2020 TDDW Abstract Book

台灣消化醫學週

D a t e : September 26th (Sat) ~ 27th (Sun), 2020 Venue : National Taiwan University Hospital International Convention Center

2020 Taiwan Digestive Disease Week, TDDW Abstract Book INDEX Chairman’s Lecture ...............................................................................................1 Keynote Lecture (I) (II)

The 50th Anniversary of the Gastroenterological Society of Taiwan (GEST): The Growth, Progress and Contribution ...............................................................2 Development of Next Generation Beneficial Bacteria and Health: Focus on Cardiometabolic Disorders ....................................................................4

Special Lecture (III) (IV) (V) (VI)

FMT: Gap between Research and Clinical Practice..............................................5 Living Legend of the Surgeon Mastering Cholangiocarcinoma ............................6 Adenosine Controls Colonic Dysbiosis that Transmits Susceptibility to Colitis .....7 Updates in Functional Dyspepsia .........................................................................8

Symposium (I) (II) (III) (IV) (V) (VI) (VII) (VIII) (IX) (X) (XI)

Screening and Eradication of H. pylori for Gastric Cancer Prevention .................9 Endoscopy in Chronic Liver Diseases Patients ..................................................13 Controversies and Unmet Needs for Long-term Benefit of HBV Therapies........17 IBD Update Symposium......................................................................................20 Tradition and Innovation of Management of Cholangiocarcinoma......................24 New and Alternative Treatment for FGID ............................................................27 Colorectal Cancer Screening on the Cross Road ...............................................31 Advance in Systemic Treatment for HCC ...........................................................35 Cutting Edges of Multidisciplinary Management of Pancreatic Cancer ..............38 Bariatric and Metabolic Endoscopy: How and When? ........................................42 Multi-centered Clinical Trials, Examples of HBV and Helicobacter pylori Infection ..............................................................................................................46 (XII) NAFLD/NASH Symposium .................................................................................50 (XIII) GEST-KASID Symposium – Big Debate on Controversy in Colonoscopy Practice ...............................................................................................................55 (XIV) HIPEC and Conversion Surgery for Gastric Cancer ...........................................63

Young Investigator Award (YIA) ..................................................................66 Free Paper (I) (II) (III) (IV) (V) (VI)

HCV ....................................................................................................................74 LGI ......................................................................................................................80 HBV.....................................................................................................................85 Pancreas / Biliary ................................................................................................90 Cirrhosis & HCC..................................................................................................95 UGI....................................................................................................................100

Poster Liver ............................................................................................................................106 GI ................................................................................................................................171

2020 TDDW

Chairman’s Lecture CIRRHOTIC PORTAL HYPERTENSION: PATHOPHYSIOLOGY, ASSESSMENT, AND CLINICAL IMPLICATIONS Han-Chieh Lin Division of Gastroenterology and Hepatology, Taipei Veterans General Hospital, Taipei, Taiwan National Yang-Ming University School of Medicine, Taipei, Taiwan Portal hypertension is a major complication of cirrhosis and is associated with serious clinical consequences. Increased intrahepatic resistance is the initial phenomenon of cirrhotic portal hypertension. Cumulated evidences have documented that portal hypertension leads to a hyperdynamic splanchnic circulation. On the other hand, cirrhosis is associated with endotoxemia that resulted from intestinal bacterial translocation.

It triggers the endotoxin-TNFα-TLR4 signaling and initiates a cascade of inflammatory responses in a variety of organs. These inflammatory responses may exacerbate the pre-existed portal hypertension. It is now recognized that cirrhotic

portal hypertension can be regarded as a systemic inflammatory multi-organ syndrome. During clinical practice, measurement of HVPG is the gold standard in assessing the degree of cirrhotic portal hypertension. It is now well established that reduction of HVPG, such as the use of nonselective beta-blockers, can provide beneficial effects to cirrhotic patients. However, hepatic vein catheterization is still an invasive procedure, and many investigators have tried to search for non-invasive methods to assess portal pressure.

Current studies have suggested that elastography and MR images have potential to provide a noninvasive assessment of portal hypertension.

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2020 TDDW

Keynote Lecture (I) THE 50TH ANNIVERSARY OF THE GASTROENTEROLOGICAL SOCIETY OF TAIWAN (GEST): THE GROWTH, PROGRESS AND CONTRIBUTION Jaw-Town Lin Superintendent, Digestive Medicine Center, China Medical University Hospital Professor Emeritus, National Taiwan University Honorary President, The Gastroenterological Society of Taiwan (GEST) Honorary President, The Digestive Endoscopy Society of Taiwan (DEST)

The story Professor Juei-Low Sung and Taiwanese colleagues joined the Asia-Pacific Branch of the World Association of Gastroenterology (AOGA) and became a founding member in Tokyo, 1961.

In 1966, we became a member of the World Association of Gastroenterology (OMGE) under the name of [Group of Gastroenterologists in Republic of China] in Tokyo. Then the Gastroenterological Society of Republic of China (ROC) was founded in Taipei on March 15, 1970 with 165 members.

The title of “Gastroenterological Society of Republic of China” was re-named as “The Gastroenterological Society of Taiwan” in 1992, and then as “Chinese Taiwan Gastroenterological Society” in 1998 under the request of the World Gastroenterological Society. The name “The Chinese Taiwan Society of Gastroenterology” was removed from its World Society of Gastroenterology (WGO) website in July 2013.

After a lot of negotiation and debate, we have been listed again in the website of WGO as our old but honorable name of the “Gastroenterological Society of Taiwan (GEST)” in 2016.

