based machine learning technique. Patients with CD were included from 15 tertiary hospitals in South Korea that participated in the multicenter, retrospective case-control study (IMPACT study: identification of the mechanism of the occurrence and progression of Crohn’s disease through integrated analysis on both genetic and environmental factors). The single-nucleotide polymorphism (SNP) genotype data for 337 CD patients were typed using the Korea Biobank Array. For external validation, an additional 126 CD patients were genotyped.

The predictive model was trained using the 102 candidate SNPs and seven sets of clinical information (age, sex, cigarette smoking, disease location, disease behavior, upper gastrointestinal involvement, and perianal disease) by employing a tree-based machine learning method (CatBoost).

The importance of each feature was measured using the Shapley Additive Explanations (SHAP) model. The final model comprised two clinical parameters (age and disease behavior) and four SNPs (rs28785174, rs60532570, rs13056955, and rs7660164). The combined clinical–genetic model predicted early surgery more accurately than a clinical-only model in both internal (area under the receiver operating characteristic (AUROC), 0.878 vs. 0.782; n = 51; p < 0.001) and external validation (AUROC, 0.836 vs. 0.805; n = 126; p < 0.001).

These studies showed the application of complex data in predicting disease progression, which was followed by the use of ML methods to predict the prognosis of disease. The evolvement of transcriptomics, proteomics, and metabolomics can be further accelerated with the support of analytical approaches such as ML. When

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considering that precision medicine involves accurate diagnosis, credible risk assessment, and individual treatment, AI seems to be a technique that can boost its development and also benefit from its broadscale application. Considering the development of research about IBD, its combination with artificial intelligence (AI) technology is not simply a result of interdisciplinary thinking but an inevitable merging of the treatments.

Reference: 1. John Gubatan, Steven Levitte, Akshar Patel, et el. Artificial intelligence applications in inflammatory bowel disease: Emerging technologies and future directions World J Gastroenterol 2021 May 7;27(17):1920-1935.

2. Shirley Cohen-Mekelburg, Sameer Berry, Ryan W Stidham et el. Clinical applications of artificial intelligence and machine learningbased methods in inflammatory bowel disease J Gastroenterol Hepatol 2021 Feb;36(2):279285.

3. Akbar K Waljee, Rachel Lipson, Wyndy L Wiitala et el. Predicting Hospitalization and Outpatient Corticosteroid Use in Inflammatory Bowel Disease Patients Using Machine Learning Inflamm Bowel Dis 2017 Dec 19;24(1):45-53.

4. Ryan C Ungaro, Liangyuan Hu, Jiayi Ji et el.

Machine learning identifies novel blood protein predictors of penetrating and stricturing complications in newly diagnosed paediatric Crohn’s diseas. Aliment Pharmacol Ther.

2021 Jan;53(2):281-290.

5. Kang EA, Jang J, Choi CH et el. Development of a Clinical and Genetic Prediction Model for Early Intestinal Resection in Patients with Crohn’s Disease: Results from the IMPACT Study. J Clin Med. 2021 Feb 7;10(4):633.

2021 TDDW

Prof. Juei-Low Sung’s Research Foundation 34TH ANNUAL ACADEMIC MEETING

WHEN RECEPTOR TYROSINE KINASES MEET HEPATITIS: A WAY OF CARCINOGENESIS AND TREATMENTS Sen-Yung Hsieh Department of Gastroenterology and Hepatology, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan Receptor-tyrosine-kinase (RTK) inhibitors have successfully treated many human cancers.

However, it has not yet been very successful in the treatment of hepatocellular carcinoma (HCC).

A comprehensive screening of RTK members concluded that multiple RTKs are co-expressed in the liver and are involved in different steps of hepatocyte carcinogenesis during the evolution of chronic hepatitis and cirrhosis. Among these, TAM-R expression was strongly associated with Ishak’s hepatitis activity indices and poor clinical

outcomes. Mechanistically, TAM-Rs are not only a downstream target but also an inducer of STAT3mediated signaling, which forms a STAT3-TAMSTAT3 signaling loop to promote hepatocellular carcinogenesis. The silencing of TAM expression or inhibition of its kinase activity suppressed tumor growth in vitro and in vivo. Interestingly, TAMRs are also expressed on liver Kupffer cells and tumor-associated macrophages. Their role in the interplay between tumor cells and the hepatitis microenvironment is intriguing.

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2021 TDDW

Prof. Juei-Low Sung’s Research Foundation 34TH ANNUAL ACADEMIC MEETING

CELL-FREE VIRUS-HOST CHIMERA DNA FORM HEPATITIS B VIRUS INTEGRATION SITES AS A CIRCULATING BIOMARKER OF HEPATOCELLULAR CANCER Chiao-Ling Li Department and Graduate Institute of Medical Microbiology, National Taiwan University College of Medicine, Taipei, Taiwan Early recurrence of hepatocellular carcinoma (HCC) after surgical resection compromises the patient survival. Timely detection of HCC recurrence and its clonality is required to implement salvage therapies appropriately. This study examined the feasibility of virus-host chimera DNA (vh-DNA), generated from junctions of hepatitis B virus (HBV) integration in the HCC chromosome, as a circulating biomarker for this clinical setting.

HBV integration in 50 HBV-related HCC patients was determined by the capture-next generation sequencing (NGS) platform. For individual HCC, the vh-DNA was quantified by specific droplet digital PCR (ddPCR) assay in plasma samples collected before and two months after surgery.

HBV integrations were identified in 44 out of 50 HBV-related HCC patients. Tumor-specific ddPCR was developed to measure the corresponding vhDNA copy number in baseline plasma from each

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patient immediately before surgery. vh-DNA was detected in 43 patients (97.7%), and the levels correlated with the tumor sizes (detection limit at 1.5 cm). Among the plasma collected at 2 months after surgery, 10 cases (23.3%) still contained the same signature vh-DNA detected at baseline, indicating the presence of residual tumor cells. Nine of them (90%) experienced HCC recurrence within one year, supporting vh-DNA as an independent risk factor in predicting early recurrence. Analysis of circulating vh-DNA at recurrence further helped identify the clonal origin. 81.8% of recurrences came from original HCC clones sharing the same plasma vh-DNA, whereas 18.2% were from de novo HCC. Vh-DNA was shown to be a new circulating biomarker for detecting the tumor load in majority of HBV-related HCC patients and aided in monitoring residual tumor and recurrence clonality after tumor resection.

2021 TDDW

Prof. Juei-Low Sung’s Research Foundation 34TH ANNUAL ACADEMIC MEETING

GLUTATHIONE PEROXIDASE 8 NEGATIVELY REGULATES CASPASE-4/11 TO PROTECT AGAINST COLITIS Jye-Lin Hsu Graduate Institute of Biomedical Sciences, China Medical University, Taichung, Taiwan Human caspase-4 and its mouse homologue caspase-11 are receptors for cytoplasmic lipopolysaccharide. Activation of caspase-4/11dependent NLRP3 inflammasome is required for innate defenses and endotoxic shock, but how caspase-4/11 is regulated remains elusive. Here, we show that caspase-4/11 activity is restrained by the oxidative stress sensor Glutathione peroxidase 8 (GPx8), and that GPx8-inhibition or -deficiency relieves caspase-4/11 to cause inflammation during colitis and septic shock.

GPx8-/- mice exhibited exacerbated dextran sulfate sodium-induced colitis and reduced richness and diversity of gut microbiome. Mice that received adoptive cell transfer of GPx8-/- macrophages displayed accelerated colitis. GPx8-deficiency in macrophage potentiated caspase-11-dependent

pyroptosis and exacerbated endotoxic shock.

Mechanistically, GPx8 compromised the activation of caspase-4/11 directly through disulfide bonding mediated by cysteine 79 of GPx8 and cysteine 118 of caspase-4. Consistently, treatment with either N-acetylcysteine, a strong antioxidant, or VX-765, a caspase-4 inhibitor, suppressed caspase-4/11 activation and reduced colitis in Gpx8-deficient mice. Importantly, a positive correlation was found between lower Gpx8 and higher caspase-4 expression in the colon tissue of patients with ulcerative colitis. Taken together, these results indicate that GPx8 negatively regulates caspase-4/11 activity to protect against colitis and highlight the importance of this regulation in ulcerative colitis patients.

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2021 TDDW

Prof. Juei-Low Sung’s Research Foundation 34TH ANNUAL ACADEMIC MEETING

LONG-TERM EFFECTIVENESS OF POPULATION-WIDE MULTIFACETED INTERVENTIONS FOR HEPATOCELLULAR CARCINOMA IN TAIWAN Sih-Han Liao Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan Taiwan has launched a series of populationwide interventions to prevent hepatocellular carcinoma (HCC) related to hepatitis B and C virus infection since 1984. We took this opportunity to investigate the impact of each intervention on the incidence and case-fatality rate of HCC, and assessed their relative contributions to the overall reduction in mortality during this period. Populationbased registry data on HCC mortality and incidence from individuals aged 0 to 84 years between 1979 and 2016 were collected before (Period 1) and after universal hepatitis B vaccination from 1984 (Period 2), universal health care from 1995 (Period 3), and viral hepatitis therapy from 2003 (Period 4).

A Bayesian Poisson regression model was used for mortality decomposition analysis to estimate the respective contributions of these interventions to the reduction in age-specific incidence and

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case-fatality rates. Mortality declined substantially in children, young- and middle-aged groups, but only slightly decreased in the elderly group. The declining trends in mortality were in part explained by incidence reduction and in part by a remarkable decline in case-fatality rate attributed to universal health care. Hepatitis B vaccination led to a 35.9% (26.8% to 44.4%) reduction in incidence for individuals aged 30 years or below, whereas antiviral therapy reduced the incidence of HCC by 14.9% (11.8% to 17.9%) and 15.4% (14.1% to 16.6%) for individuals aged 30–49 years and 50– 69 years, respectively. Vaccination and antiviral therapy were effective in reducing HCC incidence and mortality for the young and middle-aged groups, while the case-fatality rate was improved by universal health care for all age groups.

2021 TDDW

Symposium (I) THIRD SPACE ENDOSCOPY – 2021 UPDATE

POEM FOR ESOPHAGEAL MOTILITY DISEASE. WHO, WHEN AND HOW? Yin-Yi Chu Ultrasonography and Endoscopy Center, New Taipei Municipal Tuchen Hospital, New Taipei City, Taiwan Department of Gastroenterology and Hepatology, Linkou Chang Gung Memorial Hospital and Chang Gung University, Taoyuan, Taiwan High-resolution manometry is now the gold standard diagnostic tool for esophageal motility diseases, which classified on the basis of lower esophageal sphincter (LES) relaxation and motility of esophageal body: (1) incomplete LES relaxation, including achalasia and EGJ outflow obstruction; (2) major motility disorders, including absent contractility, distal esophageal spasm etc.; (3) minor motility disorders; (4) normal esophageal motility.

Third space endoscopy is based on the principle that the deeper layers of the gastrointestinal tract can be accessed by tunneling in the submucosal space and maintaining the integrity of the overlying mucosa. The era of third space endoscopy started

with peroral endoscopic myotomy (POEM) for treatment of achalasia and has expanded to treat various other gastrointestinal disorders. This topic focus on POEM application to various esophageal motility diseases, (1) the indications of POEM, including non-achalasia spastic esophageal motility disorders, the extreme of age and failed previous treatment of achalasia, (2) advancements in procedural techniques such as detection of EGJ and adequacy myotomy, length and site of myotomy, full thickness or circular myotomy, (3) the effectiveness, outcomes and advers events of POEM. Up to now, POEM is rapidly emerging as minimally invasive alternatives to conventional surgery.

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2021 TDDW

Symposium (I) THIRD SPACE ENDOSCOPY – 2021 UPDATE

GASTRIC-POEM. WHO, WHEN AND HOW? Mouen A. Khashab Division of Gastroenterology and Hepatology, The Johns Hopkins University School of Medicine, Baltimore, MD, USA Gastroparesis is a morbid disorder, characterised by delayed gastric emptying in the absence of mechanical obstruction.1 Over the past two decades, gastroparesis has been a growing concern in terms of prevalence, economic cost and its negative effect on quality of life.2–4 Despite its high burden, gastroparesis remains a difficult-to-treat condition with limited treatment options. One large multicentre prospective study showed that only 28% of patients had clinical success at 48 weeks after receiving treatment according to the standard of care.5 Impairment of fundic accommodation, antral contractility, pyloric relaxation and/or duodenal feedback may contribute to delayed gastric emptying and clinical symptoms.6,7 Treatment of gastroparesis remains challenging due to contribution of various pathophysiologic mechanisms to the disease.

Diet modification and prokinetic medications are first-line therapies of gastroparesis. However, prokinetics are not tolerated well due to their significant side effects and have suboptimal efficacy.8 Pylorospasm, detected by manometry9 and endoluminal impedance planimetry (EndoFLIP; Medtronic, Minneapolis, Minnesota),10–12 has been shown to correlate with gastroparesis symptoms.

Based on these findings, pyloric-directed interventional procedures such as botulinum toxin injection, transpyloric stent placement and pneumatic dilation of the pylorus have been developed.13–16 Gastric per-oral endoscopic myotomy

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(G-POEM) was introduced by Khashab et al17 in 2013 as a minimally invasive pyloric-directed procedure for the management of refractory gastroparesis. This was followed by several studies, mostly retrospective with short follow-up periods, which showed encouraging results.18,19 Two meta-analyses reported pooled symptomatic improvement rates of 83.9% and 82% and adverse events (AEs) rate of 6.8% and 6.1%, respectively.20,21 These results have contributed to our knowledge about efficacy and safety of G-POEM.

Reference: 1. Jung H-K, Choung RS, Locke GR, et al.

The incidence, prevalence, and outcomes of patients with gastroparesis in Olmsted County, Minnesota, from 1996 to 2006.

Gastroenterology 2009;136:1225–33.

2. Wang YR, Fisher RS, Parkman HP. Gastroparesis-related hospitalizations in the United States: trends, characteristics, and outcomes, 1995-2004. Am J Gastroenterol 2008;103:313–22.

3. Wadhwa V, Mehta D, Jobanputra Y, et al.

Healthcare utilization and costs associated with gastroparesis. World J Gastroenterol 2017;23:4428.

4. Lacy BE, Crowell MD, Mathis C, et al.

Gastroparesis: quality of life and health care utilization. J Clin Gastroenterol 2018;52:20–4.

5. Pasricha PJ, Yates KP, Nguyen L, et al.

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6.

7.

8.

9.

10.

11.

12.

13.

Outcomes and factors associated with reduced symptoms in patients with gastroparesis.

Gastroenterology 2015;149:1762–74.

Kashyap P, Farrugia G. Diabetic gastroparesis: what we have learned and had to unlearn in the past 5 years. Gut 2010;59:1716–26.

Feldman M, Lawrence Friedman LB. Pathophysiology, Diagnosis, Management, Expert Consult Premium Edition - Enhanced Online Features and Print, 2010. Available: https://www.elsevier.com/books/sleisengerand-fordtrans-gastrointestinal-and-liverdisease2-volume-set/feldman/978-1-4160-6189-2 [Accessed 09 Apr 2020].

Ehrenpreis ED, Deepak P, Sifuentes H, et al.

The metoclopramide black box warning for tardive dyskinesia: effect on clinical practice, adverse event reporting, and prescription drug lawsuits. Am J Gastroenterol 2013;108:866– 72.

Mearin F, Camilleri M, Malagelada JR. Pyloric dysfunction in diabetics with recurrent nausea and vomiting. Gastroenterology 1986;90:1919–25.

Gourcerol G, Tissier F, Melchior C, et al.

Impaired fasting pyloric compliance in gastroparesis and the therapeutic response to pyloric dilatation. Aliment Pharmacol Ther 2015;41:360–7.

Malik Z, Sankineni A, Parkman HP. Assessing pyloric sphincter pathophysiology using EndoFLIP in patients with gastroparesis.

Neurogastroenterol Motil 2015;27:524–31.

Vosoughi K, Ichkhanian Y, Jacques J, et al.

Role of endoscopic functional luminal imaging probe in predicting the outcome of gastric peroral endoscopic pyloromyotomy (with video). Gastrointest Endosc 2020;91:1289– 99.

Clarke JO, Sharaiha RZ, Kord Valeshabad A, et al. Through-the-scope transpyloric stent

14.

15.

16.

17.

18.

19.

20.

21.

placement improves symptoms and gastric emptying in patients with gastroparesis.

Endoscopy 2013;45 Suppl 2 UCTN:E189–90.

Gourcerol G, Tissier F, Melchior C, et al.

Impaired fasting pyloric compliance in gastroparesis and the therapeutic response to pyloric dilatation. Aliment Pharmacol Ther 2015;41:360–7.

Arts J, Holvoet L, Caenepeel P, et al. Clinical trial: a randomized-controlled crossover study of intrapyloric injection of botulinum toxin in gastroparesis. Aliment Pharmacol Ther 2007;26:1251–8.

Wellington J, Scott B, Kundu S, et al. Effect of endoscopic pyloric therapies for patients with nausea and vomiting and functional obstructive gastroparesis. Auton Neurosci 2017;202:56 Khashab MA, Stein E, Clarke JO, et al. Gastric peroral endoscopic myotomy for refractory gastroparesis: first human endoscopic pyloromyotomy (with video). Gastrointest Endosc 2013;78:764–8. chkhanian Y, Vosoughi K, Aghaie Meybodi M, et al. Comprehensive analysis of adverse events associated with gastric peroral endoscopic myotomy: an international multicenter study.

Surg Endosc 2021;35:1755–64.

Benias PC, Khashab MA. Gastric peroral endoscopic pyloromyotomy therapy for refractory gastroparesis. Curr Treat Options Gastroenterol 2017;15:637–47.

Meybodi MA, Qumseya BJ, Shakoor D. Efficacy and feasibility of G-POEM in management of patients with refractory gastroparesis: a systematic review and metaanalysis. Endosc Int open 2019;7:E322–9.

Spadaccini M, Maselli R, Chandrasekar VT, et al. Gastric peroral endoscopic pyloromyotomy for refractory gastroparesis: a systematic review of early outcomes with pooled analysis.

Gastrointest Endosc 2020;91:746–52.

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2021 TDDW

Symposium (I) THIRD SPACE ENDOSCOPY – 2021 UPDATE

POCKET CREATION METHOD FOR EARLY GI CANCER ESD. WHO, WHEN AND HOW? Hironori Yamamoto Division of Gastroenterology, Department of Medicine, Jichi Medical University, Tochigi, Japan

Who? The pocket-creation method is recommended not only for experts but also for beginners.

This is because it is easy for beginners to learn as long as they get the hang of it, and stable ESD is possible.

ESD is a relatively difficult procedure that requires advanced skill, but one of the factors that makes it difficult for beginners is the problem of unstable endoscope operation. Stable endoscopic operation is required for delicate treatment that does not allow an error of 1 mm.

In the pocket-creation method, the control of endoscope tip is stabilized because it is fixed in the submucosal pocket.

In addition, since the operation is performed in the submucosal layer, luminal insufflation is not necessary. With the lumen collapsed without insufflation, the approach to the lesion in the tangential direction becomes easy. Avoiding overinsufflation also reduces the patient’s discomfort.

When?

We use the pocket-creation method as the first choice as a standard procedure for any lesions in the esophagus, stomach, duodenum, and large intestine. Although pocket-creation method is

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particularly useful for overcoming difficult cases with fibrosis, it is also useful to perform highquality ESD as a standard procedure, not limited to difficult cases.

How? In the pocket-creation method, mucosal incision is limited to be about 2 cm length only for the entrance of the submucosal pocket.

Submucosal dissection under the lesion is prioritized over mucosal incision. ST hood is useful for pocket-creation method because it helps easy entrance to the submucosal space and provides stable condition of the endoscope tip. In the submucosal pocket, traction and counter traction can be applied by the outer side of the ST hood.

Severe fibrosis can be overcome by creating submucosal pockets to both sides of the fibrosis.

Even if the lesion is located on a prominent fold, the fold can be flattened by the tip of ST hood during the submucosal dissection using pocket-creation method. Bleeding control is also easier in pocketcreation method because the level of dissection plane can be selected at the level where blood vessels are sparse.

In this lecture, I would like to explain the tips and tricks of the pocket-creation method of ESD.

2021 TDDW

Symposium (I) THIRD SPACE ENDOSCOPY – 2021 UPDATE

STER AND EFTR. WHO, WHEN AND HOW? Chen-Shuan Chung Division of Gastroenterology and Hepatology, Department of Internal Medicine, Far Eastern Memorial Hospital, New Taipei City, Taiwan Ultrasound and Endoscopy Center, Far Eastern Memorial Hospital, New Taipei City, Taiwan College of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan The prevalence of gastrointestinal (GI) tract subepithelial tumors (SETs) is not well understood but definitely increasing due to widespread use of GI endoscopy. Although the majority of small GI SETs remain unchanged in size but the natural course is still inconclusive. Some of GI SETs have malignant potential, particularly for gastrointestinal stromal tumors (GISTs). Tissue acquisition of GI SETs is important for preoperative histological diagnosis of GISTs. However, the yielding rate of several techniques for tissue acquisition, such as stacked or mucosa-incision biopsy and endoscopic

ultrasound-guided fine needle aspiration/biopsy, are not 100%. Therefore, en-bloc removal of the tumor by endoscopic resection could provide definite histological diagnosis and curative resection while clinically suspicious of GISTs. These advanced techniques include submucosal tunneling endoscopic resection (STER) and endoscopic full-thickness resection (ETFR). In this lecture, I will introduce the application of STER and EFTR for GI SETs in terms of indications and technical aspects.

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2021 TDDW

Symposium (II) HOW TO EXPAND AND OPTIMIZE SURGICAL CRITERIA OF LOCALLY ADVANCED PANCREATIC CANCER

DEFINITION OF BORDERLINE – RESECTABLE PANCREATIC CANCER Chien-Hui Wu Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan Surgical Oncologist, Pancreatic Cancer Precision Medicine Center of Excellence, National Taiwan University Hospital, Taipei, Taiwan After the concept of borderline resectable pancreatic cancer was established by the National Comprehensive Cancer Network in 2006, several definitions of borderline resectable pancreatic cancer were given by different organizations, such as the MD Anderson Cancer Center (MDACC), Alliance trial, Americas Hepato-Pancreato-Biliary Association (AHPBA), Society for Surgery of the Alimentary (SSAT) and Society of Surgical Oncology (SSO). In clinical practice, the initial treatment decision may be highly dependent on the quality of preoperative imaging and the surgeon’s surgical experience, as the definition of resectability is based on anatomical criteria.

Since the improvements in surgical techniques, chemotherapy, and radiotherapy, more research has focused not only on anatomical aspects but also on technical or biological aspects.

Technically, borderline resectable pancreatic cancer is highly dependent on the ability to resect/reconstruct arteries and veins. In contrast to the celiac and superior mesenteric arteries,

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the portal vein and common hepatic artery are considered to be reconstructable. Recently, borderline resectability of pancreatic cancer was redefined through international consensus criteria based on anatomical, biological (elevated serum carbohydrate antigen 19-9), and conditional (Eastern Cooperative Oncology Group performance) dimensions.

In the era of precision medicine, the definition of borderline resectable pancreatic cancer goes beyond the anatomic relationship between the tumor and vessels. Neoadjuvant chemotherapy and surgery are associated with improved outcomes. Due to the molecular diversity of borderline resectable pancreatic cancer and its impact on prognosis and treatment response, a paradigm shift to a genome-driven approach is required. This is particularly important in preoperative, potentially curative cases, where a more individualized approach is used to guide individualized treatment.

2021 TDDW

Symposium (II) HOW TO EXPAND AND OPTIMIZE SURGICAL CRITERIA OF LOCALLY ADVANCED PANCREATIC CANCER

CLINICAL SIGNIFICANCE OF MESOPANCREAS DISSECTION FOR PANCREATIC CANCER Akio Saiura Department of Hepatobiliary-Pancreatic Surgery, Juntendo University Graduate School of Medicine, Tokyo, Japan Nerve plexus around pancreas head (plPh) is a unique anatomy in pancreatic surgery and susceptible to tumor invasion. Therefore, dissection around superior mesenteric artery (SMA) and Celiac artery (CA) is the key point during pancreaticoduodenectomy. Various SMA-first or artery-first approaches have been reported. We developed artery-first approach using supra-colic anterior approach tailoring the dissection around SMA (mesopancreas). We developed tailoring dissection around SMA using supracolic anterior approach. The pancreas head is connected to retroperitoneum by inferior pancreticoduodenal artery (IPDA) and nerve plexus of the pancreas head (plPh). In our approach, SMA/plPh is dissected from the ventral side. We adjust the dissection lof the nerve plexus around SMA (plSMA) into three levels. Level1 dissection is a simple division without lymph node or nerve plexus dissection which is indicated to premalignant or low grade malingnant tumor. Level2 (LV2) dissection is an en bloc lymph node dissection with the second plexus of the nerve plexus of the

pancreas head (PlPh2) preserving the plSMA. This procedure is most widely applied and the standard dissection inpatients with malignant tumor in the pancreas head. Level3 dissection is LV dissection plus hemicrcumferencial plSMA, which is mainly performed to borderline resectable pancreatic head cancer (BRPC). For BRPC abutting the SMA (BR-SMA) up to 180 degrees, plSMA resection would often need to be extended more than 180 degrees, although total circumferential resection was strictly avoided, and such dissection was defined as beyond LV3 (B-LV3). In patients with pancreatic cancer, LV2, LV3 and B-LV3 were indicated. Our approach has several advantages, opened view, correspondence to in situ location, common landmark and a vascular field. These points can facilitate early judgement of tumor status and dissection levels.

In this symposium, we will show the technique and result of pancreatectomy using supracolic anterior approach with systematic mesopancreatic dissection.

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2021 TDDW

Symposium (II) HOW TO EXPAND AND OPTIMIZE SURGICAL CRITERIA OF LOCALLY ADVANCED PANCREATIC CANCER

CONVERSION SURGERY FOR PANCREATIC CANCER PATIENTS WITH PORTAL VEIN AND ARTERY RESECTION AND RECONSTRUCTION Hiroki Yamaue Second Department of Surgery, Wakayama Medical University, School of Medicine, Wakayama, Japan

【Introduction】 To improve the survival of patients with pancreatic cancer, preoperative neoadjuvant therapy has been reported to be an independent prognostic factor especially in borderline resectable cancer, and conversion surgery should be considered after intensive chemotherapy even in locally advanced pancreatic cancer. In conversion surgery, aggressive surgery including arterial resection should be required to obtain R0 status without increasing incidence of the postoperative complications. 【Surgical management for locally advanced pancreatic cancer and clinical impact of neoadjuvant chemotherapy】 R0 surgery is an essential requirement for long survival in patients with pancreatic cancer, however, pancreatic cancer should be considered as a systemic disease in the view point of its tumor biology. Therefore, one should consider that R0 surgery is an only issue for the impact of survival in patients with advanced pancreatic cancer (Hirono, Yamaue, et al. Pancreas 2016).

The overall survival (OS) of BR-artery (A) patients was significantly shorter than that of the patients with borderline resectable pancreatic cancer with portal vein/ superior mesenteric vein

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(PV/SMV) involvement (n=76) and resectable pancreatic cancer (n=105) who underwent surgical resection (median OS: 13.6 vs. 20.6 months, P<0.001). The OS of BR-A patient with neoadjuvant therapy followed by surgical resection was significantly longer than those with upfront surgery (median OS: 20.2 vs. 12.9 months, P=0.047). Therefore, some additional strategy is strongly needed, especially recently developed chemotherapeutic regimen including FOLFIRINOX and Gemcitabine plus nab-paclitaxel (Okada, Yamaue et al. Cancer Chemother Pharmacol 2016, Okada, Yamaue et al. Anticancer Res 2017).

First, neoadjuvant chemotherapy (NAC) and chemoradiotherapy (NACRT) will be discussed in this lecture, using new regimen (Okada, Yamaue et al. Oncology 2017).

【PancreatoDuodenectomy with Common Hepatic Artery Resection; PD-CHAR】 Next advanced surgery is combined arterial resection during pancreatoduodenectomy, and common hepatic artery (CHA) is resected and reconstructed by splenic artery. The borderline resectable or locally advanced pancreatic cancer located in pancreatic neck or dorsal pancreas tends to invade CHA, and also bifurcation of CHA and gastroduodenal artery. In these cases, CHA

2021 TDDW has to resect to obtain R0 status and reconstructed by other arteries including jejunal artery, middle colic artery, and splenic artery. Splenic artery has been preferably used in our institution and we had a good outcome in terms of short and long term results. However, it has remains unclear and debatable whether arterial resection really bring a good outcome.

borderline resectable and locally advanced pancreatic cancer has been still controversial, and further studies and discussion will be needed to confirm the appropriate treatment. Especially, according to the results of RCTs, the surgical technique should be improved to get R0 surgical margin in borderline resectable pancreatic cancer, and allow the patients to be given a suitable preoperative and postoperative adjuvant therapy.

【Summary】 The treatment strategy for patients with

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Symposium (II) HOW TO EXPAND AND OPTIMIZE SURGICAL CRITERIA OF LOCALLY ADVANCED PANCREATIC CANCER

UPDATE NEOADJUVANT CHEMOTHERAPY FOR LOCALLY ADVANCED PANCREATIC CANCER Nai-Jung Chiang National Institute of Cancer Research, National Health Research Institutes, Tainan, Taiwan Department of Oncology, National Cheng Kung University Hospital, Tainan, Taiwan Pancreatic ductal adenocarcinoma (PDAC) is associated with dismal prognosis. Only 30%40% of patients presented with locally advanced (LA) PDAC at the time of diagnosis and mostly are metastatic PDAC. The benefit of neoadjuvant chemotherapy (NAT) is to downstage primary tumor size and control potential distant metastasis.

Patients with aggressive tumor that progress under NAT wound not be fit for operation due to the difficulty of R0 resection and high risk of recurrence. Currently, NAT is generally applied in the treatment of LA PDAC but not worldwide consensus in borderline resectable (BR) and resectable PDAC. The rate of conversion surgery after NAT varies

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widely from 4% to 75%. The common regimens of NAT include FOLFIRINOX and gemcitabine-based chemotherapy, such as gemcitabine plus nabpaclitaxel with or without radiotherapy. Patients receiving conversion surgery had significantly longer survival compared to those without resection. Because there are different inclusion and resectability criteria in published studies, prospectively randomized clinical trials are needed to evaluate the definite role of NAT and the optimal time and population for conversion surgery in LA PDAC. I will review the current evidence of NAT in LA PDAC majorly and partly in BR and resectable PDAC, focusing on pivotal randomized controlled clinical trials.

2021 TDDW

Symposium (III) TRANSFORMING SCIENCE TO STANDARD PRACTICE IN GASTROENTEROLOGY

SWEET BUT TOXIC OF LIQUID BIOPSY: GLYCOSYLATED EXOSOMES FACILITATE THE FORMATION OF PRE-METASTATIC NICHES AND ITS APPLICATIONS Tang-Long Shen Department of Plant Pathology and Microbiology, National Taiwan University, Taipei, Taiwan President, Taiwan Society for Extracellular Vesicles (TSEV) Cancer metastasis is the most common cause of cancer death. Since exosome has been highlighted as an important mediator in the communication between cancer cells and distant organs, the role of exosomes in premetastatic niche formation and cancer metastasis is emerging. Although the expression of β4 integrin in both tumor cells and tumor-derived exosomes is crucial for malignant development and organotropic metastasis of cancers, the detailed regulatory mechanisms of β4 integrin in mediating organotropism is still not clear. In this study, we first investigate that N-glycosylation of β4 integrin is mandatory for β4 integrin loading into exosomes. Mechanistically, oncogenic

EGFR/Src signal regulates N-glycosylation of β4 integrin. Authentically, EGFR/Src signal-mediated N-glycosylation of tumor-derived exosomes facilitates tumor-derived exosomes uptake by normal human lung fibroblast cells, which in turn, promotes the formation of cancer-associated fibroblasts.

Moreover, cancer-associated fibroblasts contribute to the cancer malignant development. Together, our study uncovers a function of N-glycosylation of β4 integrin in tumorderived exosomes, which is important for malignant development. In addition, we provide potential uses of exosomes, one of the most promising targets in liquid biopsy, for cancer diagnosis and applications.

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2021 TDDW

Symposium (III) TRANSFORMING SCIENCE TO STANDARD PRACTICE IN GASTROENTEROLOGY

ARTIFICIAL INTELLIGENCE Joseph Sung Lee Kong Chian School of Medicine, Nanyang Technological University, Singapore, Singapore Artificial intelligence (AI) is coming to medicine in a big wave. From making diagnosis in various medical conditions, following the latest advancements in scientific literature, suggesting appropriate therapies, to predicting prognosis and outcome of diseases and conditions, AI is offering unprecedented possibilities to improve care for patients. Gastroenterology is a field that AI can make a significant impact. This is partly because the diagnosis of gastrointestinal conditions relies a lot on image-based investigations and procedures (endoscopy and radiology). AIassisted image analysis can make accurate assessment and provide more information than conventional analysis. AI integration of genomic,

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epigenetic, and metagenomic data may offer new classifications of gastrointestinal cancers and suggest optimal personalized treatments. In managing relapsing and remitting diseases such as inflammatory bowel disease, irritable bowel syndrome, and peptic ulcer bleeding, convoluted neural network may formulate models to predict disease outcome, enhancing treatment efficacy.

AI and surgical robots can also assist surgeons in conducting gastrointestinal operations. While the advancement and new opportunities are exciting, the responsibility and liability issues of AIassisted diagnosis and management need much deliberations.

2021 TDDW

Symposium (III) TRANSFORMING SCIENCE TO STANDARD PRACTICE IN GASTROENTEROLOGY

PRECISION MEDICINE Ming-Shiang Wu Department of Internal Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan Superintendent, National Taiwan University Hospital, Taipei, Taiwan President, the Gastroenterological Society of Taiwan Secretary General, Taiwan Society of Internal Medicine Traditional top-down approach to medicine based on the identification of single etiologic factor to explain disease (one size fits all), which was not suitable for explaining clinical complex conditions. Historically, Hippocrates (460-370 BC) emphasized the importance of individualizing the patient’s management, claiming that “it is often more important to know what person has a disease than to know what specific type of disease it is. However, personalized clinical phenotyping becomes a challenge when different pathophysiologic mechanisms underlie the same manifestation. The tailoring of medical treatment to the individual characteristics of each patient becomes feasible after the completion of the Human Genome Project. There has been an acceleration in methodologies on sequencing nucleic acid at a high precision and with everdecreasing turnaround time and cost. Early successes in identifying and targeting individual oncogenic drivers, together with the increasing availability of sequencing tumor genomes, have brought forth the promise of genome-driven

oncology. In 2015, President Obama announced the Precision Medicine Initiative (PMI) that will explore the genetics of cancer, improve access to personalized health information, and collect data from a diverse cohort over one million people. The power of precision medicine lies in transition from serendipity-driven to data-driven medicine, guiding health care decisions toward the most effective treatment for a given patient.

Preventive or therapeutic interventions can then be concentrated on those who will benefit, sparing expense and side effects for those who will not.

Although the emerging roles of precision medicine in Gastroenterology are clearly visible, questions and challenges remain. It remains unknown how precision medicine tools can be implemented in healthcare systems and whether all possible approaches are also affordable. Besides, data are key to success while not only host genomics but also gut microbiome, environmental and lifestyle factors should be taken into consideration for a more accurate analysis.

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2021 TDDW

Symposium (IV) NASH SYMPOSIUM

UPDATED PREVALENCE OF NAFLD AND NASH IN ASIA Jian-Gao Fan Department of Gastroenterology, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China Nonalcoholic fatty liver disease (NAFLD) is the leading cause of chronic liver disease in the world, and affects around 25% of adult population. From 2012 to 2017, the global liver-related deaths have increased 11.4% according to the Global Burden of Disease study. The Asia–Pacifc region with over 50% of the world’s population and accounted for 54% of cirrhosis-related deaths and 73% of hepatocellular carcinoma (HCC)-related deaths, respectively. NAFLD is the most rapidly growing contributor to liver mortality and morbidity both in the Western countries and the Eastern countries.

The exponential growing burden of NAFLD parallels the increasing prevalence of obesity and type 2 diabetes mellitus in the Asia region. A recent systematic review and meta-analysis of the prevalence, incidence, and outcomes of NAFLD in the Asian population comprising 237 studies (13 044 518 individuals) suggested that the overall prevalence of NAFLD was 29·62% (exceeded that in the West), and up to 25% of NAFLD have developed to nonalcoholic steatohepatitis (NASH).

NAFLD prevalence increased significantly over time from 25·28% between 1999 and 2005, through 28·46% between 2006 and 2011, to 33·90% between 2012 and 2017. The pooled annual NAFLD incidence rate was 50·9 cases per 1000 person-years. The annual incidence of HCC in NAFLD patients was 1·8 cases per 1000 person-years and overall mortality rate was 5·3 deaths per 1000 person-years.

Within the Asia–Pacifc region, NAFLD prevalence varies widely as would be predicted

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from tremendous variations in genetic background, urbanisation, overnutrition, reduced physical activity, and a sedentary lifestyle. However, there is a common trend to increasing prevalence of obesity and NAFLD with time in the entire AsiaPacific region.

Asia is a populous region with a quick spread of the childhood obesity epidemic as well.

Recently, we did a systematic review with metaanalyses to provide the prevalence of and risk factors for pediatric NAFLD in Asia. Of 33 included Asian populations, 9 studies comprising 20595 children reported a pooled NAFLD prevalence of 5.53% (95% CI 3.46%-8.72%), which increased about 1.6-fold from 2004-2010 to the last decade.

The pooled prevalence of NAFLD was ranked in increasing order for normal-weight (1.49%; 95% CI 0.88%-2.51%; 2610 participants), overweight (16.72%, n=1265), and obese (50.13%, n=6434) among Asia children. After full covariate adjustment, the multivariate meta-regression showed that boy percentage and body mass index were positively correlated with NAFLD. In this regard, pooled analysis showed that after age 10 years, boys were more prone to have NAFLD than girls. Furthermore, cardio-metabolic risk factors such as waist circumference, systolic and diastolic blood pressure, serum triglycerides, and insulin resistance were significantly associated with NAFLD. In addition, chronic hepatitis B (CHB) and NAFLD are increasingly observed together in Asian populations, and development of NASH represents

2021 TDDW another leading cause of liver-related morbidity and mortality. Patients with concomitant NASH and CHB had more incidence of HCC and shorter time to development of liver-related outcomes or death compared to patients with CHB alone.

In our newly published multicenter, prospective study including 1000 naïve biopsy-proven CHB patients, 18.2% of whom fulfilled the criteria of NASH at baseline, and 727 patients received the second biopsy at the end of 72-week entecavir treatment. Among patients with NASH, the hepatic steatosis, ballooning, lobular inflammation scores and fibrosis stages all improved during follow-up,

46% (63/136) achieved NASH resolution. Patients with baseline BMI ≥ 23 kg/m2 and weight gain were less likely to have NASH resolution. Furthermore, among CHB patients without steatosis at baseline, 7% (35/505) had incident significant steatosis during follow-up, with an incidence of 50.0 per 1000 person-years. Among CHB patients who had no or bland steatosis at baseline, 22 (4%) developed NASH at the end of follow-up, with an incidence as 14.4 per 1000 person years. Baseline BMI ≥ 23 kg/m2 and 1.5% weight gain during follow-up were predictors of incident NASH in CHB patients during antiviral treatment.

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2021 TDDW

Symposium (IV) NASH SYMPOSIUM

METABOLIC DERANGEMENT AND RESTORATION OF PATIENTS WITH NAFLD Jee-Fu Huang Hepatitis Centre and Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan Non-alcoholic fatty liver disease (NAFLD) has been recognized as one of the most common liver disorders globally. It is also on a trajectory to become the most common indication for liver transplantation worldwide. The epidemic has particularly been rapidly progressing in the past decades in AsiaPacific in parallel to the rapid Westernization in the region. The relative lower BMI in Asians is not protective from metabolic insults. Moreover, Asian people are more prone to metabolic syndrome (MetS), type 2 DM (T2DM) and NAFLD than other races. Previous studies from Taiwan clearly demonstrated that the prevalence of NAFLD has been increasing for more than 2 folds within less than 20 years. Therefore, there is a pressing need for elucidation of the clinical characteristics of NAFLD and its management in a practical fashion since the increasing trend of NAFLD epidemic can’t be overlooked in recent decade.

Non-alcoholic steatohepatitis (NASH) was defined by histopathologic evidence as an extreme form of NAFLD. NASH has been a histologically defined disease, characterized by hepatic steatosis, ballooning, and lobular inflammation with variable fibrosis. The metabolic liver disorder carries the risk of development of fibrosis, cirrhosis and liver-related deaths. It’s commonly associated with related metabolic diseases, leading to cardiovascular events as its leading cause of death. The metabolic disorders include abdominal obesity, hypertension, dyslipidemia and insulin resistance (IR) and further increase the risk of cardiovascular disease (CVD),

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T2DM and chronic kidney disease (CKD). The scenario of a higher overall mortality due to CVD as compared with controls has made it a critical global issue.

Lifestyle modification consisting of diet, exercise, and weight loss has been advocated to be the initial step for management of NASH patients.

The strategies have been widely adopted into the major current guidelines. Among them, weight loss has been reported as the most effective one in improving the histology features and regression of NASH. Several studies have evaluated lifestyle changes, particularly diet and exercise in managing NASH. The adherence of lifestyle modification remains problematic in a large proportion of NASH patients.

It is difficult for patients with morbid obesity and musculoskeletal disorders to do sufficient exercise.

Besides, the efficacy of lifestyle modification could not be applied to those lean NASH patients. In addition, the available clinical trials typically apply extensive exclusion criteria and have limited generalizability.

Therefore, pharmacological treatment may be required in some patients. Currently, there is no effective drug approved for therapeutic indication for NAFLD/NASH. With multiple agents and/or compounds currently recruited into phase 2 to 3 clinical trials, it is important to consider how the eventual approval of a pharmacologic agent for NASH will impact ongoing and future clinical trials in this aspect.

2021 TDDW

Symposium (IV) NASH SYMPOSIUM

CURRENT AND FUTURE THERAPEUTIC APPROACHES FOR PATIENTS WITH NASH Ching-Sheng Hsu Division of Gastroenterology, Department of Internal Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi, Taiwan School of Post-Baccalaureate Chinese Medicine, Tzu Chi University, Hualien, Taiwan Non-alcoholic fatty liver disease (NAFLD) is the most common liver disorder in the world and highly linked to metabolic syndrome.

Current management for NAFLD/NASH should not only target liver-related outcomes but also modulate risk factors of cardiovascular diseases and diabetes progression. Therefore, a holistic approach including liver-directed treatments, lifestyle intervention, body weight control, and correction of metabolic derangements are needed to prevent or delay liver diseases progression and minimize the risks of the development of cirrhosis-related complications, cardiovascular

diseases, chronic renal diseases, tissue damage caused by metabolic derangements, infection, and malignancy.

To optimize the current management for NAFLD/NASH, a variety of potential targets playing essential roles in the pathogenesis of NAFLD/ NASH have been identified and served to develop novel agents for the treatment of NAFLD/NASH. In today’s talk, we will review some important data regarding the current therapeutic approaches and the emerging novel agents for the treatment of NASH and NAFLD.

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2021 TDDW

Symposium (IV) NASH SYMPOSIUM

NON INVASIVE DIAGNOSIS OF NAFLD/NASH Laurent Castera Department of Hepatology, Hôpital Beaujon, Clichy, France There are two key issues in NAFLD patients: the differentiation of NASH from simple steatosis and the identification of advanced hepatic fibrosis that drives overall and liver-related mortality.

Given the epidemic proportion of individuals with NAFLD worldwide, liver biopsy, is impractical and has been challenged over the past decade by non-invasive methods. These methods rely on two distinct but complementary approaches: a “biological” approach, based on the quantification of biomarkers of fibrosis in serum, and a “physical” approach, based on the measurement of liver stiffness using either elastography- or magnetic resonance-based elastography. None of the currently available non-invasive methods can differentiate NASH from simple steatosis. As for

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the identification of advanced fibrosis, simple and inexpensive serum biomarkers such as FIB-4 or the NAFLD fibrosis score may be used as firstline tools to rule-out advanced fibrosis, given their high negative value (>90%). TE as the most widely available and validated technique worldwide could be used as second line in referral centers to select patients with suspected advanced fibrosis for liver biopsy. As for magnetic resonance elastography, although it appears as the most accurate noninvasive technique for staging fibrosis, given its high cost and limited availability, it remains a tool for research or clinical trials. Updated EASL clinical practice guidelines on non-invasive tests have been published in 2021 and will be presented.

2021 TDDW

Symposium (V) UPDATES IN THE TREATMENT OF FUNCTIONAL GI DISORDER

GUT DYSFUNCTION IN DIABETES: DIAGNOSIS AND TREATMENT Ping-Huei Tseng Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan Diabetes mellitus has been associated a myriad of upper and lower gastrointestinal complications, including reflux esophagitis, gastroparesis, diarrhea and constipation, all of which may affect the quality of life and glycemic control. The pathogenesis of gastrointestinal complications in diabetic patients is multi-factorial and has been mainly attributed to autonomic neuropathy, which can impair both gastric acid secretion and gastrointestinal motility.

Various gut hormones, including ghrelin, pancreatic polypeptide-fold peptides, amylin and glucagon-like peptide 1, also play crucial roles in regulation of food intake, gastrointestinal motility, energy balance, and body weight by working with the complex neural circuits in the brainstem, hypothalamus, and higher cortical centers.

Normal gastric emptying is the result of coordinated activity in the proximal and distal regions of the stomach, and may be affected by several factors, such as the volume, composition and total calories of the ingested food, various neurohormonal factors and personal factors, such as pregnancy, anxiety and aging. Delayed or rapid gastric emptying has been associated with a number of gastrointestinal disorders, such as diabetic gastroparesis, functional dyspepsia, gastroesophageal reflux disease and dumping syndrome. Among them, diabetic gastroparesis is the most recognized and is characterized by the delayed gastric emptying, accompanied by severe nausea, vomiting and abdominal fullness, in the absence of mechanical obstruction of the stomach. Since delayed and rapid gastric emptying may cause similar gastrointestinal symptoms, such as nausea, vomiting and bloating, and therefore the importance of determining the rate of gastric emptying to guide the treatment choice has been

stressed. Currently, gastric emptying scintigraphy with solid test meals remains the gold standard to assess delayed gastric emptying. Nevertheless, methodologies related to test meal and imaging protocols in determining gastric emptying time differ between institutions and regions. Other novel tests, including 13C-octanoate breath testing and wireless motility capsule, have been applied in several recent studies to determine gastric emptying, and each has its own advantages and limitations.

Glycemic control, dietary measures, such as low fiber, low fat food, prokinetic drugs (e.g., domperidone, metoclopramide and erythromycin) and antiemetic drugs (e.g, phenothiazines, diphenhydramine) are generally effective for symptomatic relief in the majority of gastroparesis patients. When medical treatments become ineffective over time and associated with adverse events and tachyphylaxia, various interventional therapies may be initiated. The surgical laparoscopic pyloroplasty appeared efficacious but remained technically complicated and risky.

Treatment with gastric electrical stimulation (GES) is reversible and may be a less invasive option compared to surgical intervention for the treatment of patients with chronic, drug-refractory nausea and vomiting secondary to gastroparesis. It has been proposed that GES could override the abnormal rhythms, stimulate gastric emptying and eliminate symptoms of gastroparesis. Nevertheless, the efficacy of GES remains unsatisfactory at present.

Endoscopic approaches include intra-pyloric injection of botulinium toxin, stenting, and pyloric dilatation. Recently, gastric peroral endoscopic pyloromyotomy (G-POEM) has emerging as minimally invasive therapy for gastroparesis with a promising early and mid-term efficacy.

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2021 TDDW

Symposium (V) UPDATES IN THE TREATMENT OF FUNCTIONAL GI DISORDER

SHOULD WE MANIPULATE THE GUT MICROBIOTA IN FUNCTIONAL GUT DISORDER? Yen-Po Wang Department of Internal Medicine, Endoscopy Center for Diagnosis and Treatment, Taipei Veterans General Hospital, Taipei, Taiwan Division of Internal Medicine, Department of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan Functional gut disorder is characterized by chronic abdominal discomfort without a structural or biochemical cause that can adequate explain symptoms. The pathogenesis of functional gut disorder is multifactorial where brain-gut dysregulation was regarded as one of the most important issue. In Rome IV consensus, the intestinal microenvironment was regarded having important role in functional GI disorders, where diet and gut microbiota had substantial influence on metabolism and GI symptoms. Gut dysbiosis was also frequently observed in patients with FGID. Treatment towards alteration of gut microbiota was suggested to be promising in management of FGID. 14 days of rifaximin treatment was effective in to relieve irritable bowel syndrome (IBS) symptoms in 3 months. Rifaximin was also used in management of patients with small intestinal bacteria overgrowth (SIBO). In systemic review and meta-analysis, probiotics was shown effective in treatment of IBS. Fermented milk

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product with probiotic could further modulate brain activity through gut-brain-microbiome axis.

Low Fermentable oligosaccharide disaccharide monosaccharide and polyol (FODMAP) diet could also improve IBS symptoms. The fecal bacterial dysbiosis status was found related to the treatment efficacy of low FODMAP diet. Gut microbiota composition could also be used to predict patients’ response to low FODMAP diet. Fecal microbiota transplant (FMT), which was primarily used for refractory clostridium difficile infection, was also experimented in treatment of IBS recently. The result was heterogenous among studies due to different protocols, fecal material donor, and patient’s characteristics. As gut microbiome also had impact on cardiovascular system, metabolism, immune system, neuropsychiatry and so on, the influence of manipulating gut microbiota on systems other than GI tract also warrants notice.

Limited data about long-term efficacy and adverse events exist.

2021 TDDW

Symposium (V) UPDATES IN THE TREATMENT OF FUNCTIONAL GI DISORDER

NEW PHARMACOLOGICAL TREATMENT FOR IRRITABLE BOWEL SYNDROME Keng-Liang Wu Division of Hepato-Gastroenterology, Department of internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan Department of Medicine, Chang Gung University, Taoyuan, Taiwan Irritable bowel syndrome (IBS) is one of the most common diseases of the gut-brain axis. Rome IV criteria define IBS as chronic or recurrent abdominal pain associated with altered bowel habits. IBS patients are categorized in four subtypes: IBS with predominant constipation (IBS-C), predominant diarrhea (IBS-D), mixed bowel habits (IBS-M), and unclassified (IBS-U).

Pharmacological treatment major target individual symptoms (bloating, abdominal pain and altered bowel habits). The current development of new treatment is focusing on different aspects of the complex pathophysiology of IBS: gut microenvironment, enterohepatic circulation of bile acids, gastrointestinal secretion, motility and sensation, gut–brain interactions, gut barrier function and the immune system within the gastrointestinal tract. In patients with IBS-C,

plecanatide (peptide guanylate cyclase C receptor agonist) is a promising therapeutic option in patients with IBS-C. Tenapanor (inhibitor of the GI sodium/hydrogen exchanger NHE3) increases intestinal fluid volume and transit, leading to an improvement of constipation, bloating and pain.

In patients with IBS-D, ACG suggest rifaximin to treat global IBS-D. Another drug also evaluated for IBS-D is ebastine, an antagonist of histamine receptor H1. Supplements, including probiotics and plant-derived products are safe to use in clinical practice but, high-quality evidence of efficacy is currently lack. Obeticholic acid was shown to decrease bile acid synthesis and improve stool form and symptoms of diarrhea in patients with bile acid diarrhea, but high-quality evidence of efficacy is also lack.

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2021 TDDW

Symposium (V) UPDATES IN THE TREATMENT OF FUNCTIONAL GI DISORDER

HOW TO PERFORM A SUCCESSFUL BIOFEEDBACK FOR THE PATIENTS WITH ANORECTAL DYSFUNCTION? Kee Wook Jung Department of Gastroenterology, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea Biofeedback is a scientific approach that relies on instrumentation to measure the physiological activity relevant to the problems including anorectal dysfunction.1,2 It has been widely used to treat fecal incontinence and chronic constipation due to pelvic floor dyssynergia.1 The goal of biofeedback training is to restore a normal pattern of defecation.1 In patients with dyssynergic defecation, the goal of neuromuscular training is twofold: to correct dyssynergia in coordination with the abdominal, rectal, and anal sphincter muscles and to achieve normal and complete evacuation and enhance rectal sensory perception in patients with impaired rectal sensation.3,4 The training comprises improving abdominal push efforts (diaphragmatic muscle training) and manometricguided pelvic floor relaxation followed by simulated defecation training.

The symptomatic improvement rate varies from 44% to 80%, as shown in the recent randomized controlled trials involving adults with dyssynergic defecation.5-10 However, previous studies have concluded that biofeedback therapy is superior to controlled treatment approaches, such as diet, exercise, and laxatives; the use of polyethylene glycol, diazepam, or placebo; balloon defecation therapy; or sham feedback therapy.5-9 Moreover, the effect of biofeedback was maintained for over 2 years after biofeedback therapy in a considerable proportion of patients with constipation with dyssynergic defecation.11

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The ANMS-ESNM position paper recommended biofeedback therapy for short- and long-term treatments of fecal incontinence with Level II, Grade B evidence.12 However, a metaanalysis that assessing the role of biofeedback in fecal incontinence is difficult because of limited data.13 For constipation, more than three-fold superiority of biofeedback to non-biofeedback, but equal efficacy of electromyographic biofeedback to other applications, was demonstrated.12 The ANMS-ESNM position paper recommended biofeedback therapy for short- and long-term treatments of constipation with dyssynergic defecation with Level I, Grade A evidence.12 However, a Cochrane systematic review suggested that several studies had poor methodological quality.14 Thus, evidence is insufficient for any robust conclusion.14 The biofeedback protocol in our center is as follows1,11: at the first visit, the biofeedback therapist discusses the patient’s current problems and their solutions. Instructions about prepared treatment plans and individualized education regarding ideal defecation or continence practices are provided to patients. The second phase comprises improving the abdominal push effort and biofeedback-guided pelvic floor relaxation followed by simulated defecation training. Patients with fecal incontinence are taught Kegel exercises.

After insertion of sensory probes, patients are asked to simulate defecation. Immediate feedback

2021 TDDW is provided to the patient about the pressure changes in both the abdomen and anal sphincter, and the patient is asked to modify inappropriate responses through trial and error. The patient starts to become aware of coordinated defecation through this rectoanal coordination training, and subsequently, simulated defecation training is imparted using a water-filled balloon.

In conclusion, biofeedback therapy is considered to be a safe behavioral treatment that can result in symptomatic improvement beyond the active treatment period in patients with anorectal dysfunction.

Reference: 1. Lee HJ, Jung KW, Myung SJ. Technique of functional and motility test: how to perform biofeedback for constipation and fecal incontinence. J Neurogastroenterol Motil 2013;19:532-537.

2. Yang DH, Myung SJ, Jung KW, et al. Anorectal function and the effect of biofeedback therapy in ambulatory spinal cord disease patients having constipation. Scand J Gastroenterol 2010;45:1281-1288.

3. Ahn JY, Myung SJ, Jung KW, et al. Effect of biofeedback therapy in constipation according to rectal sensation. Gut Liver 2013;7:157-162.

4. Jung KW, Yang DH, Yoon IJ, et al. Electrical stimulation therapy in chronic functional constipation: five years’ experience in patients refractory to biofeedback therapy and with rectal hyposensitivity. J Neurogastroenterol Motil 2013;19:366-373.

5. Heymen S, Scarlett Y, Jones K, Ringel Y, Drossman D, Whitehead WE. Randomized, controlled trial shows biofeedback to be superior to alternative treatments for patients with pelvic floor dyssynergia-type constipation.

Dis Colon Rectum 2007;50:428-441.

6. Rao SS, Seaton K, Miller M, et al.

Randomized controlled trial of biofeedback, sham feedback, and standard therapy for

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8.

9.

10.

11.

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dyssynergic defecation. Clin Gastroenterol Hepatol 2007;5:331-338.

Rao SS, Valestin J, Brown CK, Zimmerman B, Schulze K. Long-term efficacy of biofeedback therapy for dyssynergic defecation: randomized controlled trial. Am J Gastroenterol 2010;105:890-896.

Chiarioni G, Whitehead WE, Pezza V, Morelli A, Bassotti G. Biofeedback is superior to laxatives for normal transit constipation due to pelvic floor dyssynergia. Gastroenterology 2006;130:657-664.

Chiarioni G, Salandini L, Whitehead WE. Biofeedback benefits only patients with outlet dysfunction, not patients with isolated slow transit constipation. Gastroenterology 2005;129:86-97.

Skardoon GR, Khera AJ, Emmanuel AV, Burgell RE. Review article: dyssynergic defaecation and biofeedback therapy in the pathophysiology and management of functional constipation. Aliment Pharmacol Ther 2017;46:410-423.

Lee HJ, Boo SJ, Jung KW, et al. Long-term efficacy of biofeedback therapy in patients with dyssynergic defecation: results of a median 44 months follow-up. Neurogastroenterol Motil 2015;27:787-795.

Rao SS, Benninga MA, Bharucha AE, Chiarioni G, Di Lorenzo C, Whitehead WE. ANMS-ESNM position paper and consensus guidelines on biofeedback therapy for anorectal disorders. Neurogastroenterol Motil 2015;27:594-609.

Norton C, Cody JD. Biofeedback and/or sphincter exercises for the treatment of faecal incontinence in adults. Cochrane Database Syst Rev 2012:CD002111.

Woodward S, Norton C, Chiarelli P. Biofeedback for treatment of chronic idiopathic constipation in adults. Cochrane Database Syst Rev 2014:CD008486.

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2021 TDDW

Symposium (VI) FIRST LINE COMBINATION THERAPY OR SEQUENTIAL THERAPY FOR HCC

EXPANDING THE LANDSCAPE OF SYSTEMIC THERAPY FOR HCC: 2021 AND 2022 Ann-Lii Cheng Department of Medical Oncology, National Taiwan University Cancer Center, Taipei, Taiwan The combination of atezolizumab and bevacizumab (atezo-bev) has revolutionized the treatment of advanced HCC, for which prolonged tumor remission has now become commonplace.

Atezo-bev also bring in unprecedented improvement of the quality of life for the patients.

With the success of atezo-bev, systemic therapy is now being explored in early and intermediate stages of HCC. Contemporary guidelines for systemic therapy of HCC largely belong to two schools. The first school, including of ASCO and ESMO, indicates a preference for the use of atezo-bev for 1L therapy, and leaves sorafenib and lenvatinib for those who are unsuitable for atezo-bev. The second school, which consists of most of the other guidelines, depicts no preference of either sorafenib,

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lenvatinib, or atezo-bev for 1L therapy, and thus leaves room for physicians to make decision based on their individual real-world environments.

Second-line treatment after atezo-bev or lenvatinib is becoming a predicament. At this point, a rational approach based on individualized treatment goals, as well as real world evidence is advised.

Future landscape of development of systemic therapy includes combinations of multiple immune checkpoint inhibitors (CPI), novel CPIs, and combinations of CPI and multi-target tyrosine kinase inhibitors (TKI). Exploratory studies on triplet (e.g. double CPIs + TKI) are ongoing. We are truely in a new era of pursuing highly efficacious systemic therapy for HCC.

2021 TDDW

Symposium (VI) FIRST LINE COMBINATION THERAPY OR SEQUENTIAL THERAPY FOR HCC

COMBINATION THERAPY IN JAPAN: FIRST LINE SETTING Masatoshi Kudo Department of Gastroenterology and Hepatology, Kindai University Faculty of Medicine, Osaka, Japan A phase III IMbrave 150 trial was conducted using the combination atezolizumab plus bevacizumab with sorafenib as the active comparator. The first interim analysis revealed combination atezolizumab plus bevacizumab was statistically far superior in both co-primary endpoints (PFS and OS). After this landmark result, from 2007 onwards, drug treatment for HCC changed substantially, including with respect to the long-prevailing standard first-line treatment of sorafenib. OS data in the atezolizumab plus bevacizumab group was not fully mature, but OS in the sorafenib group was 13.2 months (95% CI: 10.4–NE) (HR = 0.58; 95% CI: 0.42−0.79; p < 0.001). PFS in the atezolizumab plus bevacizumab group was 6.8 months (95% CI: 5.7–8.3) and in the sorafenib group was 4.3 months (95% CI: 4.0–5.6) (HR = 0.59; 95% CI: 0.47–0.76; p < 0.001). Adverse events were also less frequent in the atezolizumab plus bevacizumab group, and based on patient-reported QOL, the time to QOL deterioration was far better in the atezolizumab plus bevacizumab group at 11.2 months than the 3.6 months in the sorafenib group (HR = 0.63; 95% CI: 0.46−0.85). With these results, concomitant atezolizumab plus bevacizumab firmly established its position as the first choice first-line treatment unless immunotherapy was contraindicated owing to autoimmune disease.

At the 2021 Gastrointestinal Cancers Symposium (ASCO-GI) in January, updated OS data was published up to the final follow-up period of 15.6 months (compared to 8.6 months at interim analysis). OS in the sorafenib group was 13.4 months (95% CI: 11.4−16.9) and in the atezolizumab plus bevacizumab group was 19.2 months (95% CI: 17.0−23.7) (HR = 0.66; 95% CI: 0.52−0.85; p = 0.0009). Updated PFS data also showed PFS in the sorafenib group was 4.3 months (95% CI: 4.0–5.6) and in the atezolizumab plus bevacizumab group was 6.9 months (95% CI: 5.7−8.6) (HR = 0.65; 95% CI: 0.53−0.81; p = 0.0001), results that were consistent with OS data.

By final analysis, ORR in the atezolizumab plus bevacizumab group was 30% (95% CI: 25−35), an improvement over ORR at interim analysis.

In the sorafenib group, ORR at final analysis (11%; 95% CI: 7−17) was almost unchanged from interim analysis. Duration of response in the atezolizumab plus bevacizumab group was 18.1 months compared to 14.9 months in the sorafenib group (95% CI: 4.9−17.0). In addition, in high risk patients, defined as patients with Vp4, tumor burden >50% or bile duct invasion clearly showed fairy good efficacy results COs 7.6 M, PFS 5.4 M, ORR 25%), resulting in paradigm change in treatment strategy in advanced HCC in Japan.

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2021 TDDW

Symposium (VI) FIRST LINE COMBINATION THERAPY OR SEQUENTIAL THERAPY FOR HCC

SEQUENTIAL THERAPY: TKI OR ANTI-VEGF MONOCLONAL ANTIBODY FOR ADVANCED HEPATOCELLULAR CARCINOMA Chia-Jui Yen Department of Oncology, National Cheng Kung University, Tainan, Taiwan Hepatocellular carcinoma (HCC) is the most frequent primary liver tumor, and it is a worldwide leading cause of morbidity and mortality.

During the last decades, further knowledge of HCC molecular mechanisms has led to the development of effective systemic treatment including tyrosine kinase inhibitors (TKIs) and immunotherapy. Three potential scenarios can develop during first line systemic treatment, which determine the subsequent patients’ management: (1) Tolerance or intolerance; (2) Radiological progression; and (3) Symptomatic progression.

Several advances have been made especially in

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pretreated patients; phase III trials of regorafenib, cabozantinib, and ramucirumab in patients with elevated α-fetoprotein have demonstrated efficacy in patients progressing after or intolerant to sorafenib. In this review, we describe the second line systemic treatment options for advanced HCC focusing on sequencing therapy (sorafenib-based treatment) and comparison of different second line options. We will discuss the evidence on secondline options for advanced HCC, focusing on the latest results of phase III RESORCE, CELESTIAL, and REACH-2 trials that are currently refining the treatment scenario.

2021 TDDW

Symposium (VI) FIRST LINE COMBINATION THERAPY OR SEQUENTIAL THERAPY FOR HCC

ROLE OF LOCOREGIONAL THERAPY IN THE ERA OF SYSTEMIC THERAPY Chen-Chun Lin Division of Hepatology, Liver Research Unit, Department of Gastroenterology and Hepatology, LinKuo Chang Gung Memorial Hospital, Taoyuan, Taiwan Chang Gung University, Taoyuan, Taiwan Hepatocellular carcinoma (HCC) is the fifth common cancer and the second cancer death in the world. Locoregional therapies, such as radiofrequency ablation (RFA) and transarterial chemoembolization (TACE), are the mainstay measures for treating the early and intermediate stages of HCC by guideline recommendations worldwide. In recent years, systemic therapy has advanced significantly, especially on immune checkpoint inhibitor (ICI)-based combination therapy. The landscape of systemic therapy, including tyrosine kinase inhibitors (TKI) and ICI, has approval for treating the HCC in the advanced stage. Systemic therapies may provide opportunities to eradicate the circulating tumor cells or micrometastasis in the adjuvant therapy after curative therapies and may combine with TACE

to extend the therapeutic target. The rationale of the combination of TKI and ICI is sound. Local therapies induce antigen and proinflammatory cytokine release, whereas VEGF inhibitor and TKI booster immunity and prime tumors for checkpoint inhibition. These combinations may also provide a new chance to reduce recurrence after curative therapy by adjuvant therapy or to improve resectability after downstage by neoadjuvant therapy. Radiotherapy is another kind of locoregional therapy to directly treat liver tumors and also has the abscopal effect of extending the systemic tumor control by releasing antigen and proinflammatory cytokine in combination with ICI. The ongoing phase III studies may result in a paradigm shift, changing the current treatment algorithms of HCC therapy.

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2021 TDDW

Symposium (VII) TAIWAN CAN HELP – COMBAT AGAINST DIGESTIVE DISEASES ON A NATIONAL SCALE

UNIVERSAL VACCINATION TOWARD ELIMINATING HBV: A 35YEAR JOURNEY OF TAIWAN Yen-Hsuan Ni Department of Pediatrics, College of Medicine and Children’s Hospital, National Taiwan University, Taipei, Taiwan The world’s first nationwide HBV universal vaccination program for infants was launched in Taiwan in July, 1984. Though different countries provide different schedules, most programs consist of 3 doses of recombinant HBV vaccines and hepatitis B immunoglobulin (HBIG). The first dose and the HBIG should be administered within 24 hours after birth. The program now consists of prenatal maternal screening and antiviral therapy if indicated, birth dose of HBIG and a timely 3-dose vaccination, and post-vaccination monitoring. The prevalence of hepatitis B surface antigen (HBsAg) carriers declined from 9.8% to 0.5% in children in Taipei City after 35 years of universal vaccination when we did not start the high viremic maternal antiviral therapy. Can we further reduce the chronic carrier rate to 0%? We have studied that the higher the mother’s viral load, the more likely the

48

newborn could acquire chronic HBV infection. The answer may be that mother-to-infant transmission cannot be over-emphasized and should be intervened if we attempt to eradicate HBV. To completely eliminate hepatitis B virus (HBV) infection worldwide, we need to achieve the following three tasks: (1) to eradicate all of the infectious sources, (2) to interrupt every transmission route, (3) to immunize every susceptible individual. We need to develop effective antiviral therapy to control all the infectious sources; we need to screen the blood bank and all the other possible transmission routes; surely the implementation of universal vaccination program is the most fundamental part to prevent against HBV. We are now at the point to do all these work and hopefully we can achieve this aforementioned goal in this decade.

2021 TDDW

Symposium (VII) TAIWAN CAN HELP – COMBAT AGAINST DIGESTIVE DISEASES ON A NATIONAL SCALE

TOWARD ELIMINATION OF HCV IN 2025: THE ROAD AHEAD Chien-Jen Chen National Hepatitis C Program Office, Ministry of Health and Welfare, Taiwan In 1990, the seroprevalence of antibody against hepatitis C virus (anti-HCV) in Taiwan was first documented to be 0.95% in volunteer blood donors, 90% in hemophiliacs, and 81% in parenteral drug abusers. The anti-HCV seroprevalence was 17% in HBsAg-positive and 63% in HBsAgnegative patients with hepatocellular carcinoma (HCC). The risk factors for HCV infection in Taiwan include iatrogenic transmission (medical injection, hemodialysis, acupuncture, and blood transfusion), tattooing, and sexual transmission. The long-term risk of hepatic and non-hepatic diseases has been reported by REVEL-HCV study. Prediction models for HCV-related hepatocellular carcinoma have also been developed and validated. A national program of antiviral therapy for chronic viral hepatitis was lauched in Taiwan in 2003. Mortality rates of end-stage liver diseases decreased continuously from 2000-2003 to 2008-2011 in all age and gender groups.

Elimination of HCV is an ambitious task that requires integrated national and international efforts as indicated by World Health Organization (WHO). When the World Health Assembly adopted the Global Health Sector Strategy on Viral Hepatitis in 2016, it immediately caught the attention of the people and government in Taiwan. National program to eliminate hepatitis C was very carefully evaluated. It became a consensus to reach the WHO’s goals in 2025, five years earlier than the 2030 deadline set by WHO. Taiwan Hepatitis C Policy Guideline 2018-2025 was approved and published at the beginning of 2019.

According to the most recent estimation, there are around 400,000 hepatitis C cases in Taiwan

with nearly 7,000 new infections per year. Three strategies for the national HCV elimination program include prevention, screening and therapy. The coverage of HCV screening and treatment has been increasing significantly since 2017, and the budget to cover the cost of new drugs increased from US$101 million in 2017 to US$219 million in 2019. A total of US$1.7 billion will be provided from 2017 to 2025 for the elimination of HCV. The number of chronic hepatitis C (CHC) patients receiving new drug therapy increased from 9,538 in 2017, 19,549 in 2018, to 45,807 in 2019.

However, the COVID-19 pandemic decreased the number of treated CHC patients to 36,159 in 2020 and 10,648 in the first-half of 2021. The cure rate based on SVR12 was 96.8% in 2017, 97.4% in 2018, 98.7% in 2019, 99.0% in 2020 and 99.1% in 2021. Both screening and treatment programs will be accelerated to achieve WHO targets of treating 80% eligible HCV patients by 2025.

A total of 121,701 CHC patients have been treated with DAA by June 30, 2021. Over 80,000 CHC patients have been successfully treated with peginterferon and ribavirin before 2021. Taiwan is on track to eliminate HCV by 2025 because of strong commitment by the Ministry of Health and Welfare to finance this national program.

Other measures including awareness and active screening program and funding for linkage to care programs are also reinforced. Based on the triple focus of the Taiwan Hepatitis C Policy Guideline (therapy spearheads prevention, screening supports therapy, and prevention secures outcome), it is expected that Taiwan will achieve WHO’s HCV elimination goal by 2025.

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2021 TDDW

Symposium (VII) TAIWAN CAN HELP – COMBAT AGAINST DIGESTIVE DISEASES ON A NATIONAL SCALE

ERADICATING THE BUG AND SAVE THE STOMACH Yi-Chia Lee Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan Gastric cancer is the third most common cause of death worldwide, accounting for more than 800,000 deaths each year. What may come as a surprise is that most gastric cancer is the result of Helicobacter pylori infection. H. pylori is a bacterium that can survive in the stomach’s acidic environment, leading to chronic stomach inflammation that increases the risk of stomach cancer. Eradicating Helicobacter pylori bacteria can heal the inflammation and stop the progression of mucosal and genetic damage. However, this strategy has never been adopted on a policy level due to the lack of evidence concerning long-term benefits and risks.[1] Before designing a screening program, we have considered the differences in the baseline risk, living environment, and socioeconomic status of the target populations.

In this presentation, I will demonstrate three approaches to implement this strategy on the population level.

First, starting 2004, we have launched a stomach cancer prevention program, which was called the “mass eradication method”, on the northernmost islands of Taiwan, the Matsu Islands, where the prevalence rate of H. pylori infection and incidence rate of stomach cancer are high.

[2] Residents in four townships there were invited to receive an H. pylori breath test, and those who tested positive were treated with one to two courses of antibiotics.After 6 rounds of the program, the prevalence rate of H. pylori infection was reduced from 64.2% to 15.7%, with a reinfection rate of less than 1% per person-year. The decline in H. pylori infection was accompanied by a 53% drop in the

50

occurrence of stomach cancer. The trend shows that by 2023, fewer than 6 people per 100,000 will be diagnosed with stomach cancer in the study area. By 2025, the stomach cancer mortality rate will be cut by a significant 39%.[3] Over the 15-year period, our research team has demonstrated that mass screening and eradication of H. pylori could effectively reduce the incidence of gastric cancer and make this cancer a rare affliction. Long-term follow-ups of the participants’ condition revealed zero increase in the incidence of other digestive tract cancers, such as esophageal and colorectal cancers, the sites most vulnerable to the dysbiosis associated with the antibiotic treatment.

Second, starting 2014, we carried out a community-based, randomized trial by inviting a population who faced burden associated with both gastric and colorectal cancers. Mass screening of colorectal cancer using fecal immunochemical testing (FIT) has been ongoing for more than a decade since 2004. The existing FIT screening offered an opportunity to deliver H. pylori stool antigen (HPSA) testing concurrently with FIT, to offer a two-in-one screening strategy, which was called “the combination method”. The goal of this program was to reduce the incidence of gastric given the presence of competing diseases for the limited resources, such as the colorectal cancers.

[4] Targeting an intermediate-risk population for stomach cancer, we have found that under the framework of a mass screening program for colorectal cancer, the additional HPSA testing was applicable and of benefit when performed together with FIT for simultaneous prevention of gastric

2021 TDDW and colorectal cancers. We have demonstrated that in a general population, the willingness to get antibiotics and compliance to treatment are high.

Given the higher participation rate, the detection of colorectal neoplasia has been increased.

Considering the high eradication rate, participants are likely to benefit from treatment for peptic ulcers and premalignant lesions, and chemoprevention for gastric cancer. Both of these benefits support the population-wide implementation of this strategy.

Third, in Taiwan, there were some subpopulations with high stomach cancer risk, particular in the residents living in the Indigenous communities, most of which located in the rural, remote, and high mountain areas. As a matter of fact, the number of Taiwanese Indigenous peoples has grown; however, their life expectancy remains 8.3 years lower than that of the non-Indigenous population. Cancer is the most prevalent cause of death for Indigenous peoples, who face a 1.3fold greater risk than non-Indigenous peoples and a disproportionate prevalence of certain kinds of cancer. These observations provide us with an opportunity to establish a plan of action.

Targeting the gastric cancer, starting 2018, we have developed a strategy called “the index case method”, through which we invited the family members of the test positives and provided eradication treatment with the family as the unit.[5] This policy has been gradually expended to 33/50 Indigenous Counties in Taiwan.

Overall, in this presentation, I will emphasize the step-by-step for implementing the screenand-treat program of H. pylori infection for gastric cancer prevention. Within any population, there are subpopulations that vary in risk such that a “one size fits all” approach is unlikely to be ideal.

In policy making, it will be required to identify if the programs can be utilized by the heterogeneous populations and will likely require adjustments to accommodate the needs of subpopulations.

Reference: 1. Gut and Liver. 2016;10:12-26.

2. Gut. 2013;62:676-82.

3. Gut. 2021;70:243-50.

4. Gastroenterology. 2021;160:2159-61.

5. Journal of Gastroenterology and Hepatology.

2020;35:609-16.

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2021 TDDW

Symposium (VII) TAIWAN CAN HELP – COMBAT AGAINST DIGESTIVE DISEASES ON A NATIONAL SCALE

CHEAP TEST BUT BIG EFFECT – 15-YEAR STORY OF CRC SCREENING PROGRAM Han-Mo Chiu Department of Internal Medicine, National Taiwan University Hospital for the Taiwan Colorectal Cancer Screening Program 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, although with some global geographic differences in both incidence and mortality rates, with Asia contributing the highest, 957,896 (51.8%) of incident cases and 461,422 (52.4%) of deaths (all genders and ages) per 100,000 population in the world. Fecal immunochemical test (FIT) is a stool test that detect human hemoglobin in the stool, which is specific to detect lower gastrointestinal bleeding.

Its user-friendly platform with resultant higher screening uptake, higher sensitivity for earlystage CRC, and the high-throughput features make FIT as the most popular test in population CRC screening worldwide. In 2004, Taiwanese government launched a nationwide screening program after a successful pilot program and FIT is offered biennially to individuals aged 50 to 69 (extended to 75 in 2013). The screening (coverage) rate of this screening was 21.4% and repeat screening rate was 28.3% in the inaugural 5 years (2004-2009) but improved to 56.6% and 52.3% in 2014. A recent analysis from the program have demonstrated that CRC mortality and incidence of advanced stage CRC has reduced by 35% and 29%, respectively, when comparing those who did and did not participate in FIT screening.

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Nevertheless, there were some challenges and obstacles that needed to overcome. First, the interval cancers have more unfavorable clinical outcomes and their occurrence largely affect the effectiveness of screening. Second, participation in the program is still satisfactory. Both the government and professional societies should elaborate on increasing the awareness toward CRC by the public. Third, some individuals are not compliant with colonoscopy after a positive FIT, which largely affect the effectiveness of the screening. Fourth, there is still discrepancy in the quality of colonoscopy among different units.

Continuous effort in improving colonoscopy quality and clinical audit is indispensable. Finally, long-lasting financial support for this program is necessary for its sustainable development and success. All of these problems need to be remedied via collaboration between the screening organizer, screening distributor, and professional societies.

Reference: 1. GLOBOCAN. Estimated number of Colorectal cancer new cases in 2018, worldwide, both sexes, all ages Lyon, France: IARC; 2018.

2. Chiu HM, Jen GH, Wang YW, Fann JC, Hsu CY, Jeng YC, Yen AM, Chiu SY, Chen SL, Hsu WF, Lee YC, Wu MS, Wu CY, Jou YY, Chen TH. Long-term effectiveness of faecal immunochemical test screening for proximal

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3.

4.

5.

6.

and distal colorectal cancers. Gut. 2021 Jan 25 (ePub):gutjnl-2020-322545. doi: 10.1136/ gutjnl-2020-322545.

Wang YW et al. Current status and future challenge of population-based organized colorectal cancer screening: Lesson from the first decade of Taiwanese program. J Formos Med Assoc. 2018;117:358-364.

Lee YC et al. Effects of screening and universal healthcare on long-term colorectal cancer mortality. Int J Epidemiol. 2018 ;48:538-548.

Chiang TH et al. Difference in performance of fecal immunochemical tests with the same hemoglobin cutoff concentration in a nationwide colorectal cancer screening program. Gastroenterology. 2014;147:131726.

Chiu SY et al. Faecal haemoglobin concentration influences risk prediction of interval cancers resulting from inadequate colonoscopy quality: analysis of the Taiwanese

Nationwide Colorectal Cancer Screening Program. Gut. 2017;66:293-300.

7. Lee YC et al. Association Between Colorectal Cancer Mortality and Gradient Fecal Hemoglobin Concentration in Colonoscopy Noncompliers. J Nat Cancer Inst. 2017;109.

8. Cheng SY et al. Factors affecting compliance with confirmatory colonoscopy after a positive fecal immunochemical test in a national colorectal screening program. Cancer.

2018;124:907-915.

9. Peng SM et al. Faecal immunochemical test after negative colonoscopy may reduce the risk of incident colorectal cancer in a population-based screening programme. Gut. 2021;70:1318-1324.

10. Chiu HM et al. Effectiveness of fecal immunochemical testing in reducing colorectal cancer mortality from the One Million Taiwanese Screening Program. Cancer.

2015;121:3221-9.

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2021 TDDW

Symposium (VIII) INTERVENTIONAL ONCOLOGY IN DIGESTIVE MEDICINE

LEGACY: LOCAL RADIOEMBOLIZATION USING GLASS MICROSPHERES FOR THE ASSESSMENT OF TUMOUR CONTROL WITH Y-90 Vivian Bishay Department of Radiology, Icahn School of Medicine at Mount Sinai Hospital, New York, NY, USA The LEGACY Study is the first multicenter study to report a high median perfused volume absorbed dose of 410 Gy with TheraSphere, which resulted in an 88% best response (84% complete response), durable tumor control and high overall survival rate in patients with early and advanced HCC.

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At three years the overall survival rate for patients was 93% in patients with transplant or resection following TheraSphere and 84% for patients who had TheraSphere as a primary treatment, with 96.8% of patients responding to treatment following one TheraSphere treatment and 100% response with two treatments.

2021 TDDW

Symposium (VIII) INTERVENTIONAL ONCOLOGY IN DIGESTIVE MEDICINE

Y90 FOR CURATIVE INTENT IN HCC Rheun-Chuan Lee Division of Abdominal Radiology, Department of Radiology, Taipei Veterans General Hospital, Taipei, Taiwan Radioembolization has historically been employed in the salvage setting for the treatment of unresectable HCC. However, application of segmental, high dose radioembolization or radiation segmentectomy higher radiation doses can be safely delivered, translating to robust and consistent response rates. The focused delivery also minimizes risk of collateral parenchymal damage. This approach could be considered potentially curative based on the same rationale

as resection, radiofrequency ablation, and transplantation in recent studies.

For those who exceed surgical criteria, radioembolization can be used to reduce the tumor burden and increase sufficient future liver remnant thereby enabling patients to meet the conditions for hepatectomy or liver transplantation.

It provides the possibility of long-term survival in a substantial although selected subgroup of patients with otherwise limited treatment options.

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2021 TDDW

Symposium (VIII) INTERVENTIONAL ONCOLOGY IN DIGESTIVE MEDICINE

CTACE VS DEB-TACE IN THE TREATMENT OF HCC: JAPAN’S PERSPECTIVES Toshihiro Tanaka Department of Radiology, IVR Center, Nara Medical University, Nara, Japan Due to recent development of molecular targeted agents and immunotherapies for HCC, the role of TACE has changed from palliative treatment to curative treatment in patients with preserved liver function. Previous reports indicated that selective TACE could be a curative treatment option.[1,2] A recent randomized controlled trial in Japan demonstrated the higher curability of selective cTACE compared with DEB-TACE.[3] The mechanism of action for TACE is a combination of selective vascular occlusion of tumor feeding arteries, which induce ischemic necrosis, and cytotoxic effect by chemotherapeutic agents.

Our experimental study using a rat HCC model showed advantage of embolic effect of lipiodol emulsion compared with small microspheres in ultrasonography and histology examinations.

[4] Recently developed pumping emulsification device with a microporous glass membrane can create nearly 100% W/O emulsion, which could increase antitumor effect of selective cTACE.[5-7] Several techniques were reported to enhance the therapeutic effect in selective TACE. 3D-saftymargin is one of the important factors to obtain curability.[8] On the other hand, presently, due to an increase in life expectancy of the aged, treatments for elderly patients with HCC are a critical issue.

Year by year, the average age of HCC patients has been increasing. Currently, approximately 12,000 patients with HCC over 80 years old have been newly diagnosed and approximately 13,000

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patients over 80 years old died due to HCC in Japan.[9] For extremely aged patients, current molecular targeted agents and immunotherapies might not be always acceptable due to their tolerability. Also, basically, poor liver function is contraindication. Several previous studies revealed some advantages of DEB-TACE in cases with bilobar multiple HCC or poor liver function.

The learning objective of this lecture is to understand the basic principle and clinical evidence in DEB-TAE and cTACE for HCC.

Reference: 1. Miyayama. Treatment Strategy of Transarterial Chemoembolization for Hepatocellular Carcinoma. Appl. Sci 2020,10,7337.

2. Saito N, Tanaka T, et al. Transarterialchemoembolization remains an effective therapy for intermediate-stage hepatocellular carcinoma with preserved liver function.

Hepatol Res 2020;50:1176-1185.

3. Ikeda M, et al. A prospective randomized controlled trial of selective transarterial chemoembolization using drug-eluting beads loaded with epirubicin versus selective conventional transarterial chemoembolization using epirubicin-Lipiodol for hepatocellular carcinoma: the JIVROSG-1302 PRESIDENT study. J Clin Oncol 2020;38:(15 Suppl); abstract 4518.

4. Minamiguchi K, Tanaka T, et al. Comparison of embolic effect between water-in-oil

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5.

6.

7.

emulsion and microspheres in transarterial embolization for rat hepatocellular carcinoma model. Hepatol Res 2020;50:1297-1305.

Masada T, Tanaka T, et al. Use of a Glass Membrane Pumping Emulsification Device Improves Systemic and Tumor Pharmacokinetics in Rabbit VX2 Liver Tumor in Transarterial Chemoembolization. J Vasc Interv Radiol. 2020;31:347-351.

Tanaka T, et al. Efficacy of a glass membrane emulsification device to form mixture of cisplatin powder with lipiodol on transarterial therapy for hepatocellular carcinoma.

Cardiovasc Intervent Radiol accepted in Dec.2020.

Tanaka T, et al. Drug Release Property of

8.

9.

Lipiodol Emulsion Formed by Glass Membrane Emulsification Device for Transarterial Chemoembolization. Cardiovasc Intervent Radiol. 2020;43:135-139.

Charoenvisal C, Tanaka T, et al. Feasibility and techniques of securing 3D-safety margin in superselective transarterial chemoembolization to improve local tumor control for small hepatocellular carcinoma: An intend-to-treat analysis. Liver Cancer 2021;10:63-71.

Cheng HM, Tanaka T, et al. Safety and Prognosis of Transarterial Chemoembolization for Octogenarians with Hepatocellular Carcinoma. Cardiovasc Intervent Radiol.

2019;42:1413-1419.

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2021 TDDW

Symposium (VIII) INTERVENTIONAL ONCOLOGY IN DIGESTIVE MEDICINE

CTACE VS DEB-TACE IN THE TREATMENT OF HCC: TAIWAN’S PERSPECTIVES Yi-Sheng Liu Department of Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan Division of Interventional Radiology, Department of Medical Imaging, National Cheng Kung University Hospital, Tainan, Taiwan Transarterial chemoembolization (TACE) is a major treatment for intermediate hepatocellar carcinoma (HCC). Conventional TACE (cTACE) is developed for over 30 years, and drug-eluting bead TACE (DEB-TACE) is developed for more than 10 years. More and more expertise opinions and research data are pubished, but the demographics of HCC patients highly vary in different regions.

So the perspectives of different regions may be different.

In Taiwan, the survival rates of TACE-naïve patients treated with cTACE and DEB-TACE

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during 5-year follow-up were 23.9% and 33.3% (p = 0.045). The median time to disease progression in the cTACE and the DEB-TACE groups were 11.0 months and 16.0 months (p = 0.019). And for TACE-naïve patients with large HCC, the 3-year survival rates in the cTACE and DEB-TACE groups were no difference (HR = 0.95, 95% confidence interval: 0.51 - 1.78; p = 0.880). However, the patients treated with DEB-TACE showed longer time to disease progression in the first 2 years.

Other Taiwan’s perspectives will be shared in the meeting.

2021 TDDW

Symposium (IX) NEW DIAGNOSTIC MODALITIES IN DIGESTIVE DISEASES

USING TRANSIENT ELASTOGRAPHY & MMP7 FOR EARLY DIAGNOSIS OF LIVER FIBROSIS Jia-Feng Wu Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan Biliary atresia (BA) is a neonatal, inflammatory, progressive fibro-sclerosing cholangiopathy of infancy, resulting in obstruction of the biliary tract.

To date, BA remains the major cause of chronic liver insufficiency, portal hypertension, and liver transplantation in children. Although ongoing cholestasis, which further aggravates liver cirrhosis and portal hypertension, exists in the majority of children with BA, a timely and successful Kasai operation may still delay or even decrease the need for liver transplantation. It is generally accepted that the Kasai operation is more successful in children with BA when performed before 60 days of age. However, early identification and timely Kasai operation in children with BA remain challenging.

In Taiwan, we have adopted the “stool color card” concept of Professor Akira Matsui. The universal screening for BA using infant stool color cards leads to earlier detection of BA, more timely Kasai operations, and improved long-term prognoses of children with BA in Taiwan. Other than infant stool color card, the BA screening program with urine sulfated bile acid (USBA) and serum direct bilirubin after birth were also performed in Japan and USA with promising results to detect cholestatic infant in early.

After the screening program, the clinicians

encounter more and more cholestatic infants than before. Timely identification of BA among large cholestatic infant pool become a new challenge in the universal cholestatic screening era. The diagnostic accuracy of abdominal ultrasound, MRCP, and HIDA scan are not good enough to date. Our serial study demonstrated the beneficial role of transient elastography assessment of LSM and serum MMP-7 in the non-invasive differentiation between BA and non-BA cholestatic infants.

Prompt and early detection of neonatal cholestasis is essential for early workup for the etiology of disease nature. We need the combination various kinds of modalities to assist a correct and prompt diagnosis of BA to ensure early operation.

Other than cholestatic liver disease, we also applied the transient elastography in a longterm cohort of chronic HBV infected patients from childhood to adult hood to elucidate the natural course and predictors of liver fibrosis in chronic HBV infected patients. Our serial studies demonstrated the role of transient elastography in the diagnosis and follow-up of both the pediatric viral hepatitis and cholestatic liver diseases.

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2021 TDDW

Symposium (IX) NEW DIAGNOSTIC MODALITIES IN DIGESTIVE DISEASES

IMPROVEMENT OF DIAGNOSIS METHODS FOR INFECTIOUS DIARRHEA Shiuh-Bin Fang Division of Pediatric Gastroenterology & Hepatology, Department of Pediatrics, Shuang Ho Hospital, Taipei Medical University, Taipei, Taiwan School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan Infectious diarrhea causing considerable morbidity and mortality worldwide and rehydration is the essence of its treatment regardless of pathogenic etiologies. Timely accurate diagnosis for infectious etiologies facilitates epidemiologic analysis and appropriate management, particularly in complicated bacterial infections. Reliable and accurate diagnosis prompts correct use of empirical antibiotics for reducing fatality caused by bacteremia and extra-intestinal complications. Nontyphoidal Salmonella (NTS) remains the leading cause of bacterial enteric infections in children, elderly, and immunocompromised patients and constitutes substantial socioeconomic burden because of increasing antimicrobial resistance (AMR). In 2017, WHO announced Salmonella resistant to fluoroquinolone and third generation cephalosporin as one of the priority pathogens for development and research of new antibiotics.

Good diagnostics can provide not only specific micropathogens but also their antimicrobial susceptibility tests in time, especially for bacteria.

Diagnostics for detecting virus includes ELISA, multiplex PCR, or viral culture but no AMR. The traditional CLSI bacterial cultures with subsequent antimicrobial susceptibility tests or minimal inhibitory concentrations (MICs) remain the mainstream of diagnosing NTS infection. However, drawbacks of the CLSI methods included false negative results due to partial antibiotic treatment, low detection rates, and time consuming. The currently used CLSI method for detecting bacterial SMR from patients’ samples takes at least 3 days,

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during which overuse or incorrect use of empirical antibiotics is one of the reasons why bacterial AMR increased dramatically in the past decades.

Nowadays we mainly use approaches to reduce antibiotic consumption and AMR, including institutional antimicrobial stewardship programs, infection prevention, rational use of antimicrobials, regulation on over-the-counter availability of antibiotics, improving hand hygiene, and improving infection prevention and control. However, we need more efficient approaches for combating AMR. Our team endeavored in developing improvement and innovation in diagnostics for NTS. In addition to culture-based colony-printing assisted by antibodycoated gold nanoparticles, molecular diagnostics including multiplex PCR for detecting bacteria and their AMR according to the plasmid AMR genes identified by whole genome sequencing (WGS), non-PCR based methods such as biochip, and other new platforms will be introduced. Another challenge is how to rapidly and accurately detect AMR-associated mutations from patients’ samples without relying on expensive and time-consuming WGS or gene sequencing.

Promising prospective is to extend diagnostics into prognostics for predicting invasive NTS infections from the aspects of bacterial virulence and host immunity. Taken together, precise diagnostics and prognostics can provide novel tools for efficient evaluation and prediction for better treatment and outcome of patients with infectious diarrhea.

2021 TDDW

Symposium (IX) NEW DIAGNOSTIC MODALITIES IN DIGESTIVE DISEASES

GUT ECOSYSTEM, MICROBIOTA, AND DIGESTIVE DISEASES Alessio Fasano President, European Biomedical Research Institute of Salerno (EBRIS) Mucosal Immunology and Biology Research Center, Massachusetts General Hospital for Children – Harvard Medical School, Boston, MA, USA Improved hygiene leading to a reduced exposure to microorganisms have been implicated as one possible cause for the recent ‘epidemic’ of chronic inflammatory diseases (CID) in industrialized countries. That is the essence of the hygiene hypothesis that argues that rising incidence of CID may be, at least in part, the result of lifestyle and environmental changes that have made us too “clean” for our own good. Apart from genetic makeup and exposure to environmental triggers, three more elements have been recently identified being key players in the pathogenesis of CID, including gastrointestinal diseases, including inflammatory bowel diseases (IBD), food allergies, eosinophilic enteropathy (EoE) and celiac disease (CD). A third element is the inappropriate Increase in intestinal permeability, which may be influenced by the composition of the gut microbiota, has been proposed. The immune system responsible of the tolerance-immune response represents the fourth element involved in the pathogenesis of CID. Finally, the composition of gut microbiome and its epigenetic influence on the host genomic expression has been identified as a fifth element in causing CID. The gut microbiome consists of more than 100 trillion microorganisms, most of which are bacteria. It has been just recently recognized that there is a close bidirectional interaction between gut microbiome and our immune system, and this cross talk is highly influential in shaping the host gut immune system function and, ultimately,

shifting genetic predisposition to clinical outcome.

This observation led to a revisitation of the possible causes of CID epidemics, suggesting a key pathogenic role of microbiome composition.

While factors such as modality of deliver, neonatal feeding regimens, use of antibiotics, infections can influence microbiota composition, diet is by far the most important variable affecting gut ecosystem. Therefore, re-shaping gut microbiota is becoming an extremely active area of research for the prevention or treatment of a multitude of CID. In order to achieve this goal, it is necessary to move the microbiota studies from observational to mechanistic, mainly identified diagnostic/ biomarkers tools to stratify patients for possible treatment or, more ambitiously, prevention of these GI CID. The Celiac Disease Genome, Environment, Microbiome, and Metabolome (CD-GEMM) study is a birth cohort prospective observational study designed to achieve this goal.

CD-GEMM is the first project to combine a multiomic approach with robust environmental data to identify and validate biomarker predictors of development in at-risk infants. The project provides solid mechanistic evidence of the disease onset and progression in relation to dynamic changes in abnormal gut microbiota causing epigenetic modifications controlling gut barrier and immune functions, based on the in-depth evaluation of 500 infants at risk observed from birth. The project will support novel personalized prediction

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2021 TDDW (personalize treatment) and disease interception (prevention) approaches that attempt to modulate gut microbiota to re- establish/maintain immune homeostasis. The biomarkers identified in this project will contribute to a better understanding of the pathogenesis of Cd and other GI disorders and the possibility to manipulate the microbiota through pre/pro/symbiotic administration +/dietary changes for prevention and treatment, a

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complete paradigm shift in chronic GI diseases pathogenesis and early intervention. The identification of specific CD metabolic phenotypes will also help to define biomarkers that can be used as diagnostic tools and patient stratification models for other conditions in which the interplay between genome, microbiome and metabolic profile has been suspected or proved.

2021 TDDW

Symposium (X) STRATEGIES TO IMPROVE OUTCOME FOR GASTRIC CANCER IN TAIWAN

DIFFERENCES IN THE SURVIVAL OF GASTRIC CANCER PATIENTS BETWEEN TAIWAN AND OTHER COUNTRIES Yan-Shen Shan College of Medicine, National Cheng Kung University, Tainan, Taiwan Institute of Clinical Medicine, National Cheng Kung University, Tainan, Taiwan Department of Surgery, National Cheng Kung University Hospital, Tainan, Taiwan After eradication of HP in Taiwan, the incidence of gastric cancer reached a lower plateau. The new diagnosed gastric cancer patients are around 3800people/ year since 2008. The crude incidence rate is 12.18/105 in male and 6.76/105 in female.

Though different discipline expert treated patients carefully, the 5-year survival of gastric cancer patients is still lower than eastern Asian countries about 10%.

The reasons contribute to the modest survival of Taiwan gastric cancer patients should be explored honestly. After investigated the causes, there are three reasons should be discussed deeply:

1.

2.

3.

No screening project in Taiwan, which caused 60% Taiwan gastric cancer patients was diagnosed at stage III/IV. Too many hospitals jointed the cancer patient program rapidly, increased from 50 hospitals to 92 hospitals in 5 years. Insufficient experience in diagnosis and surgical resection will increase morbidity and mortality during treatment.

Health insurance payment of DOH for advanced stage gastric cancer patients is not enough, only first line drugs and one second line drug. It will reduce the chance of patients to receive salvage chemotherapy.

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2021 TDDW

Symposium (X) STRATEGIES TO IMPROVE OUTCOME FOR GASTRIC CANCER IN TAIWAN

PERI-OPERATIVE ADJUVANT THERAPY FOR ADVANCED GASTRIC CANCER Jaw-Yuan Wang Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan Graduate Institute of Clinical Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan Multimodal treatment strategies – perioperative chemotherapy and radical surgery – are currently accepted as treatment standard for locally advanced gastric cancer (GC). Complete surgical resection remains the only chance for a cure, and multimodality treatment approaches are implemented to improve survival chances. Thus, dismal outcomes in patients with locally advanced GC (LAGC) highlight the need for effective systemic neoadjuvant treatment to improve clinical results. Recently, several clinical trials have shown that neoadjuvant chemoradiotherapy (CCRT) can benefit patient survival after surgery for GC. Moreover, neoadjuvant CCRT has more theoretical benefits than neoadjuvant chemotherapy in patients with LAGC, including more favorable progression-free survival and overall survivalwithout a significant toxicity increase in patients. These strategies improve disease-related outcomes more than surgery alone but are associated with higher rates of treatmentrelated morbidity. Illustrating this fact, only 64% of patients in the Intergroup-0116 trial and 42% in the Medical Research Council Adjuvant Gastric

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Infusional Chemotherapy trial could complete their prescribed treatment courses.

Platinum-based oxaliplatin regimens are active and well-tolerated in patients with advanced or metastatic gastric cancer. However, the prognosis remains largely unknown, and a biological parameter that can be used to evaluate whether a neoadjuvant chemotherapy should be administered in patients susceptible to the response is not available. Therefore, genetic biomarkers that can predict the response in patients with locally advanced or metastatic GC, who would greatly benefit from neoadjuvant chemotherapy, should be identified. Based on prospective randomized data, perioperative chemotherapy is the preferred treatment strategy for patients with surgically resectable GC in the United States and other Western countries. The strength of this ‘‘sandwich’’ approach is the assurance that patients receive at least some systemic therapy. However, many patients fail to receive the intended postoperative chemotherapy, calling into question its importance in the overall management of GC.

2021 TDDW

Symposium (X) STRATEGIES TO IMPROVE OUTCOME FOR GASTRIC CANCER IN TAIWAN

PROPHYLATIC HYPERTHERMIC INTRAPERITONEAL CHEMOTHERAPY FOR THE PATIENTS WITH ADVANCED GASTRIC CANCER Ting-Ying Lee Division of General Surgery, Department of Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan Patients with clinical T4 gastric cancers with high recurrent rate and lower 5-year overall survival even underwent radical gastrectomy (D2 lymphadenectomy) and adjuvant chemotherapy.

The invisible peritoneal metastasis may result in local recurrence due to tumor invaded serosa and nearby organ. We evaluated the prophylactic HIPEC post gastrectomy for the clinical T4 gastric cancer patients. Here we retrospect 132 patients with clinical T4 gastric cancer underwent gastrectomy + D2 lymphadenectomy from 2014 to 2020. There were 35 patients also underwent prophylactic HIPEC peri-operatively. We used propensity score matching (PSM) in order to reduce the selection bias. We evaluated the risk factors for the recurrence and compared the overall

survival (OS) and disease-free survival (DFS) between gastrectomy group and prophylactic HIPEC group. Among 132 eligible patients were included in the study. 70 preoperative patients’ characteristics were homogeneous post PSM. The prophylactic HIPEC seems to reduce the risk of postoperative peritoneal recurrence but not influence the risk of distal metastasis. The risk factors for recurrence included advanced N stage, ascites, and lymphovascular invasion.

The OS (p=0.035) and DFS (p=0.017) were also better in prophylactic HIPEC group. Prophylactic HIPEC plus radical gastrectomy can reduce the postoperative peritoneal recurrence and improve the OS and DFS for clinical T4 gastric cancer patient.

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2021 TDDW

Symposium (X) STRATEGIES TO IMPROVE OUTCOME FOR GASTRIC CANCER IN TAIWAN

CRS WITH HIPEC FOR ADVANCED GASTRIC CANCER WITH PM Mao-Chih Hsieh Department of Surgery, Wan-Fang Hospital, Taipei Medical University, Taipei, Taiwan Cytoreduction surgery (CRS) with hyperthermic intraperitoneal chemotherapy (HIPEC) was introduced to treat gastric cancer (GC) patients with peritoneal metastasis (PM). With curative intent, it developed early since 1981. However, complex surgical procedures and high surgical complication rates restricted this treatment to be widely accepted. At least 100 cases experience was considered to lower surgical complication rates.

Repeated intraperitoneal chemotherapy or pressured intraperitoneal aerosol chemotherapy (PIPAC) without hyperthermia also improved patient survival. Both are considered as alternative methods to treat these patients without an extensive surgery.

Neoadjuvant intraperitoneal chemotherapy

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(NIPS) followed by CRS/HIPEC developed in recent years. This made some cases with severe peritoneal disseminated became suitable for “conversion surgery.”

After surgery, early postoperative intraperitoneal chemotherapy (EPIC) or regular systemic chemotherapy is also considered important.

Patient selection is another issue in applying CRS/HIPEC for GC patients with PM. How to select patients to get the maximal benefits from CRS/HIPEC is depending on the purpose of therapy.

In recent years, more and more surgeons started to apply CRS/HIPEC to treat GC patients with PC. It is important to setup a consensus of standard protocols.

2021 TDDW

Symposium (XI) ARTIFICIAL INTELLIGENCE IN COLONOSCOPY

ARTIFICIAL INTELLIGENCE IN COLONOSCOPY: PAST, PRESENT AND FUTURE William E Karnes H.H. Chao Comprehensive Digestive Disease Center, University of California, Irvine Medical Center, Orange, CA, USA The exponential growth of computer processing power and open-source deep learning models has enabled the development of realtime artificial intelligence during colonoscopy.

Applications include 1) detection of neoplasia to improve detection rates and reduce interval colorectal cancers; 2) characterization of neoplasia to automate the recording of quality measures such as ADR, reduce costs through “leave alone” and “resect and discard” strategies, and identify high-

risk features of invasive carcinoma; and 3) provide consistent operator-independent measures of cecal intubation, withdrawal time, prep quality, and mucosal inflammation scoring. Artificial intelligence-assisted colonoscopy promises to optimize colonoscopy as a tool for colorectal cancer prevention while reducing associated costs, improving efficiency, and automating data collection for quality improvement and research.

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2021 TDDW

Symposium (XI) ARTIFICIAL INTELLIGENCE IN COLONOSCOPY

ARTIFICIAL INTELLIGENCE FOR COLON POLYP DETECTION (CADE) Peng-Jen Chen Division of Gastroenterology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan Colonoscopy is a primary screening and follow-up tool to detect colorectal cancer (CRC), the third leading cause of cancer death in Taiwan. Most colorectal cancers arise from preexisting adenomas, and the adenoma– carcinoma sequence offers an opportunity for the screening and prevention of CRCs. The removal of adenomatous polyps lowers the incidence of CRCs and results in reduced mortality from CRCs. The adenoma detection rate is inversely associated with the risks of interval colorectal cancer, advanced-stage interval cancer, and fatal interval cancer. However, adenoma detection rates vary widely among endoscopists in both academic and community settings. Polyp miss rates as high as 20% have been reported for high-definition resolution colonoscopy. An improvement in adenoma detection rate at screening colonoscopy translates into reduced risks of interval colorectal cancer and colorectal cancer death. With the continuous improvement in the quality of endoscopic imaging systems, optical diagnosis is increasingly used on adenoma detection and histology prediction of colorectal polyps.

Artificial intelligence (AI) is increasingly applied in GI endoscopy, particularly on the detection of colorectal polyps. Several studies

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have demonstrated the feasibility of using AI to detect colorectal polyps, with promising results.

Hence, AI may be considered as a virtual assistant, particularly for the less-experienced endoscopist, on the optical detection of colorectal polyps. AI could potentially increase the number of colorectal polyps detected during colonoscopy, particularly among those with a low adenoma detection rate. However, existing data on the performance of AI on colorectal polyp detection are scattered. In addition to differences in AI systems, there are considerable differences in patient selection, imaging modalities, and even outcome measures. ADR is the most important predictor of colorectal cancer risk and a key quality indicator of screening ability of detecting polyps, including both non-advanced and advanced adenomas. However, some studies disclosed that AI-assisted colonoscopy improves the detection of non-advanced adenomas, but no differences were found while detecting advanced adenoma.

Computer-aided polyp detection seem to be helpful in identifying more small and diminutive polyps, but not contributing significantly to detect advanced adenomas, which has more significant malignant potential.

2021 TDDW

Symposium (XI) ARTIFICIAL INTELLIGENCE IN COLONOSCOPY

ARTIFICIAL INTELLIGENCE IN COLONOSCOPY OTHER THAN POLYP DETECTION (CADX) Yen-Po Wang Department of Internal Medicine, Endoscopy Center for Diagnosis and Treatment, Taipei Veterans General Hospital, Taipei, Taiwan Division of Internal Medicine, Department of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan Colonoscopy is widely performed for diagnosis and management of colorectal disease worldwide.

With the increasing incidence of colorectal cancer, the demand of colonoscopy for colorectal cancer surveillance is also increasing. With the assistance of high definition colonoscopies development, longer scope withdrawal time, better colon preparation, second look in right colon, the colorectal polyp detection and adenoma detection rate increase, which is related with better colonoscopy practices.

However, the demand and cost for pathologic analysis of colorectal polyps are also increasing.

Optical biopsy using narrow band imaging had been shown accurate to differentiate adenomatous and hyperplastic polyps. A computer aided system was able to classify polyp automatically using a biopsy forcep with laser-induced autofluorescence

spectroscopy technique. Artificial intelligence (AI) based computer aided diagnosis (CADx) systems were further developed to characterization of the colon polyps, for distinction of polyps of different histopathological diagnosis, such as adenoma v.s. hyperplastic polyps, or serrated adenoma/polyps.

CADx had been proved accurate in differentiating different polyp histology using endocytoscopy, image enhanced endoscopy, and white light endoscopy. AI based CADx systems have been shown to achieve the ASGI PIVI guideline recommended threshold for characterization of colorectal polyps. Further prospective randomized clinical studies are warranted to evaluate the efficacy of CADx system in different clinical settings and among endoscopists with different experiences.

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2021 TDDW

Symposium (XI) ARTIFICIAL INTELLIGENCE IN COLONOSCOPY

IMPLEMENT AI IN HEALTH CARE: A REGULATION PERSPECTIVE IN TAIWAN Wei-Ling Chen Food and Drug Administration, Ministry of Health and Welfare, Taipei, Taiwan In endoscopy, AI (Artificial intelligence) primarily relates to computer vision technology, which allows computers to ‘see’ and interpret visual content. Through machine learning processes and, more recently, deep learning, AI systems can be trained to recognize ‘normal’ characteristics by linking a gold standard to suitable images. Initial AI development relies on creating an algorithm that uses highly accurate datasets coded in an independently staged manner by a group of specialists. This process is called the ground-truth setting, where the computer is trained to distinguish between ‘abnormal’ and ‘normal’ tissue. Once an algorithm is created, deep convoluted neural networks use vast datasets to enable the algorithm to become more intelligent.

This intelligence can extend to the algorithm becoming agnostic to manual data input, and

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it can learn unsupervised by developing its own rules and classifiers. Artificial Intelligence is a breakthrough in the medical field, and endoscopy is very fertile terrain for its development and refinement. However, it may not come without harm. The excessive reliance on AI systems may trigger relaxation in endoscopic performance with the (un-)conscious thought that “the system is watching.” Moreover, the implementation of AI may discourage endoscopists from improving optical diagnosis skills or update their knowledge.

As already discussed, the presence of false positives may also push the novice or un-expert to perform unnecessary resections or biopsies, increasing cost and pathology burden. We strongly believe that in every dominion in which we seek AI assistance, competence is the prerequisite and not the outcome of AI implementation.

2021 TDDW

Symposium (XII) ORGAN-GUT AXIS: INNOVATION TO PRACTICE

MICROBIOTA AND CARDIOVASCULAR DISEASES Wei-Kai Wu Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan The gut microbiota plays an essential role in the development of cardiovascular disease through both immune-mediated and metabolite-mediated pathways. Shared pathogenic features have been observed between cardiovascular disease and dysbiosis, including chronic inflammation, insulin resistance and an imbalanced energy expenditure. Studies have also demonstrated a significant association between gut microbiota and cardiovascular disease and some microbiotadependent molecules are identified as signals that protect or induce cardiovascular phenotypes.

Butyrate-producing bacteria such as Akkermansia muciniphila, Faecalibacterium prausnitzii, and Roseburia intestinalis were found to be depleted in patients with cardiovascular disease and have

exhibited protective effects for atherosclerosis in animal studies. At molecular level, structure components of bacteria such as lipopolysaccharide and gut microbiota-derived metabolites, including trimethylamine N-oxide, indoxyl sulphate, and phenylacetylglutamine, have shown causative effects on atherosclerotic plaque formation and enhanced thrombosis potential. Thus, the gut microbiota is becoming a potential target for the development of an intervention in preventing or treating cardiovascular disease. Further studies are required to elucidate key pathophysiological pathways from host-microbe interactions which can be manipulable to improve outcomes in patients with cardiovascular disease.

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2021 TDDW

Symposium (XII) ORGAN-GUT AXIS: INNOVATION TO PRACTICE

GUT MICROBIOTA IN PEDIATRIC HEALTH AND DISEASES Yen-Hsuan Ni Department of Pediatrics, College of Medicine and Children’s Hospital, National Taiwan University, Taipei, Taiwan Gut microbiota signatures acquired in infancy may predict the future development of diseases.

Currently, this may apply to metabolic diseases, obesity, allergic diseases, and neuropsychologic disorders. They modulate the development of immune, metabolic, neurologic and psychiatric systems, and trigger diseases onset through the metabolites generated by the microbiota. The diseases involved, such as metabolic diseases (diabetes, obesity), cancer (colon cancer and other gastrointestional malignancies), liver diseases (fatty liver, cirrhosis), immunologic diseases (atopic diseases), brain-gut disorders (irritable bowel syndrome, autism), may be attributed to the dysbiosis formed in the early life. There are many factors influencing the constitutions of the gut microbiota, including maternal nutrition, delivery routes, diet, geography, genetic factors, age, and drugs, and antibiotics. Generally speaking, the diversity of the gut microbiota composition are the measures to implicate “dysbiosis” or not.

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The origin of the bacteria colonizing the neonatal gastrointestinal tract is supposed to be affected by mode of delivery, breastmilk feeding and maternal conditions. Proteobacteria, Actinobacteria, Bacteroidetes, and Firmicutes were the major bacterial phyla patterns in infancy. The infants’ gut microbiota pattern gradually transit into the adult pattern at about the age of three, when the food intake of the children is similar to that of the adults. A long-term prospective monitoring on the development of diseases and the evolution of gut microbiota will be very helpful to unravel their critical role in the pathogenesis of many diseases and the gut microbiota may become the therapeutic target.

We have already proven an early colonization with R. gnavus in the gut promoted allergic disease in infants. The concept may be applied to many immune-related conditions. The current focus of microbiota studies is on the metabolites, which are produced by the host-microbiota interaction to affect many organs and diseases in our bodies.

2021 TDDW

Symposium (XII) ORGAN-GUT AXIS: INNOVATION TO PRACTICE

MICROBIOTA AND MALIGNANCIES Chun-Ying Wu College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan Division of Translational Research, Taipei Veterans General Hospital, Taipei, Taiwan Importance of the topic: 1. Microbiota interacts closely with host immunity and inflammation, which play important roles in digestive cancers’ carcinogenesis.

2. Microbiota can be used as biomarkers to diagnose digestive cancers and to predict treatment outcomes.

Innovations in recent years: 1. The more detailed mechanisms how microbiota interacts with host immunity and inflammation have been reported recently.

2. Lower microbiota diversity is found in several digestive cancers and specific microbes were

3.

reported to increase or reduce digestive cancer risks.

Microbiota plays important roles in cancer immunotherapy and influences treatment outcomes.

Impact on clinical practice: 1. Microbiota may become important biomarkers for digestive cancer diagnosis and outcome prediction.

2. Microbiota may become important treatment measures or adjuvant therapies for digestive cancers.

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2021 TDDW

Symposium (XII) ORGAN-GUT AXIS: INNOVATION TO PRACTICE

MICROBIOTA AND DIGESTIVE DISEASES Deng-Chyang Wu Regenerative Medicine and Cell Therapy Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan School of Internal Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan Division of Gastroenterology, Department of Internal Medical, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan The human gastrointestinal microbiota consists in a group of microorganisms that live in the digestive tract. The microbiota has established a dynamic association of mutual benefits with the human organism, which results in the maintenance of normal immunological, metabolic, and motor functions, as well as correct nutrient digestion and absorption. Although a person’s microbiome is relatively stable and resilient over time, environmental factors that can alter the composition include diet, probiotics, prebiotics, viruses, and drugs, particularly antibiotics.

Increasing evidence has shown that a permanent alteration in the microbiota composition or function can alter visceral sensitivity, intestinal motility, and permeability, as well as alter the immune response, thus promoting a proinflammatory state. Recent studies have also demonstrated the participation of the microbiota in the etiopathogenesis of many gastroenterologi¬cal diseases, such as irritable bowel syndrome, inflammatory bowel disease, celiac disease, non-alcoholic steatohepatitis and

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digestive neoplasms. As the importance of the gut microbiota in health and disease is increasingly recognized interest in interventions that can modulate the microbiota and its interactions with its host has soared. Apart from diet, prebiotics and probiotics represent the most commonly used substances taken in an effort to sustain a healthy microbiome or restore balance when it is believed bacterial homeostasis has been disturbed in disease. Besides, fecal microbiota transplantation which can directly change the patient’s gut microbiota to normalize the composition has been demonstrated to be a promising therapy in Clostridium difficile infection and other digestive diseases. Furthermore, recent studies have proved that modulation of the gut microbiota could even enhance treatment efficacy and reduce adverse effects of colorectal cancer therapies. In the future, we will look forward to the advanced personalized microbiota-modulating interventions in varied hosts and diseases along with medical and technological development.

2021 TDDW

Symposium (XII) ORGAN-GUT AXIS: INNOVATION TO PRACTICE

MICROBIOTA AND DERMATOLOGICAL DISEASES Yi-Ju Chen Department of Dermatology, Taichung Veterans General Hospital, Taichung, Taiwan The association between chronic inflammatory skin disease and comorbidities include cardiovascular disease, depression, chronic renal disease, and inflammatory bowel diseases have been explored. Alterations of skin and gut microbiome were proposed to be involved in the pathogenesis of these chronic skin diseases. I will first talk about the clinical relevance of skin and gut microbiota in diseases such as psoriasis, atopic dermatitis and rosacea. We previously have reported an altered fecal microbial composition in psoriasis, and which resembles that of

spondyloarthritis, transient ischemic stroke, and metabolic syndrome. Our recent study further demonstrated that early life infection or antibiotic exposure is independently associated with pediatric psoriasis and atopic dermatitis. These findings highlighted the significance of early colonization of gut microbiome in shaping the future immune system of individuals. I will talk about new advances in research and clinical implications on gut microbiome and chronic inflammatory skin diseases.

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2021 TDDW

Symposium (XIII) THINKING THE “NEW NORMAL” OF GASTROENTEROLOGY PRACTICE AFTER COVID PANDEMIC

APPLYING BIG DATA FOR GI PRACTICE – WHAT WE HAVE LEARNED FROM COVID-19 PANDEMIC? Ming-Shiang Wu Department of Internal Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan Superintendent, National Taiwan University Hospital, Taipei, Taiwan President, the Gastroenterological Society of Taiwan Secretary General, Taiwan Society of Internal Medicine The outbreak of coronavirus disease 2019 (COVID-19) is a serious health crisis and has a great impact on healthcare system. The rapid spread of this pandemic has led to a scarcity of equipments, consumables and staffs for hospitals. They are requested to provide timely and high-quality patient care while simultaneously protecting the staffs who are at risk for contracting this contiguous disease. Just as the saying goes” every crisis has an opportunity “, the COVID-19 also provides an unprecedented opportunity for digital transformation of healthcare systems and progress of telemedicine. Application of communication and information technologies such as smartphones, internet of things and 4G/5G transmission technology enables direct interactions among healthcare workers or patients across distance, minimizing the risk of SARSCoV-2 infection and improving access to patient

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care. Implementing telemedicine platform thus could provide healthcare services without barriers of time and space and is ideal for addressing challenges poised by the global infectious disease. In addition, patient-generated health data including physical activity level, heart rate and blood pressure, can be combined with data from social networks to depict a more complete view of person’s lifestyle and health behavior. Together with advance of genomic medicine and artificial intelligence, we are for the first-time to collect, analyze and store the high volume, high velocity and high variety health data (Big Data). Big data may improve precision in study of pathogenesis, treatment intervention, risk prediction/prevention and surveillance. Collectively, digital health, data science and precision medicine are converging in health care and will result in a paradigm shift of GI practice as well as medicine.

2021 TDDW

Symposium (XIII) THINKING THE “NEW NORMAL” OF GASTROENTEROLOGY PRACTICE AFTER COVID PANDEMIC

FUTURE ENDOSCOPY PRACTICE – RIGHT-SIZING, TEAM REBUILDING AND NEW TECHNOLOGIES Ming-Chih Hou School of Medicine, National Yang-Ming Chiao-Tung University, Taipei, Taiwan Division of Gastroenterology, Department of Internal Medicine, Taipei Veterans General Hospital, Taipei, Taiwan President, The Digestive Endoscopy Society of Taiwan COVID has changed our practice. Universal lock down to mitigate the crisis, we observed a variable decline of endoscopy volume as much as 75% and 100% at the height of the pandemic around the world. The restricting endoscopic procedures reduce in the absolute number of new cancer diagnoses and also associate with cancer progression to a more advanced stage by the time they are diagnosed and for some patients the time window for a curative treatment may have been missed. Studies also found a dramatic increase in clinically relevant findings per endoscopic procedure. It implicates that a high proportion of endoscopic procedures may be done unnecessarily, with questionable clinical benefit, exposing patients to increased risk, incurring greater cost, and requiring more resources.

Facing this challenge, some are working hard and swiftly to combat the virus transmission as well as hoping for subsidence of the pandemic that we can return to the “old normal.” But the “new normal” after COVID will not be the same. This crisis – as with any crisis – is also an opportunity to learn and to improve.

Rightsizing is the process of restructuring or reorganizing our organization (such as Endoscopy center) network by reducing its workforce, costcutting, rearranging its upper management and

adding new technologies (such as AI and virtual telehealth) in an attempt to get the maximum value from endoscopy services. Technically, the term means adapting the endoscopy practice more efficient and appropriate. Actually, after the lockdown was lifted, the endoscopy volume did not surge above the pre-lockdown volume to accommodate the waiting lists. It reflects not only the adjustments to practice safely during the ongoing pandemic (e. g. need for PPE and screening of patients) and also that indications were viewed more critically and scrutinized for true relevance and appropriateness. The pandemic has forced us to do so to some extent. It gives us an opportunity to critically assess our current practice of open access scheduling and to build a foundation of how best to receive, review, and schedule endoscopy referrals, so that we perform endoscopies with high quality for those patients who may truly benefit from the procedure.

We are not at the end of the COVID-19 crisis, and maybe not even at the end of the beginning.

But it is not too soon to build the strategies that will foster broad-based growth. In today’s fastchanging environment of “the new normal or next normal”, the ability to adapt and respond rapidly is always crucial for survival.

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2021 TDDW

Symposium (XIII) THINKING THE “NEW NORMAL” OF GASTROENTEROLOGY PRACTICE AFTER COVID PANDEMIC

CAN TELEMEDICINE HELP GI PRACTICE? Chun-Ying Wu College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan Division of Translational Research, Taipei Veterans General Hospital, Taipei, Taiwan Importance of the topic: 1. Telemedicine will be widely applied in daily practice in these years.

2. Telemedicine will significantly change physician-patient relationship.

Innovations in recent years: 1. The rapid progress of 5G communication technology has made telemedicine not only useful to diagnose diseases and prescribe medicine, but also feasible to do operation remotely.

2. The pandemic of COVID-19 has made telemedicine technology widely accepted by patients, doctors and governments as an alternative physician-patient interaction

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3.

4.

platform.

Taiwan’ Ministry of Health and Welfare has increased the ranges of insurance-paid telemedicine and has begun constructing nationwide telemedicine healthcare networks since 2021.

In GI practice, telemedicine can help in disease diagnosis, drug prescriptions, laboratory data interpretation, and doing procedures, such as ultrasonography and endoscopy, etc.

Impact on clinical practice: 1. Telemedicine will become a common physician-patient interaction norm.

2. GI doctors will be expected to be familiar with common telemedicine skills.

2021 TDDW

Symposium (XIII) THINKING THE “NEW NORMAL” OF GASTROENTEROLOGY PRACTICE AFTER COVID PANDEMIC

CONSTRUCTING AN EFFECTIVE AND HIGH-PERFORMING GI REFERRAL NETWORK Tun-Jen Hsiao Hsiao’s Clinic, Taoyuan, Taiwan Hierarchical medical system is a major policy made by officer of Taiwan NHI which wants to build accessible and consistent medical services. The whole referral system is more complex because It includes upward and downward referral. In this speech, I just want to talk about upward referral because there are some limits in primary care setting including personal ability limit and facilities limitation.

There are 2288 specialists in our society.

Among them, 660 (29%) work in primary care clinics. Among these 660 primary care GI specialists, 82% are internal medicine Drs and 18% are Pediatricians, and male to female ratio is 91:9.

In order to understand the GI primary are condition and unmet need of referral system, we organize a structural questionnaire. We send the questionnaire to the line group including 249 primary care GI specialists. Finally, there are 180 (72%) members replied the questionnaire. The mean age is 53.7 y/o and male to female ratio is 95:5.

Among the repliers, 140 are clinic holders and the other 40 are employees. The majority of them worked in primary care setting for 10-20 years.

Among all the repliers, 96% provide PES service, nearly 100% provide ultrasound examination, but only 69% provide colonoscopy examination. The number referred to hospital is diverse. The majority number of referrals is between 1-20 patients per

month. 41% GI men refer to internal medicine Drs (IM) is more than surgeons, 15% surgeon > IM and 44% are IM = surgery. 64% repliers have no selection torment in referring, 29% have a little bit, and 7% have frequent torment. And what are the major considerations when they referred patients? First is the medical skills of the doctors, and the 2nd is the distance between patient and hospital, 3rd is the hospital level, and the 4th is the distance between clinic and the hospital. The other considerations are the request of the patients, what disease of the patients, long-term assessment of the hospital, and the hospital where the GI man to be trained.

The primary care committee of our society hold a conference every 6 months before our directors’ board council. In a committee held in 2018, Dr Wang raised a proposal hoping our society to give a suggested referral list for primary care GI man to use. This proposal was adapted after some discussion. After the committee, I raised a related proposal in our directors’ board council and listed a request of 11 diseases. The diagnosis and management of these diseases are more skillful and need more facilities. So primary care GI men have some torment when referring these diseases because we don’t know who are the really experts of these diseases in hospitals.

Finally, our council adapted this proposal.

Our society asked the 35 teaching hospitals for educating GI specialist in Taiwan to give the

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2021 TDDW suggested list for these diseases. The first edition of the list is not useful, because all the GI men in hospital are listed in all diseases. Are they all really experts? We need a precision referral. Just like Secretary General Chiu said “can do is not equal to do it well”. Finally, a rule was made that no more than 3 experts in each disease can be given from each hospital. The suggested referral list was given to primary GI committee in 2020 and we sent it to all our primary care members. In this

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study, up to 97% of the repliers regard the list is helpful.

Thank for all the specialists in hospitals worked for hard GI and liver diseases. And thank for president Wu and secretary general Chiu of our society for generating the list of the specialists for referring. Thank for the 180 primary care GI men replied the questionnaire. We hope the referral list let “precision referral system” works.

2021 TDDW

Symposium (XIV) HBV/HCC SYMPOSIUMS

RISK OF OCCURRENCE AND RECURRENCE OF HCC UNDER NUCS TREATMENT I-Cheng Lee Division of Gastroenterology and Hepatology, Taipei Veterans General Hospital, Taipei, Taiwan HBV infection is the leading cause of hepatocellular carcinoma (HCC) worldwide, and patients with HBV infection are exposed to the risk of HCC occurrence throughout their life. Patients with high HBV viral load or cirrhosis are at highest risk of HCC development, and antiviral therapy has been shown to decrease the risk of HCC occurrence and recurrence. However, HCC may still occur in patients without cirrhosis, in patients

with low viral loads, in patients under antiviral therapy, and even in patients achieving HBsAg seroclearance. In this topic we will summarize the current knowledge of the mechanisms of HCC occurrence and recurrence under NUCs treatment, the predictors and risk scores of HCC occurrence and recurrence, and strategies to minimize the risk of HCC.

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2021 TDDW

Symposium (XIV) HBV/HCC SYMPOSIUMS

APPLICATION OF BIOMARKERS TO PREDICT AND MONITOR HBVRELATED HCC PATIENTS Tai-Chung Tseng Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan Patients with chronic hepatitis B virus (HBV) infection are at risk of developing hepatocellular carcinoma (HCC), and serum markers reflecting active viral replication or fibrosis are potential predictors for HCC development. Levels of serum HBV DNA, hepatitis B surface antigen (HBsAg), and hepatitis B core-related antigen (HBcrAg) are known as HCC predictors. The current data show that not only the baseline levels but also the kinetic are associated with HCC development in treatment-naïve patients. Taking HBcrAg level as an example, our published data has shown that HBcrAg level of 4 log U/mL was effective to stratify HCC risk in HBeAg-negative patients with intermediate viral loads. Their HCC risk could be further stratified by combining the HBcrAg levels

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at baseline and 3 years after follow-up. Surrogate markers of liver fibrosis, such as M2BPGi or fibrosis-4 index (FIB-4), are also important HCC predictors. In both untreated and treated patients, the kinetic of FIB-4 are shown to be associated with HCC development. Finally, not only HBV activity itself but also superinfection of other heaptotropic viruses could increase the HCC risk. Our recently published data have shown that superinfection of hepatitis E virus could increase liver mortality in HBV-related cirrhotic patients and HCC risk in patients with low viral load. In summary, we believe the monitoring the levels of these HCC biomarkers provides an accurate prediction of HBV-related HCC.

2021 TDDW

Symposium (XIV) HBV/HCC SYMPOSIUMS

IMMUNE MICROENVIRONMENT IN HBV-RELATED HCC Valerie Chew Translational Immunology Institute (TII), SingHealth-DukeNUS Academic Medical Centre, Singapore, Singapore Hepatocellular carcinoma (HCC), is the most common type of liver cancer which is derived mostly from the background of chronic inflammation. Chronic hepatitis viral infection remains one of the most common etiologies implicated in chronic liver inflammation, cirrhosis, and HCC. With such background inflammation, immunotherapy—particularly the checkpoint inhibitors—have been tested in HCC patients with unprecedented success. However, despite the initial enthusiasm, the response rate to immunotherapy remains modest in most clinical

trials (approximately 20% for monotherapy).

Therefore, it is increasingly appreciated that deeper understanding of the tumor molecular features and tumor microenvironment of hepatitis viral-related HCC is crucial in the design of more effective immunotherapeutics. We performed in-depth and multidimensional interrogation of the immune landscapes comparing immune microenvironments of HBV-related versus nonviral related HCC and revealed multiple distinct immune features in both HCC subtypes with important implications for future immunotherapy.

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2021 TDDW

Symposium (XIV) HBV/HCC SYMPOSIUMS

RISK AND MANAGEMENT OF ALT FLARE AND HBV REACTIVATION IN ICI-TREATED HCC Grace Lai-Hung Wong Institute of Digestive Disease, Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China Immunotherapy with immune checkpoint inhibitors (ICI) has dramatically improved the survival of patients with advanced hepatocellular carcinoma (HCC). Recent studies suggest that immunotherapy may increase the risk of hepatitis; whereas it may also induce functional cure of chronic hepatitis B virus (HBV) infection. We evaluated the incidence of hepatitis flare, HBV reactivation, hepatitis B surface antigen (HBsAg) seroclearance or seroreversion in patients with current or past HBV infection who had received immunotherapy. We reported a territory-wide observational cohort study of 396 HCC patients who had received ICI in Hong Kong. Hepatitis flare (ALT > 2xULN) occurred in 39.3% HBsAg-

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positive and 30.4% HBsAg-negative patients. High baseline ALT and combination of immunotherapy increased the risk of hepatitis. HBV reactivation (≥ 2 log increase in HBV DNA from baseline) occurred in two HBsAg-positive patients; HBsAg seroclearance and seroreversion was observed in one HBsAg-positive and one HBsAg-negative patient respectively (<1%). In conclusions, hepatitis flare occurs in approximately 40% of HBsAgpositive patients and 30% of HBsAg-negative patients during immunotherapy. HBV reactivation, HBsAg seroclearance and seroreversion are rare.

Current or past HBV infection has no impact on the emergence of hepatic flare associated with immunotherapy.

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Symposium (XV) INTERVENTIONAL ONCOLOGY IN HCC

NEW ADVANCE IN IR FROM MALAYSIA Basri Johan Jeet Abdullah Department of Radiology & Nuclear Medicine, Prince Court Medical Centre, Kuala Lumpur, Malaysia Faculty of Health and Medical Sciences, Taylor’s University, Selangor, Malaysia Tremendous progress has been made in both the technological advances and clinical applications of thermal ablation with improving outcomes. Recent interest of the immunological effects in moderating cellular responses has spurred increased growth of this treatment modality. This interest has been accelerated by

the explosion in immunotherapy as a third pillar of clinical oncology. We will discuss how the creation of artificial pneumothorax and use of newer muscle relaxants in general anaesthesia have enhanced the capabilities of thermal ablation i.e. MWA in our practice.

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Symposium (XV) INTERVENTIONAL ONCOLOGY IN HCC

PERCUTANEOUS RADIOFREQUENCY TUMOR ABLATION THERAPY FOR CAUDATE LOBE TUMORS UNDER CT OR US GUIDANCE Chia-Ling Chiang Department of Radiology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan School of Medicine, National Yang-Ming University, Taipei, Taiwan The caudate lobe of the liver located deeply in the central portion of the back, belongs to the Couinard I segment, and is sandwiched in a “valley of blood” among the first, second, and third portal.

Primary hepatic tumors or metastases located in the caudate lobe are not infrequent, and caudate lobectomy is technically challenging for many surgeons. Transarterial embolization for HCC at caudate lobe is also one of the most difficult procedures for many IRs due to the complex blood

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supply to caudate lesions. With the advantage of ablation and imaging resolution, percutaneous radical treatment with RFA has emerged as a novel method for treating caudate lobe tumors.

We evaluated the technical feasibility and safety of percutaneous radiofrequency ablation for caudate lobe tumors under CT or US guidance from 2008 to 2016 in our institute, and focused on the technical success rate, potential complications, recurrence rate and technical tips.

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Symposium (XV) INTERVENTIONAL ONCOLOGY IN HCC

HEPATIC ARTERIAL INFUSION CHEMOTHERAPY FOR ADVANCED HEPATOCELLULAR CARCINOMA IN THE ERA OF MOLECULAR TARGETED AGENT-DIVERSITY Hideki Iwamoto Division of Gastroenterology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan Macroscopic vascular invasion (MVI) is a critical independent factor associated with poor prognosis of patients with hepatocellular carcinoma (HCC).

Nowadays, molecular-targeted agents (MTAs) are the standard treatment for advanced HCC as the worldwide treatment guidelines recommend.

Various MTAs, such as sorafenib, regorafenib, lenvatinib and immune-checkpoint inhibitor are approved in the world, which means that now we are in the era of MTA-diversity. Although the approved MTAs prolong survival even for patients with advanced HCC, their therapeutic effects are unsatisfactory. Therefore, further progress is needed in treatment for advanced HCC. Hepatic arterial infusion chemotherapy (HAIC) is a promising treatment in treatment of HCC with MVI. HAIC is a local treatment which directly and consecutively delivers anticancer drugs into HCC. HAIC is theoretically possible to increase local concentrations of anti-cancer drugs in the liver and reduces systemic adverse events due

to anti-cancer drugs. Although HAIC is thought to be a promising therapeutic modality in treatment of HCC, it is not positioned as a standardized treatment in the world because of low evidenced treatment. Our facility has historically been conducting HAIC treatment and reported the usefulness of HAIC (Tanaka et al. Cancer 2002 1;95(3):588, Nagamatsu et al. Aliment Pharmacol Ther. 2010 32;(4):543, Iwamoto et al. Cancers 2021 5;13(4):646). We firstly reported the usefulness of a conventional HAIC regimen ‘low dose FP’ and now shifted to a novel HAIC regimen ‘New FP”.

Low dose FP is a regimen which is consisted of cisplatin and 5-fluorouracil (5-FU). And New FP is a regimen which is consisted of a fine-powder cisplatin suspended with lipiodol and 5-FU. In this presentation, we updated the current status of HAIC and summarized the therapeutic outcomes of HAIC. This presentation aimed to clarify the positioning of HAIC in the era of MTA-diversity in treatment of advanced HCC.

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Symposium (XVI) SMALL BOWEL LYMPHOMA

TASSID MULTICENTER REGISTRY OF SMALL BOWEL LYMPHOMA: OVERVIEW Hsu-Heng Yen Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan Although gastrointestinal (GI) tract is the most common extranodal site involved in nonHodgkin lymphoma (NHL), primary small intestinal lymphoma is a rare problem. Lymphoid neoplasms may consist of T or B cell lymphomas and less commonly extranodal NK/T cells. The presentation of these patient may be varied.

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With the introduction of deep enteroscopy, there has been an improvement in the diagnosis, or management of small bowel lymphomas instead of surgery alone. In this session, we present clinical, endoscopic, and radiological features of endoscopically diagnosed small bowel lymphomas from the TASSID multicenter registry study.

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Symposium (XVI) SMALL BOWEL LYMPHOMA

TASSID MULTICENTER REGISTRY OF SMALL INTESTINAL LYMPHOMA: DIAGNOSIS Chen-Shuan Chung Division of Gastroenterology and Hepatology, Department of Internal Medicine, Far Eastern Memorial Hospital, New Taipei City, Taiwan Ultrasound and Endoscopy Center, Far Eastern Memorial Hospital, New Taipei City, Taiwan College of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan Small intestinal cancers are rare malignancies compared with other parts of gastrointestinal tract. Among malignancies of small intestine, lymphoma is always ranking top 5 histology. The gold standard of diagnosis for small intestinal lymphoma is pathological immunohistochemical

stain of malignant tissues. In this lecture, I will introduce the data from Taiwan Association for the Study of Small Intestinal Diseases (TASSID) about the endoscopic diagnosis of small bowel lymphoma.

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Symposium (XVI) SMALL BOWEL LYMPHOMA

TASSID MULTICENTER REGISTRY OF SMALL INTESTINAL LYMPHOMA: TREATMENTS AND OUTCOMES Wei-Pin Lin Department of Gastroenterology and Hepatology, LinKuo Chang Gung Memorial Hospital, Taoyuan, Taiwan Traditionally, chemotherapy has been important for management of GI lymphoma, with surgical resection being recommended only under specific circumstances; however, many authors have advocated a combination of surgery and chemotherapy to improve overall survival.

Base on TASSID data, after the era of enteroscopy, since the enteroscopy has the ability for tissue sampling, most cases (45/67) received chemotherapy after diagnosis; less cases (15/67) received surgery and the main reason is tumor

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related complications: obstruction and bleeding.

Age more than 65, advanced stage disease (stage III/IV) and chemotherapy alone are associated with poor prognosis; the 5-year overall survival (44%) is similar, but not superior to previous study.

Large study randomising patients to chemotherapy or surgery plus chemotherapy should be undertaken, for the best strategy of treating small bowel lymphoma.