The presidents and their contributions Professor Juei-Low Sung was the first to the seventh President of Gastroenterological Society of Republic of China (1970-1991). Professor TehHong Wang was the Secretary-General during 2

this period. The first volume of “Transaction of the Gastroenterological Society of Republic of China” was published in March 1972. In January 1984, the first issue of the “Chinese Journal of Gastroenterology” quarterly was issued On March 23, 1974, the “International Symposium on Hepatitis” was added to the annual meeting of our society. The “3rd Asia Pacific Society of Digestive Endoscopy (APCDE)” was held in Taipei on September 25-27, 1980. The “First International Symposium on Viral Hepatitis and Hepatocellular Carcinoma” was held in 1986. Since 1988, the annual academic speech conference has been held twice a year, the spring conference in March (presented in Mandarin) and the fall conference in September presented in English).

Professor Teh-Hong Wang was elected as the eighth President (1991-1994) and Professor PeiMing Yang was the Secretary-General. Professor Pao-Huei Chen was the ninth President (19941997) and Professor Jean-Dean Liu was the Secretary-General. The journal was re-named: “Chinese Journal of Gastroenterology”, jointly published by the Digestive Endoscopy of Taiwan (DEST). Professor Ding-Shinn Chen was the tenth and the eleventh President (1997-2000, 2000-2003) and Professor Pei-Ming Yang was the Secretary-General. The 13th Conference of the Asian Pacific Association for the Study of the Liver (APASL 2002) was held in 2002.

2020 TDDW Professor Ming-Yang Lai was the 12th President (2003-2006) and Doctor Jyh-Chin Yang was the Secretary-General. The institute’s website is initially completed and online (URL: www.gest.org. tw) “National Health Insurance strengthening the pilot program for treatment of chronic hepatitis B and C” was launched. Professor Cheng-Shyong Wu was the 13th and 14th President (2006-2009, 2009-2012) and Professor Chun-Yen Lin was the Secretary-General. Asia Pacific Digestive Week 2009 (APDW 2009) was hosted by GEST at Taipei in 2009. In 2011, a pilot Taiwan Digestive Disease Week (TDDW) was held. The 22nd Conference of the Asian Pacific Association for the Study of the Liver (APASL 2012) was held in Taipei, 2012.

Professor Jaw-Town Lin was the 15th and 16th President (2012-2015, 2015-2018) and Professor Chun-Jen Liu was the Secretary-General. WGO Train the Trainer 2015 (TTT 2015) was held at on April 12-16, 2015. The Asia Pacific Digestive Week 2015 (APDW 2015) was hosted by GEST and held at Taipei on December 3-6, 2015. Expand

the organization of Taiwan Digestive Disease Week (TDDW) and participate in the expansion of the society to 10 digestive-related societies.

“Gastroenterological Journal of Taiwan” was renamed “Advances in Digestive Medicine”. In December 2016, the “Hepatitis C Prevention and Treatment Group of Gastroenterological Society of Taiwan (GEST)” was established. APASL (Single Topic Conference on Hepatitis C) will be held at the Kaohsiung Exhibition Center on June 10-12, 2016. The 1st Joint Session between JDDW & KDDW & TDDW was held in Japan for the first time in October 2017. Professor Ming-Shiang Wu is currently the 17th President (2018-2021) and Professor Han-Mo Chiu is the Secretary-General.

APASAL STC – Toward hepatitis B elimination was held at Taipei International Convention Center on June 22-24, 2018. The Three-Country Association of Digestive Medicine-hosted by JDDW of Japan (Kobe) in 2017, hosted by KDDW of South Korea (Seoul) in 2018, and hosted by TDDW of Taiwan (Taipei) in 2019.

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2020 TDDW

Keynote Lecture (II) DEVELOPMENT OF NEXT GENERATION BENEFICIAL BACTERIA AND HEALTH: FOCUS ON CARDIOMETABOLIC DISORDERS Patrice Cani UCLouvain, Université Catholique de Louvain, Louvain Drug Research Institute, WELBIO - Walloon Excellence in Life Sciences and BIOtechnology, Metabolism and Nutrition Research Group, Brussels, Belgium We and others have contributed to the discovery that gut microbes may be involved in the onset of metabolic inflammation, fat mass development and energy homeostasis via several mechanisms.

In 2007, by using metagenomics approaches we discovered that prebiotic feeding increased the abundance of a newly identified bacteria, namely Akkermansia muciniphila. We found that treating mice with this specific bacterium improved insulin sensitivity, metabolic endotoxemia, gut barrier, reduced fat mass and appetite via mechanisms involving the innate immunity and bioactive lipids production (e.g., endocannabinoids).

Besides the numerous correlations observed in humans between the abundance of this bacterium and health, a large number of studies have demonstrated a causal link between the administration of Akkermansia and the improvement of health in rodents.

Therefore, we decided to attempt to translate these exciting observations to humans. In 2019, we have completed the analysis of the first randomized

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double-blind placebo controlled exploratory study during which we have administered daily live or pasteurized Akkermansia for 3 months. We found that Akkermansia was safe and induced beneficial effects on cardiometabolic risk factors.

Besides this next generation beneficial bacterium, we have isolated a novel bug (new genus/strain/species) from a healthy human stool.

This bacterium seems to be widely present in the human gut and its administration to rodents was associated with a reduction of food intake, glucose intolerance, low-grade inflammation and obesity in high-fat fed mice (unpublished).

In conclusion, although not all the gut microbes are directly linked with the regulation of host metabolism, numerous bacteria have still not been identified or cultured. Hence, one may predict that the gut is still the “home” for several putative next generation beneficial microbes that will be progressively discovered and then possibly be used to improve human health together with nutritional and classical methods.