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Symposium (XVI) SMALL BOWEL LYMPHOMA

GASTROINTESTINAL LYMPHOMA: THE NEW MIMIC Zhi-Hua Ran Department of Gastroenterology, Renji Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China Primary gastrointestinal lymphoma (PGIL) is a type of malignant tumor that originates from the lamina propria and submucosal lymphoid tissues of the gastrointestinal mucosa. It accounts for 1% to 8% of gastrointestinal malignant tumors.

It is the most common extranodal lymphoma, which accounts for 30% to 40% of extranodal lymphoma. With the increase of microbial infections, autoimmune diseases and secondary immune dysfunction diseases, the incidence of PGIL has increased. It lacks specific clinical manifestations in the early stage and has a high rate of misdiagnosis. In Western countries, the main site of gastrointestinal lymphoma is the stomach, followed by the small intestine. A study in China have reported that PGIL sites are most common in the stomach, followed by ileocecal, ileum, colon, jejunum, rectum, and duodenum.

About 1/4 of the patients have lesions involving multiple parts of the gastrointestinal tract.

Macroscopically, lymphomas appear in various types, such as small lesions, large masses, polyp-

like features, submucosal tumor, ulcers, necrosis or perforations. Some features are similar to inflammatory bowel disease or other tumors of the digestive system, and it is often difficult to differentially diagnose. Diagnosis usually requires a combination of general morphology, microscopic features and immunophenotyping. Gastrointestinal lymphoma is dominated by B-cell non-Hodgkin lymphoma, accounting for approximately 90% of all pathological types. The most common pathological types are mucosa-associated lymphoid tissue (MALT) lymphoma and diffuse large B-cell lymphoma (DLBL). T/NK cell nonHodgkin’s lymphoma accounts for approximately 10% of all gastrointestinal lymphomas, and Hodgkin’s lymphoma is rare. For early stage MALT lymphoma, remission can usually be achieved by eradicating Helicobacter pylori. For DLBL, a chemotherapy regimen combined with rituximab is usually used. The prognosis of T/NK cell lymphoma is relatively poor.

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Young Investigator Award (YIA) ①

SUPERIORITY OF EUS-GUIDED GASTROENTEROSTOMY OVER ENDOSCOPIC STENTING FOR PALLIATION OF MALIGNANT GASTRIC OUTLET OBSTRUCTION Yu-Ting Kuo1,2, Weng-Fai Wong1,2, Ming-Lun Han1,2, Chieh-Chang Chen1, Wei-Chih Liao1, Hsiu-Po Wang1 Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan1 Division of Endoscopy, Department of Integrated Diagnostics & Therapeutics, National Taiwan University Hospital, National Taiwan University, Taipei, Taiwan2

針對惡性胃出口阻塞接受內視鏡超音 波指引胃腸造口術與內視鏡腸道金屬 支架置放術的長期預後比較 郭雨庭1,2 黃永輝1,2 韓明倫1,2 陳介章1 廖偉智1 王秀伯1 台大醫院消化內科1 台大醫院綜合診療部內視鏡科2 Background: Gastric outlet obstruction (GOO) in patients with malignancies causes nausea, vomiting, abdominal pain, malnutrition, and dehydration. EUS-guided gastroenterostomy (EUS-GE) is a novel procedure for palliation of malignant GOO; however, data comparing EUSGE to endoscopic placement of self-expandable metallic stent (SEMS) are limited.

Aims: We aimed to compare clinical outcomes between EUS-GE and endoscopic SEMS placement in the palliation of malignant GOO. Methods: We performed a retrospective analysis of patients with malignant GOO who underwent endoscopic SEMS placement (n = 48) or EUSGE (n = 19) from January 2019 through July 2021 at National Taiwan University Hospital. Primary outcome was the rate of stent failure requiring repeat intervention. Secondary outcomes included technical and clinical success, time to repeat intervention, length of hospital stay, and adverse events. We performed multivariable analyses to identify factors associated with survival.

Results: Rate of stent failure requiring repeat intervention was higher in the endoscopic SEMS

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group than the EUS-GE group (37.5% vs. 5.3%, p = 0.047). Proportions of patients with clinical success did not differ significantly between the SMES group (97.9%) and the gastrojejunostomy group (100%) (P = 1). The median length of hospital stay following stent placement was higher in the endoscopic SEMS group than the EUSGE group (11.5 days vs. 5 days, p = 0.014). The endoscopic SEMS group significantly increased adverse events (39.6% vs. 5.3%, p = 0.044). Poor performance status, presence of ascites, low albumin and distal metastasis were independent risk factors for mortality.

Conclusions: Compared to endoscopic SEMS placement, EUS-GE has a higher rate of initial clinical success and lower rate of stent failure requiring repeat intervention. EUS-GE should therefore be considered the alternative treatment option for patients with good performance status and reasonable survival expectancy.

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MACROSCOPIC ON-SITE EVALUATION NO LONGER NEEDED IN FINE NEEDLE BIOPSY ERA Meng-Ying Lin1, Chun-Te Lee1, Wei-Lun Chang1, Bor-Shyang Sheu1,2 Division of Gastroenterology and Hepatology, Department of Internal Medicine, Nation Cheng Kung University Hospital, Tainan, Taiwan1 Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan2

diagnostic consistency rate between white tissue and red tissue was 80 %. The overall diagnostic sensitivity and accuracy within 2 needle passes were the same while compare between MOSE group to no MOSE group. (85.4% v.s 93.6%, p = 0.317 & 86.0% v.s 94.0%, p = 0.318) Conclusions: Using biopsy needle in EUS tissue acquisition, all specimens had enough white tissue length and high diagnostic consistency. The diagnostic performance was also similar no matter applied MOSE or not.

在內視鏡超音波導引胰臟腫瘤組織取 樣中使用切片針具時，及時宏觀分析法 將不再被需要 林孟穎1 李俊德1 張維倫1 許博翔1,2 國立成功大學醫學院附設醫院內科部胃腸肝膽科1 高雄醫學大學醫學系臨床醫學研究所2 Background: EUS-guided fine needle biopsy is standard procedure in diagnosing pancreatic mass. Macroscopic on-site evaluation (MOSE) significantly improved diagnostic efficacy and replaced microscopic on-site evaluation in area without on-site cytopathologist. Biopsy needle had been designed with better tissue quality recently.

Aims: We aim to test if MOSE is no longer needed while applying biopsy needles in EUS pancreatic tissue acquisition.

Methods: Patients received EUS tissue acquisition of pancreatic mass from January 2020 to May 2021 in National Cheng Kung University Hospital were included. Every patient had 2 needle passes and the acquired tissue was sent to histology review separately. In MOSE group, white tissue was picked up from red tissue then put into different formalin bottles and sent for histology diagnosis separately. In no MOSE group, specimen was not separated and sent for diagnosis together. The baseline character and diagnostic performance in each group was recorded and analysis.

Results: A total 100 patients were finally enrolled.

The first 50 patients were included into No MOSE group and the other 50 patients were included into MOSE group. The baseline character was similar between groups except tumor size. (33.3 mm v.s 38.4 mm, p = 0.03) In MOSE group, 100 % specimen had adequate white tissue length and the

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INCREASED EFFICACY OF SUSCEPTIBILITY-GUIDED TREATMENT FOR TRIPLE-DRUG RESISTANT H. PYLORI ACCORDING TO REVISED AMOXICILLIN AND TETRACYCLINE MIC BREAKPOINT Ming-Tsung Hsieh1, Chung-Tai Wu1, Wei-Lun Chang1, Hsin-Yu Kuo1, Meng-Ying Lin1, Yu-Chin Tsai1, Bor-Shyang Sheu1,2 Division of Gastroenterology and Hepatobiliary, Department of Internal Medicine, National Cheng Kung University Hospital, Tainan, Taiwan1 Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan2

針對多重抗藥性幽門桿菌感染的抗生 素救援療法，採用下修後 Amoxicillin 和 Tetracycline 最小有效濃度有效提 升救援療法療效 謝名宗1 吳忠泰1 張維倫1 郭欣瑜1 林孟穎1 蔡郁清1 許博翔1,2 國立成功大學醫學院附設醫院肝膽胃腸科1 高雄醫學大學醫學院臨床醫學研究所2 Background: H. pylori with triple-drug resistance (TR) to clarithromycin, metronidazole, and levofloxacin limits the success of rescue therapy. Amoxicillin and tetracycline have the first priority because their low resistance rate.

Two bismuth quadruple therapy including ATBP (amoxicillin, tetracycline, bismuth, PPI) and MTBP (metronidazole, tetracycline, bismuth, PPI) were the commonly used in the rescue therapy. Revised amoxicillin and tetracycline MIC breakpoint (0.032 mg/L and 0.094 mg/L) better predicted the outcome of bismuth quadruple therapy.

Aims: To evaluate the efficacy of susceptibilityguided treatment for triple-drug resistant H. pylori according to revised amoxicillin and tetracycline MIC breakpoint.

Methods: During January 2020 to December 2020, 13 patients with triple-drug resistant H. pylori were enrolled for susceptibility- guided treatment according to revised amoxicillin and tetracycline MIC breakpoint. ATBP, MTBP, AMBP (amoxicillin,

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metronidazole, bismuth, PPI), and MRBP (metronidazole, rifabutin, bismuth, PPI) regimens were assigned based on the MIC of amoxicillin and tetracycline (Figure 1). Each regimen was given for 14 days. Eradication was determined by 14C-urea breath test after the rescue therapy.

Results: Five patients with H. pylori susceptible to amoxicillin and tetracycline had 100% eradication rate with ATBP therapy. One patient susceptible to tetracycline but resistant to amoxicillin was successfully treated with AMBP. Five of the seven patients (71.4%) susceptible to amoxicillin but resistant to tetracycline were successfully treated with MTBP. Overall eradication rate was 85% which was better than the historical cohort (59.4%).

Conclusions: Susceptibility-guided treatment for triple-drug resistant H. pylori according to revised amoxicillin and tetracycline MIC breakpoint showed better eradication efficacy than the historical record. A larger case number is needed to strengthen the evidence.

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THE POLYGENIC RISK SCORES DERIVED FROM WESTERN COHORT FOR FATTY LIVER PREDICTION IS NOT VALID IN TAIWANESE POPULATION Chien-Wei Peng1,2, Wen-Juei Jeng1,2, Yi-Chung Hsieh1,2, Mei-Hung Pan3, Chih-Jen Huang3, Hwai-I Yang3 Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan, Taiwan1 College of medicine, Chang Gung University, Taoyuan, Taiwan2 Genomics Research Center, Academia Sinica, Taipei, Taiwan3

西方世代研究發展之預測脂肪肝風險 之多基因風險分數無法於台灣族群中 驗證 彭建維1,2 鄭文睿1,2 謝彝中1,2 潘眉虹3 黃志仁3 楊懷壹3 林口長庚紀念醫院胃腸肝膽科系1 長庚大學醫學院2 中央研究院基因體研究中心3 Background: Polygenic risk scores (PRS) have been developed to predict hepatic steatosis and hepatocellular carcinoma in western cohorts, which were based on five single-nucleotide polymorphisms, including PNPLA3 (rs738409), GCKR (rs1260326), MBOAT7 (rs641738), TM6SF2 (rs641738) and HSD17B13 (rs72613567).

However, information about their utility in detecting hepatitis steatosis in Asian patients is limited.

Aims: We validated the association of the existing PRS and hepatic steatosis in a population-based Taiwanese cohort.

Methods: This study included 555 subjects who had available information on next-generation sequencing and liver sonography in Taiwan biobank. Subjects with seropositivity of HBsAg and/ or anti-HCV antibody were excluded. The hepatic steatosis was diagnosed by liver sonography.

Baseline age, sex, body mass index, body fat rate, use of alcohol, history of hypertension, and serum biochemistry tests including glycohemoglobin, triglyceride (TG), low density cholesterol (LDL), and alanine transaminase (ALT) level were

analyzed. PRS-HFC (Bianco et al., 2020) and simplified PRS (Liu et al., 2021) were validated in this study. PRS-HFC was the sum of each risk allele multiply its effect size to hepatic steatosis.

The simplified PRS was the sum of each risk allele multiply one, while the minor allele of HSD17B13, as a protective factor, multiply minus one. Logistic regression analysis was performed to identify the predictors of fatty liver.

Results: Among the 555 subjects, 242 (43.6%) was diagnosed with fatty liver using abdominal ultrasonography.

By multivariate logistic regression analysis, higher body fat rate (adjusted odds ratio (OR): 1.062, P < 0.001), higher levels of TG (adjusted OR: 1.005, P =0.007), LDL (adjusted OR: 1.007, P =0.0259), and ALT (adjusted OR: 1.035, P = 0.0123), and carrier of homozygous minor allele of PNPLA3 (adjusted OR: 1,905, P = 0.0124) were at increased risk of hepatic steatosis, while GCKR, MBOAT7, TMS6SF2, and HSD17B13 were not associated with hepatic steatosis. Neither PRS-HFC (crude OR: 5.09, P = 0.1232) nor simplified PRS (crude OR: 1.149, P = 0.1548) was associated with fatty liver.

Conclusions: PNPLA3 was associated with elevated risk of hepatic steatosis, while HSD17B13 was not a protective factor in our Taiwanese cohort. The PRS derived from western cohorts may not be useful for detecting hepatic steatosis in Taiwanese. Therefore, different PRS should be developed according to different ethnicity.

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SURVIVAL OF PATIENTS WITH HEPATOCELLULAR CARCINOMA IN RENAL INSUFFICIENCY: PROGNOSTIC ROLE OF ALBUMINBILIRUBIN GRADE Shu-Yein Ho1, Chih-Chieh Ko2, Chien-Wei Su2, Ming-Chih Hou2, Yi-Hsiang Huang2, Teh-Ia Huo3,4 Division of Gastroenterology and Hepatology, Min-Sheng General Hospital, Taoyuan, Taiwan1 Division of Gastroenterology and Hepatology, Taipei Veterans General Hospital, Taipei, Taiwan2 Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan3 Institute of Pharmacology, National Yang Ming Chiao Tung University, Taipei, Taiwan4

利用白蛋白 - 膽紅素等級預後模型用於 預測肝細胞癌合併腎功能不全患者的 預後 何樹仁1 柯智傑2 蘇建維2 侯明志2 黃怡翔2 霍德義3,4 敏盛綜合醫院胃腸肝膽科1 臺北榮民總醫院胃腸肝膽科2 臺北榮民總醫院醫學研究部3 國立陽明交通大學藥理研究所4 Background: Renal insufficiency (RI), defined as estimated glomerular filtration rate (eGFR) < 60 ml/min/1.73m2, is commonly seen in patients with hepatocellular carcinoma (HCC). The prognostic role of albumin-bilirubin (ALBI) grade, a marker of liver dysfunction, in this special setting is unclear.

Aims: We aimed to investigate the role of ALBI grade associated with the impact of RI on HCC. Methods: A prospective cohort of 3690 HCC patients between 2002 and 2016 were retrospectively analyzed. The Kaplan-Meier method and multivariate Cox proportional hazards model were used to determine survival and independent prognostic predictors.

Results: Of all patients, RI was an independent predictor associated with decreased survival (hazard ratio [HR]: 1.234, p<0.001). In multivariate Cox analysis for patients with RI, �-fetoprotein level ≥ 20 ng/mL (HR:1.727, p<0.001), multiple

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tumors (HR: 1.178, p=0.036), tumor size >3 cm (HR: 2.293, p<0.001), vascular invasion or metastasis (HR: 1.289, p=0.004), presence of ascites (HR: 1.288, p=0.045), performance status 1-2 (HR: 1.143, p<0.001), performance status 3-4 (HR: 1.985, p<0.001), ALBI grade 2 (HR: 1.695, p<0.001) and grade 3 (HR: 2.878, p<0.001) were independent predictors of decreased survival. In subgroup analysis of patients with RI undergoing curative and non-curative treatments, the ALBI grade remained a significant prognostic predictor associated with decreased survival in the multivariate Cox analysis (p<0.001).

Conclusions: HCC patients with RI have decreased survival compared to those without RI. The ALBI grade can discriminate the survival in patients with RI independent of treatment strategy and is a feasible prognostic tool in this special patient population.

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⑥

LONG-TERM EFFECTIVENESS OF POPULATION-WIDE MULTIFACETED INTERVENTIONS FOR HEPATOCELLULAR CARCINOMA IN TAIWAN Sih-Han Liao1,2,3, Chi-Ling Chen3,4,5, Chen-Yang Hsu3, Kuo-Liong Chien3,6, Jia-Horng Kao2,4, Pei-Jer Chen2,4, Hsiu-Hsi Chen3, Chien-Hung Chen2,7,8 Section of Gastroenterology, Department of Medicine, National Taiwan University Cancer Center, Taipei, Taiwan1 Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan2 Graduate Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan3 Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan4 Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan5 Division of Cardiology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan6 Department of Internal Medicine, National Taiwan University Hospital Yunlin Branch, Yunlin, Taiwan7 College of Medicine, National Taiwan University, Taipei, Taiwan8

台灣全國性肝癌防治介入的長期有效性

hepatitis B and C virus infection since 1984.

Aims: We took this opportunity to investigate the impact of each intervention on the incidence and case-fatality rate of HCC, and assessed their relative contributions to the overall reduction in mortality during this period.

Methods: Population-based registry data on HCC mortality and incidence from individuals aged 0 to 84 years between 1979 and 2016 were collected before (Period 1) and after universal hepatitis B vaccination from 1984 (Period 2), universal health care from 1995 (Period 3), and viral hepatitis therapy from 2003 (Period 4). A Bayesian Poisson regression model was used for mortality decomposition analysis to estimate the respective contributions of these interventions to the reduction in age-specific incidence and casefatality rates.

Results: Mortality declined substantially in children, young- and middle-aged groups, but only slightly decreased in the elderly group. The declining trends in mortality were in part explained by incidence reduction and in part by a remarkable decline in case-fatality rate attributed to universal health care. Hepatitis B vaccination led to a 35.9% (26.8% to 44.4%) reduction in incidence for individuals aged 30 years or below, whereas antiviral therapy reduced the incidence of HCC by 14.9% (11.8% to 17.9%) and 15.4% (14.1% to 16.6%) for individuals aged 30–49 years and 50– 69 years, respectively.

Conclusions: Vaccination and antiviral therapy were effective in reducing HCC incidence and mortality for the young and middle-aged groups, while the case-fatality rate was improved by universal health care for all age groups.

廖思涵1,2,3 陳祈玲3,4,5 許辰陽3 簡國龍3,6 高嘉宏2,4 陳培哲2,4 陳秀熙3 陳健弘2,7,8 台大癌醫分院綜合內科部消化科1 台大醫院內科部胃腸肝膽科2 台大公衛學院流行病學與預防醫學研究所3 台大醫學院臨床醫學研究所4 台大醫院外科部5 台大醫院內科部心臟科6 台大雲林分院內科部7 台大醫學院8 Background: Taiwan has launched a series of population-wide interventions to prevent hepatocellular carcinoma (HCC) related to

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RECURRENCE OUTCOMES LESS FAVORABLE IN T1 RECTAL CANCER THAN IN T1 COLON CANCER Jer-Wei Wu1, Li-Chun Chang1,2, Chia-Tung Shun3, Been-Ren Lin4, Ming-Shiang Wu1, Han-Mo Chiu1,2 Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan1 Health Management Center, National Taiwan University Hospital, Taipei, Taiwan2 Department of Pathology, National Taiwan University Hospital, Taipei, Taiwan3 Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan4

T1 直腸癌的復發率較 T1 結腸癌高 吳哲瑋1 張立群1,2 孫家棟3 林本仁4 吳明賢1 邱瀚模1,2 台大醫院內科部1 台大醫院健康管理中心2 台大醫院病理部3 台大醫院外科部4 Background: With the implementation of screening program worldwide, diagnosis of early-stage colorectal cancer steadily increased, including T1 cancer. Current T1 cancer treatment does not differ according to anatomic location.

Aims: We therefore compared the disease-free survival of T1 cancer arising from rectum versus colon.

Methods: The hospital-based study included subjects with T1 cancer at National Taiwan University Hospital from 2005 to 2014. Clinical, colonoscopy, and histopathology were reviewed for patients with a mean follow-up time of 7.1 (0.712.9) years. We conducted Kaplan-Meier analysis to compare the risk of recurrence by cancer location and Cox-regression analysis to identify risk factors for T1 cancer recurrence.

Results: The final cohort included a total of 343 subjects with T1 cancer (mean age, 64.9 ± 11.7 years; 56.1% males), of whom 25 underwent endoscopic resection alone. Of the subjects who underwent surgery, 50 had lymph node metastasis and 268 did not. Kaplan-Meier analysis showed that the risk of recurrence was higher in T1 rectal cancer than T1 colon cancer (p = 0.022).

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Rectal location, and larger neoplasm size were independent risk factors for recurrence, with hazard ratios (95% confidence interval) of 4.84 (1.18-19.92), and 1.32 (1.06-1.65), respectively.

The occurrence of advanced histology did not differ between T1 rectal and colon cancers (p = 0.58).

Conclusions: T1 cancers arising from the rectum had less favorable recurrence outcomes than those arising from the colon. Further studies are needed to examine whether adjuvant radiotherapy or chemotherapy can reduce the risk of recurrence in T1 rectal cancer.

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PREDICTING OUTCOMES FOR CROHN’S DISEASE USING A MOLECULAR BIOMARKER: PROFILE TRIAL INTERIM UPDATE Nurulamin M Noor1, Biljana Brezina2, Juan De La Revilla Negro2, Francis Dowling3, Leisha M O’Brien3, Sanjana Choudhury3, Simon Bond3, Lynne Whitehead4, Sara Upponi5, Paul A Lyons1,6,7, Eoin F McKinney1,6,7, Kenneth GC Smith1,6,7, James C Lee1,2,6, Miles Parkes1,2, PROFILE Trial Investigators8 Department of Medicine, University of Cambridge School of Clinical Medicine, Addenbrooke’s Hospital, Cambridge, United Kingdom1 Department of Gastroenterology, Addenbrooke’s Hospital, Cambridge, United Kingdom2 Cambridge Clinical Trials Unit, Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom3 Clinical Trials Pharmacy, Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom4 Department of Radiology, Cambridge University Hospitals NHS Foundation Trust, Cambridge, United Kingdom5 Cambridge Institute for Therapeutic Immunology and Infectious Disease, Cambridge, United Kingdom6 PredictImmune Ltd, Babraham Research Campus, Cambridge, United Kingdom7 National Health Service, United Kingdom8

diagnosed IBD patients, we simultaneously obtained a whole-blood PAXgene RNA tube and peripheral-blood CD8 T-cell sample. Gene expression in both samples was measured by microarray. Statistical modelling was used to identify a transcriptional classifier in whole-blood gene expression data re-capitulating the CD8 findings and optimised into a multi-gene qPCR assay with independent validation in a second, independent cohort of 123 newly-diagnosed patients. The PROFILE trial has incorporated this classifier to compare relative efficacy of ‘topdown’ and ‘accelerated step-up’ therapy between biomarker-defined subgroups of 400 patients with newly-diagnosed Crohn’s disease.

Results: Following application of statistical learning methods described, a 17-gene qPCR assay was developed and optimised. In the validation cohort, 123 patients could be classified into two distinct subgroups, IBDhi (high risk) and IBDlo (lower risk).

IBDhi patients experienced significantly more aggressive disease than IBDlo patients, with earlier need for treatment escalation (hazard ratio = 2.65 (CD), 3.12 (UC)). Subsequently this biomarker is being used to stratify therapy in the PROFILE trial, where at the time of writing over 300 participants have been randomised - with recruitment ongoing.

Conclusion: We have developed, optimised and validated a whole-blood qPCR classifier that is able to predict disease course from diagnosis in patients with IBD. This classifier is currently being assessed for clinical utility in the PROFILE trial, which would represent a major step towards personalised therapy in IBD.

Background: The course of IBD varies substantially between individuals, but there are a lack of reliable prognostic markers to guide clinical practice.

Previously, we have described a transcriptional signature detectable within peripheral blood CD8 T-cells at diagnosis, identifying two subgroups of patients, correlating with prognosis.

Aims: We have sought to develop a biomarker that could re-capitulate the prognostic CD8 subgroups and then assess whether this can improve clinical outcomes by appropriately matching therapy to disease course.

Methods: From a training cohort of 69 newly-

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Free Paper Section：HCV

①

EFFECTIVENESS OF GLECAPREVIR/PIBRENTASVIR FOR PATIENTS WITH HEPATITIS C AND COMPENSATED CIRRHOSIS IN A REAL-WORLD SETTING IN TAIWAN Pei-Kai Su1, Te-Sheng Chang1,2 Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chang Gung Memorial Hospital, Chiayi, Taiwan1 College of Medicine, Chang Gung University, Taoyuan, Taiwan2

台 灣 真 實 環 境 中 Glecaprevir/ Pibrentasvir 對 C 型肝炎和代償性肝 硬化患者的效力 蘇培凱1 張德生1,2 嘉義長庚紀念醫院內科部腸胃肝膽科1 長庚大學醫學院2 Background: Real-world data regarding the effectiveness of glecaprevir/pibrentasvir (GLE/ PIB) for patients with hepatitis C virus (HCV) infection and compensated cirrhosis is limited, especially in the Asian population.

Aims: Proving the effectiveness of glecaprevir/ pibrentasvir for patients with hepatitis C and compensated cirrhosis in a real-world setting.

Methods: This retrospective cohort study included consecutive patients with chronic HCV infection and compensated cirrhosis treated with GLE/ PIB from August 2018 to January 2021 at Chang Gung Memorial Hospital in Chiayi, Taiwan. The diagnosis of cirrhosis was determined using acoustic radiation force impulse (> 1.98 m/s), fibrosis-4 index (> 6.5) or the presence of clinical, radiological, endoscopic, or laboratory evidence of cirrhosis and/or portal hypertension. Sustained virological response (SVR12) was defined as undetectable HCVRNA 12 weeks after the end of treatment. Adverse events (AEs) were also evaluated.

Results: A total of 160 patients with HCV and compensated cirrhosis treated with GLE/PIB were enrolled: 57 for 8 weeks and 103 for 12 weeks.

In the per protocol analysis, 95.7% (45/47) of the 8-week group and 100% (99/99) of the 12-week group achieved SVR; in the evaluable population

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analysis, 78.9% (45/57) of the 8-week group and 96.1% (99/103) of the 12-week group achieved SVR. Two patients had no response and did not attain SVR in the 8-week group, one of them had documented poor drug adherence. The AEs were numerically higher in the 12-week group compared to the 8-week group including pruritus (26.2% vs.

12.3%), fatigue (9.7% vs. 3.5%), and dizziness (7.8% vs. 1.8%). Laboratory abnormalities were also more common in the 12-week group. Total bilirubin elevation >3× the upper normal limit (UNL) was observed in 13.6% in the 12-week group and 5.3% in the 8-week group. Patients with alanine transaminase elevation >5× the UNL were very rare in both groups of patients. No AEs resulted in treatment discontinuation.

Conclusions: GLE/PIB treatment for 8 weeks is as effective as that for 12 weeks in patients of Taiwanese ethnicity with HCV and compensated cirrhosis.

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RISK STRATIFICATION OF HEPATOCELLULAR CARCINOMA INCIDENCE BY FIB-4-BASED PREDICTION MODEL IN PATIENTS WITH CHRONIC HEPATITIS C RECEIVING ANTI-VIRAL THERAPY: A NATIONWIDE REAL-WORLD TAIWANESE COHORT (T-COACH) Hung-Wei Wang1,2, Pei-Chein Tsai3,4, Chi-Yi Chen5, Kuo-Chih Tseng6, Hsueh-Chou Lai1,7, Hsing-Tao Kuo8, Chao-Hung Hung9, Shui-Yi Tung9, Jing-Houng Wang10, Jyh-Jou Chen11, Pei-Lun Lee11, Ron-Nan Chien12, Chun-Yen Lin12, Chi-Chieh Yang13, Gin-Ho Lo14, Chi-Ming Tai14, Chih-Wen Lin14, Jia-Horng Kao15,16, Chun-Jen Liu15,16, Chen-Hua Liu15,16, Sheng-Lei Yan17, Ming-Jong Bair18, Wei-Wen Su19, Cheng-Hsin Chu20, Chih-Jen Chen20, Ching-Chu Lo21, Pin-Nan Cheng22, Yen-Cheng Chiu22, Chia-Chi Wang23, Jin-Shiung Cheng24, Wei-Lun Tsai24, Han-Chieh Lin25, Yi-Hsiang Huang25, Jee-Fu Huang3,4, Chia-Yen Dai3,4, Wan-Long Chuang3,4, Ming-Lung Yu3,4, Cheng-Yuan Peng1,2 Center for Digestive Medicine, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan1 School of Medicine, China Medical University, Taichung, Taiwan2 Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan3 School of Medicine and Hepatitis Research Center, College of Medicine, and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan4 Department of Internal Medicine, Chiayi Christian Hospital, Chiayi, Taiwan5 Department of Internal Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chia-Yi; School of Medicine, Tzuchi University, Hualien, Taiwan6

School of Chinese Medicine, China Medical University, Taichung, Taiwan7 Division of Hepatogastroenterology, Department of Internal Medicine, Chi-Mei Medical Center, Tainan, Taiwan8 Division of Hepatogastroenterology, Department of Internal Medicine, Chiayi Chang Gung Memorial Hospital, Chiayi, Taiwan9 Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung Taiwan10 Division of Gastroenterology and Hepatology, Chi-Mei Medical Center, Liouying, Tainan, Taiwan11 Division of Hepatology, Department of Gastroenterology and Hepatology, Linkou Medical Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan12 Division of Gastroenterology, Department of Internal Medicine, Show-Chwan Memorial Hospital, Changhua, Taiwan13 Division of Gastroenterology and Hepatology, Department of Medicine, E-Da Hospital, and School of Medicine, I-Shou University, Kaohsiung, Taiwan14 Graduate Institute of Clinical Medicine, National Taiwan University, College of Medicine, Taipei, Taiwan15 Division of Gastroenterology and Hepatology, National Taiwan University Hospital, Taipei, Taiwan16 Division of Gastroenterology, Department of Internal Medicine, Chang Bing Show-Chwan Memorial Hospital, Changhua, Taiwan17 Division of Gastroenterology, Department of Internal Medicine, Taitung Mackay Memorial Hospital, Taitung, Taiwan18 Division of Gastroenterology, Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan19 Division of Gastroenterology, Department of Internal Medicine, Mackay Memorial Hospital, Taipei, Taiwan20 Department of Internal Medicine, St. Martin De Porres Hospital - Daya, Chiayi, Taiwan21 101

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Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Cheng Kung University Hospital and College of Medicine, National Cheng Kung University, Tainan, Taiwan22 Division of Gastroenterology, Department of Internal Medicine, Tzuchi Hospital, The Buddhist Tzuchi Medical Foundation, New Taipei, Taiwan23 Division of Gastroenterology and Hepatology, Department of Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan24 Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan25

FIB-4 為主的預測模型可區分慢性 C 型 肝炎患者接受抗病毒治療後之肝癌發 生風險：台灣全國性 C 型肝炎世代研 究 王鴻偉1,2 蔡佩倩3,4 陳啟益5 曾國枝6 賴學洲1,7 郭行道8 洪肇宏9 董水義9 王景弘10 陳志州11 李佩倫11 簡榮南12 林俊彥12 楊基滐13 羅錦河14 戴啟明14 林志文14 高嘉宏15,16 劉俊人15,16 劉振驊15,16 顏聖烈17 白明忠18 蘇維文19 朱正心20 陳志仁20 羅清池21 鄭斌男22 邱彥程22 王嘉齊23 鄭錦翔24 蔡維倫24 林漢傑25 黃怡翔25 黃志富3,4 戴嘉言3,4 莊萬龍3,4 余明隆3,4 彭成元1,2 中國醫藥大學附設醫院內科部消化醫學中心1 中國醫藥大學醫學系2 高雄醫學大學附設中和紀念醫院肝膽胰內科暨肝 炎防治中心3 高雄醫學大學醫學系、肝炎研究中心、液態生物 檢體暨世代研究中心4 嘉義基督教醫院內科部5 嘉義大林慈濟醫院內科部暨慈濟大學醫學系6 中國醫藥大學中醫系7 奇美醫學中心內科部胃腸肝膽科8 嘉義長庚紀念醫院內科部胃腸肝膽科系9 高雄長庚紀念醫院內科部胃腸肝膽科系暨長庚大 學醫學系10 柳營奇美醫院胃腸肝膽科11 林口長庚紀念醫院胃腸肝膽科系12 秀傳紀念醫院內科部胃腸肝膽科13 義大醫院內科部胃腸肝膽科暨義守大學醫學系14 國立臺灣大學臨床醫學研究所15 國立臺灣大學醫學院附設醫院內科部胃腸肝膽科16

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彰濱秀傳紀念醫院內科部胃腸肝膽科17 台東馬偕紀念醫院內科部胃腸肝膽科18 彰化基督教醫院內科部胃腸肝膽科19 台北馬偕紀念醫院內科部胃腸肝膽科20 天主教聖馬爾定醫院內科部21 國立成功大學醫學院附設醫院內科部胃腸肝膽科 暨國立成功大學醫學系22 台北慈濟醫院內科部胃腸肝膽科23 高雄榮民總醫院內科部胃腸肝膽科24 臺北榮民總醫院內科部胃腸肝膽科25 Background: Non-invasive liver fibrosis indices have been widely utilized to predict liver fibrosis status and even liver-related complications, including hepatocellular carcinoma (HCC) in patients with chronic hepatitis C (CHC).

Aims: We aimed to stratify HCC risks by noninvasive fibrosis index-based risk model in a realworld nationwide Taiwanese chronic hepatitis C cohort (T-COACH).

Methods: T-COACH is a nationwide hepatitis C virus registry cohort between 2003 and 2015 from 23 hospitals with a median follow-up period of 4.49 years (Q1-Q3: 2.63-7.15 years). A total of 1589 patients who had received IFN-based therapy with both baseline and end of follow-up (EOF) clinical data available were analyzed by Cox proportional hazards models for risk of HCC after adjustment for competing mortality.

Results: Of 1589 patients, 1363 (85.8%) patients achieved sustained virological response (SVR).

A total of 88 (5.5%) patients suffered HCC during 7762 person-years of follow-up. Patients with SVR had 1, 3, 5, 10-year cumulative HCC incidence rates of 0.55%, 1.87%, 3.48% and 8.35%, respectively.

According to receiver operating characteristic curve analysis, FIB-4 at baseline and EOF showed remarkable and similar diagnostic performance in distinguishing HCC (area under the curve [AUC] FIB-4 at baseline: 0.832, EOF: 0.829; DeLong test, P = 0.813). According to the Cox proportional hazards model, non-SVR (adjusted hazards ratio [HR]: 1.92, P = 0.008), diabetes mellitus (adjusted HR: 2.11, P = 0.005) and FIB-4 at EOF (adjusted HR: 5.60, P < 0.0001) were significant predictors of HCC. Risk score models were developed to predict HCC according to HR. In model 1 (by sum of risk score), the 10-year cumulative incidence rates of HCC were 43.35% in patients with high risk (score 9-10), 25.48% in those with intermediate risk (score 6-8) and 4.06% in those with low risk (score 3-5).

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While in model 2 (by number of risk predictor), the 10-year cumulative incidence rates of HCC were 39.64% in patients with high risk (at least two risk predictors), 19.12% in those with intermediate risk (with one risk predictor) and 2.52% in those with low risk (without any risk predictor).

Conclusions: The FIB-4-based prediction model at EOF could help stratify the risk of HCC in patients with CHC after anti-viral therapy.

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CLUSTER ANALYSIS OF PATIENTS WITH METABOLIC-ASSOCIATED FATTY LIVER DISEASE Tung-Han Ho1, Chun-Nan Chen1, Sheng-Wei Cheng1, Fat-Moon Suk1, Gi-Shih Lien1, Ming-Shun Wu1,2 Division of Gastroenterology, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan1 Division of Gastroenterology and Hepatology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan2

利用集群分析分類新陳代謝相關脂肪 肝病人 何東翰1 陳俊男1 鄭勝偉1 粟發滿1 連吉時1 吳明順1,2 臺北市立萬芳醫院消化系內科1 臺北醫學大學醫學院醫學系消化內科2 Background: Metabolic associated fatty liver disease (MAFLD) is identified in patients with hepatic steatosis and concurrently the three metabolic conditions: obesity, diabetes and metabolic dysregulation, either alone or in combination. MAFLD is slowly progressive, the present cut-off value of the subtypes of MAFLD diagnosed by different metabolic conditions is insufficient to reflect the progression and outcome of such disease.

Aims: This study aims to classify the subtypes of MAFLD by cluster analysis and depict the characteristics of these subtypes of MAFLD. Methods: The data were retrieved from the Taipei Medical University-Wan Fang Hospital in Taiwan. We define the positive criteria of MAFLD by correlation method. After cluster analysis and optimal classification, the clinical and biochemical features in different MAFLD subtypes were compared.

Results: After the correlation analysis, triglyceride (TG), alanine aminotransferase (ALT), insulin, homeostasis model assessment-insulin resistance (HOMA-IR), TG-HDL (high-density lipoprotein cholesterol) ratio are the positive criteria of MAFLD. The optimal number of clusters is three.

The biomarkers including controlled attenuation parameter (CAP), HDL, HOMA-IR, TG-HDL ratio

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were noted for their significant difference of each variable among 3 clusters. The different severity of steatosis in the three clusters was showed in the box plot indicated that the status of MAFLD is different in the three groups.

Conclusions: The results suggest that this new clustering is a better approach to identify patients with MAFLD. CAP, HDL, HOMA-IR and TG-HDL ratio may be the effective predictive biomarkers for worsening condition of MAFLD.

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HEPATITIS B CO-INFECTION MAY ALLEVIATE FIBROSIS REGRESSION IN CHRONIC HEPATITIS C PATIENTS TREATED WITH DIRECT-ACTING ANTIVIRALS Cheng-Er Hsu1, Yen-Chun Liu1,2, Ya-Ting Cheng1,2, Wen-Juei Jeng1,2, Rong-Nan Chien1,2, Chun-Yen Lin1,2, I-Shyan Sheen1,2 Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan, Taiwan1 College of Medicine, Chang Gung University, Taoyuan, Taiwan2

合併 B 型肝炎感染，可能減輕全口服 抗 C 肝病毒藥物改善肝纖維化的效果 徐正二1 劉彥君1,2 鄭雅婷1,2 鄭文睿1,2 簡榮南1,2 林 俊彥1,2 沈一嫻1,2 林口長庚紀念醫院胃腸肝膽科1 長庚大學醫學院2 Background: High sustained virological response (SVR) rate (>95%) and fibrosis regression could be achieved by 8-24 weeks of direct acting antivirals treatment (DAA) in patients with chronic hepatitis C virus (HCV) infection. However, in chronic hepatitis C (CHC) patients co-infected with hepatitis B virus (HBV), reactivation of HBV were reported during DAA treatment which may even lead to increase ALT level or hepatitis events.

Aims: This study aims to compare the fibrosis regression proportion between patients with monoHCV and HBV + HCV dual infection who achieved SVR after DAA treatment.

Methods: CHC patients with / without HBV co-infection who received DAA treatment and achieved SVR12 from March 2015 to December 2019 in Chang Gung Memorial Hospital, Linkou branch were enrolled. Those with available liver stiffness measurements (LSM) before and during 1-year follow-up were recruited into analysis.

LSM assessed by transient elastography (TE, Fibroscan) were prospectively recorded at baseline and after SVR The exclusion criteria were human immunodeficiency virus co-infection, age < 18 years old while starting DAA treatment, unable to complete DAA treatment course, no SVR. The criterion of fibrosis regression is LSM decreased over 30% after DAA treatment. Propensity score

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matching adjusting pretherapy age, ALT, platelet, LSM, gender were done at 1:3 ratio before comparison between mono-HCV and HBV + HCV infected patients.

Results: Among 906 patients enrolled, 853 patients were HCV mono infection, 53 patients were HCV and HBV co-infection. The median age was 63 year-old, 39.8% male, 63.8% genotype 1 and the median level of HCV RNA was 6.2 log10 IU/mL. Patients with HBV + HCV coinfection are more likely to be younger age (61.8 vs.

63.2, P=0.29), male (54.7% vs. 38.9%, P=0.02) and lower pretherapy LSM level (8.3 vs. 10.2 kPA, P=0.11) while HCV RNA, HCV genotype, pretherapy ALT, platelet, BMI and type 2 DM proportion were comparable. After PSM with 1 to 3 ratio, higher proportion of mono-HCV infected patients achieved LSM improvement >30% after DAA treatment comparing to dual HBV + HCV infection (32.1% vs. 24.5%, P=0.3) Conclusions: The regression of fibrosis after DAA treatment may be alleviated by HBV co-infection.

Further validation study should be conducted to provide robust evidence of this issue.

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COMPARISON OF EFFICACY AND SAFETY BETWEEN PANGENOTYPIC HCV DIRECTACTING ANTIVIRAL AGENTS: EPCLUSA VERSUS MAVIRET – A SINGLE CENTER DATA IN SOUTHERN TAIWAN Chun-Yu Lin, Chien-Hung Chen, Tsung-Hui Hu, Jing-Houng Wang, Chao-Hung Hung, Sheng-Nan Lu Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan

C 型肝炎全基因型口服抗病毒藥宜譜 莎與艾百樂的藥效與安全性比較 ─ 台 灣南部單一醫學中心的資料分析 林俊宇 陳建宏 胡琮輝 王景弘 洪肇宏 盧勝男 高雄長庚紀念醫院內科部胃腸肝膽科 Background: Eight-week glecaprevir/pibrentasvir (Maviret) and 12-week sofosbuvir/velpatasvir (Epclusa) leads to a high rate of sustained virological response at post-treatment week 12 (SVR12).

Aims: To compare the efficacy and safety of 8-week Maviret and 12-week Epclusa in all patients and specific populations.

Methods: This study included total 972 patients who received 8-week Maviret (n=487) and 12week Epclusa (± Ribavirin) (n=485) treatment from August 2018 to October 2020.

Results: Of the 972 patents, 925 completed DAA treatment and post-treatment week12. Of the 925 patients, there was no significant difference in patients who achieved SVR12 between Epclusa and Maviret (452/458, 98.69% vs. 464/467, 99.36%; p=0.302) groups. Among the patients without SVR12, 3 were treatment failure and 3 were relapsers in Epclusa group, and all 3 were relapsers in Maviret group. There was a similar SVR12 rate in different HCV genotypes (1a, 1b, 2, 3, 6) between Epclusa and Maviret groups.

There was also no significant difference in SVR12 rate between Epclusa and Maviret groups in HBV co-infection (46/47, 97.9% vs 33/33, 100%), compensated cirrhosis (97/100, 97% vs. 23/23,

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Section：LGI 100%), history of HCC (26/26, 100% vs. 10/10, 100%) and end-stage renal disease (22/22, 100% vs. 77/77, 100%). There was significant difference in eGFR change at the end of treatment from baseline (-2.54 ± 17.8 versus 0.54 ± 12.9 mL/ min/1.73m2, p=0.008) and at post-treatment 12 weeks from baseline (-3.31 ± 16.9 versus 0.25 ± 13.6 mL/min/1.73m2, p=0.001) between Epclusa and Maviret groups in patients with eGFR ≥30 mL/ min/1.73m2 at baseline. In patients with incomplete treatment in the groups of Epclusa (n=14) and Maviret (n=13), 11 patients discontinued treatment due to side effect of drugs (Epclusa versus Maviret: 1 versus 5) or complications of other etiologies (Epclusa versus. Maviret: 2 versus 3).

Conclusions: Eight-week Maviret and 12-week Epclusa had a similar SVR12 rate in different HCV genotypes and special populations. However, Epclusa group seemed to have a worse eGFR change than Maviret group.

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TREND CHANGES OF METABOLIC RISK FACTORS OF COLORECTAL NEOPLASMS – FROM ADENOMA TO ADENOCARCINOMA Yu-Min Lin1,2,3, Tsan-Hsuan Chang1, Lee-Won Chong1,2,3, Hung-Chuen Chang1,2,3, Yu-Hwa Liu1,2, Cheuk-Kay Sun1,2,3, Kou-Ching Yang1,2 Department of Internal Medicine, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan1 Division of Gastroenterology and Hepatology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan2 School of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan3

結直腸腫瘤的代謝危險因子之變化趨 勢分析 ─ 從腺瘤到腺癌 林裕民1,2,3 張燦璿1 張麗文1,2,3 張鴻俊1,2,3 劉玉華1,2 孫灼基1,2,3 楊國卿1,2 新光吳火獅紀念醫院內科1 新光吳火獅紀念醫院胃腸肝膽科2 天主教輔仁大學醫學系3 Background: Colorectal cancer (CRC) is the third leading cause of cancer death in Taiwan. Recent reports suggest that metabolic derangements are important risk factors of colorectal neoplasm (CRN), however, the alterations of metabolic factors in the malignant transformation remain not clear.

Aims: We evaluate the trend of changes of key metabolic factors in the colorectal adenomacarcinoma sequence.

Methods: We enroll participants for health examination with complete colonoscopy between Jan. 2014 and Feb. 2020 in our hospital.

Individuals of colorectal adenomatous neoplasms with diameter larger than 0.5cm were enrolled for analysis. We design an age and gender matched case-control study (case to control ratio: 1:2). The differences in the proportions of common chronic disorders including hepatitis B, hepatitis C, obesity, hypertension, dyslipidemia, glucose intolerance and positivity of fecal Hb (FIT) are compared between individuals with and without CRN. The associations between the histological trends of CRN and chronic disorders are determined by the

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Mantel-Haenszel Chi-squared Test for Trends. A p value <0.05 is considered as significant.

Results: A total of 28511 colonoscopies were completed in the study period. Among them, there are 2341 cases with CRNs meet the criteria for analysis including: 1809 tubular adenomas, 428 advanced adenomas, 60 severe dysplasia and 44 adenocarcinomas. Comparing with the age and gender matched controls, the metabolic derangements are common in patients of CRN but not consistence in the adenoma-carcinoma sequence. The histological severity of CRN (tubular adenoma, villous adenoma, severe dysplasia and cancer) is associated with an increasing odds ratio of chronic hepatitis C (0.65, 0.88, 1.33 and 2.00; p for trend = 0.021), metabolic syndrome (1.48, 1.56, 1.65 and 2.00; p for trend = 0.021) and positivity of FIT (2.73, 12.43, 22.00 and 31.00; p for trend <0.001).

Conclusions: In conclusion, in the adenomacarcinoma sequence of large bowel, the more advanced histological grade is associated with a higher proportion of chronic hepatitis C, metabolic syndrome and positivity of FIT. The dose dependent relationships not only imply causations but also are helpful for developing more precision strategies for CRC screening.

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ANTICOAGULANT DRUGS WITH OR WITHOUT PROTON PUMP INHIBITOR AND COLORECTAL CANCER RISK: A POPULATIONBASED, CASE-CONTROL STUDY Pei-Huan Ho1, Hung-Chun Hsiao2, Chun-Wei Chen3, Hui-Ming Chen4, Siew-Na Lim5,6, Chau-Ting Yeh2,3,6, Chia-Jung Kuo3,6, Wey-Ran Lin2,3,6 Department of Internal Medicine, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan1 Liver Research Center, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan2 Department of Gastroenterology and Hepatology, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan3 Center for Big Data Analytics and Statistics, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan4 Department of Neurology, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan5 College of Medicine, Chang Gung University, Taoyuan, Taiwan6

使用抗凝血藥物、氫離子幫浦抑制劑與 大腸直腸癌風險之關係 何沛桓1 蕭宏峻2 陳俊瑋3 陳薈茗4 林秀娜5,6 葉昭廷2,3,6 郭家榮3,6 林蔚然2,3,6 林口長庚紀念醫院內科部1 林口長庚紀念醫院肝臟研究中心2 林口長庚紀念醫院肝膽腸胃科3 林口長庚紀念醫院巨量資料及統計中心4 林口長庚紀念醫院神經內科5 長庚大學醫學院6 Background: Colorectal cancer (CRC) is one of the most common types of cancer worldwide.

Low-dose aspirin and clopidogrel have been demonstrated their potential chemoprevention effects of CRC. Proton-pump inhibitors (PPI) are commonly prescribed with anticoagulation drugs, but the relationship between PPI and CRC is controversial. Moreover, the evidences of CRC risk under direct oral anticoagulant (DOAC), are limited.

Aims: This study aimed to investigate the effects of anticoagulation drugs combined with or without

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PPI on the risks of CRC in Taiwan population.

Methods: A retrospective case-control study of total 1,024,227 cases based on Chang Gung Research Database from 2011 to 2017 was performed. The clinical characteristics, the indications and durations for anticoagulation drugs and PPI, and the CRC occurrence were collected.

Logistic regression was applied to adjust known confounders of CRC risk.

Results: Low-dose aspirin plus clopidogrel decreased the risk of CRC (AOR: 0.65; 95% CI: 0.44-0.96), while no protective effect was observed in aspirin or clopidogrel alone. DOAC did not affect CRC significantly. The risk of CRC increased in patients with PPI (AOR: 1.45; 95% CI: 1.341.57) and PPI plus DOAC (AOR: 2.81; 95% CI: 1.11-7.12). There were no significant association between CRC and other PPI combination therapy.

Conclusions: This study demonstrated that lowdose aspirin plus clopidogrel presented chemopreventive effects against CRC in Chinese population, though the same effect was not observed in DOAC. Moreover, the significant increase of CRC was observed in patients with monotherapy of PPI and PPI plus DOAC, suggesting its possible hazards effects on the risk of CRC.

⑧

PROTON PUMP INHIBITORS INCREASED MORTALITY IN CLOSTRIDIOIDES DIFFICILE INFECTED PATIENTS BY INDUCING GUT DYSBIOSIS Cheng-Yu Lin1,2, Hao-Tsai Cheng2,3, Chia-Jung Kuo1,2, Yun-Shien Lee4, Sen-Yung Hsieh1,2 Division of Gastroenterology and Hepatology, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan1 College of Medicine, Chang Gung University, Taoyuan, Taiwan2 Division of Gastroenterology and Hepatology, TuCheng Hospital, New Taipei City, Taiwan3 Department of Biotechnology, Ming Chuan University, Taoyuan, Taiwan4

質子幫浦抑製劑通過誘導腸道菌群失 調增加艱難梭菌感染患者的死亡率 林正祐1,2 鄭浩材2,3 郭家榮1,2 李御賢4 謝森永1,2 林口長庚紀念醫院胃腸肝膽科系1 長庚大學醫學院2 新北市立土城醫院胃腸肝膽科3 銘傳大學生物科技學系4 Background: Clostridioides difficile infection (CDI) increases mortality, particularly in patients with chronic illness. Proton pump inhibitor (PPI) use is assumingly associated with CDI and gut dysbiosis.

Aims: We aimed to elucidate the role of PPIassociated gut dysbiosis in the mortality of CDI patients.

Methods: CDI was diagnosed by positive for a stool tcdB assay. Risk factors associated with mortality were identified by Cox regression analyses. Fecal microbiota was determined by sequencing of 16S rRNA. Results: Of the 306 diarrhea patients, 240 patients were diagnosed with CDI, including 117 (48.8%) males (mean age 69.1 years). Thirty-six (15.0%) and 91 cases (37.9%) were dead within 30 and 180 days, respectively. Multivariate analysis revealed that male gender, high Charlson’s index and McCabe score, high serum C-reactive protein level, low hematocrit, low absolute eosinophil counts, high neutrophil/lymphocyte ratios, and

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longer daily PPI were independent risk factors of overall mortality. PPI prescribing is particularly important because of its avoidance might benefit patients. Cumulative analyses confirmed the association of daily PPI with higher mortality (P < 0.001). Moreover, the daily PPI duration was positively correlated with higher mortality (P < 0.001). Fecal microbiota analyses showed the association of decreased relative abundance of Ruminococcus gnavus and Prevotella copri and increased relative abundance of Parabacteroides merdae with higher mortality in CDI patients.

Moreover, the microbe changes were correlated to the duration of daily PPI. Conclusions: PPI use increased the mortality of CDI patients by inducing gut dysbiosis. Our findings provide a global notion of PPI use particularly in CDI patients.

⑨

THE CHANGE OF GUT MICROBIOTA IS ASSOCIATED WITH INTESTINAL STRICTURE IN TAIWANESE PATIENTS WITH INFLAMMATORY BOWEL DISEASE Tien-Yu Huang1,2,3,4, Peng-Jen Chen1, Yu-Lueng Shih1, Wei-Kuo Chang1,2, Tsai-Yuan Hsieh1 Division of Gastroenterology, Department of Internal Medicine, Tri-Service General Hospital, National Defense General Hospital, Taipei, Taiwan1 Taiwan Association for the Study of Small Intestinal Diseases2 Taiwan Society of Inflammatory Bowel Disease3 Taiwan Microbiota Consortum4

腸內菌的改變與國人發炎性腸道疾病 產生腸道狹窄具相關性 黃天祐1,2,3,4 陳鵬仁1 施宇隆1 張維國1,2 謝財源1 國防醫學院三軍總醫院胃腸科1 台灣小腸醫學會2 台灣發炎性腸道疾病學會3 台灣微菌聯盟4 Background: Inflammation bowel disease (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), is an idiopathic chronic intestinal inflammation. Stricture of gut is the major complication of disease progression of IBD, especially in patients with CD. The actual pathogenesis of fibro-stricture is inconclusive. Gut microbiota contributes to the disease development of IBD but the data associated with intestinal stricture is limited.

Aims: To determine the changes of gut microbiota between normal subjects and Taiwanese patients with IBD and study the correlation of gut microbiota and the existence of intestinal stricture.

Methods: We prospectively collected the stools from the patients with IBD including CD and UC for analysis of gut microbiota. We also collected the clinical characteristics (age, gender, BMI, smoking, EIM, duration of disease, previous intestinal resection), types of IBD, disease activity, and disease locations from the enrolled patients. We further analyzed the differences of gut microbiota

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between normal subjects (n=37) and IBD patients (n=37) with/without intestinal stricture.

Results: From our data, compared with normal subjects, the Beta-diversity showed significant differences in gut microbiota of CD and UC patients. Both Alpha- and Beta- diversities revealed significant differences between CD and UC patients. Furthermore, Gut microbiota also showed significant differences between IBD with stricture and without stricture in Alpha- and Betadiversities. Fusobacterium showed markedly higher levels in IBD patients with stricture as compared with those without stricture.

Conclusions: Gut microbiota showed significant differences between CD and UC Taiwanese patients. The change of gut microbiota showed association with intestinal stricture in IBD patients.

The genus of Fusobacterium might play some role in IBD patients with stricture.

⑩

FEASIBILITY OF SMALL BOWEL EXPLORATION BY USING THE NOVEL STRING AND MAGNETICASSISTED CAPSULE ENDOSCOPY SYSTEM Wei-Chu Tsai1, GiShih Lien2,3, Hong-Ming Tsai4, Chiung-Yu Chen1, Chiao-Hsiung Chuang1, Wei-Ying Chen1, Wei-Lun Chang1, Po-Jun Chen1, Jui-Wen Kang1, Ming-Tsung Hsieh1,5, Juei-Seng Wu1, Hsin-Yu Kuo1,5 Departments of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan1 Division of Gastroenterology, Department of Internal Medicine, Taipei Municipal Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan2 Department of Internal Medicine, Taipei Medical University Hospital, Taipei, Taiwan3 Diagnostic Radiology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan4 Institute of Clinical Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan5

磁力輔助帶線膠囊內視鏡於小腸疾病 診斷的可行性研究 蔡惟竹1 連吉時2,3 蔡宏名4 陳炯瑜1 莊喬雄1 陳威穎1 張維倫1 陳柏潤1 康瑞文1 謝名宗1,5 吳叡森1 郭欣瑜1,5 國立成功大學醫學院附設醫院內科部1 臺北市立萬芳醫院內科部消化內科2 臺北醫學大學附設醫院內科部3 國立成功大學醫學院附設醫院放射診斷部4 國立成功大學醫學院附設醫院臨床醫學研究所5 Background: Balloon-assisted enteroscopy and capsule endoscopy were two standard tools for small-bowel diagnostics. However, the clinical application of these two examinations was limited due to some unavoidable drawbacks. The String and Magnetic-Controlled Capsule Endoscopy

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Section：HBV (SMCCE) (InsightEyes EGD System) has been introduced as successful evaluation of stomach and duodenum with non-invasiveness, allowance to anchor on difficult positions and maneuver the capsule repeatedly.

Aims: This study aims to evaluate the feasibility of SMCCE for small bowel evaluation.

Methods: Between October 2020 and December 2020, we enrolled 10 patients in need of small bowel examination at National Cheng Kung University Hospital, Tainan, Taiwan. Two patients had clinically confirmed Crohn’s disease with ileum involvement and one patient were diagnosed as small bowel polyposis syndrome. The study outcomes included small bowel insertion depth, maneuverability, procedure time, and adverse events.

Results: A total of 10 patients were consecutively enrolled in the study (mean age, 40-year-old, 20% male). Mean examination time for SMCCE during whole procedures was 8 hours 38 minutes.

Visualization of duodenal papilla was achieved in 7 cases (70%). The mean small bowel insertion depth was around 77.8 cm (range, 12.5 cm177.4 cm). The estimated reached small bowel segments were: duodenum 3th portion (n = 1, 10.0%), proximal jejunum (n = 6, 60.0%), middle jejunum (n = 2, 20.0%), and distal jejunum (n = 1, 10.0%). In 9 patients, findings on SMCCE beyond the second part of the duodenum were normal.

For the remaining one patient with polyposis syndrome, small bowel polyps were detected over the duodenum and proximal jejunum. No serious complications occurred. 70% (n = 7) of patients were willing to undergoing further SMCCE examination if they are needed to examine again.

Conclusions: SMCCE might be a potential diagnostic tool for proximal small bowel disease owing to less invasiveness, safety, and without need of anesthesia. To evaluate the performance and diagnostic yield for evaluation of the small bowel, it’s definitely needed to conduct largescale research and head-to-head comparison with conventional enteroscopy in the near future.

⑪

TWO-YEAR RISK OF HBV REACTIVATION AFTER RITUXIMAB THERAPY IN PATIENTS WITH HEMATOLOGIC AND RHEUMATOLOGIC DISEASES WITH AND WITHOUT HEPATITIS B SURFACE ANTIGEN Kuan-Chu Hou1, Tung-Hung Su2,3, Chien-Neng Kao4, Song-Chou Hsieh5, Chun-Jen Liu2,3,6, Jia-Horng Kao2,3,6 School of Medicine, College of Medicine, National Taiwan University Taipei, Taiwan1 Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan2 Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan3 Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Hsin-Chu Branch, Hsinchu, Taiwan4 Division of Rheumatology, Immunology & Allergy, National Taiwan University Hospital, Taipei, Taiwan5 Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University Taipei, Taiwan6

不同 B 型肝炎表面抗原狀態的血液及 風濕疾病患者在 Rituximab 治療後的 二年 HBV 復發風險之比較 侯冠竹1 蘇東弘2,3 高健能4 謝松洲5 劉俊人2,3,6 高嘉宏2,3,6 國立臺灣大學醫學院1 國立臺灣大學醫學院附設醫院胃腸肝膽科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新竹臺大分院新竹 醫院胃腸肝膽科4 國立臺灣大學醫學院附設醫院免疫風濕過敏科5 國立臺灣大學醫學院臨床醫學研究所6 Background: Hepatitis B virus (HBV) reactivation is common in patients receiving rituximab therapy without prophylactic antiviral therapy. The rate of HBV reactivation had not been compared between patients with hematologic or rheumatologic diseases with and without hepatitis B surface

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antigen.

Aims: We aimed to investigate HBV reactivation rate in patients with hematologic or rheumatologic diseases with and without hepatitis B surface antigen for risk stratification.

Methods: Patients who received rituximab therapy without prophylactic anti-HBV therapy at National Taiwan University Hospital between May 2000 and July 2016 were retrospectively collected. Their characteristics and HBV reactivation rate were recorded and compared.

Results: A total of 378 patients who received immunosuppressive biological agents were screened. After exclusion of those without any serostatus of HBV, a total of 117 patients who received rituximab therapy without prophylactic anti-HBV therapy were enrolled. Among them, 78 had hematologic diseases (mostly lymphoma), and 39 had rheumatologic diseases. After rituximab therapy, the HBV reactivation rate at 6, 12, 18, and 24 months were 19.3%, 28.7%, 41.9%, and 55.5% in HBsAg-positive hematologic patients; 27.5%, 44.5%, 48.5%, and 52.5% in HBsAg-positive rheumatologic patients. These reactivation rates were 21.6%, 38.4%, 44.0%, and 50.7% in HBsAgnegative hematologic patients; 0%, 16.7%, 16.7%, and 33.3% in HBsAg-negative rheumatologic patients. There is no statistical difference in risk of HBV reactivation between hematologic and rheumatologic patients, and between HBsAgpositive and HBsAg-negative ones. However, the reactivation rates were numerically lower in HBsAg-negative rheumatologic patients. The risk of HBV reactivation was associated with HBV DNA baseline level >20 IU/mL. Conclusions: The HBV reactivation risk was extremely high in patients treated with rituximab without prophylactic antiviral therapy, regardless of underlying disease and HBsAg seropositivity.

The risk of HBV reactivation increased gradually till 2 years after rituximab therapy, which indicates a prolonged antiviral prophylaxis may be needed.

⑫

COMPARISON OF LONG-TERM CLINICAL OUTCOMES BETWEEN PATIENTS WITH SPONTANEOUS AND OFF-NUC HBSAG SEROCLEARANCE Wen-Juei Jeng1,2,3, Chien-Hung Chen1,4, Hwai-I Yang5, Tai-Chung Tseng6, Yen-Chun Liu1,3, Yi-Cheng Chen1,3, Cheng-Yuan Peng7,8,9, Tsung-Hui Hu1,4, Chao-Hung Hung1,4, Jing-Hung Wang1,4, Cheng-Nan Lu1,4, Jia-Horng Kao6, Rong-Nan Chien1,2,3, Yun-Fan Liaw1,2 College of Medicine, Chang Gung University, Taipei, Taiwan1 Liver research unit, Chang Gung Memorial Hospital, Linkou branch, Taoyuan, Taiwan2 Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan, Taiwan3 Devision of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan4 Genomic research center, Academia Sinica, Taipei, Taiwan5 Division of Gastroenterology and Hepatology, Department of internal medicine, National Taiwan University Hospital, Taiwan6 Center for Digestive Medicine, China Medical University Hospital, Taichung, Taiwan7 China Medical University Hospital, Taichung, Taiwan8 Division of Hepatogastroenterology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan9

患者自發性表面抗原消失與停藥後表 面抗原消失之長期臨床預後比較 鄭文睿1,2,3 陳建宏1,4 楊懷壹5 曾岱宗6 劉彥君1,3 陳益程1,3 彭成元7,8,9 胡琮輝1,4 洪肇宏1,4 王景弘1,4 盧勝男1,4 高嘉宏6 簡榮南1,2,3 廖運範1,2 長庚大學醫學院1 林口長庚紀念醫院肝臟研究中心2 林口長庚紀念醫院胃腸肝膽科系3 高雄長庚紀念醫院內科部胃腸肝膽科4 中央研究院基因體中心5

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國立臺灣大學附設醫院內科部胃腸肝膽科6 中國醫藥大學附設醫院消化醫學中心7 中國醫藥大學8 中國醫藥大學附設醫院內科部胃腸肝膽科9 Background: Increased HBsAg seroclearance has been observed in patients who stop nucleos(t) ide analogue therapy (off-Nuc). Limited information was available about their long-term outcomes compared to spontaneous HBsAg loss patients.

Aims: This study aims to investigate the longterm clinical outcomes between patients with spontaneous and off-Nuc HBsAg seroclearance.

Methods: Patients with spontaneous or offNuc HBsAg loss from four medical centers and REVEAL-HBV cohort were recruited. Those with HCC occurred prior to HBsAg loss or occurred within 6 months after HBsAg loss were excluded.

Age, gender, cirrhosis status, HBV genotype, serum AST, ALT, AFP level, platelet count, FIB-4 at time of HBsAg loss were compared between patients in the spontaneous or off-Nuc arm, as well as those with and without HCC development.

Multivariate cox regression analysis was applied for independent predictors of HCC in patients with HBsAg loss. To adjust the difference between host and viral factors between the spontaneous and the off-Nuc arms, propensity score matching was done at 1:1 ratio. Kaplan Meier analysis with log rank test was performed to compare the cumulative incidence of HCC between the spontaneous and off-Nuc HBsAg loss groups.

Results: A total of 1309 spontaneous and 281 off-Nuc HBsAg loss patients were recruited.

Higher proportion of male, cirrhosis, higher serum ALT, AST, FIB-4 level and lower AFP, platelet count and shorter follow-up duration were noted in the off-Nuc arm. Multivariate cox regression analysis showed age >50 (aHR: 2.0, P=0.03) and cirrhosis (aHR: 6.8, P<0.001) were the only two independent predictors for HCC development while male (aHR: 2.0, P=0.07) and off-Nuc (aHR: 1.8, P=0.08) failed to reach statistical significance.

Stratifying by cirrhotic status, off-Nuc arm was neither an independent factor in non-cirrhosis (HR: 2.1, P=0.16) or cirrhosis group (HR: 1.5, P=0.37).

The annual and 5-year cumulative incidence of HCC between spontaneous and off-Nuc HBsAg loss patients were 0.23%, 1% vs. 0.8%, 4%, respectively (log rank test, P<0.01). After PSM adjustment with age, gender and cirrhotic status, there were 230 patients in each arm. The annual

and 5-year cumulative incidence of HCC between spontaneous and off-Nuc arm were comparable (0.51%, 2% versus 0.87%, 4%, respectively, log rank test, P=0.185). Among the 281 offNuc patients with HBsAg loss, 5 mortality were documented and only one of them died of HCC progression while the other four died of non-liver related mortality.

Conclusions: This is by far the largest cohort study comparing the liver adverse outcome between offNuc and spontaneous HBsAg loss patients. The HCC incidence was comparable between these two groups after adjustment.

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⑬

SERUM CYTOKINE PROFILE PREDICTS OUTCOMES AFTER DISCONTINUING ENTECAVIR AND TENOFOVIR THERAPY Meng-Ju Lin1, Tung-Hung Su2,3, Chun-Jen Liu2,3, Hung-Chih Yang2, Jyh-Ming Liou2, Tai-Chung Tseng4, Chen-Hua Liu2,3, Pei-Jer Chen2,3,4, Jia-Horng Kao2,3,4 School of Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan1 Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan2 Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan3 Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan4

血清細胞激素預測停用貝樂克及惠立 妥的結果 林孟儒1 蘇東弘2,3 劉俊人2,3 楊宏志2 劉志銘2 曾岱宗4 劉振驊2,3 陳培哲2,3,4 高嘉宏2,3,4 台大醫學院醫學系1 台大醫院內科部胃腸肝膽科2 台大醫院肝炎研究中心3 台大醫院醫學研究部4 Background: Distinct relapse patterns were observed after discontinuing entecavir (ETV) or tenofovir disoproxil fumarate (TDF) therapy in chronic hepatitis B (CHB).

Aims: This study aims to compare serum cytokine profiles upon cessation of ETV and TDF therapy, and to use serum cytokines for outcome prediction.

Methods: Non-cirrhotic CHB patients in National Taiwan University Hospital who discontinued ETV and TDF therapy by the APASL guideline were prospectively enrolled. The serum at endof-therapy (EOT), 1st (EOT1), and 3rd month (EOT3) afterward were collected and stored in -80°C refrigerator for multiplex cytokine analysis, including IP-10, MCP-1, GM-CSF, IFN-alpha, INF-gamma, IL-1 alpha, IL-1 beta, IL-1RA, IL-2, IL-4, IL-5, IL-6, IL-7, IL-9, IL-10, IL-12 p70, IL-13, IL-15, IL-17A, IL-18, IL-21, IL-22, IL-23, IL-27, IL-31, TNF-alpha, and TNF-beta. Univariate and multivariable analyses were performed to predict

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virological relapse (HBV DNA > 2000 IU/mL), clinical relapse (VR and ALT > 2-fold upper limit of normal), or hepatitis B surface antigen (HBsAg) seroclearance.

Results: Overall, 80 patients of CHB to discontinue ETV (n=51) or TDF (n=29) therapy for greater than 3 years were enrolled and were followed for a median of 35 months. Except for TDF stoppers who were younger, sex, treatment duration, Fib-4 index, and quantitative HBsAg level were comparable between the two groups. Compared with TDF, ETV stoppers had a significantly greater IL-1 alpha, IL4, IL-5, IL-13, IL-15, and IL-17A at EOT. The IFNgamma correlated well with IL-18 (R-square: 0.9, P<0.001). Multivariable analysis showed TDF use, greater HBsAg, IL-7, either IFN-gamma or IL-18 level at EOT were predictive for VR. A greater EOT IL-7 level was predictive for CR. Moreover, a lower HBsAg level was associated with a greater chance of HBsAg seroclearance. In subgroup analysis, a greater IL-7 predicts both VR and CR, specifically in the TDF group. The 1-month increase of either IFN-gamma and IL-18 after EOT is associated with early VR within 3 months.

Conclusions: Different cytokine profiles were observed after discontinuation of ETV and TDF therapy. A greater serum IL-7, either IFNgamma or IL-18 level at EOT are predictive for subsequent VR, and IL-7 is predictive of CR after discontinuation of ETV or TDF therapy. The EOT HBsAg level predicts both VR and HBsAg seroclearance.

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⑭

DISTINCT DIFFERENT IN THE MAGNITUDE OF HBV DNA SURGE AND ITS CORRELATION WITH FLARE SEVERITY BETWEEN PATIENTS STOPPING ENTECAVIR AND TENOFOVIR Yen-Chun Liu1,2, Wen-Juei Jeng1,2, Chien-Wei Peng1,2, Rong-Nan Chien1,2,3, Yun-Fan Liaw1,3 College of Medicine, Chang Gung University, Taoyuan, Taiwan1 Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan, Taiwan2 Liver Research Unit, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan, Taiwan3 Background: Hepatitis B flare occurred much earlier and more severe in patients stopping tenofovir (TDF) than entecavir (ETV). Our previous study demonstrated early hepatitis flare in offTDF had greater magnitude of HBV DNA surge, resulting in more severe hepatitis flare.

Aims: This study aims to investigate whether the phenomenon is also valid in patients stopping ETV. Methods: HBeAg-negative chronic hepatitis B (CHB) patients who encountered off-ETV or offTDF hepatitis flare, ALT>5 upper limit of normal (ULN), were recruited. HBV DNA levels were assessed at EOT, EOT 3, 6, 9, and 12 months, as the referent level for calculating the magnitude of HBV DNA surge prior to flare. Early and late flare were defined by event onset <6 and 7-24 months from EOT, respectively. The peak ALT, total bilirubin (T.Bil) and INR levels during flare, HD rate and magnitude of HBV DNA surge were compared between patients with early and late flare. To investigate the difference in HBV DNA surge and flare severity in patients with early and late flare after stopping ETV comparing to those stopping TDF, propensity score matching (PSM) for age, gender, cirrhosis and EOT HBsAg was done at 1:1 ratio with each 107 patients in off-ETV and off-TDF arms.

Results: After PSM, 16/107 (15%) and 81/107 (76%) patients encountered early flare in off-ETV and off-TDF groups, respectively. The magnitude of HBV DNA surge was numerically higher in offETV patients with early flare than late flare (4.0 vs, 2.7 log10 IU, P=0.06). However, different from

off-TDF flare patients, off-ETV patients showing comparable peak ALT (388 vs. 486 U/L, P=0.47) and T.Bil level (1.1 vs. 1.0 mg/dL, P=0.75) between early flare and late flare. HD was observed only in off-ETV patients with late flare (0 vs. 6%, P=1.000).

Comparing to patients stopping TDF, off-ETV patients had less magnitude of HBV DNA surge in early flare (4.0 vs. 7.0 log10 IU, P<0.01), but greater DNA upsurge level in late flare group (2.7 vs. 1.5 log10 IU, P=0.02). There’s a correlation between the magnitude of HBV DNA surge and flare severity in off-TDF (r=0.26, P<0.01) but not in off-ETV patients (P=0.17).

Conclusion: Early hepatitis flare in off-ETV patients also showed greater abrupt surge in HBV DNA levels than those with late flare, but the magnitude of HBV DNA surge in early off-ETV flares patients are lower than those with early offTDF flares. The correlation between magnitude of HBV DNA surge and flare severity was only shown in patients off-TDF but not in those off-ETV.

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⑮

COMPARISON OF HEPATITIS B VIRUS RELAPSE RATES BETWEEN HEPATITIS B E ANTIGEN-NEGATIVE CHRONIC HEPATITIS B PATIENTS WHO DISCONTINUE TENOFOVIR DISOPROXIL FUMARATE WITH OR WITHOUT SWITCHING TO TENOFOVIR ALAFENAMIDE Chien-Hung Chen1, Wen-Juei Jeng2, Tsung-Hui Hu1, Yen-Chun Lin2, Jing-Houng Wang1, Chao-Hung Hung1, Sheng-Nan Lu1, Rong-Nan Chien2 Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan1 Division of Hepato-Gastroenterology, Linkou Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taoyuan, Taiwan2

e 抗原陰性慢性 B 肝患者接受惠立妥 單一治療和有轉換成韋立得停藥後 B 肝病毒復發的比較 陳建宏1 鄭文睿2 胡琮輝1 林俊彥2 王景弘1 洪肇宏1 盧勝男1 簡榮南2 長庚醫療財團法人高雄長庚紀念醫院胃腸肝膽科 系暨長庚大學醫學系1 長庚醫療財團法人林口長庚紀念醫院胃腸肝膽科 系暨長庚大學醫學系2 Background: Previous studies showed that hepatitis B virus (HBV) relapse after the cessation of tenofovir disoproxil fumarate (TDF) occurs much earlier than that after the cessation of entecavir.

Tenofovir alafenamide (TAF) is a new prodrug of tenofovir, which is concentrated in the liver.

However, the incidence of HBV relapse after the cessation of TAF therapy remains unclear.

Aims: To compare HBV relapse rates between HBeAg-negative chronic hepatitis B (CHB) patients who discontinued TDF with or without switching to TAF. Methods: A total of 445 HBeAg-negative patients who received TDF monotherapy and 39 HBeAgnegative patients who received TDF at the start treatment and switching to TAF at least 12 weeks

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(range 20-99 weeks) were recruited. The patients all had post-treatment follow-up for at least 6 months. The propensity score-matching method was used by creating a ratio of 1:3 to adjust age, sex, cirrhosis, HBV DNA at entry, treatment and consolidation duration and end-of-treatment (EOT) HBsAg. Thus, 39 and 117 patients who discontinued TDF with (Group I) and without (Group II) switching to TAF were included in this study.

Results: There were no significant differences in terms of clinical features or HBsAg levels between the two groups. In the Group I and Group II patients, the incidences of virological relapse at post-treatment 12, 24 and 36 weeks were 49.3% versus 33.3%, 71.2% versus 63.2%, and 85.4% versus 70.9% (p = 0.206), respectively, and the clinical relapse rates were 30.8% versus 27.4%, 48.8% versus 47%, and 55.1% versus 50.5% (p = 0.999), respectively. There was no significant difference in virological and clinical relapse rates between the two groups. Multivariate analysis showed that lower EOT HBsAg levels were independent predictors of virological relapse and lower baseline HBV DNA and EOT HBsAg levels are independent predictors of clinical relapse.

Conclusions: HBV relapse rate might be comparable between HBeAg-negative CHB patients who discontinued TDF with or without switching to TAF.

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Section：Pancreas / Biliary

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TRANSPANCREATIC SPHINECTEROTOMY IS EFFECTIVE AND SAFE PROCEDURE IN DIFFICULT BILIARY ACCESS: A RETROSPECTIVE STUDY IN A SOUTHERN TAIWAN MEDICAL CENTER Fai-Meng Sou, Yi-Chun Chiu, Lung-Sheng Lu, Cheng-Kun Wu, Chung-Mou Kuo, Chih-Ming Liang Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan

經胰括約肌切開術在困難膽道進接的 病人是安全既有效的：南台灣教學醫院 的回朔性研究 蘇輝明 邱逸群 盧龍生 吳鎮琨 郭仲謀 梁志明 高雄長庚紀念醫院胃腸肝膽科系

received TPS. The mean age was 63.8 years old.

43 patients (36.8%) received ERCP due to bile duct stone, 27 patients (23.1%) were liver-related malignancy, 9 patients (7.7%) were pancreatic malignancy. There was no difference in biliary cannulation successful rate between NKP and TPS groups (75% vs. 64.7%, p = 0.383), TPS group had higher percentage in receiving more than 5 cannulation attempts (70.6% vs. 37%, p = 0.016) and more than 1 pancreatic attempt (94.1% vs. 55%, p = 0.002) than the NKP group.

TPS group had more patients who received rectal NSAID for post-ERCP pancreatitis (PEP) (70.6% vs. 39%, p = 0.019). There was no difference in cannulation time (17 min vs. 22.2 min, p = 0.249) and procedure time (32 min vs 36 min, p = 0.358) between NKP and TPS groups. Total 10 (8.5%) patients complicated with PEP, 5 (4.27%) patients with bleeding, 2 (1.7%) patients with perforation. There were no significant differences in complication rates between the two groups.

Conclusions: Both NKP and TPS had acceptable cannulation rate and complication rate in patients with difficult cannulation.

Background: Endoscopic retrograde cholangiopancreatography (ERCP) is used for diagnosing and treating pancreatobiliary disease.

ESGE suggested guidewire-assisted cannulation for patients with naïve papilla, but about 10-20% of patients failed to achieve biliary cannulation 2. Different techniques were developed for difficult cannulation, including transpancreatic sphincterotomy (TPS), double guidewire technique, needle knife papillotomy (NKP), and needle knife fistulotomy (NKF). Little data was found to compare the efficacy and complications inTPS. Aims: Compared the CBD cannulation rates and complications between standard NKP and TPS. Methods: A total of 1904 patients received ERCP between Jan 2018 and Feb 2021. There were 1129 naïve papilla. 171 (15.1%) cases with difficult biliary cannulation (cannulation time >10 mins) treated with endoscopic papillotomy. Patients who received NKP and TPS were enrolled in this study after excluding the patients who had successful cannulation using traditional guidewire-assisted cannulation (n = 958) or NKF techniques (n = 54).

Results: Among 117 patients enrolled in this study, 100 patients received NKP and 17 patients

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THE EXPERIENCE OF EUS-FNB IN A MEDICAL CENTER OF CENTRAL TAIWAN Yen-Chih Lin, Kue-Yu Chen, Chia-Wei Yang, Kai-Lun Shih, Hsu-Heng Yen Division of Gastroenterology, Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan

中部一醫學中心使用 EUS-FNB 之經驗 林彥至 陳奎佑 楊佳偉 施凱倫 顏旭亨 彰化基督教醫院胃腸肝膽科 Background: The usefulness of EUS-FNA has been established. In recent years, FNB needle become more popular due to its high diagnostic ability on histology evaluation.

Aims: To compare the diagnostic ability of FNA needle and FNB needle in a tertiary referral hospital of central Taiwan.

Methods: From the summer of 2020, we used FNB needle to all the patients who received EUS guided biopsy in our hospital except those for fluid analysis. We retrospectively enrolled 22 cases from 2020.8 to 2021.1 and compared the outcome to the historic record in our hospital. Most FNB needles we used have franseen tip, and we sent the tissue to our lab for both histology evaluation and cytology evaluation in all patients. ROSE was not available in our constitution. The final diagnosis was based on the surgical pathology or imaging follow-up 6 months later.

Results: In 22 patients who received EUS-FNB, the sensitivity was 89%, specificity was 100%, and accuracy was 91%. MCV (macroscopic visible core) was obtained in 55% patient. When compared to the outcome of FNA era in our hospital, no significant difference was observed in termed of sensitivity, specificity. However, there is a trend that more MCV was obtained when we used FNB needle (55% v.s 36%, p = 0.226). Interestingly, when we confined the diagnosis to PDAC (pancreatic ductal adenocarcinoma), the accuracy of EUS-FNB is 100%, while 2 cases which didn’t have definite diagnosis by EUS-FNB was finally diagnosed as small pNET (pancreatic neuroendocrine tumor).

Conclusions: In our experience, FNB needles have good performance on histology evaluation for higher MVC yield rate. However, the diagnosis of small pNET is still challenging.

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ENDOSCOPIC AMPULLECTOMY IS SAFE AND EFFECTIVE IN TREATING PAPILLARY NEOPLASM: A SINGLE CENTER EXPERIENCE SHARING Hsueh-Chien Chiang, Meng-Ying Lin, Yao-Sheng Wang, Jui-Wen Kang, Chiao-Hsiung Chuang, Chiung-Yu Chen Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan

內視鏡壺腹部腫瘤切除的安全性與療 效：單一醫學中心經驗 姜學謙 林孟穎 王堯生 康瑞文 莊喬雄 陳炯瑜 成大醫院內科部 Background: Endoscopic ampullectomy is a safe and reliable method for resecting papillary neoplasm in selected cases. Variable rates of technique success (46% to 92%) and adverse event (0% to 25%) were reported in the previous literatures.

Aims: We aim to evaluate the performance of endoscopic ampullectomy in a tertiary center of Taiwan.

Methods: From April, 2019 to April, 2021, total 12 patients with ampullary neoplasm underwent endoscopic ampullectomy at the National Cheng Kung University Hospital. The rates of technical success and adverse events were recorded.

Results: Among the 12 patients, the baseline characteristics and tumor related features were recorded in Table 1. Most of the target lesion was small (<3 cm) and proved to be adenoma prior to ampullectomy. Ten patients (83.3%) had pretreatment EUS examination with 8 (80%) of them showed an intra-luminal invasion less than 1 cm.

The successful rates of endoscopic resection and complete tumor resection were 100% and 83.3% (10), respectively. Five patients (41.7%) had post procedure bleeding event and all of them were successfully treated by using endoscopic methods.

One (8.3%) patient failed to have prophylactic pancreatic stenting and was complicated with

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pancreatitis. The mean procedure time was 38 minutes and median hospital stay was 5 days (Table 2).

Conclusions: With careful patient selection, endoscopic ampullectomy has a high successful resection rate and can be accomplished in a short time. Its adverse event rate is high, however, it is all manageable with endoscopy.

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MANUAL CLEANING BY SOAKING ENZYME DETERGENT IMPROVES DISINFECTION EFFICACY OF DUODENOSCOPES: EXPERIENCES FROM A TERTIARY CENTER IN NORTHERN TAIWAN I-Fang Tsai1, Cheng-Shuan Chung2,3, I-Hua Lee2, Chun-Hsing Liao4, Mai-Yu Wu4, Ya-Ching Huang4, Fang-Chen Hung4 Occupational Safety and General Affairs, Far Eastern Memorial Hospital, New Taipei City, Taiwan1 Ultrasonography and Endoscopy Center, Far Eastern Memorial Hospital, New Taipei City, Taiwan2 Division of Gastroenterology and Hepatology, Department of Internal Medicine, Far Eastern Memorial Hospital, New Taipei City, Taiwan3 Infection Control Center, Far Eastern Memorial Hospital, New Taipei City, Taiwan4

膽胰鏡人工清洗效能之改善 ─ 以北部 某醫學中心為例 蔡宜芳1 鍾承軒2,3 李依樺2 廖俊星4 吳美玉4 黃雅卿4 洪芳禎4 亞東紀念醫院職業安全暨總務處1 亞東紀念醫院超音波暨內視鏡中心2 亞東紀念醫院肝膽胃腸內科3 亞東紀念醫院感染管制中心4 Background: The structures of duodenoscopes are complex and reprocessing is challenging. The elevator which facilitates cannulation is always contaminated with blood and tissue debris and wire channel cannot be brushed. There have been many reports of cluster infection and deaths due to inadequate disinfection of duodenoscopes worldwide. Some studies have shown that the manual cleaning process can prevent the residual biofilm on the surface of the endoscope and in the lumens. The soaking of enzyme detergent to improve the cleaning performance is the most important part of the disinfection process of flexible endoscopes. However, manual cleaning in soaking method is not recommended in every international society.

Aims: This study aimed to compare the efficacy of manual cleaning between under running water

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and detergent soaking.

Methods: Selection basis and target: From January to March 2020, an experienced technician in the Ultrasonography and Endoscopy Center in Far Eastern Memorial Hospital performed manual cleaning of the duodenoscopes. Control group: manual cleaning under running water. Experimental group: manual cleaning under soaking in enzyme detergent. Sampling method: using ATP detection (standard value: <200 RLU). The tested area included: 1) the surface of bending part of distal duodenoscope (10 cm from the proximal part), 2) working channel, 3) elevator channel, 4) forceps elevator, and 5) distal cover. Statistical analysis method: Mann-Whitney U test, α: 0.05.

Results: 3 dedicated duodenoscope were used to perform endoscopic retrograde cholangiopancreatography in 193 patients. The positive rate of microbial culture: 0%. A total of eight patients (4.1%) developed post-ERCP pancreatitis and no procedure related infections was reported.

Conclusions: Manual cleaning through submerge the scope under the enzyme detergent can improve the efficiency of manual cleaning of the duodenoscopes. Meanwhile, the situation of difficult cleaning of the elevator and the elevator channel is also improved by soaking method. The results show that distal cover of duodenoscope has not been significantly improved. Since distal cover has irregular surface, using brushes with matched size to enhance physical cleaning is still needed. It is recommended that endoscopes with complex structures (such as the elevator and the elevator channel) must be submerged and cleaned in order to improve the efficiency of manual cleaning and reduce the risk of potential infection of the endoscope.

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COMPARISON OF STRICTURE DILATION BEFORE OR AFTER MULTIMODAL TISSUE-SAMPLING, INCLUDING BRUSH CYTOLOGY, INTRADUCTAL SUCTION AND FORCEPS BIOPSY FOR THE DIAGNOSIS OF INDETERMINATE BILIARY STRICTURE: A PROSPECTIVE COHORT STUDY Yu-Ting Kuo1,2, Weng-Fai Wong1,2, Ming-Lun Han1,2, Chieh-Chang Chen1, Wei-Chih Liao1, Hsiu-Po Wang1 Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan1 Division of Endoscopy, Department of Integrated Diagnostics & Therapeutics, National Taiwan University Hospital, Taipei, Taiwan2

比較膽道擴張前與擴張後針對膽道不 明原因的狹窄做膽道切片及細胞刷取 準確度的前瞻性研究 郭雨庭1,2 黃永輝1,2 韓明倫1,2 陳介章1 廖偉智1 王秀伯1 台大醫院消化內科1 台大醫院綜合診療部內視鏡科2 Background: Biliary strictures present a diagnostic and therapeutic challenge to clinicians due to unsatisfied accuracy of sampling modality.

Limited data are available on the impact of dilation of biliary strictures for tissue sampling.

Aims: In our study, we aimed to compare the diagnostic accuracy of triple tissue-sampling for indeterminate biliary stricture, including intraductal suction, forceps biopsy and brush cytology before or after dilation of biliary strictures.

Methods: In this prospective study, patients with biliary obstruction with a clinical suspicion of malignancy underwent triple-tissue sampling before and after dilation of biliary strictures at one ERCP session. Final diagnosis was based on all sampling methods plus surgery and clinical followup. Tissue specimens were reported as normal, atypia, or malignant.

Results: From February 2016 and October 2019, total 60 consecutive patients with a mean age of

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Section：Cirrhosis & HCC 66.9 years who visited National Taiwan University Hospital were prospectively recruited. Forty eight patients had cancer and 12 had benign strictures.

Thirty four patients had cholangiocarcinoma, 3 had gallbladder cancer, 8 had hepatocellular carcinoma, 1 had ampullary cancer and 2 had metastatic cancer. Tissue sampling sensitivity varied according to the different sampling modalities; the highest yield was seen in forceps biopsy whenever before or after biliary dilation. The cumulative sensitivity of triple-tissue sampling in the cancer patients was as follows: sensitivity was 77.1% (before dilation) and 79.2% (after dilation) if atypia was considered malignant and 45.8% (before dilation) and 43.8% (after dilation) if atypia was considered benign. No serious complications occurred from the tissue sampling methods.

Conclusions: Tissue sampling sensitivity varied according to the different sampling modalities.

Triple tissue-sampling increased sensitivity; Dilation of biliary stricture has no influence on the diagnosis rate of tissue sampling.

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CONCURRENT IMMUNE CHECKPOINT INHIBITOR AND TYROSINE KINASE INHIBITOR THERAPY YIELDS BETTER OUTCOME THAN IMMUNE CHECKPOINT INHIBITOR MONOTHERAPY IN PATIENTS WITH ADVANCED HEPATOCELLULAR CARCINOMA Wei-Fan Hsu1,2,3, Hung-Wei Wang1,3, Hsueh-Chou Lai1,4, Cheng-Kuo Chen5, Po-Heng Chuang1, Ming-Hung Tsai6, Wen-Pang Su1, Sheng-Hung Chen1,3, Wen-Hsin Huang1, Chi-Ying Yang1, Tsung-Yu Tsai1, Wang-De Hsiao1, Chia-Sheng Chu1, Chun-Che Lin1,3, Guan-Tarn Huang1,3, Jaw-Town Lin1,3, Cheng-Yuan Peng1,3 Center for Digestive Medicine, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan1 Graduate Institute of Biomedical Science, China Medical University, Taichung, Taiwan2 School of Medicine, China Medical University, Taichung, Taiwan3 School of Chinese Medicine, China Medical University, Taichung, Taiwan4 Division of Gastroenterology & Hepatology, Department of Internal Medicine, Asia University Hospital, Taichung, Taiwan5 Division of Hematology and Oncology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan6

併用免疫點抑制劑與酪氨酸激酶抑製 劑比單用免疫點抑制劑在晚期肝癌患 者提供更好療效 許偉帆1,2,3 王鴻偉1,3 賴學洲1,4 陳政國5 莊伯恒1 蔡明宏6 蘇文邦1 陳昇弘1,3 黃文信1 楊其穎1 蔡宗佑1 蕭望德1 朱家聲1 林俊哲1,3 黃冠棠1,3 林肇堂1,3 彭成元1,3 中國醫藥大學附設醫院消化醫學中心1 中國醫藥大學生物醫學研究所2 中國醫藥大學醫學系3 中國醫藥大學中醫學系4 亞洲大學附屬醫院肝膽胃腸科5

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中國醫藥大學附設醫院血液腫瘤科6 Background: The treatment efficacy of immune checkpoint inhibitors (ICIs) with tyrosine kinase inhibitors (TKIs) for patients with advanced HCC is unknown.

Aims: We investigated whether concurrent ICI and TKI therapy yielded better progression-free survival (PFS) and overall survival (OS) than did ICI monotherapy in patients with advanced HCC. Methods: This retrospective study enrolled 61 consecutive patients with advanced HCC from May 2017 to June 2021 at China Medical University Hospital and Asia University Hospital. Patients who received locoregional therapy during ICI therapy, including transarterial chemoembolization (n=14) or liver radiotherapy (n=21), were excluded.

Patients who received concurrent ICI and TKI therapy for less than 7 days were also excluded.

Results: Of the 61 patients, 38 (62.3%) patients received combination therapy. Nivolumab and pembrolizumab were used in 50 (82%) and 11 (18%) patients, respectively. The median ICI treatment duration was 2.47 (1.28–5.37) months (first quartile–third quartile). Of the 38 (62.3%) patients who received combination therapy with TKIs, 15, 16, 2, and 5 patients received sorafenib, lenvatinib, regorafenib, and sequential TKIs, respectively, and the median duration of combination treatment was 2.48 (0.98–5.98) months. Sixteen patients did not reach the time of first radiological imaging assessment at data analysis (14 patients died and 2 patients were lost to follow-up). Objective response (OR) and disease control rates were 21.3% and 36.1%, respectively.

The median progression-free survival and overall survival was 2.40 (95% confidence interval [CI]: 2.22–2.58) and 5.87 (95% CI: 4.30–7.44) months, respectively. Alpha-fetoprotein (AFP) response, defined as ≥20% decline in serum AFP levels within the first 3 months of treatment, was the only factor associated with disease control (complete response + partial response + stable disease, odd ratio: 33.856, 95% CI: 5.188–220.941, p<0.001) by multivariate analysis. Patients with AFP response had lower alanine and aspartate aminotransferase levels, and lower Cancer of the Liver Italian Program score (2 (1–2) vs. 3 (2–4), p=0.027). Macrovascular invasion (MVI, hazard ratio [HR]: 3.045, 95% CI: 1.262–7.343, p=0.013), Child-Pugh class B (HR: 2.933, 95% CI: 1.332–6.457, p=0.008), concurrent TKI therapy (HR: 0.180, 95% CI: 0.075–0.433,

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p<0.001), and disease control (HR: 0.150, 95% CI: 0.051–0.443, p=0.001) were predictors of short PFS. Total tumor volume (>1000 cm3, HR: 2.683, 95% CI: 1.028–6.998, p=0.044), MVI (HR: 3.975, 95% CI: 1.347–11.731, p=0.012), ALBI grade 2 or 3 (HR: 4.467, 95% CI: 1.033–19.324, p=0.045), AFP response (HR: 0.281, 95% CI: 0.091–0.873, p=0.028), and concurrent TKI therapy (HR: 0.242, 95% CI: 0.093–0.632, p=0.004) were predictors of poor OS. Conclusions: Concurrent ICI and TKI therapy yielded better PFS and OS for patients with advanced HCC. AFP response was a predictor for disease control and longer OS.

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㉒

STRATIFICATION OF HEPATOCELLULAR CARCINOMA RISK THROUGH THE COMBINATION OF FIB-4 AND ALBI-BASED PREDICTION MODEL IN COMPENSATED CIRRHOTIC PATIENTS WITH CHRONIC HEPATITIS B RECEIVING NUCLEOS(T)IDE ANALOGUE THERAPY Hung-Wei Wang1, Chien-Hung Chen2, Hsueh-Chou Lai1, Chi-Yi Chen3, Jing-Houng Wang2, Cheng-Yuan Peng1 Center for Digestive Medicine, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan1 Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan2 Division of Hepatogastroenterology, Department of Internal Medicine, Chia-Yi Christian Hospital, Chiayi, Taiwan3

FIB-4 與 ALBI 為主的預測模型可區分 慢性 B 型肝炎代償肝硬化患者接受類 核苷（酸）藥物治療後之肝癌發生風險 王鴻偉1 陳建宏2 賴學洲1 陳啟益3 王景弘2 彭成元1 中國醫藥大學附設醫院內科部消化醫學中心1 高雄長庚紀念醫院內科部胃腸肝膽科系2 嘉義基督教醫院內科部胃腸肝膽科3 Background: FIB-4 index is one of the noninvasive fibrosis indices widely used in patients with chronic hepatitis B (CHB). Albumin-bilirubin (ALBI) grade has been developed objectively to measure hepatic reserve and also utilized to predict liver related events, including hepatocellular carcinoma (HCC). The performance of predicting HCC through the combination of FIB-4 and ALBI-based model remains unclear.

Aims: We investigated the predictive performance of HCC risk through liver reserve or noninvasive fibrosis markers derived from baseline parameters in compensated cirrhotic patients with CHB receiving nucleos(t)ide analogue (NA) therapy.

Methods: We enrolled 1158 NA-naïve, compensated cirrhotic patients with CHB treated with entecavir or tenofovir from 2008 to 2018.

Baseline patient characteristics and pre-treatment liver reserve and fibrosis indices were collected and analyzed to predict HCC risk by univariate and multivariate Cox regression analyses. The predictive performance was evaluated using receiver operating characteristic (ROC) curves.

We used Kaplan–Meier analysis to compare the cumulative HCC incidence among three subgroups of patients exhibiting distinct combinations of FIB4 and ALBI. The combination of FIB-4 and ALBI was used to estimate regression coefficient in the multivariate Cox regression model, which was converted to risk score to develop the prediction model.

Results: In this cohort, 161 patients (13.9%) developed HCC during a median follow-up 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. By multivariate Cox regression analysis, diabetes mellitus (DM) (yes vs no) (hazard ratio [HR]: 1.469; 95% confidence interval [CI]: 1.035–2.058; P = 0.031), AFP (> 5.28 vs ≤ 5.28 ng/mL) (HR: 1.904; 95% CI: 1.298–2.794; P = 0.001), FIB-4 (> 2.54 vs ≤ 2.54) (HR: 1.746; 95% CI: 1.212–2.515; P = 0.003), and ALBI (> -2.66 vs ≤ -2.66) (HR: 1.575; 95% CI: 1.132–2.191; P = 0.007) were significant predictors of HCC. A combination of FIB-4 and ALBI stratified the cumulative risk of HCC into three subgroups in all patients (logrank test: P < 0.001) (high [n=340]: FIB-4 > 2.54/ ALBI > -2.66 [HR: 2.862, 95% CI: 1.833–4.469, P < 0.001]; intermediate [n=411]: FIB-4 > 2.54/ALBI ≤ -2.66 or FIB-4 ≤ 2.54/ALBI > -2.66 [HR: 1.927, 95% CI: 1.218–3.049, P = 0.005]; low [n=407]: FIB4 ≤ 2.54/ALBI ≤ -2.66 [HR: 1 as reference]). The combination of FIB-4 and ALBI-based prediction model (risk score 0–6) exhibited the highest predictive performance for HCC (AUROC = 0.683) compared to other scores (FIB-4, modified FIB-4, APRI, PAGE-B, ALBI, PALBI, and MELD, all P < 0.05) and stratified the cumulative risk of HCC into three subgroups in all patients (log-rank test: P < 0.001) (high [n=315]: score 5–6 [HR: 4.231, 95% CI: 2.795–6.406, P < 0.001]; intermediate [n=336]: score 3–4 [HR: 2.478, 95% CI: 1.583–3.880, P <

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0.001]; low [n=507]: 0–2 [HR: 1 as reference]).

According to this model, the 5-year cumulative incidence rates of HCC were 23.7% in patients with high risk (score 5–6), 13.8% in those with intermediate risk (score 3–4), and 5.7% in those with low risk (score 0–2).

Conclusions: The combination of FIB-4 and ALBI-based prediction model could stratify the risk of HCC in compensated cirrhotic patients with CHB receiving NA therapy.

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THE EFFECTIVENESS OF HEPATIC ARTERIAL INFUSION CHEMOTHERAPY (HAIC) FOLLOWED BY LIPIODOL INFUSION IN ADVANCED HEPATOCELLULAR CARCINOMA (HCC) WITH PORTAL VEIN TUMOR THROMBUS (PVTT) Kun-Feng Tsai, Sheng-Yeh Tang, Ping-I Hsu Division of Gastroenterology and Hepatology, Department of Internal Medicine, An Nan Hospital, China Medical University, Tainan, Taiwan

肝動脈化學治療於嚴重侵犯性肝癌之 療效 蔡坤峰 湯昇曄 許秉毅 臺南市立安南醫院內科部 Background: The patients with advanced hepatocellular carcinoma with portal vein thrombosis have poor prognosis. The effectiveness of HAIC with follow up lipiodol infusion is uncertained.

Aims: To evaluate the effectiveness of hepatic arterial infusion chemotherapy (HAIC) followed by lipiodol infusion in advanced hepatocellular carcinoma (HCC) with portal vein tumor thrombus (PVTT).

Methods: Thirty-two patients with advanced HCC and PVTT who received HAIC with regimens of cisplatin, mitomycin-C, and 5-fluorouracil followed by lipiodol infusion were enrolled. The primary efficacy endpoint was tumor response rate. Responses were evaluated after two HAIC cycles and after completing HAIC. The secondary endpoints were overall survival (OS) and progression free survival (PFS). Prognostic factors for survival also were evaluated.

Results: The median OS and PFS were 11.9 and 9.5 months, respectively. Seventeen patients (53.1%) achieved objective response, and 23 patients (71.9%) achieved disease control. The length of survival in the responder and disease control groups was longer than in the nonresponder and progressive disease groups after two cycles of HAIC (responder vs. non-responder: 16.5 vs. 7.9 months, p=0.001; disease control vs. progressive disease: 12.3 vs. 5.6 months,

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p<0.001) and after completing HAIC (responder vs. non-responder: 15.7 vs. 6.9 months, p=0.001; disease control vs. progressive disease: 13.6 vs. 6.9 months, p<0.001). Better survival was associated with Child-Pugh A liver function (p=0.013), with early response to two HAIC cycles (p=0.009), and with response (p=0.02) and disease control (p=0.001) after completing HAIC treatment. Addition of sorafenib did not provide a survival benefit (p=0.87).

Conclusions: HAIC followed by lipiodol infusion is a safe and feasible treatment for advanced HCC with PVTT. Patients with early response could continue HAIC treatment with expected prolonged survival.

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TENOFOVIR IS ASSOCIATED WITH A LOWER RISK OF MORTALITY IN HBV-RELATED HCC AFTER CURATIVE TREATMENT Kai-Chun Chang1, Tung-Hung Su1,2, Sih-Han Liao3, Shih-Wan Chou1, Tai-Chung Tseng2,4, Hung-Chih Yang1, Chen-Hua Liu1,2, Shih-Jer Hsu1,2, Chun-Jen Liu1,2, Jia-Horng Kao1,2,5 Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan1 Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan2 Department of Medicine, National Taiwan University Cancer Center, Taipei, Taiwan3 Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan4 Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan5

Tenofovir 與 B 型肝炎相關肝細胞癌接 受治癒性治療後較低死亡率相關 張凱鈞1 蘇東弘1,2 廖思涵3 周詩婉1 曾岱宗2,4 楊宏志1 劉振驊1,2 徐士哲1,2 劉俊人1,2 高嘉宏1,2,5 國立臺灣大學醫學院附設醫院內科部1 國立臺灣大學醫學院附設醫院肝炎研究中心2 國立臺灣大學醫學院附設癌醫中心分院綜合內科 部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臨床醫學研究所5 Background: Tenofovir disoproxil fumarate (TDF) and entecavir (ETV) can reduce the risk of hepatocellular carcinoma (HCC) in patients of chronic hepatitis B. Aims: This study aims to compare the difference between ETV and TDF on risk of HCC recurrence and mortality in patients with HBV-related HCC after curative treatment.

Methods: Patients with HBV-related HCC who received curative treatment (surgery or radiofrequency ablation [RFA]) and promptly underwent long-term ETV or TDF therapy were retrospectively included. Baseline characteristics including age, sex, BMI, treatment modality, regimen and timing of antiviral therapy, BMI, Child-Pugh score, alpha-fetoprotein (AFP), FIB-

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4 index, tumor size, ALBI score and BCLC stage were obtained. The risk of tumor recurrence, allcause mortality and HCC-related mortality were compared between ETV and TDF usage.

Results: Among 9923 newly diagnosed HCC patients, we identified 314 HBV-related HCC patients post curative treatment for HCC and treated with ETV(n=264) or TDF(n=50) between January 2011 and December 2020. The mean age was 59, and 303 patients were male. After a median follow-up of 18.6 months, 145 patients developed recurrent HCC and 78 patients died.

The baseline characteristics and severity of liver disease at curative treatment were comparable between ETV and TDF groups, except more patients received RFA in the TDF group and more patients initiated NUCs after curative treatment in the TDF group. After adjustment of confounding factors, the risks of HCC recurrence were comparable between TDF and ETV, either early (< 2 years) or late recurrence (> 2years). Compared to ETV group, TDF users had significantly lower allcause mortality (adjusted hazard ratio [HR]: 0.41, 95% confidence interval [CI]: 0.17-0.96, P=0.04), and trends of lower HCC-related mortality (adjust HR: 0.34, 95% CI: 0.10-1.13, P=0.08).

Conclusions: TDF therapy is associated with a significantly reduced risk of all-cause mortality and a trend of lower HCC-related mortality among patients with HBV-related HCC after curative treatment.

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EFFICACY OF SYSTEMIC TREATMENT FOR UNRESECTABLE HEPATOCELLULAR CARCINOMA ASSOCIATED WITH NON-VIRAL HEPATITIS ETIOLOGY Chi-Jung Wu1,2, Pei-Chang Lee1,3,4, Ya-Wen Hung1, Chieh-Ju Lee1, Chen-Ta Chi1,2, I-Cheng Lee1,3, Ming-Chih Hou1,3, Yi-Hsiang Huang1,2,3 Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan1 Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan2 Faculty of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan3 Institute of Pharmacology, National Yang Ming Chiao Tung University, Taipei, Taiwan4

非病毒性肝炎相關不可手術切除晚期 肝癌全身性藥物治療療效分析 吳啟榮1,2 李沛璋1,3,4 洪雅文1 李杰如1 齊振達1,2 李懿宬1,3 侯明志1,3 黃怡翔1,2,3 臺北榮民總醫院內科部胃腸肝膽科1 國立陽明交通大學臨床醫學研究所2 國立陽明交通大學醫學院醫學系3 國立陽明交通大學藥理學研究所4 Background: Recent study showed unresectable hepatocellular carcinoma (uHCC) associated with non-viral hepatitis etiology has worse survival benefit compared with HCC associated with viral hepatitis in immunotherapy with immune checkpoint inhibitors (ICIs). However, the treatment response of sorafenib, the previous standard 1stline treatment, in this subgroup of patients is also still unclear.

Aims: This study aimed to delineate the outcomes of different systemic treatments, including sorafenib and ICIs, for uHCC associated with non-viral hepatitis, and also identify predictors associated with outcomes.

Methods: Eighty-three patients with non-viral hepatitis related uHCC who received sorafenib or ICIs as 1st-line treatment in Taipei Veterans General Hospital between January 1, 2017 and May 31, 2021 were retrospectively enrolled.

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Section：UGI Results: Among 83 enrolled patients, 60 patients received sorafenib, 23 patients received ICIs (16 patients with combination with target therapy).

Progression-free survival (PFS) was better in the patients received ICIs than sorafenib group (median 6.3 vs. 2.0 months, P<0.001), while there was no significant difference in overall survival (OS) (19.1 vs. 9.4 months, P=0.131).

Conclusions: Although ICIs might be less effective for non-viral hepatitis related HCC, for those patiens, ICIs either monotherapy or combination with target therapy still have better PFS than sorafenib.

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SYSTEMIC REVIEW AND NETWORK META-ANALYSIS: THE EFFICACY AND SAFETY OF DIFFERENT THERAPEUTIC MODALITIES IN THE TREATMENT OF IDIOPATHIC ACHALASIA Sz-Iuan Shiu1,2,3, Chung-Hsin Chang1, Yu-Kang Tu4,5,6, Chung-Wang Ko1 Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan1 Department of Critical Care Medicine, Taichung Veterans General Hospital, Taichung, Taiwan2 Evidence-based Practice and Policymaking Committee, Taichung Veterans General Hospital, Taichung, Taiwan3 Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan4 Department of Medical Research, National Taiwan University Hospital, National Taiwan University, Taipei, Taiwan5 Department of Dentistry, National Taiwan University Hospital and School of Dentistry, National Taiwan University, Taipei, Taiwan6

系統性回顧與網絡性統合分析：在食道 弛緩不能上探討不同內視鏡和手術術 式的效益和安全性 許斯淵1,2,3 張崇信1 杜裕康4,5,6 柯忠旺1 臺中榮民總醫院內科部肝膽腸胃科1 臺中榮民總醫院重症醫學部2 臺中榮民總醫院實證決策管理委員會3 國立臺灣大學流行病學與預防醫學研究所4 國立臺灣大學醫學研究部5 國立臺灣大學醫學院牙醫學系6 Background: Idiopathic achalasia is rare with annual incidence ranging from 1.07 to 1.99 per 100,000 people, but associated with higher incidence of esophageal cancer globally. Successful management of achalasia in clinical practice is an important issue of disease prevention. However, the optimum achalasia treatment regarding to different modalities remains elusive.

Aims: In the present study, we conducted an

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network meta-analyses (NMA) to compare the relative efficacy and safety of achalasia treatments among 8 endoscopic or surgical modalities for patients with idiopathic achalasia.

Methods: Three major bibliographic databases were reviewed to enroll relevant randomized controlled trials between January 2000 and June 4, 2021. We focused on short-term plus midterm efficacy and safety of interventions in adults (aged ≥ 18 years) with symptomatic and idiopathic achalasia. We included reports that compared two or more of eight interventions including botulinum toxin injection (BTI), pneumatic dilation (PD), combined therapy of BTI plus PD (BTI + PD), LHM without fundoplication, LHM following with Dor or Toupet fundoplication, or POEM with either anterior or posterior approach.

Results: Our study demonstrated that Anterior POEM, Posterior POEM, LHM + Toupet, and LHM + Dor were significantly superior to PD in short-term efficacy with Anterior POEM and LHM + Dor showing higher improvement than PD in mid-term efficacy. BTI showing significantly lower efficacy than PD in both follow-up periods.

With respect to safety, none of the interventions for achalasia except LHM without fundoplication were significantly associated with worsen gastroesophageal acid reflux than PD. As for moderate-to-severe adverse events, there was an increasing trend in LHM + Toupet, LHM, and LHM + Dor groups, although this was not statistically significant.

Conclusions: Our NMA suggest that POEM especially anterior approach should be recommended at first, and LHM with Dor or Toupet fundoplication might be alternative treatment choices. Although PD or BTI + PD had limited efficacy in symptom control, they should still be considered in poor candidate for anesthesia. In the contrary, we recommended against BTI or LHM without fundoplication as definitive therapy for patients with idiopathic achalasia.

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A NOMOGRAM FOR PREDICTING THE LAPAROSCOPIC AND ENDOSCOPIC COOPERATIVE SURGERY DURING THE ENDOSCOPIC RESECTION OF SUBEPITHELIAL TUMORS OF THE UPPER-GASTROINTESTINAL TRACT Shun-Wen Hsiao1,3, Chia-Wei Yang1, Kuo-Hua Lin2, Hsu-Heng Yen1 Division of Gastroenterology, Changhua Christian Hospital, Changhua, Taiwan1 Department of General Surgery, Changhua Christian Hospital, Changhua, Taiwan2 Division of Gastroenterology, Yuanlin Christian Hospital, Changhua, Taiwan3

以列線圖預測內視鏡切除上消化道黏 膜下腫瘤時需要合併腹腔鏡治療的因 子 蕭舜文1,3 楊佳偉1 林國華2 顏旭亨1 彰化基督教醫院胃腸科1 彰化基督教醫院一般外科2 員林基督教醫院胃腸科3 Background: Considering the widespread use of esophagogastroduodenoscopy, the prevalence of upper-gastrointestinal (GI) subepithelial tumors (SET) increases. For a relatively safer removal of upper-GI SETs, endoscopic submucosal dissection (ESD) has been developed as an alternative to surgery.

Aims: This study aimed to analyze the outcome of endoscopic resection for SETs and develop a prediction model for the need of laparoscopic and endoscopic cooperative surgery (LECS) during the procedure.

Methods: We retrospectively analyzed 123 patients who underwent endoscopic resection for upper-GI SETs between January 2012 and December 2020 at our institution. Intraoperatively, they underwent ESD or submucosal tunneling endoscopic resection (STER). The nomogram was constructed using the regression coefficient for each clinical valuable feature. The predictive accuracy and discriminative ability of the nomogram were determined by the area under the curve (AUC) and the calibration plot.

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Results: ESD and STER were performed in 107 and 16 patients, respectively. The median age was 55 years, and the average tumor size was 1.5 cm.

En bloc resection was achieved in 114 patients (92.7%). The median follow-up duration was 242 days without recurrence. Tumors at the gastric fundus and cardia were mostly GI stromal tumor (n = 17, 81.0%) and leiomyoma (n = 13, 61.9%), respectively. Perforation occurred in 47 patients (38.2%), and 30 patients (24.4%) underwent LECS. Most perforations occurred in the fundus.

Through multivariable analysis, we built a nomogram that can predict LECS requirement according to tumor location, size, patient’s age, and sex. The prediction model exhibited good discrimination ability, with an area under the curve (AUC) of 0.893.

Conclusions: Endoscopic resection is a noninvasive procedure for small upper-GI SETs. Most perforations can be successfully managed endoscopically. The prediction model for LECS requirement is useful for treatment planning.

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RANDOMISED CLINICAL TRIAL: A 36-WEEK ORAL ESOMEPRAZOLE 20 MG TWICE DAILY VERSUS ONCE DAILY OR CONTROLS AFTER AN INITIAL 16-WEEK PROTON PUMP INHIBITOR TREATMENT FOR LONG-TERM RECURRENT PEPTIC ULCER BLEEDING IN PATIENTS WITH ROCKALL SCORES ≥6 Hsueh-Chien Chiang1, Er-Hsiang Yang1, Wei-Ying Chen1,2, Wei-Lun Chang1, Huang-Ming Hu3, Yu-Ching Tsai1,4, Wei-Chun Cheng2,4, Chung-Tai Wu1,5, Deng-Chyang Wu3, Bor-Shyang Sheu1,3,5,6, Hsiu-Chi Cheng1,4,5 Department of Internal Medicine, National Cheng Kung University Hospital, Tainan, Taiwan1 Department of Public Health, College of Medicine, National Cheng Kung University, Tainan, Taiwan2 Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Chung-Ho Memorial Hospital, Kaohsiung, Taiwan3 Department of Internal Medicine, Tainan Hospital, Ministry of Health and Welfare, Tainan, Taiwan4 Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan5 Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan6

隨機臨床試驗：針對高復發風險的消化 道潰瘍，在 16 週氫離子幫浦阻斷劑治 療後，繼續使用 36 週雙重劑量氫離子 幫浦阻斷劑、使用 36 週標準劑量氫離 子幫浦阻斷劑、以及停用的預後比較 姜學謙1 楊貳翔1 陳威穎1,2 張維倫1 胡晃鳴3 蔡郁清1,4 鄭維鈞2,4 吳忠泰1,5 吳登強3 許博翔1,3,5,6 鄭修琦1,4,5 國立成功大學醫學院附設醫院內科部1 國立成功大學公共衛生學科暨公共衛生研究所2

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3

高雄醫學大學附設中和紀念醫院消化內科 衛生福利部臺南醫院內科部4 國立成功大學臨床醫學研究所5 高雄醫學大學臨床醫學研究所6

Background: Patients with Rockall scores ≥6 have increased risk of long-term peptic ulcer rebleeding.

Aims: To investigate whether a prolonged course of oral esomeprazole for one year decreased ulcer rebleeding for such patients.

Methods: We prospectively enrolled 120 patients with peptic ulcer bleeding and Rockall scores ≥6. After endoscopic hemostasis and a 16-week oral esomeprazole or pantoprazole 40 mg daily, patients were randomized to receive a 36-week course of oral esomeprazole 20 mg twice daily (Group D, n=60) or once daily (Group S, n=60).

After 52-week treatment, they used oral proton pump inhibitors at liberty. The patients with Rockall scores ≥6 in our previous cohort served as controls (Group C, n=135); they received an initial 8-week oral esomeprazole only. Peptic ulcer rebleeding during the study period and thereafter were the primary and the second endpoint.

Results: During the study period, Group D and S had a higher cumulative rebleeding-free proportion than Group C (P=0.014 and 0.048, log rank test), but had the similar proportions (P=0.322). The rebleeding rates were lower in Group D (0%) and S (1.7%) than in Group C (10.4%) (intentionto-treat, P=0.006 and 0.04), but not significantly different between Group D and S (P=1.0). After the study period, 16 patients in Group D and S who discontinued oral esomeprazole had peptic ulcer rebleeding.

Conclusions: A prolonged course of oral esomeprazole, 20 mg either twice or once daily for one year reduced peptic ulcer rebleeding in patients with Rockall scores ≥6; however, bleeding recurred in those discontinuing esomeprazole thereafter.

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CAN DATA AUGMENTATION IMPROVE THE RESULT OF ARTIFICIAL INTELLIGENCE (AI) LEARNING FOR SEGMENTATION ESOPHAGOGASTRIC JUNCTION IN PATHOLOGICAL-PROVED BARRETT’S? Ping-Ju Wu1, Ching-Hsiung Chang1, Chih-Hao Lin1, I-Chen Wu1,2, Chao-Hung Kuo1,2,3, Deng-Chyang Wu1,2, Jeng-Yih Wu1,2 Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan1 Department of Medicine, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan2 Department of Internal Medicine, Kaohsiung Municipal Siaogang Hospital, Kaohsiung, Taiwan3

數據增強能否提高人工智慧 (AI) 對於 胃食道交界處的學習結果？ 吳秉儒1 張景翔1 林志豪1 吳宜珍1,2 郭昭宏1,2,3 吳登強1,2 吳政毅1,2 高雄醫學大學附設中和紀念醫院胃腸內科1 高雄醫學大學醫學系2 高雄巿立小港醫院內科3 Background: In decades, gastroesophageal reflux disease including non-erosive reflux disease and erosive esophagitis increased gradually.

Moreover, chronic erosive esophagitis increased the risks of Barrett’s esophagus and early esophageal adenocarcinoma. Clinically severity evaluation of EE mostly made subjectively by endoscopist, variations between inter-observer or intra-observer could exist. Current diagnostic yield and biopsy protocol was also clinical impractical for Barrett’s esophagus. Recent advances of artificial intelligence (AI) provided help to identify the suspicious lesions.

Aims: The current study is aimed to access the feasibility of artificial-intelligence (AI)-aided system to segment esophagogastric junction in pathological-proved Barrett’s esophagitis.

Methods: Retrospectively, Esophagogastroduodenoscopy (EGD) pictures from January 1,

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2015 to December 31, 2019 were preliminary collected in screening stage after IRB approval.

Results: Totally, 13,109 pictures were enrolled in present study. 8,008 pictures were excluded due to poor quality of the images. Among 5,101 images that had quality can be recognized by physicians, 251 images were pathologically reported to be Barrett’s esophagitis. An AI system based on backbone of EfficientNetB3 + Unet + DeConv can help locate the margin of esophagogastric junction in pathological-proved Barrett’s images with a Dice coefficient to 0.7186 ± 0.0848. In the present study, transfer learning through sharing database ImageNet can improve the Dice coefficient to 0.7292 ± 0.0762. it was not observed the hypothesis that data augmentation can increase the Dice coefficient.

Conclusions: Data augmentation did not improve the result of artificial intelligence (AI) learning for segmentation. The initial model can provide a reliable tool for marking the margin of esophagogastric junction in pathological-proved Barrett’s images compared to other study. Based on this model, it is expected to prospectively compare the accuracy of Barrett’s esophagus between AIaided biopsy and endoscopist experience-based biopsy in further study.

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APPLICATION OF ARTIFICIAL INTELLIGENCE IN ENDOSCOPIC IMAGE ANALYSIS FOR THE DIAGNOSIS OF HELICOBACTER PYLORI INFECTION Ping-I Hsu1, Chih-Hsueh Lin2, Che-Yu Chan2, Chin-Dar Tseng3, Chih-An Shih4, I-Ting Wu1, Chang-Bih Shie1, Tsair-Fwu Lee3,5,6 Division of Gastroenterology, Department of Medicine, An Nan Hospital, China Medical University, Tainan, Taiwan1 Department of Electronics Engineering, National Kaohsiung University Science and Technology, Kaohsiung, Taiwan2 Medical Physics and Informatics Laboratory of Electronics Engineering, National Kaohsiung University Science and Technology, Kaohsiung, Taiwan3 Department of Internal Medicine, Antai Medical Care Corporation Antai Tian-Sheng Memorial Hospital, Pingtung, Taiwan4 PhD program in Biomedical Engineering, Kaohsiung Medical University, Kaohsiung, Taiwan5 Department of Medical Imaging and Radiological Sciences, Kaohsiung Medical University, Kaohsiung, Taiwan6

「內視鏡影像人工智慧分析系統」於幽 門螺旋桿菌診斷上之運用 許秉毅1 林志學2 詹哲瑜2 曾慶達3 石志安4 吳奕霆1 施長碧1 李財福3,5,6 中國醫藥大學臺南市立安南醫院消化內科1 國立高雄科技大學電子工程系2 國立高雄科技大學電子工程系醫學物理與資訊實 驗室3 安泰醫療社團法人安泰醫院內科部4 高雄醫學大學生物醫學工程系5 高雄醫學大學醫學影像暨放射科學系6 Background: Currently, endoscopy with rapid urease test, histology and culture is often used in the diagnosis of H. pylori infection. Whether artificial intelligence (AI) with convolutional neural network (CNN) for analysis of endoscopic images can be applied in the diagnosis or screening of H. pylori infection remains unclear.

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Aims: To develop a novel AI decision system by CNN model with deep learning of endoscopic gastric images for the diagnosis of H. pylori infection.

Methods: Gastric images of the antrum and body captured from patients whose H. pylori status had been confirmed by rapid urease test were used for the derivation study. We designed a hybrid classification network based on CNN, CBAM, and XGboost to perform deep learning on images that underwent image pre-processing and dynamic enhancement, developing a new AI decisionmaking system through gastric image analysis for the diagnosis of H. pylori infection.

Results: During the study period, a total of 336 image samples from 136 patients were included for the development of the AI decision system. The sensitivity, specificity and accuracy of the novel AI decision system for the diagnosis of H. pylori infection were 90%, 83% and 89%, respectively.

The area under receiver operating characteristic (ROC) curve was 0.79.

Conclusions: An endoscopic image AI decision system is developed for the diagnosis of H. pylori infection. Whether the accuracy of AI diagnostic system is superior to histology, rapid urease test and culture deserves further investigations.

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Poster Section：Liver P.01

BASELINE HBSAG TITER AT CHILDHOOD PREDICT THE RISK OF LIVER FIBROSIS IN ADULTHOOD Jia-Feng Wu1, Hong-Yuan Hsu1, Mei-Hwei Chang1,2 Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan1 Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan2

兒童期 B 型肝炎表面抗原效價能預測 成人期肝臟纖維化的進展 吳嘉峯1 許宏遠1 張美惠1,2 台大醫院小兒部1 台大醫院肝炎中心2 Background: Hepatitis B virus (HBV) infection remains the leading cause of liver fibrosis and end-stage liver diseases in the world. Hepatitis B surface antigen (HBsAg) and HBV core related antigen (HBcrAg) are regarded as surrogate quantification markers of intrahepatic HBV cccDNA. Aims: We aimed to elucidate the relationship between the baseline HBsAg and HBcrAg titers in childhood on the progression of liver fibrosis in adulthood in this study.

Methods: We recruited 214 initially HBeAgpositive chronic HBV infected patients (122 males, 92 females) followed since 8.44 ± 0.26 (95% CI = 7.93-8.95) years of age till 38.21 ± 0.37 (95% CI = 37.48-38.94) years of age in this study. Serum HBcrAg and HBsAg titers were assessed in the initial serum samples and the available samples collected at 10, and 15 years of age. Regular transient elastography every 6-12 months were performed at their 4th decade of life.

A liver stiffness measurement (LSM) > 9.5 kPa by transient elastography is defined as advanced liver fibrosis (METAVIR F3-4) in this study.

Results: During the 6,371 person-years follow-up period, 11 subjects (5.14%) developed METAVIR F3-4 liver fibrosis at their 4th decade of life in this cohort. Subjects with METAVIR F3-4 liver fibrosis were noted to have more genotype C HBV infection, higher HBsAg titer at their 10 and 15 years of age (P = 0.009, 0.04, and 0.008, respectively). HBcrAg titer at 10 and 15 years

of age are not correlated with the occurrence of METAVIR F3-4 liver fibrosis at their 4th decade of life (P = 0.08 and 0.10, respectively). The ROC curve analysis identified the cutoff of HBsAg > 4.23 log10 IU/mL at 10 years of age, and > 4.44 log10 IU/mL at 15 years of age for the best prediction of METAVIR F3-4 liver fibrosis at their 4th decade of life (AUC = 75.1% and 73.1%, P = 0.001 and < 0.001, respectively). Subjects with HBsAg > 4.23 log10 IU/mL at 10 years of age had significant higher risk of METAVIR F3-4 liver fibrosis at their 4th decade of life than others (risk difference = 0.1, 95% CI = 0.03-0.17, P = 0.008).

Conclusions: The HBsAg titers at 10 and 15 years of age, indicating the baseline intrahepatic HBV cccDNA, are positively correlated with LSM assessed at the 4th decade of life. Chronic HBV infected patients with HBsAg > 4.23 log10 IU/ mL at 10 years of age and > 4.44 log10 IU/mL at 15 years of age significantly increase the risk of METAVIR F3-4 liver fibrosis at their 4th decade of life, and warrant intensive management.

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P.02

SERUM MAC-2-BINDING PROTEIN GLYCOSYLATION ISOMER AT ONE YEAR OF TREATMENT PREDICTS HEPATOCELLULAR CARCINOMA AND LIVER-RELATED MORTALITY IN CHRONIC HEPATITIS B PATIENTS WITH CIRRHOSIS Chien-Hung Chen1, Cheng-Yuan Peng2, Tsung-Hui Hu1, Jing-Houng Wang1, Hsueh-Chou Lai2, Chao-Hung Hung1, Sheng-Nan Lu1 Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan1 Center for Digestive Medicine, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan2

治療一年的血清 M2BPGi 值預測慢性 B 型肝炎肝硬化病人發生肝癌和肝臟 有關的死亡 陳建宏1 彭成元2 胡琮輝1 王景弘1 賴學洲2 洪肇宏1 盧勝男1 長庚醫療財團法人高雄長庚紀念醫院胃腸肝膽科 系暨長庚大學醫學系1 中國醫藥大學附設醫院內科部消化系2 Background: It remains unclear whether M2BPGi levels could predict hepatocellular carcinoma (HCC) in chronic hepatitis B (CHB) with cirrhosis who received nucleos (t)ide analogues.

Aims: To investigate the role of M2BPGi in predicting HCC, cirrhotic event and liver-related mortality in CHB patients with cirrhosis received entecavir or tenofovir disoproxil fumarate (TDF) therapy.

Methods: The study enrolled 753 CHB patients with cirrhosis from 2008 through 2018. All patients received entecavir or TDF monotherapy for at least 12 months before enrollment. Patients who had HCC or liver transplantation at initial treatment or within the first year of entecavir or TDF therapy were excluded.

Results: In the entire cohort, the cumulative rates of HCC at 3, 5, and 10 years were 10.8%, 16.9%, and 28.4%, respectively. The N2BPGi levels at

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baseline was higher than those at one year of treatment (3.44 ± 3.97 versus 2.29 ± 2.77 COI, p < 0.001). Multivariate analysis showed that old age, male gender, hepatic decompensation and higher INR at baseline, and higher M2BPGi and AFP levels at one year of treatment were independent predictors of HCC development for all patients. In addition, platelet count at baseline and higher M2BPGi and FIB-4 levels at one year of treatment were independent factors of cirrhotic event development in patients without hepatic decompensation at baseline. Hepatic decompensation and higher INR at baseline and M2BPGi at one year of treatment were independent predictors of liver related mortality.

The M2BPGi ≥2 COI at one year of treatment significantly increased the risk of HCC (the 10year cumulative rate of HCC: ≥2 versus <2 COI: 42.6% versus 19.4%, p < 0.001) and liver-related mortality (the 10-year cumulative rate of HCC: ≥2 versus <2 COI: 28% versus 0.05%, p < 0.001).

Conclusions: The higher M2BPGi levels at one year of treatment could predict clinical outcomes in CHB patients with cirrhosis who received entecavir or TDF therapy.

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P.03

SUPPRESSION OF DESULFOVIBRIO IN THE GUT BY PROBIOTIC LACTOBACILLUS AND BIFIDOBACTERIUM PROTECTS AGAINST FATTY LIVER Yu-Chen Lin1,2, Hsueh-Fang Lin1, Chi-Chien Wu1, Yen-Hsuan Ni3 Department of Pediatrics, Far Eastern Memorial Hospital, New Taipei City, Taiwan1 Department of Healthcare Administration, Asia Eastern University of Science and Technology, New Taipei City, Taiwan2 Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan3

steatosis and fibrosis changes. Furthermore, mice fed with D. piger had a decrease in the villus length, crypt depth, and zonula occludens-1 expression in ileum tissue. Interestingly, the addition of D. piger up-regulated the expression of CD36 in the liver.

Knockdown of CD36 decreased lipid droplets in HepG2 cells. Furthermore, D. piger cell-free supernatant increased CD36 expression in HepG2 cells.

Conclusions: Probiotic Lactobacillus and Bifidobacterium can suppress Desulfovibrio spp. in the gut, thereby improving NAFLD. The mechanisms linking Desulfovibrio with NAFLD include increased intestinal permeability and upregulation of CD36 expression in the liver.

益生菌乳桿菌和雙歧桿菌經由抑制腸 道脫硫弧菌可緩解脂肪肝 林裕誠1,2 林雪芳1 吳季謙1 倪衍玄3 亞東紀念醫院小兒科1 亞東科技大學醫務管理系2 國立臺灣大學醫學院附設醫院小兒科3 Background: Recent evidence suggests that gut dysbiosis is associated with nonalcoholic fatty liver disease (NAFLD).

Aims: We hypothesized the probiotics, Lactobacillus reuteri (L. reuteri) and Lactobacillus rhamnosus GG (LGG) plus Bifidobacterium animalis subsp. lactis BB12 (BB12), can improve fatty liver. If this hypothesis is verified, we’d explore its mechanism.

Methods: C57BL/6JNarl male mice were divided into chow diet, high-fat diet (HFD), HFD + L. reuteri, and HFD + LGG plus BB12 groups. 16S rRNA sequencing was used to assess fecal microbiome composition. The microbial differences found were verified in a human fatty liver cohort. Mice were administered with the candidate bacteria identified above by intragastric gavage. Liver and intestinal tissues were collected. The histopathological changes and expression levels of lipid metabolismrelated genes in the liver were measured.

Results: Probiotics improved the severity of liver steatosis and fibrosis in HFD fed mice, which was related to the lower abundance of the Desulfovibrio spp. in feces. Fecal microbiomes of obese children showed that subjects with NAFLD have higher abundance of D. piger. Administration of D. piger in HFD-fed mice induced more severe hepatic

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P.04

HYDROXYCHLOROQUINE (HCQ) MODULATES AUTOPHAGY AND OXIDATIVE DNA DAMAGE STRESS IN HEPATOCELLULAR CARCINOMA TO OVERCOME SORAFENIB RESISTANCE VIA TLR9/SOD1/HSAMIR-30A-5P/BECLIN-1 AXIS Ming-Yao Chen1,2, Vijesh Kumar Yadav1,2, Yi-Cheng Chu3, Jiann-Ruey Ong4,5, Ting-Yi Huang6, Kwai-Fong Lee6, Kuen-Haur Lee7,8, Chi-Tai Yeh9,10, Wei-Hwa Lee11 Division of Gastroenterology and Hepatology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan1 Division of Gastroenterology and Hepatology, Department of Internal Medicine, Shuang Ho Hospital, New Taipei City, Taiwan2 Department of Medicine, St. George’s University School of Medicine, St. George SW17 0RE, Grenada3 Department of Emergency Medicine, Taipei Medical University-Shuang Ho Hospital, New Taipei City, Taiwan4 Department of Emergency Medicine, School of Medicine, Taipei Medical University, Taipei, Taiwan5 Biobank management Center, Taipei Medical University-Shuang Ho Hospital, New Taipei City, Taiwan6 Graduate Institute of Cancer Biology and Drug Discovery, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan7 Cancer Center, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan8 Department of Medical Research & Education, Taipei Medical University Shuang Ho Hospital, New Taipei City, Taiwan9 Department of Medical Laboratory Science and Biotechnology, Yuanpei University of Medical Technology, Hsinchu, Taiwan10 Department of Pathology, Taipei Medical University Shuang Ho Hospital, New Taipei City, Taiwan11

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奎寧透過 TLR9/SOD1/hsa-miR-30a5p/Beclin-1 訊息傳遞鍊調節細胞自噬 和氧化壓力 DNA 損傷以克服蕾莎瓦耐 藥性肝癌細胞 陳明堯1,2 魏吉士1,2 朱翊承3 翁健瑞4,5 黃庭儀6 李桂芳6 李崑豪7,8 葉淇臺9,10 李偉華11 臺北醫學大學附設醫院消化內科1 臺北醫學大學雙和醫院消化內科2 聖喬治大學醫學院3 臺北醫學大學雙和醫院急重症醫學部4 臺北醫學大學附設醫院重症醫學部5 臺北醫學大學雙和醫院生物資料庫中心6 臺北醫學大學癌症生物學與藥物研發博士學位學 程7 臺北市立萬芳醫院癌症中心8 臺北醫學大學雙和醫院研究部9 元培醫事科技大學醫學檢驗生物技術系10 臺北醫學大學雙和醫院病理科11 Background: Hepatocellular carcinoma (HCC) is one of the major causes of cancer-associated death worldwide. Development of sorafenib resistance presents a major failure of HCC therapy.

Autophagy modulates the growth of cancer cells depending on the cell status. Under cellular stress, such as nutrient deficiency, radiation, and chemotherapy, autophagy is activated to promote tumor cell survival and induce chemoresistance.

Sorafenib induces autophagy and apoptosis, which may lead to sorafenib resistance in HCC. Aims: In this study, we investigated the mechanisms underlying acquired sorafenib resistance in HCC cells and targeted them to re-sensitize them to sorafenib, and explored the importance of TLR9 and how HCQ affects TLR9 expression.

Methods: We applied a combination therapy approach of hydroxychloroquine (HCQ)– sorafenib, both in vitro andin vivo, with data demonstrating the synergistic effect of HCQ in modulating the expression of toll-like receptor (TLR)-9 and regulating the cancer cells stemness, mesenchymal state, autophagy, and sorafenib resistance through inducing the antioxidant superoxide dismutase (SOD)-1 and apoptosisallied gene expression and reducing the oxidative DNA damage stress in HCC sorafenib-resistant cells via hsa-miR-30a-5p epigenetic regulation axis. All assays were performed at least thrice

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in triplicate. Values are expressed as mean ±standard deviation (SD).

Results: In silico analysis indicated that toll-like receptor (TLR)-9 was significantly overexpressed, and that miRNA (hsa-miR-30a-5p) was downregulated in sorafenib-resistant HCC cells, which modulated HCC cell proliferation, oxidative stress, and apoptosis. TLR9 overexpression increased HCC cell proliferation, whereas TLR9 inhibition from hydroxychloroquine (HCQ) decreased HCC cell proliferation, tumor growth, oxidative stress marker (SOD1), and the formation of autophagosome bodies (reduced ATG5 and Beclin-1 expression). Moreover, HCQ treatment reduced epithelial–mesenchymal transition, leading to decreased clonogenicity, migratory ability, and invasiveness. HCQ targeted and reduced the self-renewal capacity phenotype by inhibiting tumorsphere generation. Both in vitro and in vivo results demonstrated the synergistic effect of the HCQ–sorafenib combination on sorafenibresistant HCC (Huh7-SR) cells, increasing their sensitivity to treatment by modulating TLR9, autophagy (ATG5 and Beclin-1), oxidative stress (SOD1), and apoptosis (c-caspase3) expression and thus overcoming the drug resistance.

Conclusions: This study’s findings indicate that TLR9 overexpression occurs in sorafenibresistant HCC cells and that its downregulation aids HCC suppression. Moreover, HCQ treatment significantly increases sorafenib’s effect on sorafenib-resistant HCC cells.

P.05

EFFECTS OF DIPEPTIDYL PEPTIDASE-4 INHIBITION ON PORTAL HYPERTENSIVE AND 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 Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan1 National Yang Ming Chiao Tung University, Taipei, Taiwan2

Dipeptidyl Peptidase-4 抑制劑對門脈 高壓及肝硬化大鼠之影響 張景智1,2 黃惠君1,2 許劭榮1,2 莊喬琳1,2 侯明志1,2 李發耀1,2 臺北榮民總醫院內科部1 陽明交通大學2 Background: Portal hypertension is a pathophysiological abnormality with distinct vascular derangements in liver cirrhosis. The inhibitor of dipeptidyl peptidase-4 (DPP-4) is an anti-diabetic agent which exerts pleiotropic vascular effects, but its relevant impact on portal hypertension and liver cirrhosis remains unclear.

Aims: This study aims to clarify the effect of DPP-4 inhibition on portal hypertensive and cirrhotic rats.

Methods: Rats receiving partial portal veinligation (PVL) and common bile duct-ligation (BDL) served as portal hypertensive and cirrhotic experimental models respectively. After linagliptin (a DPP-4 inhibitor) treatment, the survival rate, hemodynamics, biochemistry parameters and liver histopathology were evaluated. In addition, the collateral vascular responsiveness and severity of portal-systemic shunting were examined. The mRNA and protein expressions in the vasculature and liver were also examined.