2020 TDDW

Special Lecture (III) FMT: GAP BETWEEN RESEARCH AND CLINICAL PRACTICE Siew C. Ng Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese Univetsity of Hong Kong, Hong Kong Faecal microbiota transplantation (FMT) is an important therapeutic option for Clostridioides difficile infection. Promising findings suggest that FMT may play a role also in the management of other disorders associated with the alteration of gut microbiota. Although the health community is assessing FMT with renewed interest and patients are becoming more aware, there are technical and logistical issues in establishing such a nonstandardised treatment into the clinical practice with safety and proper governance. The underlying microbial basis, predictors of therapeutic outcome and active constituent(s) of fecal microbiota transplantation (FMT) mediating benefit remain unknown. Five questions should be considered regarding (i) the role of donor and recipient

microbial (bacteria, viruses, fungi) parameters in FMT; (ii) methods to assess microbiota alterations; (iii) concept of keystone species and microbial predictors of FMT, (iv) influence of recipient profile and antibiotics pre-treatment on FMT engraftment and maintenance, and (v) new developments in FMT formulations and delivery; (vi) efficacy of FMT and long term outcomes in various gut and non-gut diseases. FMT is not a one size fits all and studies are required to identify components of microbiota that have specific effects in patients with different diseases. The use of shotgun metagenomics to predict FMT success can be instrumental in formulating clinical trials for screening beneficial and unfavourable microorganisms.

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2020 TDDW

Special Lecture (IV) LIVING LEGEND OF THE SURGEON MASTERING CHOLANGIOCARCINOMA Yuji Nimura Division of Surgical Oncology, Department of Surgery, Aichi Cancer Center, Nagoya, Japan The successful resection of hilar cholangiocarcinoma has been performed since 1953 by Brown with bile duct resection, by Altemeier with left hepatectomy in 1962 and by Bird with right trisectionectomy in 1969. And the first successful right liver, bile duct, portal vein resection and reconstruction were carried out by Dr. Kajitani, my mentor, in 1965.

I learned intrahepatic biliary anatomy during cholangioscopic lithotomy for difficult hepatolithiasis, and cholangiographic anatomy of the intrahepatic segmental bile ducts was established in 1980s.

I have succeeded in surgical resection of hilar cholangiocarcinoma since 1970s, the first hilar bile duct resection in 1977, left hepatectomy with caudate lobectomy in 1979 and several types of hepatic segmentectomy with caudate lobectomy in 1980s. And portal vein resection and hepatobiliary resection or hepatopancreatoduodenectomy have also been performed for locally advanced hilar

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cholangiocarcinoma since 1980s. Furthermore hepatobiliary resection with simultaneous portal vein and hepatic artery resection has been carried out since 1990s. As perioperative management of infectious complications is very important to improve the surgical results, selective PTBD for segmental cholangitis was started in 1970s which was replaced by endoscopic nasobiliary drainage in 2000s. Portal vein embolization increased the safety of major hepatobiliary resection. Bile replacement during external biliary drainage and synbiotics combined with early enteral nutrition were effective to reduce infectious complications. Aggressive hepatobiliary resection with/without vascular resection and/ or pancreatoduodenectomy have yielded an improved survival for resected patients with locally advanced hilar cholangiocarcinoma with a help of perioperative managements.

2020 TDDW

Special Lecture (V) ADENOSINE CONTROLS COLONIC DYSBIOSIS THAT TRANSMITS SUSCEPTIBILITY TO COLITIS Peter B. Ernst Division of Gastroenterology, Department of Medicine, University of California San Diego, San Diego, CA, USA In the intestine, an equilibrium exists among host responses and microbes. Relevant to inflammatory bowel disease, some microbes exist as symbionts but under abnormal circumstances, they assume a pathological role. Such microbes, or pathobionts, rely on innate lymphoid cells (ILC) and regulatory Th cells (Treg) to modify their pathological potential. One molecule that contributes to immunological homeostasis in the intestine is adenosine. Adenosine is a purine metabolite derived from ATP through its conversion to ADP and 5’AMP by CD39 while CD73 continues the metabolism to adenosine. As ATP derived from dead cells or bacteria enhances colitis, its metabolism to adenosine removes this pro-inflammatory signal. We showed that CD73 is required for preserving the function of Treg and ILC in the control of T cell-mediated colitis. While CD45RBlow Th cells from wildtype and Nt5e−/− (CD73 KO) mice are enriched for Foxp3+ Treg, in

the absence of CD73, they cannot inhibit Th cell function in vitro or in vivo. Further, Foxp3+ Treg are lost during differentiation in vitro when CD73 is absent. Following adoptive transfer into mice lacking both Rag1 and CD73, CD45RBlow cells lost all cells expressing Foxp3, acquired Th1 and Th17 transcription factors, depleted recipient’s innate lymphoid cells and caused disease in association with a dysbiosis. Replacement of intestinal microbiota of Rag1−/− with those of healthy Rag1−/− Nt5e−/− mice rendered the former vulnerable to CD45RBlow-induced colitis. Thus, when CD73 is absent, an intestinal dysbiosis is created although the tissues remain healthy. CD45RBlow Th cells, which normally do not induce disease, induced enteritis and colitis upon adoptive transfer into Rag1−/−Nt5e−/− mice that are lacking the ability to synthesize extracellular adenosine. We conclude that adenosine is required for protecting lymphoid cell function and intestinal homeostasis.

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2020 TDDW

Special Lecture (VI) UPDATES IN FUNCTIONAL DYSPEPSIA William D. Chey Division of Gastroenterology, Departments of Internal Medicine and Nutritional Sciences, Michigan Medicine, Ann Arbor, MI, USA Functional dyspepsia is a common and bothersome disorder of brain gut interaction (DGBI). Like other DGBIs, the pathogenesis of FD is heterogeneous with contributions from abnormal gastric physiology, visceral hypersensitivity, and brain-gut interactions. Recently, other issues including microbiome, gut permeability, and mucosal immune activation have been the subject of investigation. An intriguing recent observation is a surprisingly high prevalence of gastric and duodenal eosinophilia. Just as the pathogenesis is heterogeneous, so too are the treatment options.