Results: Linagliptin significantly reduced portal pressure (control vs. linagliptin: 12.9 ± 1.2 vs.

9.1 ± 2.0 mmHg, P=0.001) and up-regulated nitric oxide synthase expressions in the collateral vessel, superior mesentery artery and liver of PVL rats. However, the portal hypotensive effect was insignificant in BDL rats. The plasma levels of glucose, liver and renal biochemistry parameters were not altered by linagliptin. The portal-systemic shunting degree and collateral

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vascular responsiveness were not influenced either. Linagliptin did not improve liver fibrosis and hepatic inflammation in BDL rats.

Conclusions: DPP-4 inhibition by linagliptin reduced portal pressure in portal hypertensive rats but not in cirrhotic rats, which may be derived from decreasing intra-hepatic resistance via an upregulation of hepatic nitric oxide synthase in portal hypertensive rats.

P.06

INCIDENCE AND PREDICTORS ASSOCIATED WITH HBV RELAPSE AFTER CESSATION OF ENTECAVIR OR TENOFOVIR IN PATIENTS WITH HBSAG BELOW 40 IU/ML Tzu-Ning Tseng, Chien-Hung Chen, Tsung-Hui Hu, Jing-Houng Wang, Chao-Hung Hung, Sheng-Nan Lu Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung, Chang Gung Memorial Hospital, Taiwan

貝樂克和惠立妥停藥時表面抗原小於 40 IU/mL 的病人 B 型肝炎病毒復發的 發生率和相關因子 曾子寧 陳建宏 胡琮輝 王景弘 洪肇宏 盧勝男 高雄長庚紀念醫院肝膽胰內科 Background: Our previous study demonstrated that hepatitis B surface antigen (HBsAg) less than 40 IU/ml at the end of treatment (EOT) was a predictor of sustained response after discontinuing NAs. In clinical practical, however, patients with such low HBsAg levels still have risks of hepatitis B virus (HBV) relapse.

Aims: To investigate the incidence and predictors associated with HBV relapse in patients with levels of EOT HBsAg ≤ 40 IU/mL after cessation of entecavir or tenofovir disoproxil fumarate (TDF) treatment.

Methods: This study recruited 110 patients with levels of HBsAg less than 40 IU/mL at EOT (60 entecavir and 50 TDF). All patients had posttreatment follow-up for at least 6 months. Posttreatment virological relapse was defined as a serum HBV DNA level greater than 2000 IU/mL, and clinical relapse was defined as an alanine aminotransferase (ALT) level greater than 80 U/L and a HBV DNA level greater than 2000 IU/mL. Results: Of the 110 patients, the 5-year incidences of virological relapse, clinical relapse, and HBsAg loss were 29.8%, 21.3%, and 57.9%, respectively.

Multivariate analysis showed that age, NAexperienced status, baseline HBcrAg and HBsAg at EOT were associated independently with virological relapse. Baseline HBcrAg of 3 log U/ mL and HBsAg level of 20 IU/mL were the optimal value for predicting virological relapse. The 5-year virological relapse rates in patients with baseline

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HBcrAg ≤ 3 (n=37) and > 3 (n=73) log U/mL were 10.1 and 39.6% (p=0.005), and clinical relapse rates were 2.7% and 31.1%, respectively (p=0.003).

The 5-year virological relapse rates in patients with HBsAg at EOT ≤ 20 (n=61) and >20 (n=49) log U/ mL were 14.9% and 49.3% (p=0.001), and clinical relapse rates were 11.9 and 35%, respectively (p=0.031). Rates of virologic and clinical relapse and HBsAg loss within 5 years were 4.2%, 0% and 81.8%, respectively in patients with a combination of baseline HBcrAg ≤ 3 log U/ml and EOT HBsAg level ≤ 20 IU/mL. No patients experienced hepatic decompensation when clinical relapse occurred with a timely retreatment.

Conclusions: A combination of baseline HBcrAg less than 3 log U/ml and EOT HBsAg level less than 20 IU/mL might reduce the risk of HBV relapse and guide treatment cessation in patients with CHB in patients who achieved HBsAg ≤ 40 IU/mL.

P.07

CIRRHOSIS IS THE ONLY INDEPENDENT FACTOR FOR HEPATOCELLULAR CARCINOMA IN OFF-NUC PATIENTS WITH HBSAG SEROCLEARANCE Wen-Juei Jeng1,2,3, Chien-Hung Chen1,4, Yen-Chun Liu1,2, Yi-Cheng Chen1,2, Cheng-Yuan Peng5,6,7, Tsung-Hui Hu1,4, Chao-Hung Hung1,4, Jing-Hung Wang1,4, Sheng-Nan Lu1,4, Rong-Nan Chien1,2,3, Yun-Fan Liaw1,3 College of Medicine, Chang Gung University, Taipei, Taiwan1 Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan, Taiwan2 Liver Research Unit, Chang Gung Memorial Hospital, Linkou branch, Taoyuan, Taiwan3 Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan4 Center for Digestive Medicine, China Medical University Hospital, Taichung, Taiwan5 China Medical University, Taichung, Taiwan6 Division of Hepatogastroenterology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan7

肝硬化是停止口服抗病毒藥物患者發 生表面抗原消失後產生肝癌的唯一獨 立因子 鄭文睿1,2,3 陳建宏1,4 劉彥君1,2 陳益程1,2 彭成元5,6,7 胡琮輝1,4 洪肇宏1,4 王景弘1,4 盧勝男1,4 簡榮南1,2,3 廖運範1,3 長庚大學醫學院1 林口長庚紀念醫院胃腸肝膽科系2 林口長庚紀念醫院肝臟研究中心3 高雄長庚紀念醫院內科部胃腸肝膽科4 中國醫藥大學附設醫院消化醫學中心5 中國醫藥大學6 中國醫藥大學附設醫院內科部胃腸肝膽科7 Background: Increased HBsAg loss has been observed in off-Nuc patients comparing to those continuing long-term treatment. However, it was suspected that patients with virological relapse

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(VR) and/or clinical relapse (CR) may have experienced liver injury prior to the subsequent HBsAg loss, leading to less beneficial long-term outcome than those with sustained response (SR).

Aims: This study aims to investigate the independent factor for predicting hepatocellular carcinoma in off-Nuc patients with HBsAg loss and to clarify whether the presence of VR or CR be an unfavorable factor for HCC development.

Methods: Patients with off-Nuc HBsAg loss from three medical centers were recruited. Those with HCC occurred prior to HBsAg loss or occurred within 6 months after HBsAg loss were excluded.

VR was defined as HBV DNA ≥ 2000 IU/mL. CR was defined as VR + ALT ≥ 2X upper limit of normal. Gender, cirrhosis status, HBV genotype, last treatment regimen, treatment duration, age, serum AST, ALT, AFP level, platelet count, FIB-4 at time of HBsAg loss along with whether presence of VR or CR before HBsAg loss were compared between patients with and without HCC. Multivariate cox regression analysis was applied for independent predictors of HCC in off-Nuc patients with HBsAg loss. Kaplan Meier analysis with log rank test was performed to compare the cumulative HCC incidence between patients with and without cirrhosis or with and without relapse.

All statistical analysis was done by SAS 9.4.

The two-tailed p value. <0.05 was regarded as statistically significant.

Results: During a median of 5.3 years follow-up, 10 HCC cases were documented among 275 off-Nuc patients with HBsAg loss. There were 84 (30.6%) and 43 (15.6%) patients experienced VR and CR prior to HBsAg seroclearance, respectively. Higher proportion of pre-HBsAg loss cirrhosis (83.3 vs.

26.6%, P<0.01), age >50 (91.7 vs. 61.6%, P=0.036) and increased AFP level (2.9 vs. 2.2, P=0.025) were observed in the HCC patients comparing to those in the non-HCC arm. Multivariate analysis showed pre-HBsAg loss cirrhosis was the only risk factor for HCC in off-Nuc patients with HBsAg loss [aHR: 8.9 (1.9-42.1), P=0.006] while age >50 failed to reach statistical significance (aHR: 5.04, P=0.133). Neither HBV genotype, Nuc regimen, treatment duration, gender, stoppage by APASL stopping rule, presence of VR (aHR: 1.2, P=0.74) nor CR (aHR: 1.3, P=0.73) were significant factors for HCC development. The annual and 5-year cumulative HCC incidence for non-cirrhotic and cirrhotic off-Nuc patients with HBsAg loss was 0.15%, 1% vs. 2.2%, 10%, respectively (log rank

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test, P<0.0001). One patient (0.36%) died of HCC progression.

Conclusions: Virological or clinical relapse prior to the HBsAg loss did not increase HCC risk in offNuc patients achieved functional cure. Cirrhosis remains the only independent risk factor for HCC development in the off-Nuc patients with HBsAg loss.

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P.08

REAL WORLD LENVATINIB VERSUS SORAFENIB IN PATIENTS WITH ADVANCED HEPATOCELLULAR CARCINOMA: A PROPENSITY SCORE MATCHING ANALYSIS Yuan-Hung Kuo, Sheng-Nan Lu, Kwong-Ming Kee, Yi-Hao Yen, Chao-Hung Hung, Tsung-Hui Hu, 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

interval: 0.3-0.79, p=0.004) after adjustment with albumin-bilirubin grade and alpha-fetoprotein level. However, different agents using lenvatinib or sorafenib didn`t contribute to OS, whether for univariate or multivariate analysis. After cession of lenvatinib or sorafenib, 53% of patients could afford the following therapies, whereas 44.3% of patients received sequential systemic therapies.

Conclusions: In clinical real-life practice, lenvatinib illustrated promising survival benefits and acceptable safety for patients with unresectable HCC. Furthermore, lenvatinib could reduce the risk of progression disease compared with sorafenib.

現實世界晚期肝癌病人使用樂衛瑪與 雷莎瓦比較：一個傾向分數配對分析 郭垣宏 盧勝男 紀廣明 顏毅豪 洪肇宏 胡琮輝 陳建宏 王景弘 長庚醫療財團法人高雄長庚紀念醫院胃腸肝膽科 系暨長庚大學醫學系 Background: Lenvatinib is approved for patients with advanced hepatocellular carcinoma (HCC) due to its non-inferiority to sorafenib of overall survival (OR) in clinical trial.

Aims: This study aimed to compare the effectiveness and safety of lenvatinib and sorafenib in real world.

Methods: We retrospectively evaluated 338 patients with unresectable HCC who had undergone lenvatinib or sorafenib between January 2018 and August 2020. Propensity-score matching analysis was performed with a 1:2 ratio to reduce the real-life baseline difference between two groups.

Results: A total of 210 patients (Male/Female: 150/60, mean age: 65.8 year) were recruited including 70 patients in the Lenvatinib group and 140 patients in the Sorafenib group. Compared with sorafenib, lenvatinib had significantly longer progression-free survival (PFS) (5.2 vs 3.3 months, p=0.019) but similar OR (13.3 vs 11.8 months, p=0.714). Additionally, lenvatinib had better disease control rates (62.3% vs 48.6%, p=0.029) and equivalent incidences of treatment-related adverse events over sorafenib. In multivariate analysis, lenvatinib was associated with better PFS over sorafenib (hazard ratio: 0.49, 95% confidence

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P.09

FINDING THE LOST PATIENTS IN THE SYSTEM FOR HEPATITIS C ELIMINATION: A SINGLE-CENTER EXPERIENCE Hsu-Heng Yen, Pei-Yuan Su, I-Ling Liu, Ya-Huei Zeng, Siou-Ping Huang, Fang-Chi Yang Division of Gastroenterology, Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan

召回院內 C 型肝炎陽性個案之根除計 畫

P.10

CHARACTERISTICS AND COURSE OF CHRONIC HEPATITIS B E ANTIGEN-POSITIVE INFECTION: A SINGLE TERTIARY MEDICAL CENTER EXPERIENCE Wei-Chen Lin, Chen-Wang Chang, Ching-Wei Chang, Tsang-En Wang, Horng-Yuan Wang, Ming-Jen Chen Division of Hepatobiliary, Department of Internal Medicine, MacKay Memorial Hospital, Taipei, Taiwan

顏旭亨 蘇培元 劉怡伶 曾雅慧 黃秀萍 楊芳琦

B 肝患者 e 抗原陽性之臨床特徵與演 變：單一醫學中心之臨床經驗

彰化基督教醫院胃腸肝膽科

林煒晟 章振旺 張經緯 王蒼恩 王鴻源 陳銘仁

Background: Hepatitis C virus (HCV) is one of the major causes of chronic liver disease, cirrhosis, and liver cancer. Most of the infected people have no clinical symptoms. The current strategy for HCV elimination includes test and treatment.

Aims: In this study, we aimed to evaluate the campaign for retrieving patients who were lost to follow-up, for subsequent re-evaluation.

Methods: From January 2020 to October 2020, patients who had prior tests for positive anti-HCV antibody in 2010–2018 in our hospital were enrolled for our patient callback campaign. Patients who had unknown HCV RNA status or no documented successful antiviral therapy history were selected for anti-HCV therapy re-evaluation. To facilitate patient referral in the hospital, we developed an electronic reminding system and called the candidate patients via telephone during the study period.

Results: Through the hospital electronic system, 3783 patients with positive anti-HCV antibody documentation were identified. Among them, 1446 (38.22%) had tested negative for HCV RNA or had anti-HCV therapy, thereby excluded. Of the 2337 eligible patients, 1472 (62.99%) were successfully contacted and called back during the study period for subsequent HCV RNA testing and therapy.

We found that 42.19% of the patients had positive HCV RNA and 88% received subsequent anti-HCV therapy.

Conclusions: A significant number of patients with positive HCV serology were lost for HCV confirmatory test or therapy in the hospital.

Therefore, this targeted HCV callback approach in the hospital is feasible and effective in achieving microelimination.

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Background: The presence of hepatitis B e antigen (HBeAg) in serum indicates active viral replication in hepatocytes. HBeAg is thus a surrogate marker for the presence of hepatitis B virus (HBV) DNA. Furthermore, previous study shows positivity for HBeAg is associated with an increased risk of hepatocellular carcinoma. Therefore, treatmentinduced HBeAg seroconversion has also been shown to confer favorable outcomes.

Aims: We conducted a retrospective study to describe the characteristics and clinical course of HBV carriers with positive HBe antigen.

Methods: All HBV carriers with positive HBe antigen, with no other causes of liver disease were enrolled during the Sep. 2019- Oct. 2020 in a single tertiary medical center.

Results: One hundred and eighty-seven patients were included, with mean age 38.7 ± 13.2 years; 63% were men. The mean follow-up duration was 8.1 ± 6.1 years and there were 153 patients (81.8%) receiving the Nucleos(t)Ide Analogs (NUC) therapy. The longer follow-up duration of 9.1 ± 6.1 years was in the HBV treated group compared with 6.2 ± 5.3 years in the HBV untreated group.

In the untreated group, transaminases were normal in nearly 67.6% patients and HBV-DNA was 8.49 ± 8.22 log IU/mL. As for the treated group, HBV-DNA was 8.38 ± 8.09 log IU/mL and the alanine aminotransferase was 194 ± 84 IU/L. Abdominal ultrasound study was performed: 49.7% patients had fatty liver, 29.9% patients had chronic liver disease, 8.6% had cirrhosis and

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3.2% hepatoma. The commonly prescribed NUC therapy were Entecavir (n=65, 42.5%), followed by Tenofovir disoproxil (n=44, 28.8%) and Tenofovir alafenamide (n=16, 10.5%). Nine patients (4.8%) had HBe antigen reversion 6.0 ± 1.2 years after NUC therapy.

Conclusions: In a well-characterized reallife clinical cohort of chronically HBV-infected patients in various disease phases, only around 5% of patients reached HBe antigen reversion after 6 years therapy. The lower reversion rate in this real world study may relate to intermittent therapy of NUC therapy under that National Health Insurance. Prolonged NUC therapy till HBeAg seroconversion as an important end point in the treatment of chronic hepatitis B.

P.11

GLECAPREVIR-PIBRENTASVIR FOR COMPENSATED LIVER CIRRHOSIS WITH HEPATITIS C INFECTION: A MULTI-CENTER RETROSPECTIVE STUDY Pei-Yuan Su1,3, Yang-Yuan Chen1,2, Jun-Hung Lai3, Chih-Ta Yao4, Hung-Ming Chen5, Hsu-Heng Yen1 Division of Gastroenterology, Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan1 Division of Gastroenterology, Department of Internal Medicine, Yuanlin Christian Hospital, Changhua, Taiwan2 Division of Gastroenterology, Department of Internal Medicine, Erhlin Christian Hospital, Changhua, Taiwan3 Division of Gastroenterology, Department of Internal Medicine, Lukang Christian Hospital, Changhua, Taiwan4 Division of Gastroenterology, Department of Internal Medicine, Yunlin Christian Hospital, Yunlin, Taiwan5

使用艾百樂於非代償不全肝硬化之治 療經驗：彰化基督教醫療體系多中心 回溯性研究 蘇培元1,3 陳洋源1,2 賴俊宏3 姚志達4 陳鴻銘5 顏旭亨1 彰化基督教醫院胃腸肝膽科1 員林基督教醫院胃腸肝膽科2 二林基督教醫院胃腸肝膽科3 鹿港基督教醫院胃腸肝膽科4 雲林基督教醫院胃腸肝膽科5 Background: Glecaprevir/pibrentasvir is a protease inhibitor-containing pangenotypic direct-acting antiviral regimen approved for treating chronic hepatitis C infection. Real-world effectiveness for Asian patients with compensated cirrhosis is lacking.

Aims: We evaluated the real-world safety and efficacy of glecaprevir/pibrentasvir in patients with compensated cirrhosis from the five hospitals in the Changhua Christian Care System who initiated treatment between Aug 2018 and Oct 2020.

Methods: This retrospective study evaluated the efficacy and safety of GLE/PIB treatment in

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adults with HCV infection and compensated liver cirrhosis. The primary endpoint was sustained virological response (SVR) observed 12 weeks after completed treatment.

Results: We enrolled 90 patients, including 70 patients receiving 12-weeks therapy and 20 patients with 8-week therapy. The mean age was 65 years, and 57.8% were males. Sixteen (17.8%) patients had end-stage renal disease, and fifteen (16.7%) of patients had co-existing hepatoma. HCV genotypes 1 (40%) and 2 (35.6%) were the most common. Common side effects include anorexia (12.2%), pruritus (7.8%), abdominal discomfort (7.8%) and malaise (7.8%)). Laboratory adverse events with grade ≥3 include anemia (6.3%), thrombocytopenia (5.1%), and jaundice (2.2%).

The overall SVR12 rates were 94.4% and 97.7% in the ITT and PP analyses.

Conclusions: In this study, we found glecaprevir/ pibrentasvir was highly effective and well-tolerated for compensated cirrhotic patients in the real-world setting.

P.12

SERUM CYTOKINE/CHEMOKINE PROFILES PREDICT HEPATITIS B VIRUS REACTIVATION IN HCV/ HBV CO-INFECTED SUBJECTS RECEIVING DIRECT-ACTING ANTIVIRAL AGENTS Chieh Liu1, Shang-Chin Huang2, Pin-Nan Cheng3, Chen-Hua Liu2,4, Hung-Chih Yang2,4, Tung-Hung Su2,4, Tai-Chung Tseng2,4,5, Pei-Jer Chen2,4,5,6, Jia-Horng Kao2,4,5,6, Chun-Jen Liu2,4,6 Department of Medicine, Chung-Shan Medical University, Taichung, Taiwan1 Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan2 Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan3 Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan4 Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan5 Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan6

以細胞動素及趨化動素預測 B 型肝炎 與 C 型肝炎的共同感染患者接受直接 抗病毒藥物治療後的 B 型肝炎復發 劉潔1 黃上秦2 鄭斌男3 劉振驊2,4 楊宏志2,4 蘇東弘2,4 曾岱宗2,4,5 陳培哲2,4,5,6 高嘉宏2,4,5,6 劉俊人2,4,6 中山醫學大學醫學系1 國立臺灣大學醫學院附設醫院內科部2 國立成功大學醫學院附設醫院內科部3 國立臺灣大學醫學院附設醫院肝炎研究中心4 國立台灣大學醫學院附設醫院醫學研究部5 國立臺灣大學醫學院臨床醫學研究所6 Background: Reactivation of hepatitis B virus (HBV) in patients with chronic hepatitis C (CHC) receiving direct-acting antiviral (DAA) agents has been an existing problem; yet the relationship between host immune responses and HBV reactivation remained largely unknown.

Aims: We performed a prospective study, aiming

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to test the hypothesis whether baseline level and dynamics of cytokines/chemokines correlated with the development of hepatitis B reactivation.

Methods: Between 2017 and 2019, we prospectively recruited 25 patients with HBV and HCV co-infection, scheduled to receive a 12-week DAA therapy for CHC. Serum alanine aminotransferase (ALT) level, HBV DNA level, HCV RNA level, six cytokines, and three chemokines levels were followed at week 2, 4, 8, and 12 of the treatment period, and at week 12 after the end of treatment. Clinical reactivation of HBV was based upon an elevated ALT level comparing to that of baseline in addition to the presence of virologic reactivation of HBV (an increase of serum HBV DNA to >10 times of baseline value).

Results: There were 20 patients (80%) experiencing HBV virologic reactivation and 5 patients (20%) experiencing clinical reactivation.

Patients with clinical reactivation had higher baseline TNF-alpha (28.22 versus 19.23 pg/mL, P = 0.014), CCL2 (682.10 versus 415.84 pg/mL, P = 0.047) and lower week-4 IFN-gamma (0.98 versus 8.34 pg/mL, P = 0.019) levels as compared to those without reactivation. Single or combination of these cytokines/chemokine helped predict clinical reactivation (all P < 0.05).

Conclusions: Higher serum levels of pretreatment CCL2, TNF-alpha and lower level of IFN-gamma at week 4 were associated with HBV reactivation in patients with HBV and HCV coinfection receiving DAAs. Further studies with a larger case number and long-term outcomes are needed.

P.13

SERUM M2BPGI CAN PREDICT MILD OR SIGNIFICANT LIVER FIBROSIS IN NON-ALCOHOLIC FATTY LIVER DISEASE Yu-Ming Cheng1, Jiann-Hwa Chen1,2, Chia-Chi Wang1,2 Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taipei Tzu Chi Hospital, Taipei, Taiwan1 Buddhist Tzu Chi Medical Foundation and School of Medicine, Tzu Chi University, New Taipei City, Taiwan2

M2BPGi 可用來預測非酒精性脂肪肝 病輕微或顯著肝纖維化 鄭煜明1 陳建華1,2 王嘉齊1,2 台北慈濟醫院胃腸肝膽科1 慈濟學校財團法人慈濟大學2 Background: The serum levels of Mac-2 binding protein glycosylation isomer (M2BPGi) increase with liver fibrosis progression in patients with chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. However, the diagnostic performance of M2BPGi in non-alcoholic fatty liver disease (NAFLD) patients remains unclear.

Aims: For assessing the severity of liver fibrosis in NAFLD patients and healthy controls by M2BPGi using ARFI as standard reference.

Methods: The participants including NAFLD patients or health controls were included. The diagnosis of NAFLD was made based on fatty liver in imaging after excluding HCV, HBV, alcohol, drug, or other known causes of chronic liver disease. Acoustic radiation force impulse (ARFI) was used as standard reference for the stage of liver fibrosis.

Results: 226 subjects were included. Of them, there were 130 (57.5%) NAFLD patients. According to stage of liver fibrosis, they were divided to three groups: F0, F1, and F≥2. The serum AST, ALT, AST to platelet ratio index (APRI), M2BPGi, and the fatty liver grade were significantly different among three groups. The levels of M2BPGi correlated with median ARFI value (p < 0.001), AST to platelet ratio index (APRI) (p = 0.011) and Fibrosis 4 index (FIB-4) (p < 0.001). The area under the curve (AUC) of M2BPGi test was 0.58 for F≥1 and 0.68 for F≥2, respectively (p=0.039 and p=0.024).

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Conclusions: The M2BPGi levels correlated with ARFI, APRI and FIB-4 score in this study population. The levels of M2BPGi can predict mild (F≥1) and significant liver fibrosis (F≥2) of NAFLD patients, suggesting a surrogate marker to differentiate among normal, mild and significant fibrosis.

P.14

CHOLECYSTECTOMY IS ASSOCIATED WITH LOW RECURRENT RISK IN BCLC STAGE 0/A HEPATOCELLULAR CARCINOMA PATIENTS AFTER CURATIVE RESECTION Shih-Yu Yang1, Yu-Syuan Chen1, Chih-Chi Wang2, Yueh-Wei Liu2, Chih-Che Lin2, Chih-Chien Yao1, Yi-Hao Yen1, Wei-Ru Cho1, Ming-Chao Tsai1 Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan1 Liver Transplantation Center and Department of Surgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan2

膽囊切除與降低 BCLC 期別 0/A 肝癌 病人手術後復發率相關 楊適宇1 陳宇軒1 王植熙2 劉約維2 林志哲2 姚志謙1 顏毅豪1 卓韋儒1 蔡明釗1 長庚醫療財團法人高雄長庚紀念醫院 胃腸肝膽科 系1 長庚醫療財團法人高雄長庚紀念醫院 外科部肝臟 移植中心2 Background: Cholecystectomy has been reported to be associated with increased risk of developing hepatocellular carcinoma (HCC). However, the effect on HCC prognosis is still unclear.

Aims: To evaluate the effect of cholecystectomy on HCC recurrence and survival after curative resection among patients with HCC. Methods: We enrolled 857 BCLC stage 0/A HCC patients who received primary resection from January 2001 to June 2016. 539 patients received cholecystectomy. Factors influence the overall survival (OS) and recurrence-free survival (RFS) were analyzed by Cox’s proportional hazards models after one-to-one propensity score matching.

Results: Of 857 patients, 539 (62.9%) received cholecystectomy (cholecystectomy group) and 318 (37.1%) did not (non-cholecystectomy group).

During a mean 75.0 months of follow-up, 471

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(55.0%) patients experienced recurrence, and 158 (18.5%) patients died. RFS and OS were not significantly different between groups. After one-to-one propensity score matching, a total of 298 patients were enrolled in each group. In the multivariate analysis, age (p = 0.022), AFP (p = 0.008), liver cirrhosis (p < 0.001), diabetes (p = 0.004), tumor number (p = 0.005), tumor size (p = 0.002), histology stage (p = 0.001), vascular invasion (p < 0.001) and cholecystectomy (p = 0.021) were independent risk factors for HCC recurrence. However, cholecystectomy did not affect overall survival.

Conclusions: Cholecystectomy may reduce recurrence in early-stage HCC patients after curative resection. Further studies are needed to validate our results.

P.15

ANALYSIS OF ANTIVIRAL EFFICACY AFTER SWITCHING FROM BRAND TO GENERIC ENTECAVIR 0.5 MG IN PATIENTS WITH TREATMENT-NAÏVE CHRONIC HEPATITIS B Po-Ke Hsu, Pei-Yuan Su, Yang-Yuan Chen, Yu-Chun Hsu, Wei-Wen Su, Siou-Ping Huang, Hsu-Heng Yen Division of Gastroenterology, Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan

分析 Entecavir 原廠藥與學名藥於治 療慢性 B 型肝炎患者的有效性與安全 性 許柏格 蘇培元 陳洋源 徐友春 蘇維文 黃秀萍 顏旭亨 彰化基督教醫院肝膽腸胃科 Background: Entecavir (ETV) can suppress chronic hepatitis B (CHB) virus as a standard of treatment drug. There is little real world data regarding the clinical efficacy of switching form brand to generic entecavir.

Aims: The aim of the study was to evaluate the antiviral activity and safety of ETV from CCPC as a generic drug in comparison to BMS in patients with CHB. Methods: In this single center, retrospective, comparative study, 175 treatment-naïve patients with CHB were assigned to receive 0.5 mg of Brand entecavir (from BMS) for a least 2 years and then switch to generic entecavir (CCPC) 6 months for analysis. The primary efficacy endpoint was virologic stable with a mean stabilized from baseline in serum HBV DNA levels for 6 months. Secondary efficacy endpoints included compared the alanine aminotransferase before and after switching (ALT normalization). Safety consideration was reported of changing the estimated Glomerular filtration.

Results: From baseline to 6 months, HBV DNA levels and alanine aminotransferase (ALT) remained in stable and compared from BMS period to switching to CCPC for 6 months as HBV DNA: 3.4 IU/mL (Confidence interval CI: 2.1-4.8) to 2.6 IU/mL (CI: 1.63-3.6), and ALT: 27.2 IU/mL (CI: 24.8-29.6) to 26.2 IU/ml (CI: 24.0-28.4) with both showing no signficant. EGFR as the safety

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profile of kidney function reveals from initial 80.8 mL/min/1.73m2 (interquntile range IQR: 66.6-95.3) to 80.3 mL/min/1.73m2 (IQR: 65.6-93.5) with no adverse effect on renal function in terms of safety issue.

Conclusions: In patients with previously untreated HBV infection, the efficacy and safety profiles of ETV switching from BMS to CCPC showed no difference. Concluding the CCPC and BMS all come to exciting virologic responses and rare adverse events.

P.16

THE CHALLENGES OF DIRECTACTING ANTIVIRAL THERAPY IN PATIENTS WITH CHRONIC HEPATITIS C UNDERWENT LIVING DONOR LIVER TRANSPLANTATION Kun-Ta Wu1, Shu-Hsien Lin2,3, Chih-Chi Wang1,3,4, King-Wah Chiu2,3,4 Division of General Surgery, Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan1 Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan2 Liver Transplantation Center, Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan3 College of Medicine, Chang Gung University, Taoyuan, Taiwan4

慢性 C 型肝炎經 DAA 治療後接受活體 肝臟移植所面臨的挑戰 吳坤達1 林淑賢2,3 王植熙1,3,4 趙景華2,3,4 高雄長庚紀念醫院一般外科1 高雄長庚紀念醫院肝膽胃腸科2 高雄長庚紀念醫院肝臟移植中心3 長庚大學醫學院4 Background: Direct-acting antivirals (DAAs) have revolutionized the care of patients with hepatitis C virus (HCV) infection, with cure rate of more than 90%. In our recent report, 86% positive hepatic HCV-RNA were identified in native explanted livers in living donor liver transplantation (LDLT).

Aims: Herein, we would like to elucidate the therapeutic outcomes of DAA in chronic hepatitis C patients underwent LDLT. Methods: This cohort observational study enrolled total 153 HCV infected recipients who underwent LDLT from January 2015 to February 2021 in our liver transplantation program. The impact of DAA on changes in pre-transplant and post-transplant serum HCV viral loads, and post-transplant clinical outcomes were investigated.

Results: Among 153 LDLT recipients, there were 31 (20.3%) treated with pre-transplant DAA (defined as DAA group), and 122 (79.7%) without pre-LDLT DAA treatment (named DAA naïve group). After a

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mean follow-up of 43.2 months, DAA group had a higher rate of aviremia, in both of the before and after LDLT (3.2% vs 43.4%, p = 0.0006; 0% vs 33.6%, p < 0.0001, respectively). The incidence of pre-transplant hepatocellular carcinoma (HCCs) was significantly higher in DAA group (77.4% vs 43.4%, p = 0.001). Higher incidence of posttransplant biliary complication was observed in DAA group (32.3% vs 14.8%, p = 0.028), but there was no difference in the incidence and accumulated episodes of acute cellular rejection (ACR) between two groups (47.6% vs 35.9%; p = 0.39). There was no significant difference of posttransplant de novo HCCs or HCC recurrence in both groups (4.2% vs 4.1%, p = 1.00). Higher pretransplant anti-HCV titer was noted in DAA group, but there was no statistically significance when compared to the DAA naïve group (53.6 vs 51.2, p = 0.76).

Conclusions: Pre-transplant DAA therapy assured aviremia in both of prior and after LDLT, there was no evidence of increase the incidence of HCC development after LDLT. Higher pre LDLT anti-HCV titer as well as higher incidence of post-transplant biliary complication in the DAA group may be caused by an altered humoral immunological response due to DAA use, which interfere healing and fibrosis process of biliary anastomosis, consequently lead to a higher rate of anastomotic stricture. Further researches are required to validate this phenomenon.

P.17

LIPID PROFILE CHANGINGS AFTER SWITCHING FROM TENOFOVIR DISOPROXIL FUMARATE TO TENOFOVIR ALAFENAMIDE FOR PATIENTS WITH HEPATITIS B VIRUS INFECTION Po-Ke Hsu, Pei-Yuan Su, Hsu-Heng Yen, Wei-Wen Su Division of Gastroenterology, Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan

分析惠立妥轉韋立得治療 B 型肝炎病 人的血脂變化 許柏格 蘇培元 顏旭亨 蘇維文 彰化基督教醫院肝膽腸胃科 Background: Tenofovir alafenamide (TAF) has similar efficacy compared to tenofovir disoproxil fumarate (TDF), but a less favorable effect on lipids.

Aim of this retrospective study was to evaluate the impact on lipids of switching from TDF to TAF in a cohort of hepatitis B virus infected patients.

Aims: The aim of this study was to characterize the effect of TDF to TAF switch on plasma lipid concentrations in a real-world clinic population.

Methods: This is a retrospective study included 56 patients comparing lipid concentrations and other laboratory parameters between the last visit on TDF and the first visit after at least a 2-month exposure to TAF. Results: The median (interquartile range) increase was 13.5 (7.0–19.5) mg/dL in total cholesterol (p < 0.001); 14.0 (7.5–23.0) mg/dL in triglycerides (TG) (p < 0.001). But in low-density lipoprotein (LDL) with 4.5 (0–8.5) mg/Dl with p = 0.05, showing no significance.

Conclusions: Switching from TDF to TAF caused a statistically significant worsening of the lipid profile that may have clinical relevance. Further study is still needed in the future for lipid profile difference.

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P.18

NEUROENDOCRINE TUMORS IN THE LIVER: EIGHT-YEAR EXPERIENCE AT A MEDICAL CENTER Chen-Hao Chang1, Ching-Wei Chang1,2,3, Tsang-En Wang1,2,3, Yi-Hong Zeng4, Ming-Jen Chen1,2,3, Horng-Yuan Wang1,2,3 Division of Gastroenterology, Department of Internal Medicine, MacKay Memorial Hospital, Taipei, Taiwan1 MacKay Junior College of Medicine, Nursing and Management, Taipei, Taiwan2 MacKay Medical College, New Taipei, Taiwan3 Division of Endocrinology and Metabolism, Department of Internal Medicine, MacKay Memorial Hospital, Taipei, Taiwan4

肝臟內的神經內分泌腫瘤：在醫學中 心的八年實務經驗 張辰皓1 張經緯1,2,3 王蒼恩1,2,3 曾逸宏4 陳銘仁1,2,3 王鴻源1,2,3 台北馬偕紀念醫院胃腸肝膽內科1 馬偕學校財團法人馬偕醫護管理專科學校2 馬偕學校財團法人馬偕醫學院3 台北馬偕紀念醫院內分泌與新陳代謝內科4 Background: Primary hepatic neuroendocrine tumor (PHNET) is a rare neuroendocrine tumor (NET) that originates from the liver, whereas the vast majority of NETs in the liver are the result of metastases that arise from the gastrointestinal tract and lungs. So the diagnosis of PHNETs relies on pathological confirmation and imaging examination to exclude extrahepatic neuroendocrine tumors, that is challenging—partly due to its rarity, and partly due to its lack of unique clinical features.

Aims: We aimed to investigate the clinical presentations of patients with PHNETs. Methods: We retrospectively reviewed the medical records of patients with NET in the liver from January 2013 to December 2020 at MacKay Memorial Hospital.

Results: A total of 38 patients diagnosed with hepatic neuroendocrine tumor were enrolled. The median age was 60 years (range; 15-86 years) and 63.15% were male patients. 35 patients had metastatic hepatic NETs. The primary sites of liver metastases were mostly from the pancreas (47%,

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n=18), followed by lung (13%, n=5), stomach (11%, n=4), small intestine (5%, n=2), rectum (5%, n=2), NETs of unknown origin (5%, n=2), gallbladder (3%, n=1), and uterus (3%, n=1). After exclusion by imaging examination and pathological confirmation, three patients were diagnosed with PHNETs (8%, n=3). All patients with PHNETs were asymptomatic. None of these patients had positive for HCV Ab and HBsAg, and liver cirrhosis. All patients underwent abdominal ultrasonography and CT scan. Two patients underwent further MRI. On pathological examination, according to the 2019 WHO Classification of Tumors of the Digestive System, there was one case of lowgrade NET (G1), one case of intermediate grade NET (G2), and one case of primary hepatic NEC. Of the three cases, one had refused any medical treatment, one had received surgical resection and postoperative systemic chemotherapy, and one had undergone monthly sandostatin therapy combined with target therapy(everolimus).

Conclusions: In our hospital, most of the NETs in the liver were metastases. The primary sites of metastatic hepatic NETs were mainly from the pancreas. The diagnosis of PHNET was based on exclusion by image and pathological examination.

However, the differences in clinical presentations between primary and metastatic hepatic NETs need more patient data collection for further analysis.

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P.19

COMPARISON OF THE TREATMENT EFFICACY AND RENAL SAFETY OF TAF, ENTECAVIR AND TDF IN NUCLOS(T)IDE-NAÏVE PATIENTS Shao-Ming Chiu, Chien-Hung Chen, Jing-Houng Wang, Chao-Hung Hung, Tsung-Hui Hu, 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

15.2 versus 4.2 ± 16.8 mL/min, p=0.017) and TAF and TDF group (-1.04 ± 15.2 versus 7.7 ± 16.1 mL/min, p<0.001). One, two and six patients experienced AKI during one year of TAF, ETV and TDF therapy, respectively (p=0.235).

Conclusions: TAF, entecavir and TDF groups had similar effectiveness in virological and biochemical responses at one year of treatment. However, TAF groups had better renal safety than entecavir and TDF groups.

韋立得、貝樂克和惠立妥對於未接受 過核甘酸類似物病人的療效和腎功能 安全性的比較 邱紹銘 陳建宏 王景弘 洪肇宏 胡琮輝 盧勝男 高雄長庚紀念醫院胃腸肝膽科系 Background: The real-world treatment efficacy and renal safety of tenofovir alafenamide (TAF) in nucleos(t)ide analogues (NA)-naïve patients remains unclear.

Aims: To compare the one-year treatment efficacy and renal safety of entecavir, tenofovir disoproxil fumarate (TDF) and TAF in nucleos(t) ide analogues (NA)-naïve patients.

Methods: This retrospective study included 440 NA-naïve patients who received entecavir (n=181), TDF (n=158) and TAF (n=101) treatment for at least one year. Acute kidney injury (AKI) is defined as increase in serum creatinine by ≥0.3 mg/dL as KDIGO guideline.

Results: The rates of virological response (HBV DNA <20 IU/mL) at one year of treatment in three groups were 84.5% (entecavir group), 77.8% (TDF group) and 85.1% (TAF group), respectively (p=0.190). Multivariate analysis showed that only higher baseline HBV DNA level (OR: 0.584, 95 CI: 0.440-0.774, p<0.001) and HBeAg-positive status (OR: 0.220, 95 CI: 0.112-0.433, p<0.001) were independent factors for virological response at one year of treatment. The rates of ALT normalization (ALT≤ 40 U/L) at one year of treatment in three groups were 81.2% (entecavir group), 79.7% (TDF group) and 72.3% (TAF group), respectively (p=0.196). There was significant differences in eGFR decline at one year of treatment from baseline between TAF and ETV group (-1.04 ±

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P.20

IMPACT OF MAFLD ON HBV-RELATED STAGE 0/A HEPATOCELLULAR CARCINOMA AFTER CURATIVE RESECTION Yen-Po Lin1, Shu-Hsien Lin2, Chih-Chi Wang3, Chih-Che Lin3, Ding-Wei Chen3, Ming-Chao Tsai2 School of Medicine, Chung-Shan Medical University, Taichung, Taiwan1 Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan2 Liver Transplantation Center and Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan3

MAFLD 對與 HBV 相關的 0/A 期肝細 胞癌在可治癒切除術後的影響 林彥伯1 林淑賢2 王植熙3 林志哲3 陳定濰3 蔡明釗2 中山醫學大學醫學系1 高雄長庚紀念醫院胃腸肝膽科2 高雄長庚紀念醫院肝臟移植中心3 Background: Metabolic-associated fatty liver disease (MAFLD) is a novel term proposed in 2020 to avoid the exclusion of certain subpopulations, though the application of this term in the real world is very limited.

Aims: Here, we aimed to evaluate the impact of MAFLD on HBV-related hepatocellular carcinoma (HCC) after curative resection.

Methods: Patients with chronic hepatitis B (CHB)-related HCC who received hepatectomy between January 2010 and December 2019 were consecutively selected. The association between histologically proven concurrent MAFLD and clinical outcomes were retrospectively analyzed.

Results: Among the 812 eligible patients with CHB-related HCC, 369 (45.4%) were diagnosed with concurrent MAFLD. After a mean follow-up of 65 months, 303 patients (37.3%) developed HCC recurrence, 111 (13.7%) died, and 12 (1.5%) received liver transplantation. Although no differences in the incidences of HCC recurrence (HR: 0.902, 95% CI: 0.719–1.131, P = 0.370) and death or liver transplantation (HR: 0.743, 95% CI: 0.518–1.006, P = 0.107) were observed between patients with and without MAFLD in multivariate

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analysis, the patients with MAFLD tended to achieve better relapse-free survival compared to patients without MAFLD. Among patients with MAFLD, lean MAFLD was a relative risk factor for tumor recurrence (HR: 2.030, 95% CI: 1.117– 3.690, P = 0.020).

Conclusions: The overall prognosis in HBVrelated early-stage HCC, in terms of HCC recurrence and death or liver transplantation, was not significantly different between patients with and without MAFLD. Among patients with MALFD, lean-MAFLD was a risk factor for HCC recurrence.

Further studies are warranted to validate these results.

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P.21

PREDICTORS FOR OFF-THERAPY HBEAG SERO-REVERSION HEPATITIS AND HBEAG-NEGATIVE HEPATITIS IN HBEAG-POSITIVE PATIENTS DISCONTINUE NUC THERAPY ARE DIFFERENT Chien-Wei Peng1,2, Wen-Juei Jeng1,2, Rong-Nan Chien1,2,3, Yun-Fan Liaw2,3 Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan, Taiwan1 College of Medicine, Chang Gung University, Taoyuan, Taiwan2 Liver Research Unit, Chang Gung Memorial Hospital, Taoyuan, Taiwan3

e 抗原陽性慢性 B 型肝炎患者於核苷 / 核苷酸類似物停藥後之兩種臨床復發 ─ e 抗原陽性肝炎與 e 抗原陰性肝炎 ─有不同之預測因子 彭建維1,2 鄭文睿1,2 簡榮南1,2,3 廖運範2,3 林口長庚紀念醫院胃腸肝膽科1 長庚大學醫學院2 林口長庚紀念醫院肝臟研究中心3 Background: Clinical relapse (CR) may occur in nearly half of the HBeAg-positive patients stopping Nuc therapy. However, little information is known about whether the predictors for the two types of clinical relapse, HBeAg sero-reversion related HBeAg-positive (+) (CR-HBeAg (+) hepatitis) or HBeAg-negative (-) hepatitis (CR-HBeAg (-) hepatitis), in these patients be different.

Aims: This study aimed to investigate the predictors of the two types of CR after stopping Nuc. Methods: This study included 125 HBeAg (+) patients who stopped Nuc therapy by APASL stopping rule. Pretherapy age, gender, cirrhosis, ALT, α-fetoprotein, genotype, HBeAg signal-tonoise (s/n) ratio, HBsAg and HBV DNA levels along with on-treatment response including time to ALT normalization, time to undetectable HBV DNA, HBsAg kinetics, and end-of-treatment (EOT) HBsAg level were analyzed. The post-treatment outcomes were categorized as the non-CR, CRHBeAg (+) hepatitis and CR-HBeAg (-) hepatitis.

CR was defined as HBV DNA ≥ 2000 IU/mL + ALT

≥ 2 times upper limit of normal in two years after Nuc cessation. Multivariate polytomous logistic regression analysis was performed to identify if the predictors for CR-HBeAg (+) hepatitis and CRHBeAg (-) hepatitis be different.

Results: Among the 125 patients, 46 (36.8%), 37 (29.6%), and 42 (33.6%) patients were classified into non-CR, CR-HBeAg (+) hepatitis, and CRHBeAg (-) hepatitis respectively. Retreatment was documented in 27 of 37 (73%) CR-HBeAg (+) hepatitis and 12 of 42 (29%) CR-HBeAg (-) hepatitis patients by 2-year follow-up. Age >45-year-old (aOR: 6.05, P=0.004), male (aOR: 9.81, P=0.001), and HBeAg loss beyond two years during therapy (aOR: 0.15, P=0.022) was independent predictors of CR-HBeAg (+) hepatitis. Age > 45 years old (aOR: 3.06, P=0.035) was the only independent risk factors of CR-HBeAg (-) hepatitis. Neither EOT HBsAg level nor consolidation therapy duration is correlate with a greater risk of CR or HBeAg reversion. Among the clinical relapsers, male and those with baseline HBeAg s/n ratio > 400 have higher probability for CR-HBeAg (+) hepatitis.

Conclusions: The predictors for off-Nuc CRHBeAg (+) and CR-HBeAg (-) hepatitis are different. Those with older age, male gender and time-to-HBeAg loss beyond 2 years were more likely to encounter CR-HBeAg (+) hepatitis.

Neither longer consolidation nor EOT-HBsAg level are predictive of off-therapy outcome in HBeAg (+) CHB patients.

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P.22

DISTINCT DIFFERENT RELAPSE PATTERNS BUT SIMILAR HBEAG SERO-REVERSION RATE AFTER CESSATION OF ENTECAVIR AND TENOFOVIR IN HBEAG-POSITIVE CHRONIC HEPATITIS B PATIENTS Chien-Wei Peng1,2, Wen-Juei Jeng1,2, Yen-Chun Liu1,2, Rong-Nan Chien1,2,3, Yun-Fan Liaw2,3 Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou Medical Center, Taoyuan, Taiwan1 College of Medicine, Chang Gung University, Taoyuan, Taiwan2 Liver Research Unit, Chang Gung Memorial Hospital, Taoyuan, Taiwan3

使用 Entecavir 或 Tenofovir 之 e 抗原 陽性慢性 B 型肝炎病人於停藥後有不 同之復發型態 彭建維1,2 鄭文睿1,2 劉彥君1,2 簡榮南1,2,3 廖運範2,3 林口長庚紀念醫院胃腸肝膽科系1 長庚大學醫學院2 林口長庚紀念醫院肝臟研究中心3 Background: Disparate relapse patterns have been reported in HBeAg-negative chronic hepatitis B (CHB) patients after cessation of Entecavir (ETV) and Tenofovir (TDF) that those who stop TDF may encounter hepatitis flare more swiftly and seriously. However, such information is limited in HBeAg-positive patients after stopping Nucleot(s) ide analogue (Nuc) especially those discontinued by guidelines suggestion.

Aims: This study aimed to investigate the relapse patterns and clinical outcomes in HBeAg-positive patients after cessation of different types of Nuc. Methods: This study included 125 HBeAg-positive patients who achieved HBeAg seroconversion and stopped ETV or TDF therapy by APASL stopping rule. Pretherapy age, gender, cirrhosis, ALT, genotype, HBsAg level, HBV DNA level, and type of Nuc therapy were analyzed. Virological relapse (VR) was defined as HBV DNA ≥ 2000 IU/mL. Clinical relapse (CR) was defined as VR plus ALT ≥ 2 times upper limit of normal (ULN). Hepatitis flare was defined as VR plus ALT ≥ 5 times ULN. HBeAg sero-reversion defined as the re-appearance

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of HBeAg after HBeAg seroconversion. Cox regression analysis was performed for predictors of CR and hepatitis flare after Nuc cessation.

Propensity score matching (PSM) for pretherapy and end of treatment confounders was done at 1:1 ratio for sensitive analysis.

Results: The study included 72 and 53 patients treated with ETV and TDF respectively. The 2-yearcumulative VR, CR, hepatitis flare, and HBeAg reversion rate in patients who stopped ETV versus TDF was 61% vs. 77% (P < 0.001), 56% vs. 71% (P = 0.003), 65% vs. 46% (P = 0.004), and 38% vs.

28% (P = 0.097) respectively. By cox regression analysis, older age (CR: aHR: 2.12, P=0.002; hepatitis flare: aHR: 1.04, P = 0.001) and use of TDF (CR: aHR: 2.05, P=0.002; hepatitis flare: aHR: 2.16, P = 0.002) were independent risk factors for CR and hepatitis flare. After PSM, 70 patients were enrolled (ETV: N=35 vs. TDF: N=35). The use of TDF (CR: aHR: 1.91, P=0.026; hepatitis flare: aHR: 2.40, P=0.01) was the only risk factors for CR and hepatitis flare, while the HBeAg seroreversion rate was comparable between patients off-ETV and off-TDF (30% vs. 30%, P=0.764).

Conclusions: HBeAg-positive CHB patients stopping TDF were at higher risk of CR and hepatitis flare comparing to those off-ETV. Yet, the HBeAg reversion rate is comparable between these two regimens. More stringent monitor is required for HBeAg-positive patients with TDF cessation.

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P.23

PROTON BEAM RADIOTHERAPY COMBINED WITH IMMUNE CHECKPOINT INHIBITORS FOR ADVANCED HEPATOCELLULAR CARCINOMA: A RETROSPECTIVE STUDY Chung-Wei Su1, Ming-Mo Ho2, Pei-Wei Huang2, Yung-Chih Chou3, Chen-Chun Lin1, Jeng-Hwei Tseng4, Bing-Shen Huang3, Chao-Wei Hsu1, Tung-Chieh Chang3, Shi-Ming Lin1 Department of Gastroenterology and Hepatology, Linkuo Chang Gung Memorial Hospital, Taoyuan, Taiwan1 Department of Oncology, Linkuo Chang Gung Memorial Hospital, Taoyuan, Taiwan2 Department of Radiation Oncology, Proton and Radiotherapy Center, Linkuo Chang Gung Memorial Hospital, Taoyuan, Taiwan3 Department of Medical Imaging & Intervention, Linkuo Chang Gung Memorial Hospital, Taoyuan, Taiwan4

and overall survival.

Results: All patients completed the PBRT protocol up to 66-72.6 gray in 10-22 fractions. The median ICI duration was 3.9 months. The objective radiology response (ORR) was 57.1%, including 17.2% of complete responses. The median response duration, PFS, and overall survival were 14.1 months (95% CI, 9.1-19.1), 14.5 months (95% CI, 11.8-17.2), and not reached, respectively. The irradiated tumors had a sustained control, and the non-irradiation area TTP was 15.9 months (95% CI, 12.1-19.6). The ORR and PFS between the tumors wholly or partially covered by PBRT were comparable. Any-grade treatment-related adverse event (TRAE) was 97%. Grade 3 or 4 TRAE was 21%, including hepatitis and upper gastrointestinal bleeding. Potential TRAE deaths were a result of two in liver failure and one in duodenal perforation.

Conclusions: ICI plus PBRT effectively controls advanced HCC with a favorable and durable response and probably synergistic effects for non-irradiated tumors. Adverse events were acceptable. A further prospective randomized trial is needed to further confirm our conclusion.

免疫治療合併質子治療於晚期肝癌： 一個回顧性研究 蘇崇維1 侯明模2 黃珮媁2 周詠智3 林成俊1 曾振輝4 黃炳勝3 許朝偉1 張東杰3 林錫銘1 林口長庚紀念醫院肝膽腸胃科1 林口長庚紀念醫院腫瘤科2 林口長庚紀念醫院放射腫瘤科3 林口長庚紀念醫院影像診斷科4 Background: Previous studies have reported that immune checkpoint inhibitors (ICI) can improve the response and survival of hepatocellular carcinoma (HCC). Radiotherapy combined with ICI has a synergistic effect on the antitumor ability.

Aims: The combination of ICI with proton beam radiotherapy (PBRT) has not been investigated till date. Therefore, we conducted this retrospective study to evaluate the efficacy and safety of ICI plus PBRT in advanced HCC patients.

Methods: Twenty-nine consecutive advanced HCC patients received ICI combined with PBRT at a tertiary medical center. Modified RECIST criteria evaluated the treatment responses. Kaplan-Meier estimator was used to calculate the progressionfree survival (PFS), time-to-progression (TTP),

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P.24

UTILITY OF LONG-TERM POSTTREATMENT LIVER STIFFNESS FOLLOW-UPS IN PREDICTION OF LIVER-RELATED EVENTS IN PATIENTS WITH CHRONIC HEPATITIS C Sheng-Hung Chen1,2, Hsueh-Chou Lai1,3, Wei-Fan Hsu1,2, Hung-Wei Wang1,2, Jaw-Town Lin1,2, Cheng-Yuan Peng1,2 Center for Digestive Medicine, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan1 School of Medicine, China Medical University, Taichung, Taiwan2 College of Chinese Medicine, China Medical University, Taichung, Taiwan3

以長期追蹤之肝臟硬度預測慢性 C 型 肝炎病患治療後之肝臟相關事件 陳昇弘1,2 賴學洲1,3 許偉帆1,2 王鴻偉1,2 林肇堂1,2 彭成元1,2 中國醫藥大學附設醫院內科部消化系1 中國醫藥大學醫學系2 中國醫藥大學中醫學系3 Background: Surveillance post-viral eradication is mandatory. Liver stiffness (LS) is known to be a promising biomarker for risk stratification post-viral eradication. However, further studies are warranted to apply LS kinetics to long-term posttreatment follow-up.

Aims: This study aimed to prospectively delineate the longitudinal changes of LS values across the treatment and follow-up timeframes and to retrospectively compare the significance of longitudinal LS in prognostics of liver-related events (LREs) during long-term follow-up in patients who achieved viral eradication.

Methods: A cohort of patients with CHC underwent prespecified serial LS measurements every 6 months on and off pegylated interferonbased therapy. Shear wave velocity (meter per second) measured through point shear-wave elastography (ARFI) represented the LS. A generalized linear mixed model (GLMM) was conducted to estimate the factors and covariates that significantly explained the within-subject LS kinetics with missing follow-up visits over time. Cox

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regression models were used to identify the factors that predicted LREs including hepatocellular carcinoma, hepatic encephalopathy, variceal bleeding, ascites, hepatorenal syndrome, and liver-related mortality, during the posttreatment follow-up.

Results: A total of 426 eligible participants received at least one session of LS measurements. The median age was 54 years (interquartile range, IQR, 45–60). In total, 201 (47.2%) participants were male. Through the GLMM, baseline HCV RNA load, LS, and follow-up time points (reference: TW0) including PW24, PW180, PW300, and PW440 significantly (all P <0.05) explained all the LS (total visit n = 1249) on and off treatment. To predict post-sustained virological response (PW24) LREs (n = 19), receiver operating characteristics (ROC) analysis revealed the significance (both P = 0.001) for LS (TW0) (area under curve [AUC] = 0.722, 95% confidence interval [CI] = 0.609– 0.836, optimal cut off = 1.50, and for LS (PW24) (AUC = 0.722, 95% CI = 0.590–0.854, cut off = 1.75). LS decline (%) (AUC = 0.582, 95% CI = 0.454–0.710) was insignificant (P = 0.233).

Kaplan-Meier method identified the high versus low-risk groups (event n/ n in group: 10/ 44 versus 9/ 251) significantly (log-rank P < 0.001) stratified

by LS (PW24) ≥ 1.75 versus < 1.75 m/s. Stepwise multiple Cox regression analysis identified the following three significant predictors: serum α-fetoprotein (PW24) (adjusted hazard ratio, aHR = 1.037, 95% CI = 1.015–1.059, P = 0.001), bilirubin (PW24) (2.719,1.084–6.817, P = 0.033), and LS (PW24) (2.324, 1.325–4.074, P = 0.003), through a median follow-up period of 7.6 years (IQR = 4.7–9.9; 3237 person-years). Moreover, to predict post-PW180 LREs (n = 11), ROC analysis revealed the significance for LS (PW24) (AUC = 0.687, 95% CI = 0.511–0.863, cut off = 1.92, P = 0.036), and for LS (PW180) (AUC = 0.722, 95% CI = 0.566–0.878, cut off = 1.64, P = 0.012). By contrast, LS (TW0) (AUC = 0.666, 0.499–0.832, P = 0.053) and LS declines were insignificant. KaplanMeier method identified the high versus low-risk groups (event n/n in group: 6/33 versus 5/210) significantly (log-rank P < 0.001) stratified by LS (PW24) ≥ 1.92 versus < 1.92 m/s. The stratification of LS (PW180) by ≥ 1.64 versus < 1.64 m/s also identified the high versus low-risk groups (event n/n in group: 6/35 versus 5/267) significantly (logrank P < 0.001). Through a median follow-up period of 5.3 years (IQR = 2.8–7.3; 2241 person-

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years), stepwise multiple Cox regression analysis identified LS (PW180) as the only predictor (aHR = 7.460, 2.123–26.215, P = 0.002) to predict LREs after PW180, adjusting for baseline values and declines of patient characteristics and parameters.

Conclusions: Postreatment long-term LS measurements through elastography can serve as a significant predictor and stratify the risk of LREs during long-term follow-up in CHC patients after viral eradication.

P.25

THE INCIDENCE OF DE NOVO HEPATOCELLULAR CARCINOMA AFTER HCV CLEARANCE BY DIRECT-ACTING ANTIVIRALS WITH OR WITHOUT PRIOR INTERFERON TREATMENT Chien-Chang Liao, Kuo-Kuan Chang, Chun-Hsiang Wang, Ruey-Chang Lin, Ming-Jeng Kuo, Lein-Ray Mo Department of Hepatogastroenterology, Tainan Municipal Hospital (Managed by Show Chwan Medical Care Corporation), Tainan, Taiwan

經全口服抗病毒藥物且併或不合併先 前干擾素治療，在清除 HCV 後肝癌的 發生率 廖建彰 張國寬 王俊雄 林瑞昌 郭明正 牟聯瑞 台南市立醫院胃腸肝膽科 Background: Direct-acting antivirals (DAA) treatment achieves a very high sustained viral clearance (SVR) rate in chronic hepatitis C patients. The risk of hepatocellular carcinoma (HCC) development after HCV clearance by DAA with or without prior interferon (IFN) treatment is still in controversy.

Aims: The aim of this study was to evaluate the occurrence of de novo HCC among patients with SVR by DAA with or without prior IFN treatment.

Methods: We retrospectively analyzed a cohort with chronic HCV patients who achieved SVR by DAA. The patients were free from HCC before and during DAA treatment and without HBV coinfection. Two sub-cohorts with or without IFNexperienced were divided. The Kaplan-Meier method was used to calculate the cumulative HCC incidence.

Results: From March 2017 to November 2021, a total of 923 cases were included in this study.

The median follow-up period was 615 days (1541921). The cumulative incidence rate of de novo HCC was 1.45 person-years (22 patients). The cumulative HCC rates were 0.39, 2.73, and 5.02% at the end of 1, 2, and 3 years, respectively. For two sub-cohorts with or without IFN-experienced patients, the cumulative incidence rates yielded 1.84 and 1.32 person-years (7 and 15 patients). A trend of increased HCC occurrence (Hazard ratio

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= 1.07) was noted in IFN-experienced sub-group.

Conclusions: The study show patients with SVR

by DAA treatment still at risk for HCC occurrence and HCC risk slightly increased in prior IFNexperienced cases. Regular follow-up for HCC is mandatory for these patients.

P.26

SAFETY AND EFFICACY OF BULEVIRTIDE MONOTHERAPY AND IN COMBINATION WITH PEGINTERFERON ALFA-2A IN PATIENTS WITH CHRONIC HEPATITIS DELTA: 24 WEEKS INTERIM DATA OF MYR204 PHASE 2B STUDY Tarik Asselah1, Sorin Stefan Arama2, Pavel Bogomolov3, Marc Bourliere4, Hélène Fontaine5, George Sebastian Gherlan6,7, Vladimir Gorodin8, Marie-Noëlle Hilleret9, Stefan Lazar10, Nina Mamonova11, Morozov Viacheslav12, Victor Pantea13, Gheorghe Placinta13, Jérôme Gournay14, Francois Raffi15, Vlad Ratziu16, Christiane Stern16, Olga Sagalova17, Didier Samuel18, Tatyana Stepanova19, Vladimir Syutkin20, Adrian Streinu-Cercel2, Fabien Zoulim21, Dominique Roulot22 Hôpital Beaujon APHP, Université de Paris, INSERM, Clichy, France1 Matei Bals National Institute of Infectious Diseases, Bucharest, Romania2 Moscow regional research-clinical institute , Moscow, Russian Federation3 Hôpital Saint Joseph Marseille, Marseille, France4 Hôpital Cochin - Unité d’Hépatologie Pavillon Achard, Paris, France5 Carol Davila” University of Medicine and Pharmacy, Bucharest, Romania6 Dr. Victor Babes Foundation, Bucharest, Romania7 State Budgetary Institution of Health care8 Centre Hospitalier Universitaire Grenoble Alpes, Grenoble, France9 Dr. Victor Babes Foundation - Infectious and Tropical Diseases Hospital, Bucharest, Romania10 National Research Medical Centre for Phthisiopulmonology and Infectious Diseases, Moscow, Russian Federation11 LLC Medical Company “Hepatolog”, Samara, Russian Federation12 Infectious Clinical Hospital13 Nantes University Hospital (CHU de Nantes

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Hôtel-Dieu), Nantes, France14 Nantes University Hospital (CHU de Nantes Hôtel-Dieu), Nantes, France15 CH Pitié-Salpétrière, Paris, France16 Southern Ural State Madical University, Chelyabinsk, Russian Federation17 Centre Hépato-Biliaire - Hôpital Paul Brousse, Université Paris Saclay, Villejuif, France18 Limited liability company “Clinic of Modern Medicine”, Moscow, Russian Federation19 Institute of Emergency Medicine n.a.

NV Sklifosovsky, Liver Surgery and Transplantation, Moscow, Russian Federation20 Hospital Croix Rousee, Service Hepatologie, Lyon, France21 Hopital Avicenne, APHP, Université Sorbonne Paris Nord, Bobigny, France22 Background: Bulevirtide (BLV) is a first-in-class entry inhibitor used for the treatment of chronic hepatitis delta virus (HDV) infection. Combination therapy of BLV and Peginterferon alfa-2a (pIFN) showed strong synergistic effects on HDV RNA and Hepatitis B surface Antigen (HBsAg) levels in MYR203 trial.

Aims: We present here the 24 weeks interim on treatment data of the MYR204 phase 2b trial in HBV/HDV co-infected patients receiving BLV as monotherapy or in combination with pIFN. Methods: 175 patients with chronic HDV infection were randomized in a 1:2:2:2 ratio to receive (see Figure): arm A: pIFN; arm B: BLV 2 mg/day and pIFN; arm C: BLV 10 mg/day and pIFN for 48 weeks followed by BLV monotherapy for additional 48 weeks or arm D: BLV 10 mg/day monotherapy.

The primary endpoint is undetectable HDV RNA (<LoD) at week 24 after end of treatment; main secondary endpoints include HDV RNA decline by ≥2 log10 IU/ml, ALT normalization, combined response (undetectable HDV RNA or decrease by ≥2log10 IU/mL from baseline and ALT normalization) and HBsAg decrease.

Results: Safety: In the first 24 weeks of treatment, 998 AEs were reported by 151 patients (86.8%), being mostly mild (536) or moderate (296). 181 of 998 AEs were judged as possibly related to BLV and 724 AEs to pIFN. Overall, 7 SAEs (judged as not related to BLV) were reported, one of which (anaplastic astrocytoma, judged as non-related to BLV nor pIFN) reported in a patient in arm B

led to death. Efficacy: At week 24, the proportion of patients with HDV RNA decline of ≥2 log10 IU/ mL from baseline was 37.5%, 86.0%, 90.0%, and in 72.0% of patients in arms A-D, respectively.

Undetectable HDV RNA was demonstrated in 12.5%, 24%, 34% and 4% of patients at week 24 in arms A-D, respectively. Both, ALT and combined response had a higher proportion of responders in arm D, followed by arm B, arm C and arm A. HBsAg response (decline by ≥1 log10 IU/ml) was observed in 10 patients receiving combination therapy with BLV and pIFN (12% in arm B and 8% in arm C) and 1 patient in Arm A. Conclusions: BLV monotherapy and in combination with pIFN is safe and well tolerated through 24 weeks of therapy. Combination therapy and BLV monotherapy resulted in high rates of HDV viral decline, while BLV monotherapy resulted in the highest rate of ALT normalization.

Ongoing analysis of safety, ALT normalization and HDV viral suppression on therapy at weeks 48, 96 and SVR 24 will be performed.

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P.27

COMPARISON OF THE EFFICACIES OF DIRECT-ACTING ANTIVIRALS TREATMENT IN HCV-INFECTED METHADONE USERS AND NONMETHADONE USERS Jui-Ting Hsu1, Chang-Bih Shie1, I-Ting Wu1, Sheng-Yeh Tang1, Kun-Feng Tsai1, Li-Fu Kuo1, Wen-Wei Huang1, Seng-Kee Chuah2, Ping-I Hsu1 Division of Gastroenterology, Department of Medicine, An Nan Hospital, China Medical University, Tainan, Taiwan1 Division of Hepatogastroenterology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan2

「直接作用抗病毒藥物」治療受 C 型 肝炎病毒感染之「美沙冬使用者」與 「非美沙冬使用者」的療效之比較 許瑞廷1 施長碧1 吳奕霆1 湯昇曄1 蔡坤峰1 郭立夫1 黃文威1 蔡成枝2 許秉毅1 中國醫藥大學臺南市立安南醫院消化內科1 高雄長庚紀念醫院胃腸肝膽科2 Background: People who inject drugs (PWID) constitute a significant proportion of people with hepatitis C virus (HCV) infection. The majority of PWID have not been treated often due to concerns about poor adherence to treatment. To help guide clinical decisions, it is crucial for providers to understand the degree of adherence and efficacy of direct-acting antivirals (DAAs) treatment in HCV-infected PWID. Aims: To compare the efficacy of DAAs in the treatment of HCV infection between PWID and non-PWID patients, and to search the independent risk factors predicting treatment failure of DAAs. Methods: In this retrospective cohort study, we included 53 HCV-infected methadone users (PWID) and 106 age- and sex-matched HCVinfected non-methadone users (with the ratio of 1:2) who received anti-HCV treatment by DAAs in our hospital from March 2018 to December 2020. The charts of these patients were carefully reviewed for demographic data, types of DAAs and treatment outcomes. The primary outcome measure was sustained virological response (SVR) defined as the absence of serum HCV RNA at the

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12th week after antiviral therapy. Additionally, the host and virological factors related to the failure of SVR were analyzed by univariate analysis and subsequently by multivariate analysis.

Results: In demographic data, HCV-infected methadone users and non-methadone users had different HCV genotypes (P = 0.009). The former had higher proportions of genotype 3 (19.2% vs 7.5%) and genotype 6 (25.0% vs 14.2%) than the latter. Methadone users receiving DAAs treatment had lower SVR rate than non-methadone users (92.2% vs 99.0%; P = 0.04). Univariate analysis showed that human immunodeficiency virus (HIV) infection and methadone use were risk factors associated with treatment. In the included patients, the subjects with co-infection with HIV had a lower SVR rate than those without HIV infection (50% vs 95.7%; P = 0.027). Multivariate analysis revealed that only HIV infection was an independent risk factor predicting failure to achieve SVR (odds ratio: 22.0; 95% confidence interval: 2.0 – 247.1).

Conclusions: Methadone users have a lower treatment response to DAAs therapy for HCV infection than non-methadone users. HIV infection is an independent risk factor related to treatment failure for HCV infection with DAAs.

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BULEVIRTIDE MONOTHERAPY AT LOW AND HIGH DOSE IN PATIENTS WITH CHRONIC HEPATITIS DELTA: 24 WEEKS INTERIM DATA OF THE PHASE 3 MYR301 STUDY Heiner Wedemeyer1, Soo Aleman2, Pietro Andreone3, Antje Blank4, Maurizia Brunetto5, Pavel Bogomolov6, Vladimir Chulanov7, Natalia Geyvandova8, Gudrun Hilgard9, Nina Mamonova10, Uta Merle4, Morozov Viacheslav11, Olga Sagalova12, Tatyana Stepanova13, Julian Schulze zur Wiesch14, Sergey Zotov15, Stefan Zeuzem16, Pietro Lampertico17,18 Klinik für Gastroenterologie, Hepatologie und Endokrinologie, Medizinische Hochschule Hannover, Hannover, Germany1 Karolinska University Hospital/Karolinska Institutet, Department of Infectious Diseases, Stockholm, Sweden2 Internal Medicine, University of Modena and Reggio Emilia, Italy3 University Hospital Heidelberg, Clinical Pharmacology and Pharmacoepidemiology, Heidelberg, Germany4 U.O. Epatologia - Azienda Ospedaliero Universitaria Pisana, Pisa, Italy5 State budgetary institution of health care of Moscow region “Moscow regional research clinical institute after M.F. Vladimirsky6 Federal Budget Institute of Science7 Stavropol Regional Hospital, Stavropol, Russian Federation8 Universitätsklinikum Essen (AöR), Klinik für Gastroenterologie und Hepatologie, Essen, Germany9 FSBI National Research Medical Center for Phthisiopulmonology and Infectious Diseases of the Ministry of Health of the Russian Federation, Moscow, Russian Federation10 LLC Medical Company “Hepatolog”, Samara, Russian Federation11 Federal state-funded institution of higher education12 Limited liability company “Clinic of Modern Medicine”, Moscow, Russian Federation13 Universitätsklinikum Hamburg- Eppendorf

Medizinische Klinik Studienambulanz Hepatologie, Hamburg, Germany14 State budgetary institution of health care15 University Hospital Frankfurt, Department of Medicine, Frankfurt am Main16 Foundation IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Division of Gastroenterology and Hepatology, Milan, Italy17 CRC “A. M. and A. Migliavacca” Center for Liver Disease, University of Milan, Department of Pathophysiology and Transplantation, Milan, Italy18 Background: Bulevirtide (BLV) is a first-inclass entry inhibitor for the treatment of chronic hepatitis D virus (HDV) infection. BLV has shown pronounced virological and biochemical responses (HDV RNA and ALT declines) in two phase 2 trials (MYR202/MYR203).

Aims: We here present findings of a predefined 24 weeks interim analysis of the MYR301 phase 3 study in HBV/HDV co-infected patients receiving 2 mg/qd or 10 mg/qd dose BLV monotherapy in comparison to observation with no antiviral treatment.

Methods: 150 patients with chronic HDV infection were randomized in a 1:1:1 ratio to no antiviral treatment for 48 weeks followed by 10 mg/qd for 96 weeks (arm A, n=51, treatment with BLV 2 mg/ qd (arm B, n=49), or with BLV 10 mg/qd (arm C, n=50) for 144 weeks with a treatment-free followup of 96 weeks. The primary endpoint, combined response, is defined as undetectable HDV RNA (<LoD) or decrease by ≥2 log10 IU/ml and ALT normalization at week 48; secondary endpoints include undetectable HDV RNA, decline by ≥2 log10 IU/ml, ALT normalization and HBsAg decline by ≥1 log10 IU/ml.

Results: Baseline demographics: 57.3% of patients were male, 82.7% white and the mean age was 41.8 years. HDV RNA levels were 5.05 log10 IU/mL and ALT mean levels were 110.9 U/L. Safety: BLV was well tolerated during the first 24 weeks: overall, 421 treatment emergent adverse events (TEAE) were reported; 55 TEAE in 26 patients in the arm A, 121 TEAE in 32 patients in the arm B and 245 TEAE in 36 patients in the arm C. 48 TEAE in arm B and 100 TEAE in arm C were assessed as possibly related to BLV. One serious TEAE was reported in one patient in the arm A.

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Efficacy: After 24 weeks of study, the proportion of patients achieving combined virological and biochemical response was 36.7% in arm B and 28.0% in arm C (vs. 0% in arm A, p<0.0001). A HDV RNA decrease by ≥2 log10 IU/mL at week 24 from baseline was observed in 55.1% of patients in arm B and 68% in arm C (vs. 3.8% in arm A, p<0.0001). At week 24, ALT normalization was reached in 53.1% of arm B, 38% of arm C (vs.

5.9% in arm A, p<0.0001). One patient treated with 2 mg BLV achieved a HBsAg reduction of ≥1 log10 IU/ml at week 24.

Conclusions: This phase 3 trial confirms that monotherapy with BLV is safe and well tolerated in patients with compensated hepatitis delta. 24 weeks of treatment with BLV was associated with significant HDV RNA declines and improvements biochemical disease activity. These findings further support the conditional approval of BLV.

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A NATIONAL PATIENT SURVEY TO IDENTIFY THE AWARENESS GAP AND INSIGHTS OF PATIENTS ON CHRONIC HEPATITIS B MANAGEMENT IN TAIWAN Tung-Hung Su Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan Background: Hepatitis B virus (HBV) infection and HBV-related hepatocellular carcinoma (HCC) are prevalent in Taiwan. Patients’ awareness and insights on the management of chronic hepatitis B (CHB) help to provide better clinical care.

Aims: To understand disease awareness and healthcare needs of CHB in Taiwan.

Methods: The online survey was conducted in 2021.

Patients >20 years with CHB ≥ 1 year were eligible.

Those who received liver transplantation, cancer chemotherapy or immunotherapy, and had human immunodeficiency virus were excluded. Participants were stratified according to their sex, living regions, and hospital types (medical center, regional or area hospital, and clinic) with prespecified percentages.

Patients were categorized evenly into four groups: patients on first-time nucleoside analogues (NA) therapy, CHB relapse patients on NA retreatment, patients who stopped NA, and treatment-naïve patients, respectively.

Results: Overall, 240 patients were recruited with an average age of 51.2, and 68% of them had CHB diagnosed in hospital. Around 59% of patients are aware that CHB is associated with cirrhosis and HCC; however, 77% of them think HCC occurrence is due to irregular lifestyle. Patients over 70 years and > 20-year of CHB have the lowest degree of awareness. The perceived misconceptions for CHB cure ranges from normal liver function, negative HBV DNA, and even NA discontinuation. Healthcare professionals and Google are their main sources of information of CHB. If there is no economic concern, 53% of treatment-naive patients are willing to receive self-paid NA therapy if indicated.

Overall, only 28% of patients are satisfied with the current reimbursement criteria by the National Health Insurance.

Conclusions: We identify misconceptions and knowledge discrepancies of patients, which could lead to NA self-discontinuation or loss of follow-up.

Enhance disease awareness and patient support, and extended National Health Insurance coverage will be fundamental to improve the management of CHB in Taiwan.

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COMPARISON OF THE PHYTOCHEMICAL PROPERTIES, ANTIOXIDANT ACTIVITY AND CYTOTOXIC EFFECT ON HEPG2 CELLS IN MONGOLIAN AND TAIWANESE RHUBARB SPECIES Ming-Shun Wu1,2, Ganbolor Jargalsaikhan3, Sheng-Jie Shiue1, Sheng-Wei Cheng1, Fat-Moon Suk1, Gi-Shih Lien1 Division of Gastroenterology, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan1 Division of Gastroenterology and Hepatology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan2 Liver Center, Ulaanbaatar, Mongolia3

蒙古和臺灣大黃的植物化學特性、抗 氧化活性及對 HepG2 細胞毒性作用的 比較 吳明順1,2 Ganbolor Jargalsaikhan3 薛聖潔1 鄭勝偉1 粟發滿1 連吉時1 臺北市立萬芳醫院消化系內科1 臺北醫學大學醫學院醫學系消化內科2 Liver Center, Ulaanbaatar, Mongolia3

check cytotoxicity of Rhubarb extracts on HepG2

by MTT assay.

Results: Except for the n-hexane extract, all of the RU extracts had higher TPCs than RC extracts, and the TPCs of each extract were significantly correlated with their antioxidant capacities by ABTS, DPPH, and FRAP assays. Moreover, there was no association between antioxidant capacities and either TACs or TFCs in both RU and RC extracts. HPLC analysis revealed both RU and RC extracts contained chrysophanol, emodin, and physcion, and those bioactive compounds were relatively higher in the n-hexane solvent extracts. Additionally, the ethanol extract of RU had compelling cytotoxic effect with the lowest half-maximum inhibition concentration among the RU extracts than the ethanol extract of RC. Interestingly, the ethanol extract of RU but not RC significantly induced apoptosis in HepG2 cell line, resulting in increased PARP cleavage and DNA damage.

Conclusions: RU, showed more phytochemical contents, as well as a higher antioxidant capacity and apoptotic effect to HepG2 than RC; thus, it can be exploited for the proper source of natural antioxidants and liver cancer treatment in further investigation.

Background: The Mongolian rhubarb—Rheum undulatum L. (RU)—and Rumex crispus L. (RC)—a Taiwanese local rhubarb belonging to the family of Polygonaceae—are principal therapeutic materials in integrative medicine; however, their phytochemical and antioxidant properties, and anti-cancer activity is poorly investigated.

Aims: To study less-known Rhubarb species from Mongolia and Taiwan for their major phytochemicals, bio-active constituents, antioxidant capacity, and anti-proliferative effect on the HepG2 cell lines.

Methods: 1. To check the main effective compounds in rhubarbs by total phenolic contents (TPC), total anthraquinone contents (TAC) and total flavonoid contents (TFC). 2. To check the main rhubarb bio-activators by high-performance liquid chromatography (HPLC). 3. To check antioxidant activity by ABTS scavenging assay, DPPH scavenging assay, ferric reducing antioxidant power, and iron chelating activity. 4. To

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SERIAL ALPHA-FETOPROTEIN INCREASE PREDICTS RISK OF HEPATOCELLULAR CARCINOMA Tung-Hung Su1, Shan-Han Chang2, Chi-Ling Chen3, Tai-Chung Tseng4, Chun-Jen Liu1, Chen-Hua Liu1, Hung-Chih Yang1, Pei-Jer Chen1, Jia-Horng Kao1 Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan1 Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Yunlin Branch, Yunlin, Taiwan2 Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan3 Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan4

血清甲型胎兒蛋白序列增加預測肝細 胞癌風險 蘇東弘1 張善涵2 陳祈玲3 曾岱宗4 劉俊人1 劉振驊1 楊宏志1 陳培哲1 高嘉宏1 國立臺灣大學醫學院附設醫院胃腸肝膽內科1 國立臺灣大學醫學院附設醫院雲林分院胃腸肝膽 內科2 國立臺灣大學醫學院臨床醫學研究所3 國立臺灣大學醫學院醫學研究部4 Background: Alpha-fetoprotein (AFP) has been used as a surveillance test for the diagnosis of HCC with controversial evidences.

Aims: We aimed to evaluate the role of serial AFP increase in the prediction of incident HCC. Methods: We conducted a case-control study in a tertiary medical center in Taiwan. Patients with chronic liver diseases who received regular tri-monthly AFP and abdominal ultrasound surveillance for HCC during 2006 to 2016 were enrolled, and categorized into HCC and non-HCC groups. The outcome date for the HCC group was the date of HCC diagnosis, while it was 1-year before the end-of-follow up for the non-HCC group to confirm no subsequent HCC. The AFP level at 6 (-6M), 9 (-9M), 12 months (-12M) before the outcome date were used for HCC prediction.

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Results: A total of 2,776 patients were included.

At baseline (-12M), patients in the HCC group (n=326) was significantly older, with more severe liver diseases, and had significantly greater serial AFP levels compared with the non-HCC group (n=2450). After adjusting confounding factors, AFP ≥ 20 (vs. < 20) ng/mL at -6M significantly increased 7.2-fold risk of HCC (95% confidence interval [CI]: 3.0-17.1). We found serial 10% AFPincrease significantly predicted subsequent HCC. Compared with patients with stationary AFP level, AFP-increase ≥ 10% between -9M/-12M only, -6M/-9M only, and both -9M/-12M and -6M/-9M had 2.2-fold (95% CI: 1.4-3.3), 4.0-fold (95% CI: 2.7-5.9), and 12.1-fold (95% CI: 6.5-22.4) increase risk of HCC. Subgroup analysis demonstrated age ≥ 60, male sex, HBV and HCV infection receiving antiviral therapy, non-cirrhotic patients, and those with normal AST, and ALT levels benefit most using serial AFP-increase ≥ 10% to predict HCC (up to 59.7-fold risk). Combining AFP ≥ 20 ng/mL at -6M, and serial AFP-increase ≥ 10% from -12M to -6M increased risk of HCC up to 41.7-fold (95% CI: 13.8-126.2). These findings had been validated in patients receiving biannual AFP surveillance.

Conclusions: AFP may be used as a predictive marker for HCC. AFP ≥ 20 ng/mL and serial AFPincrease ≥ 10% in the past 6 months significantly predict HCC development in 6 months.

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EARLY REBLEEDING AND POOR LIVER FUNCTION ASSOCIATED WITH EARLY MORTALITY IN PATIENTS WITH ACUTE VARICEAL HEMORRHAGE – A REAL-WORLD, RETROSPECTIVE STUDY Chun-Te Lee, Juei-Seng Wu, Hung-Chih Chiu, Yen-Cheng Chiu, Pin-Nan Cheng, Chiao-Hsiung Chuang, Chiung-Yu Chen, Shih-Chieh Chien Department of Internal Medicine, National Cheng Kung University Hospital, Tainan, Taiwan

早期再出血以及肝功能不佳與食道靜 脈瘤出血患者之早期死亡率有關 ─ 真 實世界的回溯性研究 李俊德 吳叡森 邱宏智 邱彥程 鄭斌男 莊喬雄 陳炯瑜 簡世杰 國立成功大醫學院附設醫院內科部

median overall survival time was 160 days, (range: 11-2625 days). Patients with poor baseline renal function (eGFR < 60 vs. eGFR ≥ 60, adjusted HR = 1.76, 95% CI: 1.01-3.08, p = 0.048) had earlier rebleeding time. Patients with early rebleeding (adjusted HR: 4.61, 95% CI: 1.23-17.26, p = 0.02) and poor baseline liver function (MELD score ≧ 13 vs. < 13, HR: 4.27, 95% CI: 1.29-14.16, p = 0.02) were associated with short-term survival rate, but not overall survival rate. The degree of PV thrombosis was associated with both poor short-term and overall survival rate. The presence of active HCC (p = 0.02), large size of EV, and concomitant GV during index EGD (p = 0.04) were associated with poorer overall survival rate.

Conclusions: Early rebleeding and poor baseline liver function were factors associated with worse short-term survival rate. Instead, factors that indicated uncontrolled or progressed portal hypertension (degree of PV thrombosis, presence of active HCC, large size of EV, and concomitant GV during index EGD) were associated with worse overall survival rate.

Background: Acute variceal hemorrhage was a fatal complication in cirrhotic patients, and recurrent variceal hemorrhage compromised patients’ mortality and liver reserve. Patients with early rebleeding often indicated uncontrolled portal hypertension.

Aims: The primary aim of this study was to evaluate the impact of baseline characteristics on patients’ rebleeding time. The secondary aims were to identify factors associated with early mortality and overall survival (OS).

Methods: We retrospectively reviewed endoscopic and baseline clinical data in 317 patients with acute variceal hemorrhage, and included 62 patients with recurrent variceal hemorrhage within 60 days for final analysis. We compared baseline clinical and endoscopic characteristics in patients with early rebleeding (defined as rebleeding within 3 weeks) and late rebleeding. By Cox-regression model and Kaplan-Meier survival analysis, we determine factors that were associated with rebleeding time, short-term (≤ 6weeks) and overall survival rate.

Results: Sixty-two patients who suffered from recurrent variceal hemorrhage were enrolled in this study. The number of red color signs (p = 0.1) and size of EV (p = 0.006) were significantly decreased in the following EGD. The median time to rebleeding was 22 days (range: 6-58 days) and

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SEQUENTIAL INTRATUMORAL AND INTRAMUSCULAR INJECTIONS OF POLY-ICLC IN MURINE HEPATOCELLULAR CARCINOMA Meng-Tzu Weng Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan

系列性原位及肌肉注射聚 ICLC 於小鼠 肝癌的療效 翁孟慈 台大醫院內科部 Background: Polyinosinic-polycytidylic acidpoly-l-lysine carboxymethylcellulose (poly-ICLC) is a synthetic double-stranded RNA (dsRNA) that serves as a viral mimic able to act as a pathogen associated molecular pattern (PAMP) to stimulate endosomal Toll-like receptor 3 (TLR3) and cytosolic melanoma differentiation-associated protein 5 (MDA5). Poly-ICLC stimulates multiple innate immune populations including nature killer cells, M1 macrophages, and dendritic cells and is commonly used as vaccine adjuvant. In this study, we used poly-ICLC to treat hepatocellular carcinoma (HCC) in mice.

Aims: To evaluate the therapeutic effects of poly-ICLC and its combination with programmed death-1 (PD-1) blockade.

Methods: Syngeneic HCC mice models were established by transplanting murine Hep55.1c and BNL HCC cells into flank of immunocompetent C57BL/6J and BALB/c mice, respectively. The mice received poly-ICLC intratumoral alone, intramuscular alone and sequential intratumoral and intramuscular injections. The tumors were also established in bilateral flanks to examine abscopal effects in the non- injected tumors. Immune responses were analyzed by flow cytometry, IFN-r enzyme-linked immunospot (ELISPOT) and correlated with tumor size.

Results: Sequential intratumoral and intramuscular poly-ICLC injections significantly increased CD8 T cell proportion in tumor infiltrating leukocytes (TIL) and induced splenocyte and TIL reactivity of IFN-r ELISPOT. Sequential therapy also induced abscopal effect. This strategy most effectively inhibited the growth of tumors than only intratumoral or intramuscular poly-ICLC injection

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in both syngeneic HCC mice models. Combination of sequential poly-ICLC and anti-PD-1 antibodies significantly inhibited tumor growth than anti-PD1 monotherapy.

Conclusions: Sequential poly-ICLC therapy significantly increased CD8 T cell infiltration into tumors. Combination therapies with poly-ICLC and anti-PD1 were effective in syngeneic HCC mice models.

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NON-SELECTIVE BETA-BLOCKERS DECREASE INFECTION, ACUTE KIDNEY INJURY EPISODES, AND AMELIORATE SARCOPENIC CHANGES IN PATIENTS WITH CIRRHOSIS: A PROPENSITYSCORE MATCHING TERTIARYCENTER COHORT STUDY Ying-Ying Yang1,2, Tzu-Hao Li3,4, Chia-Chang Huang1,5, Chang-Youh Tsai6, Ming-Chih Hou1,2, Han-Chieh Lin2 Department of Medical Education, Taipei Veteran General Hospital, Taipei, Taiwan1 Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan2 Institution of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan3 Division of Allergy, Immunology, and Rheumatology, Department of Internal Medicine, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan4 Division of Endocrinology and Metabolism, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan5 Division of Allergy, Immunology, and Rheumatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan6

Aims: We aimed to investigate the effects of NSBBs on common cirrhotic complications of infection, acute kidney injury (AKI), chronic renal function declination, and sarcopenic changes.

Methods: Medical records of hospitalization for cirrhosis with at least a 4-year following-up were analyzed and selected using propensity-score matching (PSM). Generalized estimating equation (GEE) was applied to assess the association of NSBBs with infection requiring hospitalization and AKI. Chronic renal function declination was evaluated by slope of regression lines derived from re-ciprocal of the serum creatinine level. The covariates of CT-measured skeletal muscle index (SMI) alterations were analyzed by generalized linear mixed model Results: Among the 4,946 reviewed individuals, 166 (83 NSBB group, 83 non-NSBB group) were eligible. Using GEE, Charlson comorbidity index, Child-Pugh score and non-NSBB were risk factors for infection; non-NSBB group revealed a robust trend toward AKI, showed no significant difference with chronic renal function declination of NSBB group, and was negatively associated with SMI alteration.

Conclusions: Chronic NSBB use lowered the episodes of infection requiring hospitalization and AKIs, whereas non-NSBB was associated with sarcopenic changes.

非選擇性乙型交感神經接受體阻斷劑 可降低肝硬化病患的感染率、急性腎 損傷、肌少症等的發生世代研究 楊盈盈1,2 黎子豪3,4 黃加璋1,5 蔡長祐6 侯明志1,2 林漢傑2 臺北榮民總醫院教學部1 臺北榮民總醫院內科部肝膽胃腸科2 國立陽明交通大學臨床醫學研究所3 新光吳火獅紀念醫院內科部風濕免疫科4 臺北榮民總醫院內科部內分泌新陳代謝科5 臺北榮民總醫院內科部過敏風濕免疫科6 Background: Cirrhotic complications resulting from portal hypertension can be considerably reduced by non-selective beta-blockers (NSBBs); however, scarce studies have investigated therapeutic agents for other complications.

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ROLES AND MECHANISMS OF CIRCULATING CEACAM1 IN THE CIRRHOSIS-RELATED INTESTINAL HYPERPERMEABILITY: IN VITRO APPROACH Chien-Fu Hsu2, Ying-Ying Yang1,2,3,4, Tzu-Hao Li3,5, Chih-Wei Liu3, Yi-Hsiang Huang2,3,4, Ming-Chih Hou2,4, Han-Chieh Lin2,4 Department of Medical Education, Taipei Veteran General Hospital, Taipei, Taiwan1 Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan2 Institution of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan3 Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan4 Division of Allergy, Immunology, and Rheumatology, Department of Internal Medicine, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan5

血循中的 CEACAM1 對於肝硬化相關 腸道高通透性的致病機轉及角色增加 探討 徐千富2 楊盈盈1,2,3,4 黎子豪3,5 劉志偉3 黃怡翔2,3,4 侯明志2,4 林漢傑2,4 臺北榮民總醫院教學部1 臺北榮民總醫院內科部2 國立陽明交通大學臨床醫學研究所3 臺北榮民總醫院內科部肝膽胃腸科4 新光吳火獅紀念醫院內科部風濕免疫科5 Background: Cirrhosis-related intestinal hyperpermeability and endotoxemia are characterized by intestinal epithelial cell apoptosis, impaired restitution (proliferation and migration), decreased tight junction protein levels, and subsequent barrier dysfunction. In addition to endotoxin and TNFα, CEACAM1 plays crucial roles in the regulation of apoptosis, restitution, tight junction protein-maintained barrier function of intestinal epithelial cells.

Aims: This study aims to explore the roles and underlying mechanisms of CEACAM1 in cirrhosisrelated intestinal hyperpermeability through in vitro approach.

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Methods: In cirrhotic patients, high serum levels of intestinal hyperpermeability (zonulin and endotoxin) markers were accompanied by elevated serum levels of TNFα and soluble CEACAM1.

Results: In in vitro experiments, we evaluated the individual and interacted roles of TNFα and human recombinant CEACAM1 (hrCEACAM1) in LC-sera (sera of cirrhotic patients)-induced intestinal hyperpermeability-related pathogenic signals. In the Caco-2 cell culture, LC-sera, TNFα and hrCEACAM1 increased apoptosis (measured by TUNEL+/annexin-5+PI+ cells and caspase-3 activity), decreased restitution capacity (proliferation and migration), and disrupted tight junction protein-maintained barrier function in Caco-2 cells. The pathogenic changes mentioned above were accompanied by an increase in intracellular ROS levels, LDH release, and endoplasmic reticulum stress-related signals in the LC-sera or TNFα-pretreated Caco-2 cells.

Concomitant incubation of Caco-2 cells with antiCEACAM1 suppressed these LC-sera or TNFαinduced negative effects on restitution, barrier function, and cell viability.

Conclusions: This study demonstrated that sera from cirrhotic patients contain soluble CEACAM1, which is involved in the pathogenesis of intestinal hyperpermeability. Accordingly, it is noteworthy to explore the potential use of anti-CEACAM1 treatment for cirrhosis-related intestinal hyperpermeability and endotoxemia.

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INTESTINAL SIRT1 DEFICIENCYRELATED INTESTINAL DYSBIOSIS AGGRAVATE TNFΑ-MEDIATED RENAL DYSFUNCTION IN CIRRHOTIC ASCITIC MICE Tzu-Hao Li1,4, Chia-Chang Huang1,2, Ying-Ying Yang1,2,3, Yi-Hsiang Huang1,3, Ming-Chih Hou3, Han-Chieh Lin3 Institution of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan1 Department of Medical Education, Taipei Veteran General Hospital, Taipei, Taiwan2 Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan3 Division of Allergy, Immunology, and Rheumatology, Department of Internal Medicine, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan4

upregulation of the expressions of intestinal/renal TNFα-related pathogenic signal. In intestinal SIRT1 knockout groups, the positive correlations were identified between intestinal SIRT1 activity and CDR. Conclusions: In mice with advanced cirrhosis, the expression of intestinal SIRT1 is involved in the linkage between Intestinal dysbiosisrelated renal dysfunction through the crosstalk between intestinal/renal TNFα-related pathogenic inflammatory signals.

腸道 SIRT1 缺乏相關的腸道微菌相失 調會加重於肝硬化腹水小鼠 TNFα 相 關的腎功能障礙 黎子豪1,4 黃加璋1,2 楊盈盈1,2,3 黃怡翔1,3 侯明志3 林漢傑3 國立陽明交通大學臨床醫學研究所1 臺北榮民總醫院教學部2 臺北榮民總醫院內科部肝膽胃腸科3 新光吳火獅紀念醫院內科部風濕免疫科4 Background: In advanced cirrhosis, the TNFαmediated intestinal bacteria dysbiosis, are involved in the development of inflammation and vasoconstriction-related renal dysfunction. In colitis and acute kidney injury models, activation of SIRT1 attenuates the TNFα-mediated intestinal and renal abnormalities Aims: This study explores the impacts of intestinal SIRT1 deficiency and TNFα-mediated intestinal abnormalities on the development of cirrhosisrelated renal dysfunction.

Methods: Systemic and renal hemodynamics, intestinal dysbiosis [cirrhosis dysbiosis ratio (CDR) as marker of dysbiosis] were measured in bile duct ligated (BDL)-cirrhotic ascitic mice.

Results: In SIRT1IEC-KO -BDL-ascitic mice, the worsening of intestinal dysbiosis exacerbates intestinal inflammation/barrier dysfunction, the

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RISK OF NON-ALCOHOLIC FATTY LIVER DISEASE IN XANTHELASMA PALPEBRARUM Hsuan-Wei Chen1, Jung-Chun Lin1, Hsuan-Hwai Lin1, Tsai-Yuan Hsieh1, Yu-Lueng Shih1, Peng-Jen Chen1, Ying-Hsuen Wu2, Yi-Lin Chiu3 Division of Gastroenterology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan1 Department of Ophthalmology, China Medical University Hospital, China Medical University, Taichung, Taiwan2 Department of Biochemistry, National Defense Medical Center, Taipei, Taiwan3

眼皮黃斑瘤病患罹患非酒精性脂肪肝 之風險評估 陳宣位1 林榮鈞1 林煊淮1 謝財源1 施宇隆1 陳鵬仁1 吳映萱2 邱奕霖3 三軍總醫院腸胃肝膽科1 中國醫藥大學附設醫院眼科部2 國防醫學院生化研究所3 Background: Xanthelasma palpebrarum (XP) is a sign of hyperlipidemia and is closely linked to atherosclerosis. Since fatty liver shares similar risk factors with atherosclerosis, we hypothesized that patients with XP are also at risk of non-alcoholic fatty liver disease (NAFLD).

Aims: To evaluate the risk of fatty liver related hepatic injury in patients with Xanthelasma Palpebrarum.

Methods: In this retrospective cohort study, 37 patients with XP were compared with sex- and age-matched controls undergoing general health examination. Moreover, demographic information and lipid profiles were compared. The risk of NAFLD was evaluated using the hepatic steatosis and ZJU indices. In addition, we analyzed publicly available RNA sequencing data from the GSE48452 and GSE61260 datasets in the Gene Expression Omnibus database.

Results: Patients with XP had higher scores of hepatic steatosis index (37 ± 1.13 vs 32 ± 0.82, p=0.0006) and ZJU index (38.77 ± 1.0 vs 33.88 ± 0.74, p=0.0002). In addition, they had higher levels

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of lipid parameters, including total cholesterol, low-density lipoprotein (LDL), and fasting glucose.

Among patients with fatty liver, individuals presenting with XP showed higher serum levels of total cholesterol (216 ± 10.4 vs 188.9 ± 7.6, p=0.04), fasting glucose (117.1 ± 6.4 vs 98.3 ± 2.4, p=0.002), and low-density lipoprotein (145.1 ± 8.7 vs 115.6 ± 6.4, p=0.009) than those without XP. In gene expression analysis, individuals presenting with non-alcoholic steatohepatitis showed higher Z scores of xanthelasma than those without non-alcoholic steatohepatitis.

Conclusions: Our results suggest that individuals with XP have a higher risk of progression to NAFLD and develop a more severe dyslipidemia.

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EFFECTIVENESS OF DIRECTACTING ANTIVIRAL AGENT THERAPY IN ABORIGINAL PATIENTS WITH HCV INFECTION IN TAIWAN – A MULTI-CENTER REALWORLD STUDY Ching-Chu Lo1, Ming-Lung Yu2, Wei-Yi Lei3, Ming-Jong Bair4, Ying-Che Huang5 St. Martin De Porres Hospital, Chiayi, Taiwan1 Kaohsiung Medical University Hospital, Kaohsiung, Taiwan2 Hualien Tzu Chi Hospital, Hualien, Taiwan3 Taitung Mackay Memorial Hospital, Taitung, Taiwan4 Taipei Veterans General Hospital, Yuli Branch, Hualien, Taiwan5

以直接抗病毒藥物（DAA）治療台灣 原住民 C 型肝炎的療效及微清除策略 之分析 羅清池1 余明隆2 雷尉毅3 白明忠4 黃英哲5 財團法人天主教聖馬爾定醫院1 高雄醫學大學附設中和紀念醫院2 佛教慈濟醫療財團法人花蓮慈濟醫院3 財團法人台東馬偕紀念醫院4 臺北榮民總醫院玉里分院5 Background: Evidence has shown higher hepatitis C virus (HCV) infection-related mortality rate in aboriginal population than in general population.

Given the high prevalence of HCV infection and low healthcare accessibility, proportion of directacting antiviral agent (DAA) therapy for HCV in rural and remote regions was still low.

Aims: The study aims to evaluate the effectiveness of DAA therapy in this high-risk population and in regions lacking sufficient healthcare resources by using a multi-center real-world database from a pilot project aiming to micro-eliminate HCV infection.

Methods: HCV-infected patients were screened and identified in 5 rural and remote townships with high prevalence of HCV infection in Taiwan.

Clinical data were retrospectively collected from 5 medical sites at baseline, end of treatment at week 12, and follow-up at week 24. Study outcomes were sustained virology response at 12 weeks after end of DAA therapy (SVR12) and

biochemical measures at each time point. To evaluate change of biochemical measures from baseline, differences were calculated for end of treatment and follow-up period, respectively.

Results: A total of 545 HCV-infected aboriginal patients receiving DAAs were included in the study.

The average age was 63.1 years with 205 (37.6%) of males. The overall sustained virology response rate was 94.86%, regardless stratification of age, sex, comorbidities, HCV genotype, baseline HCV viral load, and liver fibrosis. There was a steady trend in normal ranges for albumin, total bilirubin, and direct bilirubin across all time points. Levels of AST and ALT significantly decreased after DAA treatment and kept in normal ranges during followup (mean difference from baseline at week 12 = -26.51 IU/L, p<0.001 for AST; mean difference at week 12 = -33.73 IU/L, p<0.001 for ALT).

There was also a prominent decrease in alphafetoprotein right after treatment (mean difference at week 12 = -1.16 ng/mL, p<0.001). The mean value of estimated glomerular filtration rate (eGFR) at baseline was 73.02 mL/min/1.73m2. The mean difference in eGFR was significantly decreased at week 12 (mean difference = -4.30, p<0,001), and returned to the baseline level at week 24 (mean difference = 0.05, p=0.596).

Conclusions: The DAA therapy for HCV has great effectiveness in aboriginal population in rural and remote regions in Taiwan. Our results may also provide an insight into population- and region-tailored policies aiming to micro-elimination of HCV infection.

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THE RECURRENCE PATTERN OF HEPATOCELLULAR CARCINOMA AFTER RESECTION WITH POSITIVE OR CLOSE MARGIN Ken-Lieh Lee1, Chien-Ru Liu2, Shih-Han Weng3, Wen-Hsin Hung2, Jyh-Der Leu2, Chih-Lin Lin1 Department of Gastroenterology, Ren-Ai Branch, Taipei City Hospital, Taipei, Taiwan1 Department of Radiation Oncology, Ren-Ai Branch, Taipei City Hospital, Taipei, Taiwan2 Department of Education and Research, Taipei City Hospital, Taipei, Taiwan3

肝癌術後病理標本邊緣有腫瘤細胞或 接近腫瘤細胞的復發型態 李耿列1 劉千如2 翁詩涵3 洪文欣2 呂志得2 林志陵1 臺北市立聯合醫院仁愛院區消化內科1 臺北市立聯合醫院仁愛院區放射線腫瘤科2 臺北市立聯合醫院教學研究部3 Background: Although the treatment of HCC has made great advances, surgical resection remains the main curative treatment. The width of surgical margin will affect the recurrence free survival (RFS) and overall survival after surgery. However, the optimal width of surgical margin has not been conclusive. Therefore, postoperative adjuvant treatment for patient with positive surgical margin has been administrated to reduce the risk of local recurrence.

Aims: The aim of this study was to investigate the recurrent pattern and risk factors for recurrence of hepatocellular carcinoma (HCC) after surgical resection with positive or close margin. In addition, the impact of post-operative adjuvant treatment on recurrence was further clarified.

Methods: The baseline clinical characteristics and pathological features of HCC patients receiving surgical resection with positive or close (≤1 mm) surgical margin were retrospectively enrolled.

Recurrence free survival analysis was performed

by Kaplan-Meier method. Factors associated with recurrence were analyzed by Cox regression.

Results: A total of 50 patients were included in this study. The median follow-up duration was 44 months. The overall recurrence rate was 36% (18/50). The cumulative recurrence free survival was 79.4%, 66.4%, 51.8% at 1, 3 and 5 years

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respectively. Among the patients with recurrence, 27.8% and 72.2% of patients had surgical margin recurrence and de novo recurrence, respectively.

The Cox regression analysis revealed that preoperative α-fetoprotein > 20 ng/ml [hazard ratio (HR): 6.37, 95% confidence interval (CI): 1.62-25.03, P=0.008] and the presence of satellite nodules (HR: 3.6, 95% CI: 1.13-11.46, P=0.031) were significantly associated with recurrence.

Among 8 patients receiving adjuvant radiotherapy, no patient had local recurrence at the surgical margin.

Conclusions: De novo recurrent HCC was the major recurrence pattern of postoperative hepatocellular carcinoma with positive or close surgical margin. Postoperative adjuvant radiotherapy has the potential to reduce surgical margin recurrence.

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DUAL HEPATITIS B AND C-ASSOCIATED HEPATOCELLULAR CARCINOMA: PROGNOSTIC ROLE OF ALBUMINBILIRUBIN GRADE Chih-Chieh Ko1,2, Shu-Yein Ho2,3, Yi-Hsiang Huang1,2,4, Ming-Chih Hou1,2, Teh-Ia Huo5,6 Division of Hepatobiliary, Department of Internal Medicine, Taipei Veterans General Hospital, Taipei, Taiwan1 School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan2 Division of Gastroenterology and Hepatology, Min-Sheng General Hospital, Taoyuan, Taiwan3 Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan4 Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan5 Institute of Pharmacology, National Yang Ming Chiao Tung University School of Medicine, Taipei, Taiwan6

2083 (62.3%), 1068 (32%), and 190 (5.7%) patients were associated with HBV, HCV, and dual viral infections, respectively, and they were intervened with different treatment modalities based on their diagnostic outcomes.

Results: The results of subgroup analyses indicated statistically significant differences in tumor nodule, total tumor volume (TTV), vascular invasion, BCLC staging, ALBI grade. ALBI grade clearly identified the OS of patients among the three groups and patients with TTV > 50 cm3 and < 50 cm3. Through the variable analysis, ALBI grade (1/2) (HR: 1.961, 95% CI: 1.271–3.025, p = 0.002) in the dual viral group and ALBI grade (1/2) (HR: 1.674, 95% CI: 1.450–1.932, p < 0.001) and ALBI grade (1/3) (HR: 3.191, 95% CI: 2.320–4.390, p < 0.001) in patients with TTV < 50 cm3 showed significant differences.

Conclusions: This study successfully unveils that ALBI grade could be used as an independent prognostic index to assess the survival of patients with HCC caused by HBV, HCV, and dual viral infections, including the obvious discrimination in patients with TTV < 50 cm3.

白蛋白 - 膽色素評分應用在 B 肝合併 C 肝的肝癌病人預後評估 柯智傑1,2 何樹仁2,3 黃怡翔1,2,4 侯明志1,2 霍德義5,6 臺北榮民總醫院肝膽腸胃科1 國立陽明交通大學醫學2 敏盛綜合醫院肝膽腸胃科3 國立陽明交通大學臨床醫學研究所4 臺北榮民總醫院醫學研究部5 國立陽明交通大學醫學院藥理學研究所6 Background: Several researches have employed the Albumin–bilirubin (ALBI) system to investigate the outcomes of patients with HCC. This retrospective study is to verify the possibility of ALBI grade to identify the overall survival (OS) and progression of patients with HCC caused by hepatitis B virus (HBV), hepatitis C virus (HCV), or dual viral hepatitis after different treatment modalities.

Aims: Identify the relationship between ALBI model and OS in patients with HCC caused by HBV or HCV alone or dual infection.

Methods: We retrospectively review the medical records of 3341 patients with HCC. Among them,

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SARCOPENIA AND SIGNATURES OF GUT MICROBIOTA ASSOCIATED WITH THE RISK OF CIRRHOTIC COMPLICATIONS Pei-Chang Lee1,2, Kuei-Chuan Lee1,2, Tsung-Chieh Yang1,2, Hsiao-Sheng Lu1,2, Tsung-Yi Cheng1,2, Yu-Jen Chen1,2, Jen-Jie Chiou3, Chi-Wei Huang3, Ueng-Cheng Yang3, Yi-Hsiang Huang1,2, Ming-Chih Hou1,2 Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan1 School of Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan2 Institute of Biomedical Informatics, National Yang Ming Chiao Tung University, Taipei, Taiwan3

肌少症和特殊的腸道微菌叢特徵與肝 硬化併發症的風險相關 李沛璋1,2 李癸汌1,2 楊宗杰1,2 呂學聖1,2 鄭琮譯1,2 陳宥任1,2 邱振傑3 黃琦瑋3 楊永正3 黃怡翔1,2 侯明志1,2 臺北榮民總醫院內科部胃腸肝膽科1 國立陽明交通大學醫學院醫學系2 國立陽明交通大學生物醫學資訊研究所3 Background: Muscle depletion and gut dysbiosis are poor prognostic factors to cirrhotic patients.

However, the spectrum of microbial alterations in different muscle phenotypes, the deviated microbial functions and their impacts on cirrhotic outcomes are still poorly investigated.

Aims: The aim of this study was to identify muscle dependent microbial changes in detail and their associated risks of cirrhotic complications.

Methods: From September 2018 to October 2020, 80 cirrhotic patients and 8 healthy volunteers were prospectively enrolled. The composition and functions of intestinal microbiota as well as serum amino acids were analyzed. Microbial compositions that associated with sarcopenia and their predicting impacts on cirrhotic complications were investigated.

Results: A spectrum of gut microbial alteration was observed in cirrhotic patients with different

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muscle phenotypes, and the obvious distinction was divided by the muscle strength condition.

Fecal microbiota of sarcopenic cirrhotic patients was enriched with Streptococcaceae, Klebsiella, Gammaproteobacteria, Bacilli, Micrococcales, and Hungatella. In contrast, Lachnospiraceae, Ruminococcus, Dialister and Allosonella were diminished. The declined microbial functions in biosynthesis of amino acids were correlated with the decreased serum levels of amino acids of patients. Fecal depletion of Lachnospiraceae and enrichment of Streptococcaceae were significantly associated with cirrhotic sarcopenia. Besides, fecal depletion of Lachnospiraceae and presence of sarcopenia could independently predict overall cirrhotic complications, including infectious and non-infectious events.

Conclusions: Alterations of gut microbial composition and functions are associated with cirrhotic sarcopenia. Sarcopenia and associated signatures of gut microbiota independently predict the occurrence of cirrhotic complications that potentially could be intervened to improve patients’ outcomes.

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DIFFERENCES OF CLINICAL FEATURES BETWEEN NONALCOHOLIC FATTY LIVER DISEASE AND HEPATITIS C VIRUSRELATED HEPATOCELLULAR CARCINOMA Bou-Zenn Lin, Tsung-Jung Lin, Chih-Lin Lin, Kuan-Yang Chen Department of Gastroenterology, Ren-Ai Branch, Taipei City Hospital, Taipei, Taiwan

非酒精性脂肪肝病與 C 型肝炎所導致 肝癌之臨床表現差異 林柏任 林聰蓉 林志陵 陳冠仰 臺北市立聯合醫院仁愛院區消化內科 Background: Hepatocellular carcinoma (HCC) has been the second leading cause of cancer death in Taiwan and the third worldwide. Hepatitis C virus (HCV) accounts for about 20-30 % of HCC cases and nonalcoholic fatty liver disease (NAFLD) has been an emerging role that could lead to chronic liver disease, nonalcoholic steatohepatitis, cirrhosis, and eventually HCC. To date, the clinical features of HCC on NAFLD and a comparison with HCC on hepatitis C have remained insufficiently known.

Aims: This study aimed to assess and compare the clinical features, such as patient age, gender, liver function, cirrhosis, largest tumor size, and cancer staging during diagnosis, between patients with NAFLD-related HCC and those with hepatitis C virus-related HCC in Taiwan.

Methods: This study retrospectively analyzed most patients with HCC who were recruited from the database of Cancer Registries in Taipei City Hospital, Ren-Ai Branch, from 2011 to 2017; and the other patients consecutively from the HCC multidisciplinary conference between January, 2018 and December, 2019. After the data collection, patients with alcohol-related HCC and HBV-related HCC were excluded first, and then HCV-related and NAFLD-related cases were selected from the remaining population. Totally, 23 NAFLD-related and 58 HCV-related HCC patients were enrolled in our study for further analysis.

Results: NAFLD-related HCC patients were more male-predominant (17/23 (73.9%) versus 23/58 (39.7%), p = 0.005) and more over-weighted

(Body mass index (BMI): 26.6 (24.2–30) kg/ m2 vs. 23.3 (20.9–25.5) kg/m2, p = 0.005) than HCV-related. Only 34.8% (8/23) of NAFLD and 87.9% (51/58) of HCV-related HCC patients were cirrhotic (p < 0.001). Child-Pugh classification A was in 95.7% (22/23) of NAFLD and in 72.4% (42/58) of HCV-related HCC patients. (p = 0.06).

The bilirubin levels were significantly higher in HCV than in NAFLD patients (1.2 (0.78-1.83) mg/ dl versus 0.73 (0.4-1.0) mg/dl, p = 0.017). There were no significant differences in age, tobacco use and international normalized ratio between the two groups. Tumor characteristics, including the level of AFP, BCLC stage and size of largest tumor, were not significantly different between the two groups.

Conclusions: In conclusion, HCC patients in NAFLD were heavier and more male-predominant than in HCV-related group. In addition, more NAFLD-related HCC patients were non-cirrhotic than HCV-related. The other factors, including age, Child-Pugh score, AFP level, BCLC stage and largest tumor size, were not significantly different between the two groups.

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THE RESPONSE OF REPEATED TRANSARTERIAL CHEMOEMBOLIZATION FOR INTERMEDIATE-STAGE HEPATOCELLULAR CARCINOMA Mo-Fan Chen1, Shih-Han Weng2, Tom Chen1, Chih-Lin Lin3 Department of Radiology, Ren-Ai Branch, Taipei City Hospital, Taipei, Taiwan1 Department of Education and Research, Taipei City Hospital, Taipei, Taiwan2 Department of Gastroenterology, Ren-Ai Branch, Taipei City Hospital, Taipei, Taiwan3

反復經動脈化學栓塞治療中期肝癌的 療效 陳墨繁1 翁詩涵2 陳韻正1 林志陵3 臺北市立聯合醫院仁愛院區影像醫學科1 臺北市立聯合醫院仁愛院區教學研究部2 臺北市立聯合醫院仁愛院區消化內科3 Background: Transarterial chemoembolization (TACE) has been widely used in the treatment of intermediate-stage hepatocellular carcinoma (HCC). However, the response and criteria for repeating TACE and the optimal number of repeated procedures still need further study.

Aims: To investigate the response of repeated TACE for patients with intermediate-stage HCC. The factors associated with early complete response (CR) were also identified.

Methods: The response of 54 patients with intermediate-stage HCC treated with repeated TACE were retrospectively evaluated during February 2016 and February 2021. The response measured after each TACE was based on mRECIST criteria via dynamic CT or MRI. The clinical parameters and tumor characteristics were analyzed by Student’s t test, chi-square test and logistic regression as appropriate.

Results: Among the 54 patients who received first TACE, 9 (16%) patients achieved CR. Of 32 patients received second TACE, one (3.1%) patient reached CR. Among 25 patients received a third session of TACE, 4 (16%) showed CR. Of 16 patients underwent four sessions of TACE, 3 (18.7%) achieved CR. Totally, 19 patients were defined as TACE refractoriness, 3 patients achieved CR after repeated TACE treatment.

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Compared to patients without CR after first TACE, patients with CR after first TACE had a significantly higher level of albumin (4.19 ± 0.49 g/dl vs. 3.80 ± 0.46 g/dl, P=0.046), lower level of AST (33.44 ± 19.65 U/L vs. 55.24 ± 49.97 U/L, P=0.049), and ALP (71.20 ± 23.29 U/L vs. 113.46 ± 57.78 U/L, P=0.041), and lower alpha fetoprotein (AFP) levels (8.79 ± 11.92 vs. 2696.19 ± 8166.51 ng/ dL, P=0.012). However, multivariate analysis did not show significant factors associated with CR after first TACE. Conclusions: Repeated TACE treatment was effective for patients with intermediate-stage HCC. CR is difficult to achieve but can occur in those patients were defined as TACE refractoriness.

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SWITCHING FROM ETV/TDF TO TAF WITH CHANGES IN EGFR FOR CHRONIC HEPATITIS B: A HOSPITAL ANALYSIS Cheng-Da Lin1, Hsin-Yi Chen1, Jui-Ting Hu1,2, Sien-Sing Yang1,2 Liver Center, Cathay General Hospital, Taipei, Taiwan1 School of Medicine, Fu-Jen Catholic University, Taipei, Taiwan2

yet reached a significant difference of P<0.005.

According to logistic regression, Cirrhosis will be a significant factor worsening renal function (P=0.0151). ALT should and may be a worsening factor (P=0.1145) than other underlying condition.

Conclusions: Switching to TAF in patients with chronic hepatitis B may improve kidney function.

Due to the limited tracking time, no significant statistical difference has been achieved The comorbidities of chronic hepatitis B can also affect kidney function.

治療慢性 B 型肝炎藥物從 ETV/TDF 轉 換至 TAF 病患之腎功能變化：一個醫 院的分析 林承達1 陳信宜1 胡瑞庭1,2 楊賢馨1,2 國泰綜合醫院肝臟中心1 天主教輔仁大學醫學系2 Background: Tenofovir alafenamide (TAF) is a newly developed prodrug of tenofovir (TFV). TAF is one of first-line treatment for chronic hepatitis B virus infection with reliable anti-viral effect and better renal function.

Aims: We compare those patients’ renal function change who had been received other nucleotide analogue before and now with Tenofovir alafenamide (TAF) for 12-60 weeks. Is the improvement in renal function of patients treated with TAF better than that of patients treated with TDF in a hospital experience?

Methods: We enrolled 143 CHB patients who had taken Entacavir/Tenofovir disoproxil fumarate for ≥1 years. This single center, retrospective, cohort study included 143 consecutive Chronic hepatitis B virus infection patients under Entacavir or Tenofovir disoproxil fumarate before then switched to tenofovir alafenamide mono therapy from May 2019 to December 2020. We regularly followed up renal function and liver function test every 3 months. We recorded these patients underlying condition.

Results: The average age of the patients was 57 ± 11 years old. There were 111 males and 32 females. Previously, the number of medications treated was TDF 120, ETV 22, and 32 other medications. The statistical results have not been particularly significant. To 60 wks in the tracking time, the results are as follows: Creatinine will decrease and eGFR will increase, but it has not

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COMPARISON OF SORAFENIB USE IN HEPATITIS B VIRUS OR HEPATITIS C VIRUS-RELATED HEPATOCELLULAR CARCINOMA Tzu-Hsin Huang, Jing-Houng Wang, Sheng-Nan Lu, Chao-Hung Hung, Tsung-Hui Hu, Chien-Hung Chen, Yuan-Hung Kuo Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan

雷莎瓦使用在 B 型肝炎或 C 型肝炎相 關肝癌的比較 黃子昕 王景弘 盧勝男 洪肇宏 胡琮輝 陳建宏 郭垣宏 長庚醫療財團法人高雄長庚紀念醫院胃腸肝膽科 系暨長庚大學醫學系 Background: In the era without effective sequential systemic therapies, hepatitis C virus (HCV)-related advanced HCC (HCV-HCC) was previously reported to have better overall survival (OS) than hepatitis B virus (HBV)-related HCC (HBV-HCC) in sorafenib use, but it was undetermined.

Aims: To appraise the effect of sorafenib between HBV-HCC and HCV-HCC patients in recent years.

Methods: We retrospectively evaluated 338 patients with unresectable HCC who had undergone sorafenib between January 2018 and August 2020. Treatment response was assessed by radiologic imaging according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST).

Results: A total of 199 patients (Male/Female: 152/47, mean age: 65.8 year) were recruited including 127 patients (63.8%) in the HBV-HCC group and 72 patients (36.2%) in the HCV-HCC group. Among them, 84.2% of HBV-HCC patients who controlled HBV infection by nucleoside analogs (NAs), whereas 66.7% of HCV-HCC patients obtained a sustained virological response by direct-acting antivirals or peg-interferon.

Compared with HBV-HCC patients, HCV-HCV patients had similar progression-free survival (3.1 vs 3.0 months) and non-significant OR (13.5 vs 11.8 months, p=0.573). HCV-HCC patients had a

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higher objective response rate (13.8% vs 8.8%) and durability rate (15.4% vs 9.8%) than HBV-HCC patients, but they were not statistically significant.

Based on whether antiviral treatment offered, HCV patients with antiviral treatment had longest OS (18.1 months) and was followed by HBV with treatment (12.1 months), HBV without treatment (10.1 months) and HCV without treatment (7.9 months). However, etiologies of HCC didn`t contribute to OS. Conclusions: For unresectable HCC patients undergone sorafenib in recent years, HCV patients seemed to have the trend of longer survival and better treatment response than HBV patients.

Further large-sample studies are required to clarify this issue.

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LONG-TERM SAFETY IN HBSAGNEGATIVE, HBCAB-POSITIVE PATIENTS WITH RHEUMATIC DISEASES AFTER RECEIVING GLUCOCORTICOID PULSE THERAPY Ying-Cheng Lin1, Yen-Ju Chen2, Shou-Wu Lee1, Teng-Yu Lee1, Yi-Ming Chen2, Sheng-Shun Yang1 Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan1 Division of Allergy, Immunology and Rheumatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan2

from the first episode of GC pulse therapy. These cases concurrently had maintained high dose oral prednisolone (≥20 mg prednisolone daily for over 4 weeks).

Conclusions: Conclusions: Amongst HBsAgnegative, anti-HBc-positive rheumatic patients treated with GC pulse therapy, the risk of HBVassociated hepatitis within the first year was low.

HBsAg seroreversion might develop in the later stage, but only in those with maintained high-dose oral steroid.

風濕科病人合併慢性 B 型肝炎接受脈 衝式類固醇後的長期追蹤 林穎正1 陳彥如2 李少武1 李騰裕1 陳一銘2 楊勝舜1 臺中榮民總醫院胃腸肝膽科1 臺中榮民總醫院過敏免疫風濕科2 Background: The risk of hepatitis B virus (HBV) reactivation in hepatitis B surface antigen (HBsAg)negative, antibody to hepatitis B core antigen (antiHBc)-positive patients after glucocorticoid (GC) pulse therapy remains unclear.

Aims: Our study aimed to examine the safety of GC pulse therapy in HBsAg-negative, anti-HBcpositive rheumatic patients.

Methods: Medical records of HBsAg-negative, anti-HBc-positive patients receiving GC pulse therapy to treat rheumatic diseases were reviewed.

The primary outcome was HBV-associated hepatitis occurring within the first year after GC pulse therapy; the secondary outcome was HBsAg seroreversion during the follow-up period.

Results: Results: We identified 5,222 HBsAgnegative, anti-HBc-positive patients with rheumatic diseases who had attended Taichung Veterans General Hospital from October 2006 to December 2018. A total of 689 patients received GC pulse therapy, with 424 patients being analyzed.

Hepatitis was noted in 28 patients (6.6%) within the first year after GC pulse therapy, but none had been diagnosed as HBV-associated hepatitis.

Three patients (0.7%) later developed HBsAg seroreversion, with a median interval of 97 months

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ERITORAN SUPPRESSED TLR4 SIGNALING IN MOUSE PRIMARY KUPFFER CELLS AND HEPATIC STELLATE CELLS Yun-Cheng Hsieh, Kuei-Chuan Lee, Pei-Shan Wu, Yi-Hsiang Huang, Ming-Chih Hou, Han-Chieh Lin Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan

Eritoran 可抑制小鼠初代庫佛式細胞 與肝星狀細胞之 TLR4 訊號傳遞路徑 謝昀蓁 李癸汌 吳佩珊 黃怡翔 侯明志 林漢傑 臺北榮民總醫院肝膽胃腸科 Background: Toll-like receptor 4 (TLR4) signaling plays a key role in liver inflammation and fibrosis. Kupffer cells (KCs) express TLR4 and respond to lipopolysaccharide (LPS) by releasing proinflammatory and profibrogenic mediators.

LPS also sensitizes hepatic stellate cells (HSCs) to transforming growth factor-β signals. The effects of eritoran, a TLR4 antagonist, in liver cells remained unclear.

Aims: To investigate the effects of eritoran on TLR4 signaling in primary mouse liver cells.

Methods: C57BL/6 mice were treated with carbon tetra-chloride (CCl4) for 12 weeks to induce chronic liver injury. Primary mouse liver cells were isolated from CCl4 mice and cultured with lipopolysaccharide (LPS, 10 ng/mL) or eritoran (10 μg/mL). To silence MyD88 expression in KCs, mouse MyD88-siRNA was used for transfection.

After siRNA transfection for 48 h, KCs were incubated with or without LPS or eritoran for 6 h.

Results: Immunofluorenscence and flow cytometry showed that eritoran decreased LPSinduced NF-κB p65 nuclear translocation in primary mouse HSCs. Western blotting of primary KCs and hepatocytes revealed that LPS-induced NF-κB p65 nuclear translocation in KCs was significantly suppressed by eritoran but was not altered by eritoran in hepatocytes. Incubation of isolated KCs with LPS for 6 h resulted in an increase in MyD88 expression, phosphorylation of p38 and JNK, which was downregulated by coincubation with eritoran or treatment of MyD88siRNA. In addition, the LPS-induced increased

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expression of TGF-β1 in KCs was decreased by eritoran or MyD88-siRNA treatment.

Conclusions: Eritoran is effective in suppressing the TLR4-mediated response to LPS in primary HSCs and KCs. Therefore, eritoran may serve as a potential drug for chronic liver disease.

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A COMPARISON OF CLINICAL SIGNIFICANCE OF ESOPHAGEAL VARICES IN CIRRHOTIC AND NONCIRRHOTIC PATIENTS WITH RESECTABLE HEPATOCELLULAR CARCINOMA Yu-Jen Chen, Chien-Wei Su, Ming-Chih Hou Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan

比較肝硬化存在與否對可手術切除肝 癌病人合併食道靜脈曲張的臨床意義

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NOVEL BIOMARKER FOR PREDICTION OF BILIARY ATRESIA IN CHOLESTATIC INFANT Yu-Hsueh Hsiao, Mei-Hwei Chang, Kai-Chi Chang, Chi-San Tai, Cheng-Yu Chen, Jia-Feng Wu Department of Pediatrics, National Taiwan University Children’s Hospital, National Taiwan University, Taipei, Taiwan

一個創新的指標協助在膽汁鬱積的嬰 兒族群中診斷膽道閉鎖 蕭玉雪 張美惠 張凱琪 戴季珊 陳政宇 吳嘉峯

陳宥任 蘇建維 侯明志

台大兒童醫院小兒部

臺北榮民總醫院胃腸肝膽科

Background: Biliary atresia (BA) is one of the most serious cholestatic liver diseases in early infancy.

BA remains to be the leading cause of pediatric liver transplantation in the world, while early Kasai operation was proved to decrease the risk of early transplantation. It is difficult to differentiate BA and non-BA cholestatic liver disease in clinical practice due to lack of reliable markers.

Aims: We aimed to generate an easy and noninvasive diagnostic parameter to assist the prediction of BA among cholestatic infants in this study.

Methods: We prospectively enrolled 145 cases with neonatal cholestasis from June 2015 to October 2020 in NTUCH. We collected the clinical data of cholestatic workup. The diagnosis of BA was confirmed by intra-operative cholangiography.

We used Stata and MedCalc to perform statistical analysis.

Results: The mean age of cholestatic workup in this cohort was 43.03 days old (97 males and 48 females). In these 145 cases, there were 42 patients (28.97%) diagnosed with BA. Several clinical data were statistically significant difference between BA and non-BA cholestatic infants. The cutoff of clinical parameters for the best prediction of BA among cholestatic infants included direct bilirubin ≥ 2.9 mg/dL, GGT ≥ 190 U/L, AST ≥ 72 U/L, Direct/Total-bilirubin ratio > 0.36 and LSM > 7.7 kPa. We assigned the score of Direct bil ≥ 2.9 mg/dL, AST ≥ 72 U/L and D/T-bil ratio > 0.36 as 1, GGT ≥ 190 U/L as 2 and LSM > 7.7 kPa as 3, and generate a novel Non-invasive Indicator of Biliary Atresia (NIBa) score as the sum of

Background: The clinical significance of esophageal varices (EV) in cirrhotic and noncirrhotic patients with resectable hepatocellular carcinoma (HCC) is unclear.

Aims: We aimed to compare different outcome of HCC patients after liver resection.

Methods: From July 2003 to July 2019, 111 patients with HCC who underwent liver resection were retrospectively reviewed, including 85 patients with cirrhosis and the remained without.

Prognostic factors were analyzed using the Cox proportional hazards model and Logistic regression model.

Results: Of the 111 patients with esophageal varices and resectable HCC, there was no difference of overall survival and recurrence free survival between patients with or without cirrhosis. Cirrhotic patients had higher risk of post hepatectomy decompensation compared to non cirrhotic patients (hazard ratio: 7.738, p=0.036).

Patients with high risk varices were more likely to experience EV bleeding (hazard ratio: 15.554, p<0.001), prophylactic EV ligation or non selective beta blocker could reduce risk of EV bleeding (risk ratio: 0.107, p=0.010) Conclusions: Compare to non cirrhosis, cirrhotic patients with HCC and EV are under high risk of post hepatectomy decompensation. However, cirrhosis is not a poor prognostic factor of overall survival and recurrence for HCC patients after resection surgery.

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each score of the clinical parameters. The ROC analysis identified the NIBa score > 4 (AUC = 0.94, P < 0.001) for the best prediction of BA (sensitivity 0.81 and specificity 0.97) among cholestatic infant.

The PPV and NPV of NIBa score > 4 was 85% and 92.38% respectively. The diagnostic accuracy was 90.34%.

Conclusions: In this cholestatic cohort, we generate a novel biomarker with Non-invasive Indicator of Biliary Atresia (NIBa) score and identify the cutoff > 4 is a reliable predictor for BA among cholestatic infants.

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HEPATIC (PRO)RENIN RECEPTOR SILENCING REDUCES STEATOSIS, INFLAMMATION AND FIBROSIS IN MICE FED WITH FAST FOOD DIET Pei-Shan Wu1,2,3, Yun-Cheng Hsieh1,3, Kuei-Chuan Lee1,3, Yi-Hsiang Huang1,3, Ming-Chih Hou1,2,3, Han-Chieh Lin1,3 Division of Gastroenterology and hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan1 Endoscopy Center for Diagnosis and Treatment, Taipei Veterans General Hospital, Taipei, Taiwan2 Department of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan3

腎素（原）受體阻斷減少非酒精性脂 肪肝病小鼠的肝臟脂肪變性、炎症和 纖維化 吳佩珊1,2,3 謝昀蓁1,3 李癸汌1,3 黃怡翔1,3 侯明志1,2,3 林漢傑1,3 臺北榮民總醫院胃腸肝膽科1 臺北榮民總醫院內視鏡診斷暨治療中心2 國立陽明大學內科學科3 Background: The prevalence of nonalcoholic fatty liver disease (NAFLD) in Taiwan is increasing.

However, no drug has been proven to treat steatohepatitis and its fibrosis. We have found some roles of (pro)renin receptor (PRR) in hepatic stellate cells (HSCs) and liver fibrosis, and mouse and human HSCs have PRR activation. Inhibiting hepatic PRR expression can reduce the TGF-β/ pSMAD3 pathway to improve fibrosis in mice chronically injured by thioacetamide. Importantly, in patients with NAFLD and fibrosis, we found high expression of PRR in the fibrotic livers. Additionally, inhibiting PRR in hepatocytes was found to reduce its fat accumulation.

Aims: We aimed to investigate the effects of chronic inhibition of intrahepatic PRR on hepatic steatosis, inflammation, and fibrosis in mice with NAFLD. Methods: A mouse model of NAFLD was made using a special fast food diet (FFD). We used PRR-shRNA or scrambled shRNA to treat FFD or normal mice.

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Results: FFD mice receiving placebo exhibited severe steatosis with moderate inflammation, hepatocyte ballooning and fibrosis in liver. By PRR-shRNA, the degrees of severity of steatosis, inflammation, ballooning and fibrosis were reduced significantly with decreased hepatic triglyceride, hepatic hydroxyproline content and serum alanine aminotransaminase levels. PRR-shRNA treatment in FFD mice activated peroxisome proliferators activated receptor alpha, carnitine palmitoyltransferase 1 alpha, and lowered total acetyl-CoA carboxylase protein levels, contributing to the decreased hepatic steatosis.

Moreover, PRR-shRNA inhibited the recruitment of inflammatory cells, and reduced the expression of tissue inhibitor of metalloproteinase-1 and collagen 1 alpha 1 in livers of FFD fed mice, which could contribute to the improvement of inflammation and fibrosis.

Conclusions: Hepatic PRR knockdown attenuated steatosis, inflammation, and fibrosis in a mouse model with NAFLD.

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THIOACETAMIDE-INDUCED CHRONIC LIVER INJURY IMPAIRS GUT BARRIER WITH BACTERIAL TRANSLOCATION IN MICE Yu-Ling Pan1, Pei-Shan Wu1,2, Yun-Chen Hsieh1,2, Kuei-Chuan Lee1,2, Yi-Hsiang Huang1,2, Ming-Chih Hou1,2, Han-Chieh Lin1,2 Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan1 Department of Medicine, National Yang-Ming Chiao-Tung University, School of Medicine, Taipei, Taiwan2

硫乙醯胺誘導的慢性肝損傷在小鼠損 害腸道屏蔽並有腸道細菌位移 潘鈺聆1 吳佩珊1,2 謝昀蓁1,2 李癸汌1,2 黃怡翔1,2 侯明志1,2 林漢傑1,2 臺北榮民總醫院內科部腸胃肝膽科1 國立陽明交通大學醫學院2 Background: In health gut, bacterial invasion can be prevented from the gut immune system.

However, gut bacterial translocation may occur in patients with chronic liver injury or liver cirrhosis.

Translocated bacteria or its products may cause spontaneous bacterial peritonitis, bacteremia, sepsis. Besides, it would activate Kupffer cells and hepatic stellate cells in liver, which deteriorates inflammation and fibrosis in liver and causes mortality in patients with chronic liver disease or liver cirrhosis. In previous studies which used mouse models of bile duct ligation and CCl4 to induce liver injury, they found that chronic liver injury increased intestinal permeability and bacterial translocation. However, the correlation between bacterial translocation and liver injury in mice with thioacetamide-induced liver injury is unknown. Therefore, we hypothesized that gut permeability and bacterial translocation increased in mice with thioacetamide-induced liver injury.

Aims: To investigate the interaction between gut barrier and bacteria, and the pathogenesis of gut bacterial growth and translocation in mouse model of thioacetamide-induced chronic liver injury.

Methods: We used TAA injection 100 cc/kg three times weekly to induce chronic liver injury in mice.

Results: Liver inflammation and fibrosis

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developed since the 4th weeks after TAA injection.

Gut leakage was evaluated through fecal albumin and serum FD-4 level, which showed increased amount since 4th week. Bacterial overgrowth and translocation were evaluated through fecal 16S DNA and MLN 16S DNA, which showed presence of bacterial translocation but no obvious change 4 weeks after TAA administration.

Conclusions: We found that with the development of liver inflammation and fibrosis, intestinal permeability increased, and bacterial translocation was noted simultaneously in TAA-treated mice, similar to other liver disease models. However, bacteria overgrowth was not seen in TAAtreatment mice.

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SEVEN CENTIMETERS AS AN OPTIMAL CUTOFF VALUE FOR PROGNOSIS STRATIFICATION IN LARGE MONOFOCAL HEPATOCELLULAR CARCINOMA Yi-Hao Yen1, Wei-Feng Li2, Kwong-Ming Kee1, Chih-Chi Wang2, Yu-Fan Cheng3, Jing-Houng Wang1, Sheng-Nan Lu1, Chao-Hung Hung1 Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan1 Liver Transplantation Center and Department of Surgery, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan2 Liver Transplantation Center, Department of Diagnostic Radiology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan3

單顆肝癌大於 7 公分和中期肝癌的預 後相同 顏毅豪1 李韋鋒2 紀廣明1 王植熙2 鄭汝汾3 王景弘1 盧勝男1 洪肇宏1 長庚醫療財團法人高雄長庚紀念醫院胃腸肝膽科 系暨長庚大學醫學系1 長庚醫療財團法人高雄長庚紀念醫院肝臟移植中 心暨一般外科2 長庚醫療財團法人高雄長庚紀念醫院肝臟移植中 心暨放射診斷科系3 Background: Barcelona Clinic Liver Cancer (BCLC) guidelines designate monofocal hepatocellular carcinoma (HCC) >2 cm as BCLC A, and large monofocal HCC is defined at >5 cm.

Aims: We aimed to evaluate the optimal cutoff value for large monofocal HCC based on prognosis stratification.

Methods: From 2011–2018, 3,055 patients with newly diagnosed HCC, who were managed in our institution, including 868 patients with monofocal HCC > 2 cm and 330 patients with BCLC B, were enrolled in this retrospective study.

Results: Monofocal HCC >5 cm patients had worse overall survival (OS) than monofocal HCC 2–5 cm patients (5-year OS: 54% vs. 57%;

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p=0.047), confirmed by multivariate analysis (hazard ratio [HR]: 1.492, 95% confidence interval (CI): 1.055–2.110; p=0.024). Monofocal HCC >5 cm patients had better OS than BCLC B HCC patients (5-year OS: 54% vs. 25%; p<0.001), confirmed by multivariate analysis (HR: 0.670, 95% CI: 0.481–0.934; p=0.018). Using 7 cm as the monofocal HCC cutoff value resulted in worse OS than monofocal HCC 2–7 cm (5year OS: 50% vs. 57%; p=0.02), confirmed by multivariate analysis (HR: 1.625, 95% CI: 1.039– 2.540; p=0.033). Monofocal HCC >7 cm patients had better OS than BCLC B patients (p=0.006).

However, no significant difference was identified in the multivariate analysis (HR: 0.726; 95% CI: 0.473–1.115; p=0.144) Conclusions: The prognosis of monofocal HCC >7 cm was similar to that of BCLC B, indicating that 7 cm represents an optimal cutoff value for prognosis stratification in large monofocal HCC.