Evidence-based treatment options include H.

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pylori eradication, PPI therapy, prokinetic therapy, neuromodulators, drugs which relax the gastric fundus, herbal therapies including peppermint/ caraway oil and STW-5, and acupuncture. The low FODMAP diet and rifaximin have also been tested in clinical trials from Hong Kong. In general, these treatments lead to significant symptom improvement in fewer than half of treated patients and offer a therapeutic gain over placebo of less than 20%. This speaks to the need for biomarkerbased strategies which offer the possibility of increasing treatment response by identifying the right therapy for the right patient.

2020 TDDW

Symposium (I) SCREENING AND ERADICATION OF H. PYLORI FOR GASTRIC CANCER PREVENTION

GASTRIC CANCER PREVENTION AND SCREENING: WHO, WHEN, AND HOW? Yi-Chia Lee Department of Internal Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan Graduate Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan Even though the incidence rate of gastric cancer is declining, it remains the fifth most frequently diagnosed cancer and the third leading cause of cancer death. Gastric cancer, when diagnosed at the symptomatic stage, is associated with poor prognosis despite aggressive treatment and the only way to improve this is through early diagnosis which requires active endoscopic screening. Although endoscopic screening is accurate for both cancer detection and risk prediction, it cannot arrest the natural disease course. To stop the progression of carcinogenesis and reduce the occurrence of new gastric cancers, the modifiable risk factors must be eliminated. In addition to lifestyle modifications, including abstinence from excessive salt intake, cigarette smoking, and excessive alcohol use, and the encouragement of fresh fruit and vegetable intake, screening and treating H. pylori infection, which accounts for about 90% of non-cardiac gastric cancers, are the most effective means by which to heal the mucosal inflammation, halt the histological progression, and thus reduce the gastric cancer risk. Non-invasive tests for H. pylori may include the immunoglobulin serological test, C13-urea breath test, and stool antigen test. The screening choice depends on the prevalence rate of H. pylori infection and the resources available for a specific population.

In the other aspect, endoscopic screening involves morphological examination of the stomach

and risk stratification. Upper endoscopy is the most reliable tool by which to reach both goals, which not only identifies subjects with early-stage neoplasms so that curative treatment can be begun, but theoretically also evaluates the severity of gastritis and quantifies the patient’s future risk of gastric cancer. Nonetheless, endoscopic examination requires training, is costly and not completely safe.

To utilize resources most efficiently, priorities must be set by considering which patients to screen, when is the best time to screen, and how to increase the diagnostic yield. Ultimately, screening involves examination of the stomach but because of the large population, there may be a role for noninvasive screening to choose. Also, screening must incorporate the treatment of Helicobacter pylori infection along with endoscopic examination, to maximize the benefit derived from both strategies.

To eliminate the threat from gastric cancer, both H. pylori eradication (primary prevention) and endoscopic screening (secondary prevention) are needed to, respectively, reduce the incidence rate of gastric cancer by ameliorating mucosal inflammation and improve the mortality rate through the detection of early-stage neoplasms. The connection between the two strategies involves careful risk stratification based on the population risk, family history and/or pepsinogen tests, so as to maximize the use of the available resources.

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2020 TDDW

Symposium (I) SCREENING AND ERADICATION OF H. PYLORI FOR GASTRIC CANCER PREVENTION

HOW TO TREAT H. PYLORI-INFECTED SUBJECTS? Ping-I Hsu Division of Gastroenterology and Hepatology, Department of Internal Medicine, An Nan Hospital, China Medical University, Tainan, Taiwan The Kyoto Consensus Report on Helicobacter Pylori Gastritis recommended that only regimens which reliably produce eradication rates of ≥ 90% in that population should be used for empirical treatment for H. pylori infection. With the rising prevalence of clarithromycin resistant strains, the eradication rate of standard triple therapy has recently declined to unacceptable levels in most countries. According to predicted efficacy, treatment success of clarithromycin triple therapy falls below 90% by per protocol analysis in areas with 7% clarithromycin resistance for 7-day treatment and in areas with 11% resistance for 14day treatment. Therefore, either 7-day or 14-day clarithromycin triple therapy should be avoided to use in areas with clarithromycin resistance rate more than 11%.

In areas with high clarithromycin resistance, bismuth quadruple, hybrid (or reverse hybrid) or concomitant therapies are the recommended regimens for H. pylori eradication. Recent studies demonstrated that 14-day bismuth quadruple, hybrid and concomitant therapies are equivalent in efficacy for the first-line treatment of H. pylori infection. However, hybrid therapy has fewer

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adverse effects than bismuth quadruple and concomitant therapies. Novel regimens, e.g., vonoprazan containing triple therapies and highdose dual therapies require further studies to assess their efficacy in the treatment of H. pylori infection.

Currently, the recommended second-line therapies include bismuth quadruple therapy, fluoroquinolone-amoxicillin triple therapy, fluoroquinolone-amoxicillin quadruple therapy, tetracycline-levofloxacin (TL) quadruple therapy and high-dose dual therapy. Ten-day TL quadruple therapy has great potential to become a universal rescue treatment following eradication failure by all first-line eradication regimens for H. pylori infection.

Most guidelines suggest that patients requiring third-line therapy should be referred to medical center and treated according to the antibiotic susceptibility test. Nonetheless, an empirical therapy (such as levofloxacin-containing, rifabutincontaining, or furazolidone-containing therapies) can be tried to terminate H. pylori infection if antimicrobial sensitivity data are unavailable.