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IMPAIRMENT OF FOCAL PERFUSION IN LIVING DONOR LIVER TRANSPLANTATION WITHOUT RECONSTRUCTION OF MIDDLE HEPATIC VEIN Ya-Ting Cheng1, Ching-Song Lee1, Chen-Fang Lee2, Wei-Chen Lee2 Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan, Taiwan1 Department of Liver and Transplantation Surgery, Chang-Gung Memorial Hospital, Linkou Branch, Taoyuan, Taiwan2

在未重建中肝靜脈活體肝臟移植對局 部血流灌注的影響及受損情況 鄭雅婷1 李青松1 李正方2 李威震2 林口長庚紀念醫院肝膽胃腸科1 林口長庚紀念醫院肝臟移植科2 Background: Congestion of the anterior section of the grafted liver might be a problem when performing living donor liver transplant using a right lobe graft without middle hepatic vein reconstruction.

Aims: To realize the perfusion state aside cut surface of graft and the congestion in MHVTs, patients receiving liver donor liver transplantationright lobe (LDLT-RL) without reconstruction of middle hepatic vein tributories (MHVTs) are enrolled in this study.

Methods: From Sep., 2018 to Dec, 2020, total 93 patients receiving LDLT-RL without MHVTs reconstruction are enrolled in this study.

Results: During gray scale ultra-sonography, the parenchyma aside the cut-surface is either bright (55/93, 59.7%) or not-bright (38/93, 40.3%). The incidence of hepato-pedal flow in foal portal vein increases from day 1 to day 7 (67.7% to 88.2%).

The incidence of reverse flow in MHVTs also increases from day 1 to day 7 (59.1% to 82.8%).

The dominant focal blood pattern aside cut-surface is hepato-pedal in focal portal vein and reverse in MHVTs. The incidence of this focal blood pattern increases from day 1 to day 7 (47.8% to 76.7%).

The incidences of such flow pattern in bright and not-bright are statistically significant on day 1 (36.4% Vs 65.8%), but similar on day 7 (70.9% Vs 84.2% on day 7). Totally, the incidence of hepatic

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congestion in MHVTs improves from 77.8% in 0.7-1 M to 14.9% in 3-4 M by CT evaluation.

Only the bright parenchyma in MHVTs can predict high incidence of hepatic congestion on 1-M post transplantation. Others parameters such as D1 or D7 normal focal blood flow or D7 has similar result of hepatic congestion later.

Conclusions: In patents of LDLT-RL without MHVTs reconstruction, there are more than half patients will develop parenchyma change in MHVTs area and frequent focal abnormal flow.

The focal abnormal flow improves within 1-wk after transplantation. However, the hepatic congestion is still high in the 0.7-1 M CT follow-up. But time will ensure the improvement of MHVTs congestion.

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IMPROVING HEPATIC FUNCTIONAL RESERVE IN LIVER DECOMPENSATED PATIENTS AFTER SUCCESSFUL SOFOSBUVIR-BASED DIRECTACTING ANTIVIRAL THERAPY FOR HEPATITIS C VIRUS INFECTION Pin-Shuo Su1, Chi-Jen Chu1,2, Chien-Wei Su1,2, Sih-Hsien Wu1, Tien-Hsin Wei1, Chung-Chi Lin2,3, Shou-Dong Lee2,4, Yuan-Jen Wang2,3, Fa-Yauh Lee1,2, Yi-Hsiang Huang1,2, Ming-Chih Hou1,2 Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan1 Faculty of Medicine, National Yang-Ming Chiao Tung University, Taipei, Taiwan2 Healthcare and Services Center, Taipei Veterans General Hospital, Taipei, Taiwan3 Division of Gastroenterology, Department of Medicine, Cheng Hsin General Hospital, Taipei, Taiwan4

以 Sofosbuvir-Based 口服抗病毒藥 物成功治療代償失調 C 肝患者可部分 改善肝臟功能 蘇品碩1 朱啟仁1,2 蘇建維1,2 吳思賢1 魏天心1 林崇棋2,3 李壽東2,4 王苑貞2,3 李發耀1,2 黃怡翔1,2 侯明志1,2 臺北榮民總醫院內科部胃腸肝膽科1 國立陽明交通大學醫學系2 臺北榮民總醫院健康管理中心3 振興醫療財團法人振興醫院胃腸科4 Background: Sofosbuvir, a direct-acting antiviral (DAA) agent has revolutionized the treatment of chronic hepatitis C virus (HCV) infection, especially in patient with hepatic compensation. Real-world data on the hepatic functional reserve, including biochemistries profiles, Model for End-Stage Liver Disease (MELD) score, Child Turcotte Pugh (CTP) score and Fibrosis-4 (FIB-4) Index in patients with HCV related hepatic decompensation after DAA treatment is limited in Taiwan.

Aims: This study was aimed to investigate the hepatic benefits after successful HCV eradication in patients with hepatic decompensation.

Methods: From December 2015 to July 2021, total

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42 consecutive HCV related liver decompensation patients who treated with sofosbuvir-based regimens (sofosbuvir/daclatasvir: 6, sofosbuvir/ ledipasvir: 28, sofosbuvir/velpatasvir: 8) successfully achieving sustained virological response (SVR) were enrolled for analyses.

Biochemistries profiles, MELD score, CTP score and FIB-4 index were assessed before DAA treatment, 12 weeks and 48 weeks after the completion of therapy (SVR12 and SVR48).

Results: Mean age of enrolled patients was 67 ± 11.4 years, 71% of them was female and seven (17%) of them failed to previous IFN. Five (12%) patients has CTP score C. Genotype distribution was as follows: 1a: two, 1b: 31, 2: seven, 6: two.

HCV RNA level before treatment was 5.64 ± 1.1 log10 IU/mL and 33% of them with a baseline HCV RNA > 2,000,000 IU/mL. The median FIB4 index, CTP and MELD scores of cases at before treatment were 10.37 (0.41-29.19), 8 (7-12) and 12 (6-21) respectively. After HCV treatment, 20 (48%) and 29 (69%) patients had resolved of hepatic decompensation at SVR12 and SVR48 (improve to CTP score A at 12 weeks and 48 weeks after the completion of therapy). The hepatic function (alanine aminotransferase, albumin, total bilirubin, CTP and MELD scores, FIB4 index) were significant improved during follow-up (baseline vs. SVR12, baseline vs. SVR48). However, there were six patients had persisted hepatic decompensation and exacerbation of MELD score even after successful HCV eradication.

Conclusions: Most of patients with HCV related hepatic decompensation can improve hepatic function including CTP and MELD scores, and FIB4 index after successful HCV treatment.

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CLINICAL IMPACT OF ENTECAVIR THERAPY IN HEPATITIS B PATIENTS WITH CIRRHOSIS Kuang-Tsu Yang1, Chia-Ming Lu1, Yuan-Rong Li1, Wei-Chih Sun1, Sung-Shuo Kao1, Kung-Hung Lin1, Tzung-Jiun Tsai1, Huay-Min Wang1, Feng-Woei Tsay1,2, Hsien-Chung Yu1, Wei-Lun Tsai1,2, Wen-Chi Chen1,2 Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan1 School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan2

Entecavir 對於 B 型肝炎合併肝硬化病 患的臨床影響 楊光祖1 呂家名1 李沅融1 孫煒智1 高崧碩1 林恭弘1 蔡騌圳1 王惠民1 蔡峯偉1,2 余憲忠1 蔡維倫1,2 陳文誌1,2 高雄榮民總醫院內科部胃腸肝膽科1 國立陽明交通大學醫學系2 Background: Hepatitis B virus gradually cause cirrhosis in people, which is a high risk factor for the development of hepatocellular carcinoma (HCC). The current literature suggests that hepatitis B patients with cirrhosis will benefit from being treated with nucleotide analogue (NA). NA is used to reduce the concentration of hepatitis B virus DNA in order to protect the liver, prevent the progression of cirrhosis, and even the development of HCC. However, there is still a lack of real-world research and long-term follow-up data on this population.

Aims: Long-term clinical outcomes in hepatitis B patients with cirrhosis using entecavir were studied.

Methods: This retrospective cohort study included hepatitis B patients with cirrhosis being treated with entecavir from January 2010 to June 2021 at Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Veterans General Hospital. The start of entecavir use was identified as the index date, and the end points of follow-up were the diagnosis of HCC by imaging (computed tomography/magnetic resonance imaging), death, or June 30, 2021.

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Patients will receive regular clinic visits, blood tests, and imagings during the follow-up period.

If necessary, endoscopy will be arranged to assist in the diagnosis and treatment of cirrhosisrelated diseases. Patients’ clinical cirrhosis data are recorded in detail. The incidence of HCC and clinically significant outcomes related to cirrhosis are tallied. Patients’ medication status is evaluated through telephone interviews and outpatient clinic follow-up.

Results: In our study, 75 hepatitis B patients with cirrhosis under regular entecavir use were included, with a mean age of 58.8 years and 66.7% were male. In the cirrhosis-related lab data, 5 patients (6.7%) had alpha fetoprotein over 10 ng/ml. 65 patients (86.7%) had an initial Child’s score of A and 10 patients (13.3%) had B. 15 patients (20%) were HBeAg positive and 60 patients (80%) were negative. The clinical follow-up results showed that 14 patients (18.7%) were found to have HCC after a mean follow-up of 444 weeks (1.2 years). 5 patients (6.7%) died of cirrhosis-related diseases after long-term follow-up, and 10 patients (13.3%) presented to the emergency department and were hospitalized because of cirrhosis-related diseases.

Conclusions: This retrospective cohort study demonstrated that entecavir is able to control hepatitis B patients with cirrhosis. However, the cirrhotic liver is already damaged so within 1-2 years, nearly 20% of patients will develop liver cancer. Though clinicians apply various screening tools and pay attention to this special population, certain percentages of patients will develop HCC and cirrhosis-related mortality or hospital visits.

At this time, we can minimize the subsequent diseases or complications of hepatitis B by enhancing patient health education, regular followup and testing, and use of antiviral drugs. With this study, we might seek better antiviral drugs, investigate new treatment mechanisms, and even develop therapies to eradicate the hepatitis B virus to achieve precise medicine for the elimination of cirrhosis and HCC.

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EFFECTS OF HEPATITIS C VIRUS ERADICATION ON BONE MINERAL DENSITY IN PATIENTS Jung-Chun Lin, Yi-Ting Chou, Hsuan-Wei Chen, Hsuan-Hwai Lin, Yu-Lueng Shih, Tsai-Yuan Hsieh Division of Gastroenterology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan

C 型肝炎病毒根除對患者骨密度的影響 林榮鈞 周益霆 陳宣位 林煊淮 施宇隆 謝財源 國防醫學院三軍總醫院內科部胃腸科 Background: Low bone mineral density (BMD) has been described in patients with chronic hepatitis C. Little is known about the effects of eradication of hepatitis C virus (HCV) on BMD in HCV-infected patients.

Aims: The study objective was to evaluate the effect of antiviral therapy on BMD in HCV patients with sustained virological response (SVR).

Methods: We conducted a prospective study in 73 chronic hepatitis C outpatients initiating antiHCV therapy. Determinations of BMD (dual X-ray absorptiometry at lumbar spine and left hip) were made at baseline, at the end of treatment, and by the end of a 12 or 24-week follow-up period.

Results: The median age was 52.8 years, 43.8% were males, and 30.1% had severe hepatic fibrosis. The prevalence of osteoporosis at baseline at the lumbar spine and left hip was 1.3% and 6.8%, respectively. Anti-HCV therapy comprised pegylated interferon (peg-IFN) and ribavirin (RBV) in 86.3% and direct-acting antiviral agents (DAA) in 13.7%. A total of 49 (67.1%) patients achieved SVR. In the peg-IFN and RBV cohort, antiviral therapy led to significant on-treatment increases of lumbar spine and left hip BMD (p < 0.05) irrespective of subsequent treatment response. Compared to end-of-treatment values, BMD tended to decrease in lumbar spine and left hip by the end of the 24week follow-up period and thereafter, that did not differ from baseline values. In the DAA group, no significant effect of SVR was observed on BMD for the interaction between time and SVR either in the lumbar spine or the left hip.

Conclusions: Interferon-based therapy leads to an on-treatment increase of BMD. However, SVR was not associated with significant changes in BMD in HCV-infected persons.

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P.57

RADIOLOGICAL FEATURES AND OUTCOMES IN PATIENTS WITH INTERMEDIATE STAGE HEPATOCELLULAR CARCINOMA UNDERGOING TRANSCATHETER ARTERIAL CHEMOEMBOLIZATION 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, Yi-Hsiang Huang1,2,3 Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan1 Faculty of Medicine, National Yang Ming Chiao Tung University School of Medicine, Taipei, Taiwan2 Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan3 Department of Radiology, Taipei Veterans General Hospital, Taipei, Taiwan4 Cancer Center, Taipei Veterans General Hospital, Taipei, Taiwan5

肝腫瘤影像學的特徵於接受經動脈肝 臟栓塞術的中期肝癌病人的預後分析 洪雅文1 李懿宬1,2 齊振達1,2,3 李潤川4 柳建安4 邱乃祈4 黃宣恩4 趙毅5 侯明志1 黃怡翔1,2,3

with extranodular growth.

Results: The patients with radiological features classified to confluent multinodular type, infiltrative type, and simple nodular type HCCs with extranodular growth tend to respond to TACE worse and have a poorer overall survival (OS) than simple nodular type. In patients with simple nodular type, confluent multinodular type, infiltrative type, and simple nodular type HCCs with extranodular growth, the progressive disease (PD) rate after second session of TACE was 13.2%, 45.8%, 52.1% and 40.2%, respectively (p<0.001), and the median OS was 42.2, 16.6, 11.3 and 21.0 months, respectively (p<0.001). By multivariate analysis, HCC patients with radiologic features were significantly associated with PD (confluent type, odds ratio=5.003, p<0.001; infiltrative type, odds ratio=5.217, p=0.001; simple nodular type HCCs with extranodular growth, odds ratio=4.281, p<0.001) and OS (confluent type, hazard ratio=1.818, p=0.001; infiltrative type, hazard ratio=2.129, p=0.002; simple nodular type HCCs with extranodular growth, hazard ratio=1.586, p=0.001).

Conclusions: Intermediate-stage HCC patients with specific radiological features tend to respond poorly to TACE and have a worse overall survival.

Thus, target therapy, immunotherapy, TACE plus sorafenib, or other modalities may be considered better choice of first-line treatment for TACE unsuitable patients.

臺北榮民總醫院內科部腸胃肝膽科1 國立陽明交通大學醫學院醫學系2 國立陽明交通大學臨床醫學研究所3 臺北榮民總醫院放射線部4 臺北榮民總醫院腫瘤醫學部5 Background: For patients with intermediate stage hepatocellular carcinoma (HCC), the subgroup of TACE-unsuitable patients has been debated.

Aims: This study aimed to compare the outcome and survival of different radiological features in patients with intermediate HCC undergoing transarterial chemoembolization (TACE).

Methods: From 2007 to 2019, 403 treatment-naïve patients with intermediate stage HCC undergoing repeated TACE were retrospectively enrolled. We compared different radiological features of tumor in radiologic response and survival, including simple nodular type, confluent multinodular type, infiltrative type, and simple nodular type HCCs

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Section：GI P.58

ONE-MINUTE HIGH PRESSURE FORCEFUL AIR FLUSH BY AIR-GUN AFTER ENDOSCOPIC REPROCESSING IMPROVES MOISTURE AND ADENOSINE TRIPHOSPHATE BIOLUMINESCENCE VALUE OF ENDOSCOPE INSTRUMENT CHANNEL Hsiao-Mei Hung1, Ching-Yi Ni2, Yao-Sheng Wang1, Chiao-Hsiung Chuang1, Chiung-Yu Chen1 Division of Gastroenterology & Hepatology, Department of Internal Medicine, National Cheng Kung University Hospital, Tainan, Taiwan1 Division of Gastroenterology and Hepatology, Department of Internal Medicine, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi, Taiwan2

內視鏡再處理後在輔以 1 分鐘高壓氣 槍除水可以改善內視鏡工作管腔內的 水分殘留與 ATP 檢測值 洪曉媚1 倪靜儀2 王堯生1 莊喬雄1 陳炯瑜1 國立成功大學醫學院附設醫院胃腸肝膽科1 嘉義基督教醫院胃腸肝膽科2 Background: Residual moisture in instrument channel of endoscope may increase microorganism colonization or even biofilm formation.

Removing fluid of endoscope instrument channel after endoscope reprocessing was recommended.

Routinely air flush by automatic endoscope reprocessor (AER) around 10 minutes was also been emphasized by experts’ recommendations.

The advantage of Manual forceful air flush by air gun may also help to remove residual fluid after endoscope reprocessing, however, noise, time and human power consuming may be concerned by staff. This study was aimed at direct inspection by borescope evaluation for residual moistures and adenosine triphosphate bioluminescence (ATP) check-up before and after 10 minutes automatic air flush by AER, after manual air-flush by air-gun, and after endoscope storage on the next day before clinical utility.

Aims: We aimed at using ATP test and inspection by borescope to evaluate endoscope instrument

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channel with or without forceful air flush by air-gun.

Methods: Twenty-four gastroscopes, eighteen colonoscopes, and six duodenoscopes bear 84 daily endoscopies practicing in the National Cheng Kung University Hospital were enrolled in this study.

Steps and practices of endoscope reprocessing was performed according to guideline of digestive endoscopy society of Taiwan. Routinely air flush by automatic endoscope reprocessor (AER) around 10 minutes was included as part of automatic endoscope reprocessing before endoscope storage. Between AER and storage, application of air-gun or not was randomly selected. Prototypes of borescopes made

by National Cheng Kung University were applied to check the working channel. Borescope evaluation was performed after high level disinfection, automatic endoscope reprocessing, forceful air flush by air-gun, and storage. Degree of residual fluid droplets was defined none, mild, moderate, and severe fluid retention by 0, 1-5, 6-10, and more than 10 droplets. ATP check-up was performed after manual cleaning, high level disinfection, and on the next day before clinical use (after one-night storage). The ATP test was done with a value lower than 200 RLU to indicate effective endoscope reprocessing.

Results: Inspection of endoscope instrument working channel by using borescope revealed 100% severe residual moistures after high level disinfection, however, still 90.5% (76/84) severe fluid retention even after 10 minutes automatic air flush. Ineffective fluid removal by machine (AER) air flush was noted. Groups of forceful air flush by airgun showed 93% (40/43) zero fluid retention, and 7% (3/43) were mild comparing to group without airgun (p=0.001). The same group before forceful air flush by air-gun showed 93% (40/43) severe fluid retention, and other 7% (3/43) were moderate. After one-night storage, group of air-gun using showed 100% (43/43) zero residual fluid comparing to 17.1% (7/41) without prior air-gun using (p=0.001). Value of ATP testing after one-night endoscope storage significantly decreased in the group of air-gun using (23.63 ± 2.84 vs. 60.66 ± 12.68, p=0.007).

Conclusions: For removing residual fluid before endoscope storage, only 10 minutes air flush by automatic endoscope reprocessor (AER) is not effective. Replace 10 min AER air flush by 1 min air-gun air flush significantly showed improvement of fluid retention and is also considered time saving.

Otherwise, complete removal of fluid in endoscope may also improved results of ATP test.

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P.59

THE STUDY OF OCCUPATIONAL RADIATION EXPOSURE OF ERCP ENDOSCOPIST AND ASSISTANTS BETWEEN TWO DIFFERENT TYPES OF FLUOROSCOPY Ying-Jung Wu, Wan-Jou Tseng, Yao-Sheng Wang, John-Han Wu, Jui-Wen Kang, Chiung-Yu Chen Division of Gastroenterology & Hepatology, Department of Internal Medicine, National Cheng Kung University Hospital, Tainan, Taiwan

研究兩種不同流動 X 光透視機對於執 行治療性逆行性膽胰管攝影術之醫師 與技術師之職業輻射暴露 吳瓔蓉 曾婉柔 王堯生 吳忠翰 康瑞文 陳炯瑜 國立成功大學醫學院附設醫院內科部胃腸肝膽科 Background: Fluoroscopy is necessary to endoscopic retrograde cholangiopancreatography (ERCP). However, occupational radiation exposure of staffs (endoscopists, nurses, or assistants) is inevitable. Best personal protection of radiation exposure and regular monitoring is recommended.

Personal occupational radiation exposure is mainly resulted from reflection or diffuse scattering from the patient under fluoroscopy. Not only personal protection like lead cloths, neck prone with or without combining cap or gloves, but also environmetal protection with lead shield are basic setting. Besides, It dose matter the way of radiation reflection. Fluoroscope with tube over the couch (OC) rather than under the couch (UC) may have more radiation reflection dosage on staff’s upper body theoratically, where the most vital organs are.

The study we assessed the radiation exposure on staffs by two different types of fluoroscopes in real world practice.

Aims: Using radiation dosimeter to measure the radiation dosage on endoscopist and assistants in each ERCP procedure under two different fluoroscopes.

Methods: Forty-one ERCP procedures practiced in National Cheng Kung University Hospital were enrolled in this study. The procedures of therapeutic ERCP were limited to endoscopic biliary cannulation for naïve papilla with normal anatomy for the first time followed by endoscopic

sphincterotomy, stone extraction with or without biliary stenting. Indications of ERCPs were selected for treatment of cholangitis or obstructive jaundice due to bile duct stones. Dosimeters were used NanoDots (Nagase Landauer Ltd.) for measurement of personal radiation exposure in every single procedure and its unit is mGy. Those dosimeters were attached to endoscopist’s and assistants’ left upper chest outside the lead clothes. The first assistant (assistant 1) is next to doctor participating intervention like scrub nurse, and the second (assistant 2) helps preparing the accessories or as been mobile nurse. The other dosimeters were attached to the patient side of lead shield, the wall of ERCP room, where around more 1.5m from patient, 1.8m from floor, and the last dosimeter was put in the controlling room as control group. Night-teen ERCPs were performed under over the couch fluoroscope, and the other twenty-two ERCPs were under the couch method. Personal protection, protective shield, and procedure environmental setting in these two groups were similar. Continuous variables were present as median, and range. Mann-Whitney U test and Wilcoxon paired rank test were applied for statistical analysis.

Results: Time duration of fluoroscopy in two groups were 159 [71-882] sec (OC) and 150 [24720] sec (UC), p = 0.88 and output of radiation dose from fluoroscopy were 656.8 [427.7-2761.2] uGym2 (OC) and 628.7 [114.6-4413.5] uGym2 (UC), p = 0.88. Radiation exposure by Nanodot in endoscopist were 0.0911 [0.1041-0.3974] mGy (OC) vs. 0.0276 [0.0080-0.2924] mGy (UC), p < 0.01 for the hand; and 0.0318 [0.0070-0.2628] mGy (OC) vs. 0.0182 [0.0088-0.1628] mGy (UC), p = 0.04 for the doctor’s body. Radiation exposure of patient side of lead shield were 0.0949 [0.0138-0.3123] mGy (OC) vs. 0.2206 [0.04811.6067] mGy (UC), p = 0.27. As to assistant 1 and 2, had no different in radiation exposure (assistant 1: 0.0098 [0.0070-0.1848] mGy (OC) vs. 0.0120 [0.0064-0.0524] mGy (UC), p = 0.08; assistant 2: 0.0098 [0.0058-0.1563] mGy (OC) vs. 0.0112 [0.0068-0.0224] mGy (UC), p = 0.63).

For radiation exposure detection for each ERCP procedure, the order from high to low is doctor’s hand (0.0519 [0.0080-0.3974] mGy) > doctor’s body (0.0238 [0.0070-0.2628] mGy) > assistant 1 (0.0122 [0.0066-0.1848] mGy) > assistant 2 (0.0100 [0.0058-0.1564] mGy) > wall of ERCP room (0.0098 [0.0058-0.1360] mGy) (p < 0.01).

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Radiation detection from wall of ERCP room (0.0098 [0.0058-0.1360] mGy) is slightly higher but close to from wall of controlling room (0.0094 [0.0066-0.1212] mGy) (p = 0.06).

Conclusions: For the safety of occupational radiation protection, tube of fluoroscope under the couch is better than over the couch, especially for the endoscopists. As to assistants, the assistant 1 took higher radiation exposure than assistant 2 for each ERCP procedure. However, type of fluoroscopy may have no impact on assistants.

P.60

ESOPHAGEAL-SPECIFIC HYPERVIGILANCE AND VISCERAL ANXIETY: A NOVEL PSYCHOPHYSIOLOGICAL INTERVENTION FOR LARYNGOPHARYNGEAL REFLUX Ming-Wun Wong1, Shih-Hsuan Hsiao2, Jui-Sheng Hung1, Shu-Wei Liang1, Lin Lin1, Wei-Yi Lei1, Tso-Tsai Liu1, Chih-Hsun Yi1, Chih-Hsun Yi2, Chien-Lin Chen1 Division of Gastroenterology, Department of Internal Medicine, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan1 Department of Otolaryngology, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan2

食道警覺及臟器焦慮評估 ─ 新型咽喉 逆流症心理生理學介入模式 翁銘彣1 蕭士軒2 洪睿勝1 梁書瑋1 林霖1 雷尉毅1 劉作財1 易志勳1 陳培榕2 陳健麟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1 佛教慈濟醫療財團法人花蓮慈濟醫院耳鼻喉科2 Background: The pathogenesis of laryngopharyngeal reflux (LPR) is complex and lack of a gold standard for diagnosis. The esophageal hypervigilance and anxiety scale (EHAS) is a novel cognitive–affective evaluation of visceral sensitivity, whereas mean nocturnal baseline impedance (MNBI) indicates esophageal mucosal injury from cumulative reflux burden.

Aims: This study aimed to investigate the interrelationship among EHAS, esophageal mucosal integrity, acid reflux burden, and symptoms severity in patients with gastroesophageal reflux disease (GERD) symptoms overlapping with LPR symptoms.

Methods: Consecutive patients with chronic (at least 3 months) reflux symptoms were prospectively enrolled and divided into two groups: those with LPR overlapping and those with GERD symptoms alone. Eligible patients with negative endoscopy underwent 24-hour impedance-pH monitoring for phenotyping, reflux burden, and esophageal mucosal integrity with mean MNBI calculation.

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Validated scores for patient-reported outcomes including GERD questionnaire (GERDQ), reflux symptom index (RSI), and EHAS were recorded.

Results: We enrolled 183 eligible patients, aged 21–64 (mean 48.1) years, of whom 57.3% were female, of whom 92 patients had LPR overlapping and 91 patients had GERD symptoms alone.

Patients with LPR overlapping had higher EHAS (P = 0.002) but similar AET (P > 0.05), distal and proximal MNBI (P > 0.05) compared to those with GERD symptoms alone. Overall, RSI significantly correlated with EHAS (r = 0.428, P < 0.001) but not with AET (P > 0.05) or MNBI (P > 0.05). In patients with LPR overlapping, those with pathologic AET had higher GERDQ (P = 0.003), higher? EHAS (P = 0.041), lower distal and proximal MNBI (P < 0.05) than those with physiological AET. Conclusions: Our study has revealed that EHAS may contribute to LPR symptoms perception.

In patients with LPR overlapping, those with pathologic AET are characterized with greater symptom burden and psychological distress as well as impaired esophageal mucosal integrity.

Combined psycho-physiological evaluation provides a precision approach in the management for LPR patients.

P.61

THE HOST AND BACTERIAL FACTORS PREDICTING ERADICATION FAILURE OF BISMUTH QUADRUPLE THERAPY IN THE FIRST-LINE TREATMENT OF H. PYLORI INFECTION Yu-Hwa Liu1,11, Deng-Chyang Wu2,11, Seng-Kee Chuah3,11, Jyh-Chin Yang4,11, Kuan-Yang Chen5,11, Feng-Woei Tsay6,11, Chia-Long Lee7,11, Shiu-Sz Iuan8,11, Chien-Lin Chen9,11, Hsi-Chang Lee5,11, Wei-Yi Lei9,11, Chao-Hung Kuo2,11, Ping-I Hsu10,11 Division of Gastroenterology, Department of Internal Medicine, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan1 Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan2 Division of Hepatogastroenterology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan3 Division of Gastroenterology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan4 Division of Gastroenterology and Hepatology, Department of Internal Medicine, Renai Branch, Taipei City Hospital, Taipei, Taiwan5 Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan6 Division of Gastroenterology and Hepatology, Department of Internal Medicine, Cathay General Hospital, Taipei, Taiwan7 Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan8 Division of Gastroenterology, Department of Medicine, Buddhist Tzu Chi General Hospital and Tzu Chi University, Hualien, Taiwan9 Division of Gastroenterology, Department of Medicine, Tainan Municipal An Nan Hospital and China Medical University, Tainan, Taiwan10 Taiwan Acid-related Disease & Microbiota (TARD-M) Consortium11 193

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鉍劑四合療法治療幽門螺旋桿菌時影 響除菌失敗之宿主與細菌因子 劉玉華1,11 吳登強2,11 蔡成枝3,11 楊智欽4,11 陳冠仰5,11 蔡峯偉6,11 李嘉龍7,11 許斯淵8,11 陳健麟9,11 李熹昌5,11 雷尉毅9,11 郭昭宏2,11 許秉毅10,11 新光吳火獅紀念醫院 胃腸肝膽科1 高雄醫學大學附設醫院胃腸內科2 高雄長庚紀念醫院胃腸肝膽科3 國立臺灣大學醫學院附設醫院胃腸肝膽科4 臺北市立聯合醫院仁愛院區消化內科5 高雄榮民總醫院胃腸肝膽科6 國泰綜合醫院腸胃內科7 臺中榮民總醫院胃腸肝膽科8 花蓮慈濟醫院肝膽胃腸科9 臺南市立安南醫院消化內科10 台灣胃酸相關疾病暨微菌叢聯盟11 Background: Bismuth-containing quadruple therapy is recommended as the choice treatment for H. pylori infection in areas of either low or high clarithromycin resistance in the Maastricht V/Florence Consensus Report. Although the optimal treatment duration of bismuth-containing quadruple therapy remains unclear, a 10-14 day course is most commonly employed in clinical practice.

Aims: To investigate the host and bacterial factors predicting eradication failure in the firstline treatment of H. pylori infection by of bismuth quadruple therapy.

Methods: From August 2018 to March 2021, 199 H. pylori-infected patients receiving first-line eradication therapy with 10-day bismuth quadruple therapy (rabeprazole 20 mg b.i.d., tripotassium dicitrato bismuthate 300 mg q.i.d., tetracycline 500 mg q.i.d, and metronidazole 250 mg q.i.d. for 10 days) in a clinical trial were prospectively assessed for drug adherence and adverse effects at the end of week 2. Post-eradication H. pylori status was examined by urea breath test 6 weeks after the end of treatment. To determine the independent factors affecting the treatment response, 16 host and bacterial parameters (including age, gender, smoking, alcohol consumption, type of gastrointestinal disease, drug adherence, and antibiotic resistances) were assessed by univariate and multivariate analyses.

Results: Modified intention-to-treat analysis showed that 13 out of 236 infected participants failed to eradicate H. pylori by 10-day bismuth quadruple

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therapy. Univariate analysis demonstrated that metronidazole resistance of H. pylori (P = 0.034) was a risk factor related to eradication failure.

The patients harboring metronidazole-resistant strains had a lower eradication rate than those harboring sensitive strains (87.8% vs 96.2%).

Although patients with poor drug adherence had a lower eradication rate than those with good drug adherence (82.4% vs 94.5%), the difference was borderline (P = 0.087). Multivariate analysis revealed that only metronidazole resistance was an independent risk factor predicting eradication failure with an odds ratio of 3.5 (P = 0.045; 95% confidence interval: 1.03 – 12.20).

Conclusions: Metronidazole resistance is an independent risk factor predicating eradication failure in the first-line treatment of H. pylori infection by 10-day bismuth quadruple therapy.

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P.62

THE MIDTERM OUTCOME OF GASTRIC PERORAL ENDOSCOPIC MYOTOMY FOR REFRACTORY GASTROPARESIS Ning-Hsuan Chin1, Tien-Yu Huang1, Cheng-Lu Lin1, Jiann-Ming Wu2, Kuo-Hsin Chen2, Kuan-Chih Chen1, Tzong-Hsi Lee1, Cheng-Kuan Lin1, Chen-Shuan Chung1,3 Division of Gastroenterology and Hepatology, Department of Internal Medicine, Far Eastern Memorial Hospital, New Taipei City, Taiwan1 Department of Surgery, Far Eastern Memorial Hospital, New Taipei City, Taiwan2 College of Medicine, Fu Jen Catholic University, New Taipei City, Taiwan3

經口內視鏡括約肌切開術治療難治性 胃輕癱之中期預後研究

The mean (± standard deviation (SD)) procedure time was 61.82 (± 18.99) min. The technical and clinical success rates were 100% and 81.82%, respectively. The clinical severity (mean GCSI score 36.00 vs. 14.73, p < 0.0001) and gastric emptying time (mean T1/2 341.92 vs. 65.92 min, p = 0.016) significantly improved after G-POEM. Hospital stay was 7.18 (± 4.49) days without mortality. Procedure-related minor complications included 4 (36.36%) patients with self-limited abdominal pain and 3 (27.27%) patients with intraprocedural pneumoperitoneum which resolved after abdominal needle puncture. During the mean follow-up period of 554.36 days, one (9.09%) patient had relapsed clinical symptoms after 6 months.

Conclusions: G-POEM is an efficient and safe pylorus-directed endoscopic therapy for refractory gastroparesis with promising mid-term results.

金寧煊1 黃天佑1 林政錄1 吳建明2 陳國鋅2 陳冠至1 李宗熙1 林政寬1 鍾承軒1,3 亞東紀念醫院肝膽胃腸科1 亞東紀念醫院外科部2 天主教輔仁大學醫學院3 Background: Gastroparesis is one of the functional complications of diabetic mellitus (DM).

Patients with diabetic gastroparesis refractory to medical therapy have poor quality of life and gastric peroral endoscopic pyloromyotomy (G-POEM) is a promising treatment option.

Aims: In this study, we aimed to evaluate the efficacy and safety of G-POEM for patients with refractory gastroparesis.

Methods: Between December 2017 and 2020, we consecutively enrolled patients with gastroparesis who failed after the administration of several kinds of medication and repeated admission for nutritional support. All patients underwent gastric emptying scintigraphy (GES) and answered a questionnaire on Gastroparesis Cardinal Symptom Index (GCSI). Demographic data, endoscopic procedure, and postprocedural outcome were analyzed.

Results: A total of 11 (9 women and 2 men) patients with refractory gastroparesis (nine with diabetes mellitus, one systemic lupus erythematosus, and one idiopathic lupus erythematosus) were enrolled.

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P.63

CLINICAL OUTCOMES OF COLON ENDOSCOPIC SUBMUCOSAL DISSECTION FOR COLON NEOPLASMS: A SINGLE CENTER EXPERIENCE IN SOUTH TAIWAN Chen-Yu Ko, Chih-Chien Yao, Yu-Chi Li, Lung-Sheng Lu, Yeh-Pin Chou, Ming-Luen Hu, Yi-Chun Chiu, Wei-Chen Tai Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gang Memorial Hospital, Kaohsiung, Taiwan

針對大腸腫瘤執行內視鏡下黏膜剝離 術之回溯性分析：南台灣單一醫學中 心經驗分享 葛振瑜 姚志謙 李育騏 盧龍生 周業彬 胡銘倫 邱逸群 戴維震 高雄長庚紀念醫院肝膽腸胃科 Background: Although most colonic and rectal superficial lesions can be effectively removed by standard polypectomy and/or by Endoscopic mucosal resection (EMR). The Endoscopic submucosal dissection (ESD) can be considered for removal of colonic and rectal lesions with high suspicion of limited submucosal invasion or cannot be optimally removed by snare-based techniques.

It is an advanced endoscopic procedure with more technical difficulties and risks than other snarebased technique.

Aims: We aimed to analyze retrospectively the clinical outcomes of colonic ESD for colonic neoplasms in our hospital.

Methods: We retrospectively enrolled 230 patients with 244 colonic neoplasms, who received ESD procedure from April 2012 to October 2020 at Kaohsiung Chang Gung memorial hospital.

Clinicopathological data were collected by charts review. We also recorded ESD related complications and clinical outcomes.

Results: Among the 230 patients with 244 colonic lesions, the average ESD time was 51.9 minutes with one ESD failure (0.4%). 98.4% lesions achieved En-bloc resection while 84.8% achieved R0 resection. Most lesions (89%) were diagnosed as lateral spreading tumor (LST) and most with non-granular type (50.4%) under endoscopic gross appearance and tubulovillous adenoma (47.1%)

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as pathology. Malignancy included carcinoma (14.8%), NET (1.2%) and MALT (0.4%). Most invasion depths of tumors were limited to mucosal layer (82%). No local recurrence was developed during follow-up (mean: 22.59 months) with 34 loss of follow-up (13.9%). Nine cases (3.7%) have procedure-related complication, including two minimal perforations (0.8%) closed by endoscopic clips and 7 delayed bleeding (2.9%). There was no procedure-related mortality. Four patients were referred to further surgical intervention (1.7%), due to either adenocarcinoma with submucosal invasion or piecemeal resection. One-way analysis of variance for mean ESD time and ESD speed identifies decreasing time and increasing speed during 8-year-period. Independent T test reveals lesion size > 10 cm2 have significance on ESD speed (cm2/min). The endoscopic ultrasound (EUS) exam before ESD was performed in 55 (22.5%) patients with good prediction in both mucosal (Sensitivity: 0.90) and submucosal lesion (Specificity: 0.67).

Conclusions: Endoscopic submucosal dissection (ESD) of colonic neoplasm is an effective and relatively safe treatment for lesion with high suspicion of limited submucosal invasion or unable to be optimally removed by snare-based techniques.

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P.64

RANDOMIZED TRIAL OF CONTRAST-ENHANCED HARMONIC GUIDANCE VERSUS FANNING TECHNIQUE FOR ENDOSCOPIC ULTRASOUNDGUIDED FINE-NEEDLE BIOPSY OF SOLID PANCREATIC LESIONS Yu-Ting Kuo1,2, Yu-Lung Chu1, Weng-Fai Wong1,2, Ming-Lun Han1,2, Chieh-Chang Chen1, I-Shiow Jan3, Wern-Cherng Cheng3, Chia-Tung Shun4, Tsu-Yao Cheng1,3, Wei-Chih Liao1, Hsiu-Po Wang1 Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan1 Division of Endoscopy, Department of Integrated Diagnostics & Therapeutics, National Taiwan University Hospital, National Taiwan University, Taipei, Taiwan2 Department of Laboratory Medicine, National Taiwan University Hospital, National Taiwan University, Taipei, Taiwan3 Department of Pathology, National Taiwan University Hospital, National Taiwan University, Taipei, Taiwan4

technique.

Methods: Patients with SPLs were prospectively enrolled and randomly assigned (1:1) to 2 parallel groups, the interventional group (CEH-EUS guidance) or the control group (standard EUSFNB with fanning technique). The primary outcome was total number of passes required to establish a diagnosis and the secondary outcomes were overall diagnostic accuracy and complications for the two sampling techniques.

Results: Total 118 patients were enrolled from February 2019 and January 2021, with 59 patients assigned to each group. No significant difference was seen for total number of passes required to establish a diagnosis between CEH-EUS group (1.5 ± 1.1) and fanning groups (1.5 ± 1.1). The sensitivity, specificity, and diagnostic accuracy in the CEH-EUS group and fanning groups were 100%, 66.7%, and 98.3% versus 100%, 100%, and 100%, respectively (P = 1). There was also no statistically significant difference between the groups in terms of age, sex, lesion size (38.5 ± 13.3 mm in the CEH-EUS group vs 38 ± 10.3 mm in the fanning group; P = .959), lesion location, adverse event rate, and disease distribution.

Conclusions: EUS-FNB demonstrated high diagnostic accuracy of SPLs independently on CEH-EUS guidance and fanning technique.

針對胰臟固態腫瘤接受內視鏡超音波 導引下細針切片在對比劑增強內視鏡 超音波導引與扇形技術的隨機對照試 驗 郭雨庭1,2 朱祐龍1 黃永輝1,2 韓明倫1,2 陳介章1 詹一秀3 鄭文誠3 孫家棟4 鄭祖耀1,3 廖偉智1 王秀伯1 台大醫院消化內科1 台大醫院綜合診療部內視鏡科2 台大醫院檢驗醫學部3 台大醫院病理醫學部4 Background: Contrast-enhanced harmonic EUS (CEH-EUS) is useful in the differential diagnosis of solid pancreatic lesions (SPLs). CEH-EUS guidance fine-needle biopsy (FNB) can improve diagnosis in SPLs. However, there is limited data about the usefulness of CEH-EUS-guided FNB. Aims: We aimed to assess whether CEH-EUSFNB is superior to standard EUS-FNB with fanning

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1-DAY VERSUS 3-DAY LOW RESIDUE DIET FOR BOWEL PREPARATION – A SINGLE CENTER, RETROSPECTIVE STUDY Jen-Hao Yeh1,2, Tsung-Chin Wu2, Po-Jen Hsiao2, Daw-Shyong Perng1,2, Jen-Chieh Chen2, Gin-Ho Lo1,2, Chia-Chang Hsu1,2, Chih-Wen Lin1,2 Division of Gastroenterology and Hepatology, Department of Internal Medicine, E-DA Hospital/I-Shou University, Kaohsiung, Taiwan1 Division of Gastroenterology and Hepatology, Department of Internal Medicine, E-DA Dachang Hospital, Kaohsiung, Taiwan2

低渣飲食天數與清腸乾淨度之單一中 心，回溯性研究 葉人豪1,2 吳宗勤2 蕭博仁2 彭道雄1,2 陳仁傑2 羅錦河1,2 許家彰1,2 林志文1,2 義大醫院胃腸肝膽科1 義大大昌醫院胃腸肝膽科2 Background: Low residue diet (LRD) is recommended as a part of bowel preparation before colonoscopy. However, the optimal duration of LRD is unclear.

Aims: To compare the efficacy of 1-day and 3-day low residue diet for bowel preparation.

Methods: A retrospective, cross-sectional study was therefore performed in E-DA Dachang hospital. We compared the bowel preparation by Aronchick score and other quality metrics during two consecutive periods: May 2019 to December 2019 (period 1: 3-day LRD) and January 2020 to August 2020 (period 2: 1-day LRD).

Results: 2823 patients were enrolled (1592 with 3-day LRD, and 1231 with 1-day LRD). Most of them used sodium picosulfate and magnesium citrate (SPMC, 84.2%) followed by polyethylene glycol (PEG, 10.0%) and sodium phosphate (5.8%) as the main laxatives. Compared to those in the 3-day LRD group, patients in the 1-day LRD group tended to have more SPMC (88.1% vs.

81.3%, P < 0.001) and supplementary laxative use (19.3% vs. 25.9%, P < 0.001). The proportion of adequate bowel preparation (84.3% vs. 85.1%, P = 0.563), cecal intubation rate, adenoma detection rate, and right-side adenoma detection rate were

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not significantly different in both groups. More advanced adenomas (3.4% vs. 5.9%, P = 0.002) and sessile serrated lesions (6.3% vs. 8.9%, P = 0.014) were found in the 1-day LRD group.

In addition, types of laxatives including SPMC, sodium phosphate, and PEG as well as the presence of supplemental laxatives did not affect the bowel preparation score.

Conclusions: In conclusion, 1-day LRD leads to similar bowel preparation compared to 3-day LRD regardless of type of main laxatives and the presence of supplemental laxatives.

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INCREASED SHORT AXIS OF PSOAS MUSCLE WAS ASSOCIATED WITH SHORTER HOSPITAL STAYS IN GASTRIC CANCER PATIENTS UNDERGOING GASTRECTOMY Ching-Fang Chang1, Jin-Ming Wu1, Kao-Lang Liu2, Ming-Tsan Lin1 Department of Surgery, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan1 Department of Medical Imaging, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan2

interval 0.44–8.87; P = 0.030). In addition, the lesser short axis of the psoas muscle gets longer lengths of hospital stay (coefficients = -0.8; 95% confidence interval: -1.59 – -0.02; P = 0.042).

Conclusions: The parameters of psoas muscle were not associated with both major complications and mortality. The short axis of the psoas muscle, not the long axis or volume, was associated with length of hospital in this eastern population.

腰大肌面積增加和縮短住院天數的關 聯：胃癌病患接受胃切除 張菁芳1 吳經閔1 劉高郎2 林明燦1 國立臺灣大學醫學院附設醫院外科部1 國立臺灣大學醫學院附設醫院影像醫學部2 Background: Sarcopenia is characterized by the degenerative loss of skeletal muscle and is associated with increased adverse surgical outcomes. In our study, we calculate the psoas muscle of the third lumbar vertebral body as the reference of skeletal muscle.

Aims: The aim of this study was to validate whether it was associated with surgical outcomes.

Methods: The gastric cancer patients who undergoing gastrectomy were enrolled for the study. Preoperative computed tomography was used to assess the short axis, long axis, and the total volume of the bilateral psoas muscles. The multiple logistic regression models were developed to determine the odds ratio of major complications and mortality. A linear regression model to predict the outcomes with hospital stays was performed.

Results: Five hundred and two patients were included. The median age was 65.4 years (range: 57.3 – 78.4) and 228 patients (44.2%) were women.

The demographic factors, operative method, cancer staging, parameters of the psoas muscle, which were found no significant associated with major complications and mortality. However, we found the patients aged above 75 were associated with longer hospital stay compared with to other age groups (coefficients = 4.65; 95% confidence

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TREATMENT OUTCOMES AND PREDICTORS OF MORTALITY IN PATIENTS OF ACUTE MESENTERIC ISCHEMIA Yao-Jen Chang, Po-Chu Lee Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan

急性腸系膜缺血之預後及影響因子 張耀仁 李柏居 國立臺灣大學醫學院附設醫院外科部 Background: Acute mesenteric ischemia (MI) is a rare life-threatening condition. The mortality rate has gradually improved but has not changed remarkably during the past decade, despite progress in diagnostic and treatment options.

Aims: To investigate the treatment outcomes and possible risk factors in patients of acute mesenteric ischemia.

Methods: We retrospectively studied 201 patients with MI from January 2012 to October 2018. Each patient underwent contrast-enhanced computed tomography (CT) as part of the initial diagnosis.

For the analysis of the risk factors for MI, patients were divided into vascular related and nonvascular related groups by different pathogenic mechanisms. Outcomes of different treatment and predictors were analyzed.

Results: Of 201 patients, 83 (41.2%) was vascular related. The 30-day mortality rate of 201 patients was 53.2%. The mean length of hospital stay was 24 days, and ICU length of stay was 14 days. Multivariate analysis showed that male (Odds ratio (OR): 3.1 (1.28–8.09); P = 0.015), white blood cell count > 15 K/μL (OR: 4.7 (1.77–13.86); P = 0.002), serum lactate levels > 4 mmol/L (OR: 2.69 (1.14–6.48); P = 0.02), serum hemoglobin < 10 g/dL (OR: 4.72 (1.67–14.63); P = 0.004), estimated glomerular filtration rate < 45 mL/min/1.73m2 (OR: 3.5 (1.46–9); P = 0.006), and pneumoportal sign on CT (OR: 4.4 (1.7–12.3); P = 0.003) were independent predictor for 30-day mortality. The 30-day survival rate was 46.8% and 71.4% of all patients and surgical intervention group, respectively.

Conclusions: The MI patients consisted of

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relatively old age, poor renal function, and having lactic acidosis when initial diagnosed. Additionally, prolonged hospital stays and high 30-day mortality rates were noted. The predictor of surgical risk associated with high mortality were patient in admission, poor renal function, and present of penumoportal signs in images. Aggressive treatment may help in preserving survive.

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THE POOR PROGNOSTIC PREDICTORS OF PATENCY OF ENTERAL METAL STENT AT DAY 30 I-Cheng Shih, Yao-Sheng Wang, Chien-Jui Huang, Ying-Jung Wu, Chiung-Yu Chen Division of Gastroenterology and Hepatobiliary, Department of Internal Medicine, National Cheng Kung University Hospital, Tainan, Taiwan

腸道金屬支架在第 30 天能暢通性的不 良預測因子 史易正 王堯生 黃千睿 吳瓔蓉 陳炯瑜 國立成功大學醫學院附設醫院內科部消化內科 Background: Malignant gastric outlet obstruction is one of serious complication resulted from primary or metastatic upper gastrointestinal cancer. Palliative treatment of gastric outlet obstruction including bypass surgery, endoscopic stenting, or total parenteral nutrition. Self-expandable metal stent is applied for treatment of malignant stricture of GI tracts by endoscopy with or without fluoroscopy, but the patency of metal stent was variable.

Aims: The study is to identify predict factors of patency of enteral metal stent at day 30.

Methods: Patients with malignant gastric outlet obstruction bear endoscopic metal stenting was enrolled in National Cheng Kung University Hospital from 2018 to 2020 retrospectively. Characteristic of patients, cancers, and malignant stricture of guts, and metal stenting were analyzed. Gastric Outlet Obstruction Scoring System (GOOSS) was used for assessment of successful treatment.

Results: Total fifty-one patients with 26 men and 25 women (age: 61.2 ± 12.9 years old) were enrolled finally. The technically successful rate was 100%, and clinical successful rate was 78.4%. The patency of metal stent at D30 is better than D7 for prediction of long-term stent success. Among the failed metal stenting at day 7 around 23.5% still may succeed at D30 (66.7%). The predictor of failed metal stenting at Day 30 are metastatic malignancy, distal duodenal obstruction, and poor stent opening less than 8mm.

Conclusions: For patient with malignant gastric outlet obstruction due to metastatic disease, distal obstruction, or poor stent opening, combining other intervention rather than single metal stenting maybe needed.

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COMPARISON OF DIFFERENT ENDOSCOPIC METHODS USED FOR MANAGING CHOLEDOCHOLITHIASIS IN PATIENTS WITH END-STAGE RENAL DISEASE UNDERGOING HEMODIALYSIS Jhong-Han Wu, Jui-Wen Kang, Yao-Sheng Wang, Chiung-Yu Chen Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan

評估不同內視鏡取石術在接受血液透 析之末期腎病變患者的效果與安全性 吳忠翰 康瑞文 王堯生 陳炯瑜 國立成功大學醫學院附設醫院胃腸肝膽科 Background: The adverse event rate of endoscopic retrograde cholangiopancreatography (ERCP) is high in patients with end-stage renal disease (ESRD) undergoing hemodialysis (HD).

Endoscopic sphincterotomy (EST), endoscopic papillary balloon dilation (EPBD), and endoscopic sphincterotomy plus balloon dilation (ESBD) are all techniques used to manage choledocholithiasis.

However, few reports have compared the results of these three techniques in HD patients.

Aims: We aim to analyze the efficacy and safety of these techniques for treating choledocholithiasis in this specific population.

Methods: We performed a retrospective study of 80 patients with ESRD on HD who underwent ERCP for choledocholithiasis management between August 1st, 2012, and December 31st, 2020, at a medical center in southern Taiwan.

These patients were divided into three groups: EST (n = 21), EPBD (n = 28), and ESBD (n = 31).

Post-ERCP complications, including pancreatitis, bleeding, cholangitis, and perforation, were reviewed for analysis.

Results: There were no significant among-group differences in the rate of complete stone clearance and hospitalization day after ERCP. Patients in the EST group had a higher post-ERCP complication rate than was the case in the other groups (p = 0.016). ESBD significantly reduced post-ERCP

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bleeding, compared with that occurring with EST (OR 0.07; 95% CI, 0.01-0.072, p = 0.026). There were no significant among-group differences in the rates of pancreatitis and cholangitis. There were no ERCP-related perforations or deaths in this study.

Conclusions: EST, EPBD, and ESBD are efficient methods for treating choledocholithiasis in ESRD patients. ESBD was found to lead to a lower risk of bleeding than EST, and the rate of pancreatitis or cholangitis was comparable for EST and EPBD. Our results suggest that ESBD is the best choice of treatment of choledocholithiasis in patients with ESRD undergoing HD.

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CONTRAST ENHANCED HARMONIC ENDOSCOPIC ULTRASONOGRAPHY FOR PANCREATIC TUMORS Jiann-Hwa Chen1,2, Wei-Chih Su1, Tsung Hsien Hsiao1, Sean T Kung1, Chih-Hsiang Chen1, Lung Yuan Hsu1,2, You Chen Chao1,2 Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taipei, Taiwan1 School of Medicine, Tzu Chi University, Hualien, Taiwan2

對比劑內視鏡超音波可區別不同性質 的胰臟腫瘤 陳建華1,2 蘇偉志1 蕭宗賢1 龔子翔1 陳至翔1 徐榮源1,2 趙有誠1,2 佛教慈濟醫療財團法人台北慈濟醫院胃腸肝膽科1 慈濟大學醫學院2 Background: Ultrasound contrast agent is used in the clinic practice for a period of time. Sonazoid® is a second-generation ultrasound contrast agent that has excellent stability and resistance to ultrasound destruction and can stably exert a good contrast effect for a prolonged period. Contrast enhanced hormonic endoscopic ultrasonography (CEHEUS) is useful for the evaluation of pancreatic disease because it permits the observation of the hemodynamics of masses in real time.

Aims: To investigate the usefulness of CEH-EUS for histological differentiation of pancreatic tumors.

Methods: A total of 25 consecutive patients are enrolled from 2019-07-01 to 2021-06-25. CEHEUS was performed for these patients having a pancreatic solid lesion. Contrast enhanced character was classified into two phases, the vascular phase and perfusion phase. The former includes two enhancement patterns (hypoenhancement or hyper- & iso-enhancement) and the latter is divided into two patterns, homogeneous and heterogeneous. Correlation between vascular patterns and histo-pathology of biopsy or resected pancreatic tissues was ascertained.

Results: The final diagnoses of 25 examined tumors were pancreatic cancer (PC) (𝑛 = 17), neuroendocrine tumor (NET) (𝑛 = 4), lymphoma

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(𝑛 = 1), metastasis from lung cancer (𝑛 = 1) and uncertain etiology (𝑛 = 2). In late-phase images, 16 of 17 PCs had the heterogeneous perfusion pattern, for a diagnostic sensitivity and specificity of 94.1% and 94.1%, respectively. All the PCs and the metastatic tumor reveal hypo-enhancement pattern in vascular phase. Four NETs had hyperenhancement patterns on the early-phase image.

The other two cases with uncertain etiology showed iso-enhancement in early-phase image.

Conclusions: CEH-EUS could be useful for distinguishing PC from other solid pancreatic lesions.

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THE CLINICOPATHOLOGIC CHARACTERISTICS OF PATIENTS WITH BIOPSY-PROVEN BARRETT’S ESOPHAGUS: SINGLE-CENTER EXPERIENCE IN TAIWAN Shu-Hsien Lin, Wei-Chen Tai, Chung-Mou Kuo, Chih-Ming Liang, Shih-Cheng Yang, Lung-Sheng Lu, Yi-Chun Chiu, Ming-Luen Hu, Keng-Liang Wu, Seng-Kee Chuah, Yeh-Pin Chou Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan

經切片證實的巴瑞特氏食道病變患者 其臨床與病理特徵：台灣單一醫學中 心經驗 林淑賢 戴維震 郭仲謀 梁志明 楊世正 盧龍生 邱逸群 胡銘倫 吳耿良 蔡成枝 周業彬 高雄長庚紀念醫院胃腸肝膽科系 Background: Barrett’s esophagus (BE), a premalignant condition for esophageal adenocarcinoma (EAC), is characterized by a change of the normal squamous epithelium of the distal esophagus to a columnar-lined intestinal metaplasia (IM) in histology. The prevalence of BE in the general populations of Asian countries is increasing.

Aims: We would like to evaluate the clinicopathologic features of patients with BE and to investigate risk factors associated with BE. Methods: This retrospective study enrolled total 210 patients undergoing esophagogastroduodenoscopy examinations diagnosed with endoscopically suspected esophageal metaplasia (ESEM) between May 2020 and March 2021 in Kaohsiung Chang, Gung Memorial Hospital.

Patients with the presence of IM in the metaplastic esophageal epithelium were confirmed to have BE. Clinicopathologic of patients with or without BE were compared. Risk factors predicting BE were also analyzed.

Results: A total of 210 subjects with endoscopically suspected esophageal metaplasia were included, and 114 of them (114/210, 56.7%)

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were confirmed to have biopsy-proven IM. Subjects diagnosed with BE were male gender in particular (71.9% vs 28.1%, p=0.0016), having higher body mass index (BMI) compared to non-BE subjects (p=0.004). The majority of these individuals with BE were classified as short segment BE (88/114, 77.19%). Compared to subjects with short-segment BE, those with long-segment BE had higher proportion of male gender (92.3% vs 65.9%, p=0.012), higher BMI (p=0.014), higher rate of heartburn symptoms (100% vs 79.5%, p=0.011), peptic ulcer disease (38.5% vs 14.8%, p=0.01) and use of protonpump inhibitors (84.6% vs 58.0%, p=0.013). In the long-segment BE group, subjects had trend of taking more biopsies, and the most frequent number of biopsies to diagnose short-segment BE was ≤ 3 per esophagogastroduodenoscopy (p=0.043). Compared to long-segment BE group in histologic classification, higher incidence of non-dysplasia and lower incidence of low gradedysplasia were observed in the short-segment BE group (86.4% vs 61.5%, p=0.009; 13.6% vs 38.5%, p=0.009).

Conclusions: In this study, we found that male gender and high BMI significantly increased the likelihood of discovering IM in ESEM lesions. More attention should be paid on obesity male patient while performing esophagogastroduodenoscopy examinations due to higher risk of developing BE in this populations.

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THE EXPERIENCE OF UNSCHEDULED GASLESS LAPAROSCOPIC ANTERIOR RESECTION DUE TO INTOLERANCE OF PNEUMOPERITONEUM Tien-Yu Hsu1,2, Chin-Hung Tsai1 Department of Surgery, Taichung Hospital, Ministry of Health and Welfare, Taichung, Taiwan1 Department of Surgery, Changhua Hospital, Ministry of Health and Welfare, Changhua, Taiwan2

無氣腹腔鏡前位切除術因未預期的無 法忍受二氧化碳充氣之可行性 徐天佑1,2 蔡金宏1 衛生福利部臺中醫院外科部1 衛生福利部彰化醫院外科部2 Background: Pneumoperitoneum with CO2 gas has long been the standard technique for creating a working space in the peritoneal cavity for laparoscopy. Complications of pneumoperitoneum include cardiopulmonary compromise, venous stasis, hypothermia, extra-peritoneal insufflation, and risk of gas embolism. Carbon dioxide also causes hypercarbia and respiratory acidosis by peritoneal absorption and is thought to increase postoperative discomfort through conversion to carbonic acid on the peritoneal surfaces.

Alternative gases such as nitrous oxide, argon, and helium have been suggested, but they have their own particular disadvantages, in addition to the problems associated with pneumoperitoneum in general. There were several reports of performing laparoscopy without pneumoperitoneum by using various devices for mechanically elevating the anterior abdominal wall. Gasless laparoscopy has many potential advantages beyond eliminating the problems with pneumoperitoneum.

Aims: Because of the ageing society of Taiwan, the patient was older and older in the recent years. Pneumoperitoneum was a huge stress for these people. We could rule out some patient who may not tolerate the pneumoperitoneum before operation by cardia echo and lung function test.

But there was still some patient met the problems during pneumoperitoneum such like bradycardia,

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desaturation, CO2 retention and subcutaneous emphysema. Gasless laparoscopy maybe a solution for these people with high risk during pneumoperitoneum.

Methods: To avoid the complication of pneumoperitoneum with CO2 gas, we had recently made the research of gasless laparoscopic TEP under local anesthesia for old age people with underlying illness. During the research, we had met this case a 60-year-old male with past history of dementia, old CVA for 11 years and bed-ridden for 7 years. He had sigmoid colon cancer and we had performed the scheduled laparoscopic anterior resection. Pre-operation evaluation included lab data, chest X-ray, ECG and cardia echo. The EF was 63% and wall motion was normal. Under general anesthesia, we had approached the first trocar and started inflation.

The patient had bradycardia and desaturation. We had decreased the inflated pressure to 8 mmHg and even to 5 mmHg, but it was not working.

We had deflation and the patient became stable in 5 minutes. Because of the intolerance of the pneumoperitoneum, we decided to transverse operation to gasless laparoscopic anterior resection.

Results: We finished the gasless laparoscopic anterior resection smoothly. We used the lifting system with iron intern retractor and wound protector (Alexis O Wound Retractor). We made a 5 cm incision on the lower midline abdomen and set the wound protector in the wound. We retracted the wound protector with iron intern to create space. Another one 10 mm trocar and one 5 mm trocar was inserted on left lower abdomen and right lower abdomen. The total operation time was about 136 minutes. We had recorded the whole procedure with laparoscopic camera. The patient was discharged without complication after two weeks.

Conclusions: The intolerance of pneumoperitoneum was not very rare now. We had met three cases during 2019 to 2020. Another two case was laparoscopic TEP. One patient had sudden PEA during inflation. We had done CPCR for him and he had ROSC after 3 minutes. The operation was hold and we sent the patient to ICU. Another case had VT after general anesthesia.

We also hold the operation. The older patient had more risk during anesthesia. The laparotomy was a good solution for these people with intolerance of pneumoperitoneum. But the laparotomy had

higher rate of complication including pneumonia and surgical site infection compared with laparoscopy. The gasless laparoscopy maybe a better choice for these old patients. We could decrease the post operation complication and the patient recovered fast. These old patients were fragile and even the pneumonia would lead mortality. The gasless laparoscopy was not hard for the matured surgeon. Although it takes more time but the benefit was stronger. We should consider the gasless laparoscopy if we met this situation. It was a good experience for our hospital.

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A CASE REPORT: EMPHYSEMATOUS CHOLECYSTITIS COMPLICATED WITH PYLEPHLEBITIS AND NECROTIZING PANCREATITIS Jui-Ju Kao1,2, Po-Hsuan Wu1,2 Division of General and Digestive Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan1 Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan2

產氣性膽囊炎併發門靜脈炎及壞死性 胰臟炎之罕見病例報告 高睿汝1,2 吳柏宣1,2 高雄醫學大學附設中和紀念醫院一般及消化系外 科1 高雄醫學大學附設中和紀念醫院外科部2 Background: Among all forms of acute cholecystitis, emphysematous cholecystits (EC) is one of the most life-threatening one, with a high mortality rate up to 25%. EC is defined as inflammation of the gallbladder with the presence of air in the wall, the lumen or adjacent to it without communication between the gallbladder and the hollow viscus, along with organ dysfunction.

Concomitant with necrotizing pancreatitis (NP) or pylephlebitis were rarely seen in EC and often thought to be fatal.

Aims: Cases of EC complicated with pylephlebitis were scantly reported in the past literature, cases of synchronous EC and necrotizing pancreatitis were even rarer. Moreover, emphysematous cholecystitis complicated with both pylephlebitis and necrotizing pancreatitis has not yet been reported according to our PubMed search (Accessed in May 2021).

Herein, we report a case of emphysematous cholecystitis complicated with pylephlebitis and necrotizing pancreatitis.

Methods: A 66-year-old female with known uncontrolled diabetes mellitus was admitted through the emergency department with acute onset of epigastric dullness pain for about a week.

In addition, several episodes of fever with chills and vomiting were also presented. She was brought to the hospital with conscious disturbance (E3V4M6),

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tachycardia (123 beats/min), blood pressure of 113/46 mmHg, and fever (40.3°C). The physical examination revealed marked tenderness over epigastric area. Laboratory investigations showed no leukocytosis but significant bandemia (white cell count of 6.7/mm3, band form:45%) and elevated C-reactive protein (74.92 mg/dL, normal range: <5 mg/dL), liver enzymes (AST: 230 IU/L, ALT: 131 IU/L), lipase (>400 U/L), and amylase (2122 U/L). Abdominal ultrasound showed thickened gallbladder wall with several stones and air inside the gallbladder. There were no intrahepatic or extra-hepatic dilatations. Abdominal computed tomography confirmed emphysematous cholecystitis. Moreover, Atlanta classification grade C acute pancreatitis was also detected. Wedge shape poor enhancement was noted over liver S5 and S8, thrombosis was seen in the right anterior branch of portal vein, which was consistent with pylephlebitis. The patient received broad-spectrum antibiotic treatment and percutaneous transhepatic gallbladder drainage (PTGBD) was performed on the first day of admission for her septic condition.

Rapid progression of sepsis with further conscious deterioration was encountered on the second day, thus she was intubated and transferred to surgical intensive care unit. Further blood and bile culture yield Escherichia coli and Enterococcus faecalis growths. Her condition gradually became stable and extubation was arranged on day 6, after her consciousness was fully recovered, she was transferred to the general ward on the next day. Antibiotics was continued for 14 days and conservative treatment was chosen for pancreatitis.

Cholecystectomy was suggested but patient refused due to personal reasons. She was discharged on day 14 after admission with PTGBD indwelled.

Fistulography via PTGBD was performed 2 weeks later after discharge, cholelithiasis remained with no evidence of choledocholithiasis, the drainage was then removed. The patient remained stable in the 3 months follow-up period.

Results: Emphysematous cholecystitis (EC) is defined as the inflammation of the gallbladder (GB), with the presence of air in the wall or lumen or adjacent to it without communication between the gallbladder and the hollow viscus, along with organ dysfunction. Among all forms of acute cholecystitis, emphysematous cholecystits (EC) is one of the most life-threatening one, which lead to mortality rate high as 25%. Two major theories on the pathophysiology of EC formation were

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proposed in the past literature. One suggested that hypoperfusion in a critically-ill patient leads to gallbladder ischemia and flourishment of gasforming organisms. On the other hand, obstruction of the cystic duct could also lead to EC. The most common pathogens isolated from bile cultures in those with EC were E. coli (40%), Bacteroides (30%), Clostridium species (25%), along with other organisms like P. vulgaris, A. aerogenes, Klebsiella, Streptococcus, Staphylococcus, and Enterococcus (40%). EC predominantly affects elder men and occurs frequently in diabetic patients. Necrotizing pancreatitis (NP) is a serious condition affecting the pancreas with possible grave prognosis. The combination of EC and NP would be expected in critically ill patients in the ICU setting with sepsis and systemic hypoperfusion without evidence of gallstones. Other possibility was gallstone pancreatitis. Although ultrasound is highly sensitive and specific for identifying gallbladder disease and pancreatic lesion, there is still a possibility of a poor examination window due to air interference. Therefore, CT scan might be the best diagnostic tool of choice for EC and NP, which could detect the exact location of air and also associate complications. On the other hand, pylephlebitis can complicate any intraabdominal or pelvic infection that occurs in the region drained by the portal venous system, especially in diverticulitis and appendicitis. It was also shown to be associated with cholangitis/cholecystitis or inflammatory bowel disease, pancreatitis, and hemorrhoidal banding. Diagnosis is based on CT images showing portal vein thrombosis (pylethrombosis) and accompanied by bacteremia (23 to 88%) in a febrile patient. The treatment of emphysematous cholecystitis is cholecystectomy, either conventional or laparoscopic. Percutaneous drainage of the gallbladder along with antibiotics may be an alternative treatment for those with multiple comorbidities, especially in the elderlies, who are not feasible for carrying out surgery.

Constitute major treatment approach of NP and pylephlebitis were resuscitation properly and antibiotics.

Conclusions: Emphysematous cholecystits (EC) is a form of acute cholecystitis which usually affects elderly men and occurs frequently in diabetic patients. EC concomitant with pylephlebitis and necrotizing pancreatitis is extremely rare and life-threatening. Early recognition and prompt treatment are crucial.

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THE CLINICAL EXPERIENCE OF ENDOSCOPIC AND PERCUTANEOUS IMPLANTATION OF SELF-EXPANDABLE METALLIC STENTS IN PATIENTS WITH BILIARY DISEASES: A SINGLECENTER EXPERIENCE IN NORTHERN TAIWAN Tze-Sian Chan1,2, Pei-Chia Liu1, Chao-Ling Cheng1, Po-Jui Huang1, Chun-Nan Chen1, Kelvin Kun-Chih Tsai1,2, Fat-moon Suk1,2, Gi-Shih Lien1,2, Min-Shung Wu1,2 Division of Gastroenterology, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan1 Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan2

內視鏡及經皮膽道自擴金屬支架在肝 膽胰疾病病人的臨床使用經驗 張智翔1,2 劉佩嘉1 鄭照霖1 黃柏瑞1 陳俊男1 蔡坤志1,2 粟發滿1,2 連吉時1,2 吳明順1,2 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1 臺北醫學大學醫學院醫學系內科學科2 Background: Malignant pancreatic and hepatobiliary diseases are frequently diagnosed at their later stages, and palliative treatment modalities have become useful to provide an improved quality of life in patients suffering from such diseases. Multiple studies have shown the efficacy of self-expandable metallic stents (SEMS) in these patients with short life expectancies due to their comorbid conditions. However, the real clinical outcomes of patients who undergone SEMS remained under-reported.

Aims: This study aims at disclosing the clinical outcome of patients who received biliary SEMS in the real world.

Methods: We have recently collected clinical data of patients who had undergone SEMS in our hospital. A retrospective review of all patients undergoing SEMS placement between June 2010 to May 2021 was performed. We aimed at presenting the clinical indications, outcomes, and

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complications related to biliary stenting, as well as possible independent variables that could predict the clinical outcome. All the patients were followed until their demise, whenever possible.

Results: We identified 28 patients (15 ladies and 13 males) whose mean age was 74 years (range, 47-93 years). Both benign and malignant diseases were found; malignant diseases included pancreatic 9 (32%), biliary 8 (29%), gallbladder 3 (11%), periampullary 3 (11%) and ovarian metastatic 1 (4%) tumors. While SEMS were deployed endoscopically-assisted with endoscopic retrograde cholangiopancreatography (ERCP) in 22 (79%) patients, 8 (21%) of them were performed percutaneously due to difficult access on ERCP. From the diseases presentations, the majority of SEMS placed were semi-covered, 20 (71%), while 4 (14%) fully-covered and 4 (14%) uncovered stents were used in the remaining patients. None of the patients had immediate complications except for one lady with asymptomatic hyperlipasemia, which resolved upon observation, and another lady with liver perforation. Most of the chronic complications were related to in-stent tumor growth, 7 (25%), stent migration, and sludge obstruction, 3 (11%) in each group. The mean hospital stay after SEMS insertion was 6.25 days (range, 1-31 days).

Twenty-three patients (82%) demised during follow-up. Five of them remained survived and the mean survival time was 842.6 days (range, 144-2076 days); interestingly, three of them got SEMS due to benign biliary diseases. Though not statistically significant, the multivariate regression analysis showed that clinical indications or causes of obstruction may determine post-SEMS hospital stay (p=0.053). Meanwhile, in this long-term follow-up study, the year of stent insertion may also determine patients’ overall survival (p=0.009), probably due to endoscopists’ skill and clinical care level.

Conclusions: SEMS remains to be an effective and safe palliative modality for patients with malignant pancreatic-hepatobiliary diseases, with acceptable clinical outcomes. Even with benign chronic biliary diseases, SEMS with long patency rates were reported.

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P.75

PERCUTANEOUS ENDOSCOPIC GASTROSTOMY PRIOR TO ESOPHAGECTOMY FOR ESOPHAGEAL CANCER – A SYSTEMATIC REVIEW AND META-ANALYSIS Hua-Chen Fang1, Musa Hassan Farah2, Chau-Ling Cheng1, Fat-Moon Suk1, Gi-Shih Lien1, Ming-Shun Wu1,3 Division of Gastroenterology, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan1 Department of Internal Medicine, Hargeisa Group Hospital, Hargeisa, Somalia2 Division of Gastroenterology and Hepatology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan3

食道切除術前施以經皮內視鏡胃造廔 術 ─ 系統文獻回顧及統合分析 方華珍1 Musa Hassan Farah2 鄭照霖1 粟發滿1 連吉時1 吳明順1,3 臺北市立萬芳醫院消化系內科1 Department of Internal Medicine, Hargeisa Group Hospital, Hargeisa, Somalia2 臺北醫學大學醫學院醫學系消化內科3 Background: For resectable esophageal cancer, it remains controversial whether to place percutaneous endoscopic gastrostomy (PEG) before the curative surgery to provide nutritional support during the neoadjuvant therapy.

Aims: This study is to compare surgical outcomes for patients who received preoperative percutaneous endoscopic gastrostomy (PEG) and those without percutaneous endoscopic gastrostomy placement (No-PEG) insertion prior to surgery in a potentially operable esophageal cancer.

Methods: A comprehensive literature search was conducted using (PubMed, Cochrane, EMBASE and Scopus) from 1980 to 2019 to identify randomized and non-randomized studies comparing PEG and No-PEG groups. A systematic review and meta-analysis were then performed.

Review Manager 5.3 software and Comprehensive Meta-Analysis, version 2.0 was used for statistical

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analysis.

Results: Four retrospective studies with a total number of 1,027 patients were identified and included in this meta-analysis. 152 cases had undergone percutaneous endoscopic gastrostomy (PEG) prior to surgery and 875 had not. The differences in anastomotic leakage (OR = 1.12; 95% CI = 0.60–2.08; P = 0.73), anastomotic stricture (OR = 0.70; 95% CI = 0.31-1.55; P = 0.38) , morbidity (OR = 1.12; 95% CI = 0.44-2.84; P = 0.82), mortality (OR = 1.02; 95% CI = 0.20–5.27; P = 0.98), pulmonary complications (OR = 0.44; 95% CI = 0.17–1.19; P = 0.11), wound infection (OR = 1.03; 95% CI = 0.38-2.79; P = 0.96), hospital stay (SMD, 0.12; 95% CI = -0.207 to 0.447; P = 0.472) were not statistically significant between the two groups. Operation time was significantly shorter in the PEG group (SMD, 0.391; 95% CI = 0.0630.720; P = 0.020). There was no PEG-related gastric conduit failure and no leak from the PEG site in the PEG group.

Conclusions: We conclude preoperative PEG for resectable esophageal cancer is a safe procedure with no adverse effect on the gastric tube construction and anastomosis, it can be selectively inserted for EC patients with marked weight loss and malnutrition or those at risk of developing malnutrition during neoadjuvant therapy.

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VEDOLIZUMAB THERAPY IN PATIENTS WITH INFLAMMATORY BOWEL DISEASE, FROM REALWORLD EXPERIENCE IN SOUTH TAIWAN Yu-Chieh Tsai, Chih-Chien Yao, Lung-Sheng Lu, Yeh-Pin Chou, Ming-Luen Hu, Chih-Ming Liang, Shih-Cheng Yang, Yi-Chun Chiu, Keng-Liang Wu, Wei-Chen Tai, Seng-Kee Chuah Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan

Vedolizumab 治療發炎性腸病患者， 來自南台灣的真實世界經驗 蔡雨潔 姚志謙 盧龍生 周業彬 胡銘倫 梁志明 楊世正 邱逸群 吳耿良 戴維震 蔡成枝 高雄長庚紀念醫院肝膽腸胃科 Background: Vedolizumab (VDZ) is an antiintegrin monoclonal antibody effective in inflammatory bowel disease (IBD). Several realworld experience studies have been published for the efficacy of VDZ in treatment of Crohn’s disease (CD) and ulcerative colitis (UC) to date.

Aims: This study aimed to share our real-life experience with VDZ in south Taiwan.

Methods: In this retrospective analysis, adult IBD patients who received a new biologics therapy with VDZ were included. Clinical response was access at week 10 (post 3 induction doses of VDZ), Week 30 (post 6 doses VDZ) and week 46 (post 8 doses of VDZ). Clinical remission defined as activity index (CDAI) ≤150 points in CD patients and Mayo clinic score ≤2 or partial Mayo score ≤1 points in UC patients. We also evaluated the relapse rate after discontinuation of VDZ. Results: A total of 16 patients were included (6 CD patients with mean age of 43 years and 10 UC patients with mean age of 55.5 years) and 56% were male. The disease activity at baseline was median CDAI 325 (300-367) in CD and median Mayo Clinic score 11 (10-12) in UC. The bio-naïve/ bio-experienced anti-TNF-α was 17% in CD and 30% in UC. The clinical remission of induction

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therapy at Week 10 were achieved in 33% of CD and 10% of UC. About the efficacy of maintenance therapy, clinical remission was achieved in 60%/100% of CD patients and 37.5%/42.9% of UC patients at week 30 and week 46, respectively.

The steroid free remission rate was 60% in CD patients and 42.9% of UC patients at week 46. No patients had severe adverse events or withdraw during VDZ treatment. Disease relapse were observed in 2 CD patients (one at 3 months and one at 10 patients post VDZ therapy discontinued) and 1 UC patients (at 6 months post VDZ therapy discontinued).

Conclusions: VDZ is effective in both CD and UC seemed have favorable safety in clinical practice. However, disease flare up after VDZ discontinuation is still a problem need to concern.

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TO EVALUATE THE EFFICACY AND SAFETY OF ENDOSCOPIC ULTRASOUND-GUIDED PLACEMENT OF HOT AXIOS STENT FOR TREATMENT OF CHRONIC PANCREATIC FLUID COLLECTIONS – EXPERIENCES OF A TERTIARY CENTER IN NORTHERN TAIWAN Kuan-Chih Chen1, Kuo-Hsin Chen2, Cheng-Kuan Lin1, Hsiu-Po Wang3, Chen-Shuan Chung1 Department of Internal Medicine, Far Eastern Memorial Hospital, New Taipei City, Taiwan1 Department of Surgeon, Far Eastern Memorial Hospital, New Taipei City, Taiwan2 Department of Internal Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan3

探討內視鏡超音波導引阿克西奧斯支 架（Hot AXIOS Stent）置放治療胰臟 假性囊腫及胰臟壞死積液的療效及安 全性 ─ 台灣北部單一醫學中心經驗 陳冠至1 陳國鋅2 林政寬1 王秀伯3 鍾承軒1 亞東紀念醫院內科1 亞東紀念醫院外科2 台大醫院內科3 Background: Chronic pancreatic fluid collections (PFCs) including pancreatic pseudocysts (PP) and walled-off pancreatic necrosis (WON) are conventionally treated with surgery or percutaneous drainage. However, surgical intervention may have potentially higher morbidity/ mortality and percutaneous drainage may have higher re-intervention procedures and risk of infection/ fistula formation. Nowadays, with the advancement in endoscopic ultrasound (EUS) technique and the introduction of lumen-apposing metal stent (LAMS), PFCs can be treated by EUS-guided LAMS with placement in one-step procedure.

Aims: We aimed to demonstrate the efficacy and safety of EUS-guided LAMS placement for chronic PFCs. Methods: This retrospective study was conducted by medical chart review for the patients diagnosed of chronic PFCs who received EUS-guided LAMS

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at Far Eastern Memorial Hospital from January 2019 to July 2021. Effectiveness outcome measurements included technical and clinical success rates, procedure time, successful stent removal rate, and indwelling time. Safety outcome measurements included procedure and/or stentrelated adverse events (AEs).

Results: A total of 6 (4 females and 2 males) patients were enrolled. Five (83%) patients were WON and one (17%) was PP case. HotAxios stent (Boston Scientific, Natick MA, USA) with lumen diameter 15 mm with transgastric route were used in all cases. The mean age (± SD) was 63.7 (± 14.6) years old. The mean size of WON and PP was 13.0 (± 5.8) cm. The technical and clinical success rate was 100% (6/6) and 86.7% (5/6), respectively. The patient with clinical failure was due to multi-lobulated WON formation which needed further surgical intervention to control infection. The mean procedural time from needle puncture to stent deployment was 2.2 (± 0.6) minutes. The mean number of direct endoscopic necrosectomy was 5.6 (± 2.9) times. The mean indwelling time was 31.5 (± 14.1) days. All stents were successfully removed. No procedure-related AEs were noted however one stent-related delay bleeding in one patient with chronic kidney disease under aspirin usage was noted with eventually spontaneous resolution.

Conclusions: This study showed that EUSguided placement of LAMS with HotAxios stent is technically feasible and effective for treatment of chronic PFCs.

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PRE-ENDOSCOPIC COVID-19 SCREENING FOR OUTPATIENTS RECEIVING PANENDOSCOPY DURING A COVID-19 EPIDEMIC IN TAIWAN (PES COVID-19 SURVEY) Chih-An Shih1,11, Deng-Chyang Wu2,11, Seng-Kee Chuah3,11, Kuan-Yang Chen4,11, Chia-Long Lee5,11, Yu-Hwa Liu6,11, Chien-Lin Chen7,11, Jyh-Chin Yang8,11, Sz-Iuan Shiu9,11, Ping-I Hsu10,11 Division of Gastroenterology and Hepatology, Department of Internal Medicine, Antai Medical Care Corporation, Antai Tian-Sheng Memorial Hospital, Pingtung, Taiwan1 Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan2 Division of Hepatogastroenterology, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan3 Division of Gastroenterology and Hepatology, Department of Internal Medicine Taipei City Hospital, Renai Branch, Taipei, Taiwan4 Division of Gastroenterology and Hepatology, Department of Internal Medicine Cathay General Hospital, Taipei, Taiwan5 Division of Gastroenterology, Department of Internal Medicine Shin Kong Wu Huo-Shih Memorial Hospital, Taipei, Taiwan6 Division of Gastroenterology and Hepatology, Department of Internal Medicine, Hualien Tzu Chi Hospital, Hualien, Taiwan7 Division of Gastroenterology, Department of Internal Medicine, Hospital and College of Medicine, National Taiwan University, Taipei, Taiwan8 Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan9 Division of Gastroenterology, Department of Medicine, Tainan Municipal An Nan Hospital and China Medical University, Tainan, Taiwan10 Taiwan Acid-related Disease & Microbiota (TARD-M) Consortium11

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台灣新冠肺炎流行期間之門診內視鏡 檢查前病患 COVID-19 篩檢調查 石志安1,11 吳登強2,11 蔡成枝3,11 陳冠仰4,11 李嘉龍5,11 劉玉華6,11 陳健麟7,11 楊智欽8,11 許斯淵9,11 許秉毅10,11 安泰醫療社團法人安泰醫院內科部胃腸肝膽科1 高雄醫學大學附設醫院內科部胃腸內科2 高雄長庚紀念醫院胃腸肝膽科3 臺北市立聯合醫院仁愛院區消化內科4 國泰綜合醫院內科部腸胃內科5 新光吳火獅紀念醫院內科部胃腸肝膽科6 花蓮慈濟醫院內科部肝膽胃腸科7 國立臺灣大學醫學院附設醫院內科部胃腸肝膽科8 臺中榮民總醫院內科部胃腸肝膽科9 臺南市立安南醫院暨中國醫藥大學消化內科10 台灣胃酸相關疾病暨微菌叢聯盟11 Background: The possible ways of COVID-19 transmission can occur in endoscopy suite include person-to-person via direct contact, as endoscopy involves close contact with patients or respiratory droplets, generation of infected aerosols during endoscopy, and through contact with contaminated equipments and accessories.

Aims: To investigate (1) the pre-endoscopic COVID-19 screening methods for outpatients receiving panendoscopy during a COVID-19 epidemic in Taiwan, and (2) the parts responsible for the payment of pre-endoscopic screening fees.

Methods: This was a cross-sectional survey using a self-administered questionnaire. From June 7 to 30, 2021, questionnaire was distributed to the gastroenterologists in medical centers and regional hospitals who provided endoscopic service in Taiwan. The questionnaire contained eight questions focusing on the pre-endoscopic COVID-19 screening methods for outpatients receiving panendoscopy from June 1 to 14, 2021, and the parts responsible for the payment of screening fees.

Results: A total of 19 physicians from different medical centers and 40 physicians from different regional hospitals participated in this survey.

The proportions of pre-endoscopic screening

by Travel-Occupation-Contact-Cluster (TOCC) medical history only, TOCC plus rapid antigen test, TOCC plus PCR test, and TOCC plus antigen or PCR test were 22.0%, 25.4%, 35.6% and 16.9%, respectively. No significant differences in preendoscopic screening methods between medical

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centers (26.3%, 15.8%, 52.6%, and 5.3%) and regional hospitals (20.3%, 30.0%, 27.5%, and 22.5%). In the hospital applying pre-endoscopic screening for COVID-19 infection by rapid antigen test, the proportions of government, patients and hospitals responsible for the payment of screening fee were 35.5%, 61.3% and 3.2%, respectively. In the hospital applying pre-endoscopic screening for COVID-19 infection by PCR, the proportions of government, patients and hospitals responsible for the payment of screening fee were 23.8%, 61.9% and 14.3%, respectively. The expected parts responsible for the payment of screening fee of the physicians participating in the survey were 54.2%, 40.7%, and 5.1% for the government, patients and hospital, respectively.

Conclusions: TOCC history plus PCR test is the most commonly used pre-endoscopic screening method for outpatients receiving panendoscopy during the COVID-19 epidemic study period in Taiwan. There were no differences in preendoscopic screening methods between medical centers and regional hospitals.

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P.79

WATER EXCHANGE INCREASED ADVANCED ADENOMA NEOPLASIA DETECTION IN THE ASCENDING AND PROXIMAL COLON AS COMPARED TO AIR INSUFFLATION Yu-Hsi Hsieh1,2, Chih-Wei Tseng1,2, Chi-Tan Hu2,3, Felix W. Leung4 Division of Gastroenterology, Department of Internal Medicine, Dalin Tzu Chi Hospital, Tzu Chi Medical Foundation, Chiayi, Taiwan1 School of Medicine, Tzu Chi University, Hualien, Taiwan2 Division of Gastroenterology, Department of Internal Medicine, Hualien Tzu Chi Hospital, Tzu Chi Medical Foundation, Hualien, Taiwan3 David Geffen School of Medicine at UCLA, Los Angeles, CA, USA4

比較換水法和充氣法大腸鏡的進展姓 大腸種瘤發現率 ─ 四個隨機對照試驗 的整合分析 謝毓錫1,2 曾志偉1,2 胡志棠2,3 梁永亨4 大林慈濟醫院腸胃科1 慈濟大學醫學系2 花蓮慈濟醫院肝膽腸胃科3 加州大學洛杉磯分校4

procedure related outcomes, ADR and ANDR were tabulated.

Results: Both the WE and air insufflation group included 503 patients. The demographic characteristics were similar between the two groups. WE had significantly shorter withdrawal time [mean (SD), 13.0 (6.8) vs. 12.6 (8.5), P=0.017], and higher Boston Bowel Preparation Scale scores than the air insufflation group. The ratio of aspirate water volume to infused water volume at cecum (107%) indicated proper implementation of WE. The WE group had significantly higher overall ADR (46.4% vs. 54.9%, P=0.008), with the difference mainly occurring in the ascending colon (23.0% vs. 30.9%, P=0.005) than the air insufflation group. The WE group had significantly higher ANDR in the ascending (4.6% vs. 7.8%, P=0.048) and proximal (6.4% vs. 10.5%, P=0.023) colon. The overall ANDR (16.3% vs. 19.7%) was numerically higher in the WE group (P=0.189, possibly a type II error).

Conclusions: The aggregated data of 4 RCTs showed WE had significantly higher ANDR in the right colon and proximal colon as compared to air insufflation. Future studies to evaluate the impact of WE on the occurrence of interval cancers are justified.

Background: Randomized control trials (RCT) showed significant increase in adenoma detection rate (ADR) with water exchange (WE) compared with usual air or CO2 insufflation colonoscopy.

Advanced neoplasia detection (including carcinoma and advanced adenoma) rate (ANDR) is a validated surrogate marker for colorectal cancer risk (GI Endosc Clin N Am 2002;12:1).

There was limited data of the impact of WE on ANDR, probably due to the small sample sizes of RCTs. The impact of WE on ADR and ANDR in the ascending colon, where interval cancers tend to cluster (AJG 2014;109:1375), is unknown.

Aims: We test the hypothesis that WE increased ANDR by aggregating the data of 4 RCTs conducted by our group in Chiayi and Hualien, Taiwan.

Methods: Data from 4 RCTs (NCT01894191, NCT02737514, NCT01535326, and NCT01699 399) comparing WE and air insufflation were aggregated. The demographic characteristics,

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P.80

UPPER GASTROINTESTINAL ENDOSCOPY WITH AN ADDITIONAL ORAL-PHARYNX-LARYNX EXAMINATION: DISCOVERY OF NEWLY DIAGNOSED HEAD AND NECK CANCERS Chih-Wei Yang, Wei-Chen Huang, Peng-Jen Chen, Wei-Kuo Chang Division of Gastroenterology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan

常規上消化道內視鏡合併口腔咽喉檢 查以發現新診斷頭頸癌 楊志偉 黃瑋琛 陳鵬仁 張維國 國防醫學院三軍總醫院腸胃科 Background: Most head and neck cancers are diagnosed at an advanced stage and have a poor performance status. However, newly diagnosed head and neck cancers, ranged from 67% to 100% at an early potentially curable stage, have been incidentally found during regular upper gastrointestinal (GI) endoscopy.

Aims: This study aims to investigate the role of regular upper GI endoscopy to detect early stages of head and neck cancers.

Methods: From December 2015 to December 2019, 2,849 patients underwent 3,275 upper GI endoscopies with an additional oral-pharynxlarynx examination. Patients less than 20 years of age, pregnant, undergoing emergency endoscopy, and having poor laryngopharyngeal view were excluded. We investigated the presenting symptom, incidence, location, pathology, and stages of malignant neoplasms.

Results: A total of 2,849 (87%) patients successful completed the upper GI endoscopy with oralpharynx-larynx examination. The mean additional endoscopic time was 30 seconds. Endoscopic observable abnormal findings (n = 23) included 18 benign lesions and 5 malignant neoplasms. Five newly diagnosed malignant neoplasms (0.15%) were observed in 2,720 patients without history of head and neck cancer. Notably, the majority of 80% patients (n = 4) was found at an early stage (American Joint Committee on Cancer stage 0, I and II). Three patients were treated by local

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surgery or endoscopic submucosal dissection.

Conclusions: Upper GI endoscopy with oralpharynx-larynx screening requires minimal extra time. Most endoscopic observable malignant neoplasms were detected early enough for curative therapy. Endoscopy with an additional oral-pharynx-larynx examination, is therefore recommended, as a regular procedure for every patient in endoscopy units.

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P.81

RISK FACTORS FOR ESOPHAGEAL NEUROENDOCRINE TUMORS: A CASE-CONTROL STUDY Yao-Kuang Wang1,2, Chao-Hung Kuo1,2,3, Hsiu-Po Wang4, I-Chen Wu1,2, EUS and NET Working Group5 Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan1 Department of Medicine, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan2 Department of Internal Medicine, Kaohsiung Municipal Siaogang Hospital, Kaohsiung, Taiwan3 Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University, College of Medicine, Taipei, Taiwan4 The Digestive Endoscopy Society of Taiwan5

食道神經內分泌瘤之危險因子：病例 對照研究

esophagogastroduodenoscopy, and there were 8082 patients after excluding patients with other upper gastrointestinal tract tumors. Taiwan biobank is a dataset enrolled 5000 healthy subjects. By using the combining data, these 42 ENETs cases were matched to 213 controls (1:5) on age and sex.

Results: There is significantly higher proportion of alcohol drinking and cigarette smoking in patients with ENETs as compare with control, while betel nut showed no significant difference. Alcohol consumption was significantly associated with the development of ENETs and adjusted odds ratio (aOR) was 4.22 (P<0.001). A borderline significant trend for cigarette smoking was also observed (aOR=2.27, P=0.057). After stratification for drinking and smoking, we found a interaction between alcohol and cigarette; dual substance users had almost 10 times the risk to have ENETs than none users.

Conclusions: Alcohol drinking is an important risk for the development of ENETs and the risk might be higher in drinkers who also have smoking.

王耀廣1,2 郭昭宏1,2,3 王秀伯4 吳宜珍1,2 EUS and NET Working Group5 高雄醫學大學附設中和紀念醫院胃腸內科1 高雄醫學大學醫學系2 高雄市立小港醫院內科3 國立臺灣大學醫學院附設醫院內科部4 台灣消化系內視鏡醫學會5 Background: Esophageal neuroendocrine tumors (ENETs) is extremely rare and patients with ENETs have very poor prognosis. Only a few studies of ENETs have been published and the risk factors for ENETs have been scarcely covered.

Aims: In the present study, we aimed to evaluate the influence of substance use in the development of ENETs by case-control study.

Methods: Forty-two ENETs patients reported to the neuroendocrine tumor working group of Digestive Endoscopy Society of Taiwan or diagnosed in Kaohsiung Medical University Hospital (KMUH) between 2002 and 2020 were used as cases. We used two databases to match for controls, including KMUH endoscopic cohort and Taiwan biobank. Our endoscopic cohort has enrolled 8135 patients, all of whom received

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P.82

4-ACETYL-ANTROQUINONOL B IMPROVES THE SENSITIZATION OF CETUXIMAB ON BOTH KRAS MUTANT AND WILD TYPE COLORECTAL CANCER BY MODULATING THE EXPRESSION OF RAS/RAF/MIR-193A-3P SIGNALING AXIS Yi-Cheng Chu , Tung-Yao Tsai , Vijesh Kumar Yadav5,6, Yew-Min Tzeng7, Chi-Tai Yeh8,9, Ming-Yao Chen5,6 1

2,3,4

Department of Medicine, St. George’s University School of Medicine, St. George SW17 0RE, Grenada1 Department of Emergency Medicine, Taipei Medical University-Shuang Ho Hospital, New Taipei City, Taiwan2 Graduate institute of injury prevention and control, Taipei Medical University, Taipei, Taiwan3 Department of Emergency Medicine, School of Medicine, Taipei Medical University, Taipei, Taiwan4 Division of Gastroenterology and Hepatology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan5 Division of Gastroenterology and Hepatology, Department of Internal Medicine, Shuang Ho Hospital, New Taipei City, Taiwan6 Center for General Education, National Taitung University, Taitung, Taiwan7 Department of Medical Research & Education, Taipei Medical University Shuang Ho Hospital, New Taipei City, Taiwan8 Department of Medical Laboratory Science and Biotechnology, Yuanpei University of Medical Technology, Hsinchu, Taiwan9

4AAQB 透過調節 Ras/Raf/miR-193a3p 訊息路徑改善 KRAS 突變及原生型 大腸癌對爾必得舒的耐藥性 朱翊承1 蔡同堯2,3,4 魏吉士5,6 曾耀銘7 葉淇臺8,9 陳明堯5,6 聖喬治大學醫學院1 臺北醫學大學雙和醫院急重症醫學部2

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臺北醫學大學傷害防治學研究所3 臺北醫學大學附設醫院急重症醫學部4 臺北醫學大學附設醫院消化內科5 臺北醫學大學雙和醫院消化內科6 國立臺東大學通識教育中心7 臺北醫學大學雙和醫院研究部8 元培醫事科技大學醫學檢驗生物技術系9 Background: The KRAS mutation is one of the leading driver mutations in colorectal cancer (CRC), and it is usually associated with poor prognosis and drug resistance. Therapies targeting the epidermal growth factor receptor (EFGR) are widely used for end-stage CRC. However, patients with KRAS mutant genes cannot benefit from this therapy because of Ras signaling activation by KRAS mutant genes.

Antrodia cinnamomea is a unique fungus, which is exclusively found in Taiwan. It is traditionally known to have anticancer properties. In a broad spectrum of cancers, 4-acetyl-antroquinonol B (4AAQB) isolated and purified from A. cinnamomea exerts anti-proliferative effects.

Aims: Our previous study revealed the antiproliferative effect of 4-acetyl-antroquinonol B (4-AAQB) on CRC cells, but whether the drug is effective in KRAS-mutant CRC remains unknown. In this study, we specifically targeted CRC cells harboring the KRAS mutation and the results showed that KRAS-mutant CRC cells are adequately resistant to cetuximab (anti-EGFR monoclonal antibodies).

Methods: We screened CRC cell lines harboring the KRAS mutation, namely G12A, G12C, G12V and G13D, with one wild type cell line as the control; SW1463 and Caco-2 cell lines were used for further experiments. Sulforhodamine B assays, together with the clonogenicity and invasion assay, revealed that KRAS-mutant SW1463 cells were resistant to cetuximab; however, 4-AAQB treatment effectively resensitized CRC cells to cetuximab through the reduction of colony formation, invasion, and tumorsphere generation and of oncogenic KRAS signaling cascade of CRC cells. Thus, inducing cells with 4-AAQB before cetuximab therapy could resensitize KRASmutant, but not wild-type, cells to cetuximab.

Results: In silico analysis of the publicly available GEO (GSE66548) dataset of KRAS-mutated versus KRAS wild-type CRC patients confirmed that miR-193a-3p was significantly downregulated in the former compared with the latter patient

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population. Overexpression of miR-193a-3p considerably reduced the oncogenicity of both CRC cells. Furthermore, KRAS is a key target of miR193a-3p. In vivo treatment with the combination of 4-AAQB and cetuximab significantly reduced the tumor burden of a xenograft mice model through the reduction of the expression of oncogenic markers (EGFR) and p-MEK, p-ERK, and c-RAF/ p-c-RAF signaling, with the simultaneous induction of miR-193a-3p expression in the plasma.

Conclusions: Our findings provide strong evidence regarding the therapeutic effect of 4-AAQB on KRAS-mutant CRC cells. Both in vivo and in vitro, 4-AAQB significantly targets KRASmutated CRC through the induction of miR-193a3p expression, thus targeting KRAS-mutant CRC tumorigenesis. Further investigation of 4-AAQB is in progress to understand the complete mechanism and to develop 4-AAQB as a therapeutic agent.

P.83

BILIARY DRAINAGE BY SELFEXPANDABLE METAL STENT (SEMS) IS BETTER THAN PLASTIC DRAINAGE TUBE FOR PANCREATIC CANCER WITH OBSTRUCTIVE JAUNDICE AS TREATMENT OF BRIDGE TO SURGERY Chien-Jui Huang, I-Cheng Shih, Yao-Sheng Wang, Jhong-Han Wu, Jui-Wen Kang, Chiung-Yu Chen Division of Gastroenterology and Hepatobiliary, Department of Internal Medicine, National Cheng Kung University Hospital, Tainan, Taiwan

治療手術前胰臟癌合併阻塞性黃疸使 用膽道金屬支架優於塑膠引流導管 黃千睿 史易正 王堯生 吳忠翰 康瑞文 陳炯瑜 國立成功大學醫學院附設醫院胃腸肝膽科 Background: Obstructive jaundice is one of the common complications of pancreatic cancer.

Curative surgery is still the gold standard of treatment of pancreatic cancer. Bile duct drainage for obstructive jaundice as bridge to surgery may be needed in selective patient. Endoscopic retrograde biliary drainage with plastic stent (ERBD + PS), self-expandable metal stent (SEMS) by endoscopic retrograde biliary drainage (ERBD + MS) or external drainage with percutaneous transhepatic biliary drainage (PTBD) by interventional radiologist are the three common choices. However, recurrent biliary obstruction (RBO) due to stent or drainage failure may be possible and recurrent obstructive may come with acute cholangitis, jaundice, impaired liver function, need for another session of invasive intervention, re-hospitalization, and even to interfere schedule of surgery or neo-adjuvant chemotherapy.

Aims: To comparing the outcomes of drainage patency between PTBD, ERBD + PS, and ERBD + MS in patient with pancreatic cancer with obstructive jaundice before surgery.

Methods: Patients had pancreatic cancer treated by curative surgery at the end, who had initial obstructive jaundice bear biliary drainage were enrolled in National Cheng Kung University Hospital from 2015 to 2021 retrospectively. Electric

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medical records were reviewed. Characteristic of patients, stage of cancer, location of cancer, type of drainage (PTBD, ERBD + PS, ERBD + MS) were analyzed. Successful drainage patency was defined no recurrent biliary obstructive (RBO) before curative surgery. Failure of drainage was defined repeated intervention for recurrent jaundice or cholangitis due to drainage dysfunction (occlusion or migration). Time duration of follow up was set from day of drainage to successful drainage (day of operation), or failed drainage (day of RBO) Results: Total eight-four patients with 42 men and 42 women (age: 61.8 ± 10.4 years old) with pancreatic cancer underwent curative surgery were enrolled finally. Distribution of clinical stage of pancreatic cancer were stage 1 = 19% (n = 16); stage 2 = 48.8% (n = 41); stage 3 = 23.8% (n = 20); stage 4 = 8.3% (n = 7). Location of pancreatic cancer were in head (92.9%, n = 78); neck (2.4%, n = 2); body (1.2%, n = 1); and tail (3.6%, n = 3).

Successful drainage patency without RBO before curative surgery by PTBD, ERBD + PS, and ERBD + MS were 60.7% (n = 16); 51.1% (n = 23); and 90.9% (n = 10), p = 0.054. As to comparing to successful drainage patency between drainage with SEMS (MS) and without SEMS (PS and PTBD), 90.9% (n = 10) vs. 54.8% (n = 40), p = 0.025 were noted. The median stent patency time between PTBD, ERBD + PS, and ERBD +SEMS were present by median and interquartile range (IQR) as follows: 14,5 [6.25-193.0], 27.0 [13.589.5], 116.0 [98.0-217.0], p < 0.05.

Conclusions: For drainage of obstructive jaundice in pancreatic cancer before curative surgery, endoscopic retrograde biliary drainage with selfexpandable metal stent is recommended.

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P.84

HELICOBACTER ERADICATION TREATMENT MAY INCREASE RISK OF SHORT-TERM DEPRESSIVE DISORDER Hung-En Lin1,2, Chia-Fen Tsai3,4,5, Mu-Hong Chen3,4,5, Yen-Po Wang1,2,3,5, Pei-Yi Liu1,3, Ming-Chih Hou1,2,3,5, Fa-Yauh Lee2,3,4, Ching-Liang Lu1,2,3,5 Endoscopy Center for Diagnosis and Treatment, Taipei Veterans General Hospital, Taipei, Taiwan1 Division of Gastroenterology and Hepatology, Taipei Veterans General Hospital, Taipei, Taiwan2 Institute of Brain Science, National Yang Ming Chiao Tung University School of Medicine, Taipei, Taiwan3 Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan4 Faculty of Medicine, National Yang Ming Chiao Tung University School of Medicine, Taipei, Taiwan5

幽門螺旋桿菌殺菌治療可能增加短期 憂鬱疾患的風險 林弘恩1,2 蔡佳芬3,4,5 陳牧宏3,4,5 王彥博1,2,3,5 劉佩怡1,3 侯明志1,2,3,5 李發耀2,3,4 盧俊良1,2,3,5 臺北榮民總醫院內視鏡診斷暨治療中心1 臺北榮民總醫院胃腸肝膽科2 國立陽明交通大學腦科學研究所3 臺北榮民總醫院精神醫學部4 國立陽明交通大學醫學系5 Background: Chronic Helicobacter pylori infections are common in the general population and using multiple antibiotics is required for its eradication, which is associated with gut dysbiosis and may lead to depression.

Aims: We aimed to evaluate the risk of psychiatristdiagnosed depression in patients with peptic ulcer diseases receiving anti-H. pylori therapy.

Methods: Data were collected from the National Health Insurance Research Database in Taiwan on PUD patients undergoing antibiotic treatment for H. pylori infection; patients and controls were matched for age, sex, income, level of urbanization, and comorbidities.

Results: Of the 1 million beneficiaries in the

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NHIRD, we identified 7087 patients for inclusion in the eradication cohort and 7087 matched noneradication controls with PUD. Antibiotic therapy is associated with a short-term (<30 days) increase in the incidence of psychiatrist-diagnosed depressive disorder (p = 0.009, after multiple comparisons with Bonferroni correction) in the eradication cohort compared with the controls.

Conclusions: Antibiotic eradication treatment for H. pylori infection is associated with a significant short-term (less than 30 days) increase in the incidence of psychiatrist-diagnosed depressive disorder.

P.85

IN ROOM CYTOLOGICAL EVALUATION BY ENDOSONOGRAPHERS IN ENDOSCOPIC ULTRASOUNDGUIDED FINE NEEDLE BIOPSY OF SOLID PANCREATIC LESIONS Weng-Fai Wong1, Yu-Ting Kuo1, Ming-Lun Han1, Hsiu-Po Wang2 Department of Integrated Diagnostics & Therapeutics, National Taiwan University Hospital, Taipei, Taiwan1 Departments of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan2

關於胰臟腫瘤接受內視鏡超音波導引 細針切片配合內視鏡醫師現場立即細 胞學評估的準確度之研究 黃永輝1 郭雨庭1 韓明倫1 王秀伯2 台大醫院綜合診療部1 台大醫院內科部2 Background: Tissue acquisition is important to establish the diagnosis of pancreatic malignancies.

The efficacy and safety of tissue sampling via endoscopic ultrasound-guided fine need biopsy (EUS-FNB) have been proofed. However, the diagnostic yield of needle biopsy is compromised by fibrotic and necrotic areas of the tumors. Rapid on-site evaluation (ROSE) by cytologists can minimize the false-negative rate. However, they are fully occupied by their works usually.

Aims: Comparison of the interpretation accuracy of rapid on-site evaluation by endosonographers and cytologists.

Methods: It was a single-center retrospective observational study. The cases of EUS-FNB for pancreatic tumors from January 2021 to June 2021 in NTUH were included. Smears of those tissue samples were made and stained by our endosonographers right after tissue acquisition.

The interpretation results by endosonographers were compared with the formal cytological reports.

Results: 47 cases were identified during the study period. Most of the diagnosis was adenocarcinoma (60%), following by mucinous cystic lesion (12%), neuroendocrine tumor (9%), metastatic tumor

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(2%), and benign tumor (17%). The kappa value of consistency between the endosonographers and the cytologists was 0.644 (p<0.001) in determination of pancreatic malignancy. However, their agreement in sample adequacy was quite different (kappa value = 0.426, p<0.001).

Conclusions: Smear interpretation of EUS-FNB samples can be performed by endosonographers if cytologists are not available. However, more training is necessary to improve the accuracy.

P.86

COMPARING TOLERANCE OF UNSEDATED PERORAL ESOPHAGOGASTRODUODENOSCOPY USING TRADITIONAL ENDOSCOPE V.S. ULTRASLIM ENDOSCOPE IN PATIENTS WITH MALLAMPATI CLASSIFICATION I AND II: A PROSPECTIVE RANDOMIZED TRIAL Yoen-Young Chuah1, Lian-Feng Lin1, Seng-Howe Nguang1, Chih-Jung Kuo1, Yi-Chun Chan1, Chun-Feng Lin1, Lin-Suei Jhang1, Yeong Yeh Lee2,3 Division of Gastroenterology and Hepatology, Department of Internal Medicine, Ping Tung Christian Hospital, Pingtung, Taiwan1 Department of Medicine, School of Medical Sciences, Universiti Sains Malaysia, Kota Bharu, Malaysia2 GI Function and Motility Unit, Hospital Universiti Sains Malaysia, Kota Bharu, Malaysia3

使用無麻醉經口傳統內視鏡以及纖細 內視鏡於 Mallampati Classification I 以及 II 的病患的容忍度的比較：前瞻 式隨機對照試驗 蔡元榮1 林連豐1 阮盛豪1 郭志榮1 詹益群1 林群峰1 張琳遂1 Yeong Yeh Lee2,3 屏東基督教醫院內科部胃腸肝膽科1 馬來西亞理科大學醫學科學院醫學部門2 馬來西亞理科大學附設醫院胃腸功能以及動力學 研究中心3 Background: Patients with Mallampati class I and II are traditionally regarded to be easy for endotracheal intubation because of clear laryngopharyngeal view if compared to Mallampati class III and IV. Aims: We aimed to investigate the tolerance of unsedated traditional endoscope versus ultraslim endoscope in patients with Mallampati classification class I and II. Methods: Using a randomized trial design, patients with Mallampati classification I and II were assigned to either ultra-slim (US) or traditional (T)

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endoscope. EGD tolerance was prospectively assessed in three ways: 1) Gag reflex assessed by the endoscopist during procedure, 2) postprocedural patient satisfaction assessed by questionnaire and 3) the degree of change in postprocedure vital signs. Intolerance was defined based on two out of the three abovementioned criteria. Statistical significance was defined by P < 0.05. A total of 200 patients were recruited with 98 and 102 allocated to traditional endoscope group and ultra-slim endoscope group respectively from 2019 January till 2021 February at outpatient clinic.

Results: The differences in the change of vital signs, gag reflex and patient satisfaction in the US group versus T group were P=0.125, P<0.001 and P<0.001 respectively. Further sub-analyses have shown that US was more tolerable (change of vital signs, gag reflex and patient satisfaction) than T among men (P=0.135, P=0.006, P<0.001), patients with a previously satisfied endoscopic experience (P=0.002, P<0.002, P<0.021), an endoscopic duration of more than 4 mins (P=0.317, P=0.001, P<0.001) or less than 7 mins (P=0.789, P=0.006, P=0.063) .

Conclusions: Ultra-slim endoscope is preferred over traditional endoscope in un-sedated patients with Mallampati I and II especially in men, patients with a previously satisfied endoscopy experience, and endoscopic duration in the interval of 4 to 7 minutes.

P.87

TWO-TIME-PREPROCEDURE BIOPSY STRATEGY AVOID UNNECCESSARY ENDOSCOPIC PAPILLECTOMY IN PATIENTS WITH AMPULLA ADENOMA Sung-Yin Wang1, Yu-Ting Kuo1,2, Weng-Fai Wong1,2, Ming-Lun Han1,2, Chieh-Chang Chen1, Wei-Chih Liao1,2, Hsiu-Po Wang1 Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan1 Division of Endoscopy, Department of Integrated Diagnostics & Therapeutics, National Taiwan University Hospital, National Taiwan University, Taipei, Taiwan2

針對接受內視鏡胰乳頭切除術的病 患，術前施行兩次切片有助於提升壺 腹腺瘤的診斷正確率 王崧穎1 郭雨庭1,2 黃永輝1,2 韓明倫1,2 陳介章1 廖偉智1,2 王秀伯1 台大醫院內科部肝膽腸胃科1 台大醫院綜合診療部2 Background: Ampullary adenoma represents at least 95% lesion of ampulla and has malignant potential. Compared with surgical management, endoscopic papillectomy not only has comparable efficacy but also less invasive. Guideline recommends endoscopic papillectomy be an alternative to surgical treatment for selected ampullary adenoma. Therefore, the accuracy of endoscopic biopsy and histological examination before procedure is important to avoid over- or underestimation of ampullary adenoma. Whether preprocedural biopsy more than one time increases the diagnostic accuracy of subsequent endoscopic papillectomy is unclear.

Aims: We aimed to assess how two-time-biopsy strategy impacts the final diagnostic accuracy.

Methods: Patients receiving endoscopic papillectomy after confirming ampullary adenoma by endoscopic biopsy between December 2010 and April 2021 at National Taiwan University Hospital were retrospectively enrolled for analysis. The primary outcome was the diagnostic accuracy of preprocedure endoscopic biopsy

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and the secondary outcome was safety, efficacy, recurrence rate, and survival after endoscopic papillectomy.

Results: A total of 100 patients were included in this study. The median age was 65 and 50% were male. There were 33 patients received twotime-biopsy and 62 patients received one-timebiopsy before endoscopic papillectomy. No basic characteristics was different between two groups.

Preprocedure diagnostic accuracy of two-timebiopsy (92.1%) can increased 21% than onetime biopsy (70.9%). Two-time biopsies strategy showed significant lower rate of discrepancy compared to one-time biopsy strategy (Odds ratio: 0.20, P=0.012). The overall complication of endoscopic papillectomy was 22% and the most common complication was delayed bleeding (8%).

Conclusions: Two-time biopsy strategy provides better accuracy of diagnosis for ampulla adenoma before endoscopic papillectomy and can avoid unnecessary endoscopic papillectomy.

P.88

COMPARISON OF ENDOSCOPIC BILATERAL STENT-IN-STENT AND STENT-BY-STENT DEPLOYMENT FOR MALIGNANT HIGH-GRADE HILAR BILIARY STRICTURE Ming-Han Wei1,2, Shan-Chin Huang1,2, Yu-Ting Kuo2,3, Weng-Fai Wong2,3, Ming-Lun Han2,3, Chieh-Chang Chen1,2, Wei-Chih Liao1,2, Hsiu-Po Wang1,2 Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan1 Department of Internal Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan2 Division of Endoscopy, Department of Integrated Diagnostics & Therapeutics, National Taiwan University Hospital, National Taiwan University, Taipei, Taiwan3

Stent-In-Stent 及 Stent-By-Stent 膽 道支架置放對於惡性肝門膽道狹窄之 比較 魏銘漢1,2 黃上秦1,2 郭雨庭2,3 黃永輝2,3 韓明倫2,3 陳介章1,2 廖偉智1,2 王秀伯1,2 國立臺灣大學醫學院附設醫院內科部肝膽腸胃科1 國立臺灣大學醫學院內科部2 國立臺灣大學醫學院附設醫院綜合診療部內視鏡 科3 Background: Bilateral self-expanding metal stents have been shown to be effective for malignant high-grade hilar biliary stricture. The clinical differences between side-by-side (SBS) and stent-in-stent (SIS) deployment is inconclusive.

Aims: We aim to compare the efficacy and safety between the SBS and SIS deployment for the patients with high-grade hilar biliary stricture in Taiwan.

Methods: The patients with inoperable high-grade hilar biliary stricture receiving either SBS or SIS deployment at National Taiwan University Hospital between 2014 to 2020 were retrospectively enrolled. The primary outcome was the rate of adverse events, whereas secondary outcomes were technical and clinical success, reintervention, therapeutic outcomes, stent patency, and survival duration.

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Results: During a median follow-up of approximately 5 months, a total of 31 patients including 16 patients in the SIS group and 15 patients in the SBS group were evaluated.

Compared with the SBS group, the SIS group had higher overall adverse events (31.3% vs 13.3%) without significant difference (P = 0.394). The rate of stent dysfunction was also higher in the SIS group (7/16, 43.8%) compared to the SBS group (5/15, 33.3%) (P = 0.392). There were no significant differences in technical success (SBS vs. SIS, 93.8 vs. 93.3%, P = 0.962), functional success (86.7 vs. 81.3 %, P = 0.682). The procedural time was significantly shorter in the SBS group (40.5 minutes) compared with the SIS group (70.4 minutes) (P = 0.003).

Conclusions: The technical success, functional success, recurrent biliary obstruction, and adverse events of bilateral SIS and SBS deployment for malignant high-grade hilar biliary stricture may be similar. However, the procedural time was shorter in the SBS deployment.

P.89

COMPARABLE EFFICACY AND SAFETY OF ENDOSCOPIC ULTRASOUND-GUIDED FINE NEEDLE BIOPSY VERSUS PERCUTANEOUS APPROACHES FOR LEFT HEPATIC SOLID LESIONS Yi-Chung Chan1,2, Yu-Ting Kuo2,3, Weng-Fai Wong2,3, Ming-Lun Han2,3, Chieh-Chang Chen1,2, Tsu-Yao Cheng1,2, Wei-Chih Liao1,2, Hsiu-Po Wang1,2 Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan1 Department of Internal Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan2 Division of Endoscopy, Department of Integrated Diagnostics & Therapeutics, National Taiwan University Hospital, National Taiwan University, Taipei, Taiwan3

內視鏡超音波指引細針切片與經皮切 片用於肝臟左葉腫瘤的準確性和安全 性比較 詹益宗1,2 郭雨庭2,3 黃永輝2,3 韓明倫2,3 陳介章1,2 鄭祖耀1,2 廖偉智1,2 王秀伯1,2 台大醫院胃腸肝膽科1 台大醫院內科部2 台大醫院綜合診療醫學部內視鏡科3 Background: Endoscopic ultrasound-guided fine needle biopsy (EUS-FNB) sampling is a safe and effective technique for diagnosis of pancreatic lesions. However, the data are limited in its role in solid liver lesions.

Aims: In this study, we aim to compare the diagnostic accuracy and safety between EUSFNB, trans-abdominal ultrasound (US)-guided and computed tomography (CT)-guided percutaneous liver biopsy of solid liver lesions.

Methods: The patients who were underwent EUS-FNB, US-guided biopsy, or CT guided biopsy for diagnosis of solid left hepatic lesions were retrospectively enrolled and analyzed. The primary outcome was the diagnostic accuracy. The secondary outcomes were the median numbers of passes required to establish a diagnosis and

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complication rate. The baseline characteristics between the 3 groups were compared by Fisher exact test for categorical variables and by MannWhitney U test for continuous variables. Statistical analyses were performed using Stata version 14 (StataCorp, College Station, TX). All tests were 2-tailed, and differences were considered significant if P < .05.

Results: Total 246 patients with solid liver lesions receiving liver biopsy at National Taiwan University Hospital between October 2017 and April 2021 were retrospectively recruited. 89 patients underwent EUS-FNB, 92 patients underwent US-guided and 65 patients underwent CT-guided biopsy.

There were no significant differences in patient’s baseline characteristics and diagnostic accuracy between the three groups. The mean tumor size for EUS-FNB, US-guided, and CT-guided were 12 mm, 40 mm, and 50.8 mm respectively. In EUS-FNB group, the sensitivity, specificity and diagnostic accuracy for solid liver lesions were 97.6%, 100.0%, and 97.8%, respectively. In USguided and CT-guided biopsy group, sensitivity, specificity and diagnostic accuracy for solid liver lesions were 98.7%, 100.0%, 98.9% versus 98.8%, 100.0%, 99% respectively. Post-procedure complications only developed in the CT-guided biopsy group, including hematoma for 2 cases (3.1%) and infection for 3 cases (4.6%).

Conclusions: Compared to percutaneous approaches (US-guided and CT-guided liver biopsy), EUS-FNB for left hepatic solid lesions can be a safe and efficient alternative method.

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A STUDY OF ELDERLY PATIENTS UNDERGOING UPPER GASTROINTESTINAL ENDOSCOPY IN THE EMERGENCY DEPARTMENT: A REAL-WORLD EXPERIENCE IN A TERTIARY MEDICAL CENTER Kuang-Tsu Yang1, Yi-Cyun Jhuang1, Yun-Da Li1, Wei-Chih Sun1, Kung-Hung Lin1, Tzung-Jiun Tsai1, Huay-Min Wang1, Wei-Lun Tsai1,2, Feng-Woei Tsay1,2, Hsien-Chung Yu1, Wen-Chi Chen1,2 Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan1 School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan2

高齡患者在急診接受上消化道內視鏡 之研究：一家醫學中心的真實世界經驗 楊光祖1 莊逸群1 李昀達1 孫煒智1 林恭弘1 蔡騌圳1 王惠民1 蔡維倫1,2 蔡峯偉1,2 余憲忠1 陳文誌1,2 高雄榮民總醫院內科部胃腸肝膽科1 國立陽明交通大學醫學系2 Background: The number of elderly patients in Taiwan has been gradually increasing in the past decade. According to current statistics, by the end of January 2021, there will be 3.804 million elderly people (aged 65 or older) in Taiwan, reaching 16.2% of the total population. Many of these patients often seek emergency department (ED) care for upper GI symptoms and undergo upper GI endoscopy, in order to receive immediate medical assistance.

Although there have been studies of elderly patients undergoing upper GI endoscopy, there has been little discussion of the clinical outcomes and detailed endoscopic findings. Moreover, does this pattern of access create an unnecessary drain on clinical resources for ED care?

Aims: This study examined the current status of elderly patients undergoing upper GI endoscopy in the ED, and provides statistics on relevant clinical and endoscopic outcomes.

Methods: Elderly patients (older than 65 years old) who came to the ED of Kaohsiung Veterans General Hospital receiving upper gastrointestinal endoscopy from January 2016 to December 2020

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were retrospectively enrolled in this study. Their emergency-related medical values, past medical history, and medication history were recorded.

Relevant clinical and endoscopic outcomes were also investigated. Primary clinical outcomes included mortality rates, ICU admission rates, rates of angiography/vascular embolization or surgery, and prolonged ED stay rates. Secondary clinical outcomes involved general ward admission, 60-day return to ED, and return to outpatient clinic followup. Endoscopic statistics included indications, endoscopic diagnosis, hemostasis success, side effects and complications.

Results: In this study, 1121 elderly patients were enrolled (Figure 1). Table 1 showed that there were 856 elderly patients (65-84 years old) and 265 extremely-elderly patients (≥ 85 years old). In the elderly group and the extremely-elderly group, the proportion of males and the status of veterans were 56.0%/74.0% and 78.0%/34.0%, respectively.

Other physiological indices, blood sampling values, underlying diseases, and medication use are also shown in Table 1. Table 2 shows that none of the elderly patients receiving upper GI endoscopy died in the emergency department. The rate of ICU admission was less than 5%, and the rate of angiography/vascular embolization or surgery was less than 20%. Nearly 15% of patients return to the ED at 60 days and nearly half return to the outpatient clinic for follow-up. Table 3 showed that more than 90% of patients aged ≥ 65 years underwent upper GI endoscopy for the indication of suspected recent upper GI bleeding. The majority of endoscopic findings were ulcers or gastroesophageal reflux disease (GERD), and the associated side effects, including dyspnea, decreased blood oxygen concentration, and intolerability, were less than 2%.

Conclusions: Clinical results showed no deaths in these patients aged ≥ 65 years receiving upper GI endoscopy in the ED and low rates of either ICU admission or transfer to angiography/vascular embolization or surgery. The safety profile is also statistically acceptable. In addition, most of the endoscopic findings are still related to diseases caused by excess gastric acid. Notably, the tumor risk in elderly patients is important to be aware of. This study provides clinicians with a real-world approach to early screening of the upper GI tract in elderly patients for the purpose of precise medical treatment. In addition, patients with less severe GI symptoms or conditions may be considered to be treated at GI outpatient clinics, to reduce the medical crowding out effect.

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THE PROGNOSIS AND POSSIBLE OPTIMAL TREATMENT FOR SQUAMOUS CELL CARCINOMA PATIENTS INITIALLY INVOLVE TO ESOPHAGO-CARDIAC JUNCTION: A RETROSPECTIVE COHORT STUDY Ching-Hsiung Chang1, I-Chen Wu1,2, Yao-Kuang Wang1,2, Chun-Sheng Shen3, Chien-Yu Lu1,2 Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan1 Department of Medicine, Faculty of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan2 Department of Internal Medicine, Kaohsiung Municipal Siaogang Hospital, Kaohsiung, Taiwan3

初始合併胃侵犯的食道鱗狀上皮癌的 預後及可能的合適治療：一個回溯式 世代研究 張景翔1 吳宜珍1,2 王耀廣1,2 沈群勝3 盧建宇1,2 高雄醫學大學附設中和紀念醫院胃腸內科1 高雄醫學大學醫學系2 高雄市立小港醫院內科部3 Background: The prognostic values and treatment of stomach involvement in esophageal squamous cell carcinoma (ESCC) remain unclear.

Aims: This study aimed to evaluate the impacts of esophago-cardiac junction (EGJ) involvement on the survival of patients with in esophageal squamous cell carcinoma.

Methods: We performed a retrospective cohort study of all patients whose pathologyproved esophageal squamous cell carcinoma at Kaohsiung Medical University Hospital, a medical center in southern Taiwan between October 2011 and December 2020. The tumor staging and nodal classification were performed according to the AJCC TNM staging system for esophageal cancer from computed tomography imaging and esophagogastroduodenoscopy.

Nested-casecontrol study was conducted from our registry, ESCC patients with EGJ involved were selected and matched control case without EGJ involved

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was recruited by 1 to 1-3 ratio from our cohort in order to compare prognosis of survival time.

We also used Kaplan-Meier model to compare the survival curve between operative treatment and non-operative treatment in ESCC involving stomach patient and use questionnaire to evaluate quality of life between with and without operative treatment in two group.

Results: In total, 75 patents were enrolled to our study, 21 patients with ESCC had EGJ involved and 54 patients had ESCC limited to esophageal.

Kaplan-Meier analysis revealed that the survival rate was no different in two group (Crude HR: 1.63, 95% CI: 0.86-3.07, P=0.13; Adjusted HR: 1.65, 95% CI: 0.87,3.15, P=0.13). In terms of management, 12 case in EGJ arm received surgical intervention with concurrent chemoradiotherapy and 9 case only concurrent chemoradiotherapy. Kaplan-Meier analysis revealed that the survival rate was significantly lower in the nonoperative group (Crude HR: 0.25, 95% CI: 0.070.82, P=0.04; Adjusted HR: 0.18, 95% CI: 0.030.98, P=0.047). Quality of life between operation and non-operation group in two group were no significantly difference.

Conclusions: To date, the impact on EGJ involvement of ESCC outcome is yet to be clarified. The study we conducted showed that ESCC with or without EGJ involved as no different survival outcome. However, in the ESCC involved to stomach group, surgical intervention with concurrent chemo-radiotherapy showed significantly high survival rate.

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LONG-TERM EXPOSURE TO RANITIDINE AND RISK OF INFLAMMATORY BOWEL DISEASE: A POPULATION-BASED FOLLOWUP STUDY Chien-Chang Liao, Yuan-Tsung Tseng, Ruey-Chang Lin, Lein-Ray Mo Division of Gastroenterology and Hepatology, Department of Internal Medicine, Tainan Municipal Hospital (Managed by Show Chwan Medical Care Corporation), Tainan, Taiwan

長期使用雷尼替丁引起發炎性腸道疾 病的風險：以大量群眾為基礎的追蹤 研究 廖建彰 曾元聰 林瑞昌 牟聯瑞 台南市立醫院（委託秀傳醫療社團法人經營）肝 膽腸胃科 Background: N-nitrosodimethylamine (NDMA) was recently detected in ranitidine, and all such medications were recalled. Currently, there is insufficient scholarly evidence on the risk of inflammatory bowel disease from ranitidine use.

Aims: We conducted a population-based cohort study to assess whether ranitidine use is associated with an increased incidence of Crohn’s disease and ulcerative colitis.

Methods: We conducted a population-based cohort study using data obtained from the Taiwanese National Health Insurance Research Database. The study cohort included 42 741 patients 40 years or older with no history of Crohn’s disease or ulcerative colitis and who were using ranitidine for over 3 months between January 1, 2000, and December 30, 2018. Moreover, 42 741 patients who received a ranitidine prescription were randomly selected by propensity matching to the study cohort at a 1:1 ratio based on age, sex, and Charlson comorbidity index; the presence of hypertensive cardiovascular disease, diabetes mellitus, and chronic kidney disease; and the use of aspirin, statin, ACEi, β-blockers, famotidine, NSAID, spironolactone, glucocorticoids, and selective serotonin reuptake inhibitors. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using multivariate Cox proportional hazard regression analysis after competing mortality was adjusted for.

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Results: The treatment and control cohorts were followed up for the mean periods of 9.17 and 9.24 years, with a mean age of 64.9 ± 13.4 years, a 46.2% male proportion, and a mean CCI of 3.5 ± 2.5. After potential confounding factors were adjusted for, patients prescribed ranitidine had a higher risk (adjusted HR: 1.91; 95% CI: 1.63 to 2.25; P <.0001) of subsequent diagnosis of Crohn’s disease relative to the controls after the index date. Similarly, the HR for ulcerative colitis (adjusted HR: 1.98; 95% CI: 1.44 to 2.73; P < .0001) was significantly higher among patients who received ranitidine than those who did not.

Conclusions: Ranitidine use in Taiwan is associated with significantly increased risks of Crohn’s disease and ulcerative colitis in patients receiving a prescription for over 3 months.

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PREDICTIVE BIOMARKERS OF IMMUNOTHERAPY IN GASTRIC CANCERS: REAL WORLD EXPERIENCES Hung-Yuan Yu1, Ming-Huang Chen2,3, Chung-Pin Li1,4, Fen-Yau Li5, Yi-Ping Hung2, Rheun-Chuan Lee6, Yee Chao2 Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan1 Department of Oncology, Taipei Veterans General Hospital, Taipei, Taiwan2 Center for Immuno-oncology, Department of Oncology, Taipei Veterans General Hospital, Taipei, Taiwan3 Division of Clinical Skills Training, Department of Medical Education, Taipei Veterans General Hospital, Taipei, Taiwan4 Department of Pathology and Laboratory Medicine, Taipei Veterans General Hospital, Taipei, Taiwan5 Department of Radiology, Taipei Veterans General Hospital, Taipei, Taiwan6

胃癌患者接受免疫治療的預測因子探 討：真實世界經驗 于洪元1 陳明晃2,3 李重賓1,4 李芬瑤5 洪逸平2 李潤川6 趙毅2 臺北榮民總醫院內科部胃腸肝膽科1 臺北榮民總醫院腫瘤醫學部2 臺北榮民總醫院腫瘤免疫治療中心3 臺北榮民總醫院教學部臨床技能中心4 臺北榮民總醫院病理檢驗部5 臺北榮民總醫院放射線部6 Background: Immune check-point inhibitors were proved to have survival benefit in patients with gastric cancer, not only in third- or later-line treatment, but also in first-line setting. Several potential predictive biomarkers were identified recently, such as High Microsatellite Instability (MSI-H), Epstein-Barr encoding region (EBER), and programmed death ligand (PD-L1).

Aims: The purpose of this study was to explore the potential predictive values in efficacy through MSI status, EBER, and PD-L1 expression in advanced gastric adencarcinoma patients under immune checkpoint inhibitor therapy.

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Methods: Total 54 patients receiving immunotherapy in single institution were retrospectively enrolled from June, 2016 to December, 2020.

The relationship between clinical response and biomarkers were analyzed by Fisher’s exact test and survival analyses were performed with Kaplan-Meier method.

Results: There were 9 patients with MSI-H, 6 patients with EBER positive, 29 patients with PD-L1 CPS ≥ 1, and 20 patients without any biomarker. The overall response rate (ORR) in patients with MSI-H, EBER positive, PD-L1 CPS ≥ 1 were 67%, 50%, and 41%, respectively, which were numerically higher than ORR in all negative group (20%). The overall survival (OS) and progression-free survival (PFS) were 7.3 months and 3.2 months in all negative patients, respectively. Comparing to all negative group, the OS and PFS were not reached in MSI-H group (p = 0.16 and 0.04, respectively); 7.5 months and 5.6 months in EBER positive group (p = 0.43 and 0.10, respectively); 7.5 months and 2.4 months in CPS ≥ 1 group (p = 0.30 and 0.31, respectively). The ORR in patients with CPS ≥1, ≥5 and ≥10 were 41%, 56% and 67%, respectively. Median OS and PFS were 7.5 months and 2.4 months in patients with CPS ≥1 and both OS and PFS were not reached in patients with CPS ≥5 and ≥10. The median PFS were longer in patients with CPS ≥ 5 (not reached versus 2.6 months, p = 0.011) and CPS ≥ 10 (not reached versus 2.6 months, p = 0.005).

Conclusions: MSI-H, EBER and PD-L1 CPS were useful biomarkers to predict the efficacy of immunotherapy, with better ORR, and the tendency of longer OS and PFS.

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THE STUDY OF CARDIAC EVENTS AFTER USING ANTIHELICOBACTER PYLORI REGIMEN WITH CLARITHROMYCIN IN THE PATIENTS WITH CORONARY ARTERY DISEASE Cheng-Kuan Lin, Cheng-Lu Lin, Tzong-Hsi Lee Division of Gastroenterology and Hepatology, Department of Internal Medicine, Far Eastern Memorial Hospital, New Taipei City, Taiwan

冠狀動脈疾病病人使用 Clarithromycin 配方治療胃幽門桿菌後之心臟安全性 研究 林政寬 林政錄 李宗熙 亞東紀念醫院內科部肝膽胃腸科 Background: The patients with ischemic heart diseases are predisposing to have peptic ulcer bleeding and need anti-Helicobacter pylori regimen. Clarithromycin forms part of antibiotic regimens against Helicobacter pylori. In 2018, the U.S. and Taiwan Food and Drug Administration was advising caution before prescribing the clarithromycin to patients with heart disease because of a potential increased risk of cardiac events or death that can occur. Therefore, the safety issue of using clarithromycin for antiHelicobacter pylori infection in the patients with coronary artery disease needs further studied.

Aims: We aim to investigate the cardiovascular events between after using clarithromycin and non-clarithromycin-based anti-Helicobacter pylori regimen in the patients with coronary artery diseases and analysis of the risk factors.

Methods: A hospital-based retrospective chart review was conducted on the subjects with coronary artery disease who underwent anti-Helicobacter pyloric therapy at Far Eastern Memorial Hospital from January 2013 to December 2017.

Results: Totally 7884 patients received antiHelicobacter pylori therapy in five-year period. In 228 patients with angiographic proved coronary artery diseases and received 243 courses of antiHelicobacter regimens. The age was 67 ± 9.8 year-old (range: 32-88) and the male patient was predominant (73.7%). There were 193 patients using clarithromycin-based regimen, 35 patients

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using non-clarithromycin-based regimen. The major cardiac event (such as unstable angina, myocardial infarction) developed within 3 months was increasing in using clarithromycin group, but not statistically significant (4.15% versus 0%, p=0.22). The event within one year was also increasing, but also not statistically significant (8.29% versus 5.71%, p=0.603). Neither lifethreating dysrhythmia nor cardiac death was noted after anti-Helicobacter therapy. Analysis of the risk factors of cardiac events within 3 months after using clarithromycin-based regimen were smoking (OR: 6.7, 95% CI: 1.5-29.2, p=0.004) and using esomeprazole (OR: 5.3, 95% CI: 1-26.9, p=0.027); within one year were smoking (OR: 4.2, 95% CI: 1.5-12, p=0.004) and diabetes mellitus (OR: 3.7, 95% CI: 1.2-12, p=0.02).

Conclusions: There was no significant association between clarithromycin use for anti-Helicobacter pylori and subsequent cardiac events in the patients with coronary artery disease.

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EFFICACY AND SAFETY OF ENDOSCOPIC ULTRASOUNDGUIDED GASTROENTEROSTOMY WITH A LUMEN-APPOSING METAL STENT: TAIWAN MULTICENTER EXPERIENCE Yu-Ting Kuo1,2, Jiann-Hwa Chen3,4, Szu-Chia Liao5, Jung-Chun Lin6, Cheuk-Kay Sun7, Hsiu-Po Wang1,2 Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan1 Division of Endoscopy, Department of Integrated Diagnostics & Therapeutics, National Taiwan University Hospital, National Taiwan University, Taipei, Taiwan2 Department of Gastroenterology and Hepatology, Taipei Tzuchi Hospital, Taipei, Taiwan3 School of Medicine, Tzuchi University, Hualien, Taiwan4 Division of Gastroenterology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan5 Division of Gastroenterology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan6 Division of Hepatology and Gastroenterology, Department of Internal Medicine, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan7

內視鏡超音波導引下胃腸造口術使用 雙蘑菇頭金屬支架的台灣多中心經驗 郭雨庭1,2 陳建華3,4 廖思嘉5 林榮鈞6 孫灼基7 王秀伯1,2 台大醫院消化內科1 台大醫院綜合診療部內視鏡科2 台北慈濟醫院消化內科3 花蓮慈濟大學醫學系4 臺中榮民總醫院消化內科5 三軍總醫院消化內科6 新光吳火獅紀念醫院消化內科7 Background: The advent of lumen apposing metal stents (LAMS) has revolutionized the management of many complex gastroenterological

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conditions that previously required surgical or radiological interventions. As such, EUS-guided gastroenterostomy (EUS-GE) has emerged as an attractive procedure to treat patients with gastric outlet obstruction as an alternative to surgery and enteral self-expanding metal stents.

Aims: We aimed to assess clinical outcomes of EUS-GE with LAMS for the management of gastrointestinal obstruction in Taiwan.

Methods: Patients who underwent EUS-GE between July 2020 and July 2021 as part of a prospective multicenter registry at five academic centers in Taiwan were included. Technical success was defined as successful placement of a gastroenteral LAMS. Clinical success was defined as the ability of the patient to tolerate an oral diet or clinical symptom relief. Post-procedural adverse events were recorded.

Results: The study included 24 patients, of whom 13 (54.2%) were male. 23 patients (95.8%) receiving EUS-GE for the palliation of malignant gastric outlet obstruction and the remaining one patient (4.2%) for the relief of afferent loop syndrome. The mean procedural time was 52 minutes. Technical and clinical success was achieved in 24 patients (100%). During a mean follow-up of approximately 3 months, no any patient had stent dysfunction.

Only one patient (4.2%) had adverse event (jejunal ulcer at the margin of LAMS) occurred about one month after procedure.

Conclusions: EUS-GE is an emerging and minimally invasive procedure that has efficacy and safety comparable with those of current therapies for the management of gastrointestinal obstruction.

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