2020 TDDW

Symposium (I) SCREENING AND ERADICATION OF H. PYLORI FOR GASTRIC CANCER PREVENTION

LONG-TERM SAFETY ISSUES OF MASS ERADICATION OF H. PYLORI FOR GASTRIC CANCER PREVENTION Jyh-Ming Liou Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan Emerging evidence shows that eradication of Helicobacter pylori (H. pylori) reduces the risk of gastric cancer in infected subjects. However, there are some potential concerns regarding the mass screening and eradication of H. pylori infection for gastric cancer prevention in the community. These include the emergence of antibiotic resistance for all bacteria, the disturbance of human microbiota, increasing the risk of metabolic disorders, gastroesophageal reflux disease (GERD), and allergic diseases. The experts have achieve the following consensus on these issues. As with all antibiotic therapies, H. pylori eradication may lead to an increase in antimicrobial resistance, but it should not preclude its use for gastric cancer

prevention.There is short-term perturbation of fecal microbiota diversity after H. pylori eradication that largely recovers subsequently. Eradication of H. pylori does not increase the risk of new onset GERD. H. pylori eradication therapy does not increase the risk of relapse of GERD. H. pylori eradication may be associated with a small increase in body weight, but does not increase the risk of metabolic syndrome. H. pylori eradication does not increase the risk of asthma, inflammatory bowel disease and other immune related diseases.

However, more well-designed prospective studies or trials are warranted to provide further evidence on these issues.

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2020 TDDW

Symposium (I) SCREENING AND ERADICATION OF H. PYLORI FOR GASTRIC CANCER PREVENTION

SCREENING ENDOSCOPY AT BASELINE AND SURVEILLANCE ENDOSCOPY AFTER H. PYLORI ERADICATION: WHOM AND HOW? Hsiu-Chi Cheng Department of Internal Medicine and institute of Clinical Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan Endoscopy plays an important role in early diagnosis of gastric cancer because the prognosis is highly correlated with the stage at diagnosis.

Therefore, there should be strategies for clinicians to identify subjects who are at risk of gastric cancer and to arrange screening and surveillance endoscopy.

Gastric cancer occurs consequently through the Correa’s cascade after H. pylori infection, including chronic active gastritis, atrophic gastritis, intestinal metaplasia, dysplasia, and adenocarcinoma. Accordingly, a baseline screening endoscopy is suggested for subjects who are at risk of gastric cancer, including those with age > 50 years, male sex, smoking, serum pepsinogen I/II ratio < 3, a personal history of H. pylori infection, gastric ulcer, and gastric surgery for benign diseases, and a family history of gastric cancer in first degree relative. Family history is a valuable indicator especially in the low-incidence areas of gastric cancer.

Moreover, because of the cancer potential for gastric mucosa which attains to an irreversible

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stage after H. pylori infection, surveillance endoscopy is recommended for high risk subjects.

The incidence rates of gastric cancer are 1.24 (95% CI 0.80~1.76) and 3.38 (95% CI 2.13~4.85) cases per 1,000 person-years for subjects with atrophic gastritis and intestinal metaplasia, and the incidence rates of metachronous cancer are 14~29.9 cases per 1,000 person-years for those with low/high-grade dysplasia or early gastric cancer after endoscopic mucosal resection or endoscopic submucosal dissection. Accordingly, endoscopic surveillance intervals are within 6~12 months for subjects with low/high-grade dysplasia, within 6~12 months and then 1 year thereafter for those with gastric adenomas after complete endoscopic excision, every 3 years for those with OLGA/OLGIM stages III-IV, and longer than 3 years or even not suggested for those with precancerous conditions which are confined to antrum only or with OLGA/OLGIM stages 0-II. Moreover, such a strategy, endoscopic surveillance every 1 or 3 years for extensive precancerous conditions, is cost-effective.

2020 TDDW

Symposium (II) ENDOSCOPY IN CHRONIC LIVER DISEASES PATIENTS

ENDOSCOPIC TREATMENT OF GASTROESOPHAGEAL VARICES Wen-Chi Chen Division of Gastroenterology and Hepatology, Department of Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan Medical School, National Yang-Ming University, Taipei, Taiwan Gastroesophageal variceal bleeding is a severe complication of liver cirrhosis. The related mortality has reduced from 50% to 1520% in theses decades due to advancement of endoscopic therapy and the care during the bleeding episode. Acute esophageal variceal bleeding can be controlled in more than 80% of the patients managed by vasoactive agent, antibiotics prophylaxis and endoscopic treatments including sclerosant injection and band ligation. Obturation by tissue glue injection is more effective than band ligation and is regarded as the therapy of choice in the management of gastric variceal bleeding.

Recently, EUS-guided glue and/or coil deployment for gastric variceal bleeding can be attempted with a high hemostasis and variceal obliteration rate.

Human thrombin injection is comparable with tissue glue injection with less adverse events. Up to 10 to 20 percent of the bleeding is refractory

to the current standard treatment. Application of hemostatic powders is an emerging endoscopic hemostasis technique of gastroesophageal variceal bleeding. Further definitive therapies are required after hemostasis achieved by hemostatic powders. Placement of fully covered selfexpanding metal stents showed promising results with 97% of success rate of stent deployment, 96% of hemostasis rate, and 68% of 30-day mortality in a meta-analysis. A recent randomized controlled trial showed self-expanding metal stents is more effective than balloon tamponade in the control of esophageal variceal bleeding with less transfusion requirements and severe adverse effects.

Similarly, self-expanding metal stent is a bridging therapy to more definitive treatments of variceal bleeding. Transjugular intrahepatic porto-systemic shunt or liver transplantation are rescue therapies for patients with refractory variceal bleeding.

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2020 TDDW

Symposium (II) ENDOSCOPY IN CHRONIC LIVER DISEASES PATIENTS

RISK MANAGMENT OF ENDOSCOPY IN THE CIRRHOTIC PATIENTS: SEDATION AND ENDOSCOPIC INTERVENTIONS Kuei-Chuan Lee Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan Department of Medicine, National Yang-Ming University, Taipei, Taiwan Endoscopy has undergone a period of rapid expansion. Numerous novel and specialized modalities are developed in recent years.

However, the investigation and management of GI tract disease is still complex and challenging in patients with chronic liver disease. In this speech, I will provide a brief review and update of endoscopy in patients with liver cirrhosis,

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including the safety of sedation, the preparation in patients with coagulation abnormalities, risk of procedure complications, common esophagogastroduodenoscopy/colonoscopy/ endoscopic ultrasonography, and advanced procedures such as polypectomy, sphincterotomy, fine needle aspiration, and endoscopic submucosal dissection.

2020 TDDW

Symposium (II) ENDOSCOPY IN CHRONIC LIVER DISEASES PATIENTS

EUS GUIDED LIVER BIOPSY: WHEN AND HOW Wei-Chih Liao Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan Several modalities can enable liver biopsy for diagnosing liver lesions, including ultrasound (US)guided or computed tomography (CT)-guided percutaneous biopsy, and endoscopic ultrasoundguided fine needle aspiration/biopsy (EUS-FNA/B. In addition to its wide applications in the diagnosis of pancreatobiliary diseases, EUS-guided FNA/B has also been increasingly used for obtaining liver tissues for histologic diagnoses.

The interest in EUS-guided liver biopsy has been growing because of several potential advantages. First, EUS-guided liver biopsy is little affected by body habitus, because the needle only needs to traverse the gastric or duodenal wall to reach the hepatic parenchyma. Second, it does

not require puncture across the abdominal wall.

Furthermore, real time guidance by EUS allows visualization and avoidance of blood vessels and thus improves safety. Additionally, it provides easy access to the entire left lobe and most of the right lobe from the stomach and duodenal bulb. For regions that are deep-seated and thus difficult via percutaneous approaches, EUS-guided liver biopsy may provide easier access, minimizing sampling error and reducing the risk of inadvertent puncture of vessels or bile ducts. In addition to obtaining tissue for the diagnosis of diffuse liver diseases, EUS-guided liver biopsy can also be performed on focal hepatic lesions.

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2020 TDDW

Symposium (II) ENDOSCOPY IN CHRONIC LIVER DISEASES PATIENTS

COLONOSCOPY AND POLYPECTOMY IN CIRRHOTIC PATIENTS Li-Chun Chang Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan Colonoscopy with polypectomy for removal of colorectal neoplasm is useful for reducing mortality and the incidence of colorectal cancers.

However, polypectomy is associated with a risk of complications, such as post-polypectomy bleeding, perforation, etc. PPB is the most common complication after polypectomy, and its frequency ranges from 0.2% to 6.1%. PPB may occur immediately after colonoscopic polypectomy or can be delayed up to 30 days after the procedure.

The previous studies demonstrated that old age, underlying comorbidities such as hypertension, cardiovascular disease and chronic kidney

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disease, large-sized polyps, and neoplasms’ proximal location are known risk factors for PPB. Patients with chronic liver disease (CLD) tend to bleed due to a disruption of coagulation factor synthesis in the liver, and this disruption is often accompanied by thrombocytopenia and portal hypertension. Previous studies indicated that patients with CLD are more prone to bleeding following an invasive procedure such as surgery or liver biopsy. Therefore, the risk of bleeding after polypectomy among patients with a CLD such as chronic hepatitis or liver cirrhosis (LC) is a critical issue and worth further discussion.

2020 TDDW

Symposium (III) CONTROVERSIES AND UNMET NEEDS FOR LONG-TERM BENEFIT OF HBV THERAPIES

UPDATE OF HBV PRACTICE GUIDELINE Chia-Yen Dai Hepatology Division, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan School of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan Chronic hepatitis B (CHB) is one the major health threatens all over the world. With the development of the clinical guidelines in the USA, united European and Asia, the progresses of the treatment of CHB have been made. The goal of therapy is to improve survival and quality of life by preventing disease progression and hepatocellular carcinoma (HCC). With the optimal endpoint of HBsAg loss (± anti-HBs seroconversion), induction of long-term suppression of HBV DNA is the main endpoint.

The indications for treatment are primarily based on the combination of 3 criteria: HBV DNA, serum ALT and severity of liver disease. Patients with no current indication of antiviral therapy should be monitored with periodical assessments of serum ALT, HBV DNA and non-invasive markers for liver fibrosis. Current major treatment strategies for CHB are pegylated interferon (PegIFN) and nucleos(t)ide analogues (NAs). Long-term administration of a potent NA with a high barrier to resistance is the treatment of choice regardless of severity of liver disease. Long-term therapy with

NAs is usually required and HBV eradication is not usually achieved. Management of treatment failure should be based on cross-resistance data and treatment should be adapted as soon as virological failure under NAs is confirmed. Patients treated with PegIFN require ongoing monitoring during treatment and after virological response.

Predictors of response and stopping rules have been elucidated. For the special patient groups, patients with decompensated cirrhosis should be referred for liver transplantation and treated with NAs as early as possible. All patients with chronic HBV infection should be screened for HCV and other blood-borne viruses. For pregnant women, management may depend on severity of liver disease and timing of a future pregnancy.

All HBsAg-positive patients for chemotherapy and immunosuppressive therapy should receive entecavir (ETV), tenofovir alafenamide (TAF) or tenofovir disoproxil fumarate (TDF) as treatment or prophylaxis. HBsAg-positive dialysis patients who require treatment should receive ETV or TAF. The unresolved and unmet issues need more efforts.

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2020 TDDW

Symposium (III) CONTROVERSIES AND UNMET NEEDS FOR LONG-TERM BENEFIT OF HBV THERAPIES

SHOULD WE TREAT CHB PATIENTS EARLIER? Tai-Chung Tseng Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan Chronic hepatitis B virus (HBV) infection continues to be a major public health issue worldwide. A recent worldwide estimate suggests that 248 million individuals were HBsAg positive.

These individuals with chronic hepatitis B (CHB) infection are at an increased risk of developing liver cirrhosis, liver failure, and hepatocellular carcinoma; 15% to 40% of these individuals will develop these serious sequelae during their lifetime.

Prolonged nucleos(t)ide analogue (NA) therapy is effective to prevent the disease progression and to lower the risk of HCC development. However, it remains unclear whether early antiviral therapy is indicated in all the patients as only less then half progress to end-stage liver disease.

Hepatitis B e antigen (HBeAg)-positive patients with normal or near-normal ALT levels are usually assumed to be at immune tolerance (IT) phase. Although studies report conflicting results of their HCC risk, a low HBeAg seroconversion rate has been reported across different clinical trials. For example, Chan et al explored the treatment response of IT patients with tenofovir disoproxil furamate–based therapy and found the HBeAg seroconversion rate was less than 5% after treatment for 4 years. Recent studies of entecavir administered for an initial 8 weeks followed by pegylated interferon for the subsequent 40 weeks

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in either young adult or children with IT chronic HBV infection revealed low HBeAg seroconversion rates. As most of the data suggest the response is poor using antiviral treatment of defined duration, the decision to initiate early antiviral treatment in IT patients should be justified.

HBeAg-negative patients with intermediate viral load (IVL, HBV DNA between 2000-20,000IU/ mL) are regarded as those with moderate risks of disease progression. As prolonged NA therapy is usually needed in HBeAg-negative patients once the treatment initiated, the cost and benefits should be balanced, especially in those with moderate risk. Our recent study has shown hepatitis corerelated antigen (HBcrAg) level of 10 KU/mL is effective in stratifying the HCC risk in IVL patients.

When shifting the endpoint to the leading adverse liver events, including cirrhosis and hepatitis flare, their risks were stratified by this biomarker consistently. In other words, HBcrAg may guide the physicians who to start early antiviral treatment by complementing serum HBV DNA levels to predict the long-term outcomes.

In summary, early antiviral therapy may improve long-term outcomes of CHB patients.

More biomarkers are needed to identify the patients who benefit most, which could help physicians to provide individualized medicine.

2020 TDDW

Symposium (III) CONTROVERSIES AND UNMET NEEDS FOR LONG-TERM BENEFIT OF HBV THERAPIES

SHOULD WE INDIVIDUALLY DISCONTINUE NUCS IN CHB PATIENTS? Yi-Cheng Chen Department of Gastroenterology & Hepatology, Chang Gung Medical Foundation, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan Current guidelines have recommendations for nucleos(t)ide analogue (NA) discontinuation.

In Asian Pacific Association for the Study of the Liver (APASL) guidelines, the treatment can be withdrawn (1) after HBsAg loss following either anti-HBs seroconversion or at least 12 months of a post-HBsAg clearance consolidation period or (2) after at least 2-year treatment with undetectable HBV DNA documented on 3 separate occasions, 6 months apart in HBeAg-negative patients without liver cirrhosis. The therapy can be stopped after at least 1 year (preferably 3 years) of additional therapy after HBeAg seroconversion with undetectable HBV DNA and persistently normal ALT in HBeAg-positive, non-cirrhotic patients. In European Association for the Study of the Liver (EASL) guidelines, NAs can be discontinued in non-cirrhotic HBeAg-positive CHB patients who achieve stable HBeAg seroconversion and undetectable HBV DNA and who complete at least 12 months of consolidation therapy. Discontinuation of NAs in selected non-cirrhotic HBeAg-negative patients who have achieved long-term (≥3 years) virological suppression under NA(s) may be considered. In American Association for the Study of Liver Diseases (AASLD) guidelines, HBeAg-

positive adults without cirrhosis who seroconvert to anti-HBe on therapy can discontinue NAs after a period of treatment consolidation (for at least 12 months). Indefinite antiviral therapy for adults with HBeAg-negative, immune-active CHB is suggested or treatment discontinuation may be considered in persons who have demonstrated loss of HBsAg. However, these recommendations can not fit all CHB patients.

Clinical conditions after NA cessation include clinical relapses which may lead to severe flares, decompensation or even death, or inactive disease status with HBsAg decline or loss. Predictors for virological or clinical relapses have been investigated like age, pretreatment HBV DNA levels and HBsAg at baseline or end of treatment (EOT). On the other hand, associated factors for HBsAg loss reported in past studies are low EOT HBsAg (<100 IU/mL), HBsAg reduction, and no retreatment.

In this session, we will try to find the beneficial factors for chronic hepatitis B patients who discontinue NA therapy to minimize clinical relapse and increase the possibility of HBsAg seroclearance.

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2020 TDDW

Symposium (IV) IBD UPDATE SYMPOSIUM

REDEFINING DISEASE SEVERITY AND THERAPEUTIC TARGETS IN UC AND CD Siew C. Ng Department of Medicine and Therapeutics, Faculty of Medicine, The Chinese Univetsity of Hong Kong, Hong Kong Therapeutic goals in UC and CD have evolved with the introduction of biologic therapies.

Mucosal healing has been associated with fewer complications and better patient outcomes.

Mucosal healing is now the principal target. It is well established that the purpose of an adequate and complete control of the intestinal inflammation measured not only by clinical symptoms, but also with more objective data such as fecal biomarkers (calprotectin) and endoscopy. The treat to target approach possibly correlates with minor risk for complications associated with IBD, specially

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surgery and cancer. Resolution of histological inflammation has also been associated with better outcomes, however, the evidence is limited and the definition of histologic healing is still not clear.

Ongoing research is evaluating new biomarkers as potential future targets. Evidence- and consensusbased recommendations for selecting the goals for treat-to-target strategies in patients with IBD are made available. Prospective studies are needed to determine how these targets will change disease course and patients’ quality of life.

2020 TDDW

Symposium (IV) IBD UPDATE SYMPOSIUM

TREATMENT CONSIDERATIONS IN THE NEWLY DIAGNOSED IBD PATIENT Chen-Wang Chang Department of Gastroenterology and Hepatology, Mackay Memorial Hospital, Taipei, Taiwan MacKay Medical College, Taipei, Taiwan MacKay Junior College of Medicine, Nursing, and Management, Taipei, Taiwan The incidence and prevalence of IBD, which includes Crohn’s disease (CD) and ulcerative colitis (UC), are lower in Asian countries than in Western countries. However, this has been recently changing. CD and UC are complex disorders reflected by wide variation in clinical practice. CD is characterised by patchy, transmural inflammation, which may affect any part of the gastrointestinal tract. It may be defined by location (terminal ileal, colonic, ileocolic, upper gastrointestinal), or by pattern of disease (inflammatory, fistulating, or stricturing). UC is characterised by diffuse mucosal inflammation limited to the colon.

After the diagnosis of CD or UC has been confirmed, the disease extent should be defined, because it determines the best route for therapy.

Initial treatment strategies for newly diagnosed patients must not only take into account current clinical presentation but must also take into consideration treatment options for the long-term.

For CD, both small bowel and colon should be assessed. Most current treatment guidelines recommend the use of a socalled step-up approach for mild to moderate CD, which comprises initial treatment with topical or systemic corticosteroids, followed by treatment intensification if the initial therapy fails. For moderate to severe CD, patient s are treated with corticosteroids until resolution of symptoms and resumption of weight gain.

Infection or abscess requires appropriate antibiotic

therapy or drainage. Thiopurines are effective for maintaining a steroid-induced remission. The biologics are effective in the treatment of moderate to severely active CD in patients who have not responded despite complete and adequate therapy with corticosteroids or an immunosuppressive agent.

For UC, the extent is defined as the proximal margin of macroscopic inflammation, because this is most clearly related to the risk of complications, including dilatation and cancer. Mild-to-moderate UC can be managed with aminosalicylates, mesalamine, and topical corticosteroids with oral corticosteroids reserved for unresponsive cases.

Moderate-to-severe UC generally requires oral or intravenous corticosteroids in the short-term with consideration of long-term management options such as biologic agents or thiopurines.

Patients with severe or fulminant UC who are recalcitrant to medical therapy or who develop disease complications (such as toxic megacolon) should be considered for colectomy. Early surgical referral in severe or refractory UC is crucial, and colectomy may be a life-saving procedure.

In conclusion, treatment considerations in the newly diagnosed IBD patient are complicated.

Stratification of patients based on clinical parameters, disease extent, and severity of illness is paramount to determining the course of therapy.

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2020 TDDW

Symposium (IV) IBD UPDATE SYMPOSIUM

UNDERSTANDING BIOLOGICAL THERAPIES IN IBD Puo-Hsien Le Department of Gastroenterology and Hepatology, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan Inflammatory bowel disease is a chronic, relapsing-remitting, immune-mediated inflammatory disorders with a complex multifactorial pathogenesis, where different pathways may predominate in different individuals. Over the last two decades, biologics targeting several immune

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pathways have been developed. In biological era, the colectomy rate significantly decreases.

However, the timing of starting biological treatment, monitoring and adjustment are important to optimize the therapeutic effects.

2020 TDDW

Symposium (IV) IBD UPDATE SYMPOSIUM

APPROACHES TO DISEASE MONITORING AND DE-ESCALATION IN IBD Hsu-Heng Yen Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan With the increased case number of IBD in Taiwan, the introduction of multiple new agents allows patients for better medical therapy. Unlike other GI diseases, patients with IBD may not be monitored by symptom or laboratory examinations.

An integrated disease monitoring approach is essential for effective medical therapy for such patients. In addition, despite achieving deep remission, therapeutic de-escalation in this patient

population is associated with significant disease relapse risk within one-year and two-years. This risk is more pronounced in patients requiring antiTNFα for management, likely because of more severe disease. In this section, we will discuss currently available approaches for disease monitoring and de-escalation in IBD especially in Taiwan.

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2020 TDDW

Symposium (V) TRADITION AND INNOVATION OF MANAGEMENT OF CHOLANGIOCARCINOMA

VASCULAR RESECTION FOR PERIHILAR CHOLANGIOCARCINOMA – TECHNIQUES AND PITFALLS Yuji Nimura Division of Surgical Oncology, Department of Surgery, Aichi Cancer Center, Nagoya, Japan Combined liver and portal vein resection is indicated for locally advanced hilar cholangiocarcinoma involving the portal bifurcation. In a case of wedge resection of the lateral wall of the portal vein, transverse suture or patch closure with the great saphenous vein is performed. After segmental resection of the portal bifurcation, end to end anastomosis is usually possible in right sided hepatectomy or external iliac vein grafting is preferably used for left sided hepatectomy because of the anatomical length of the right and left portal veins. Running suture with 5-0 prolene is preferably used for portal vein reconstruction. After releasing the proximal vascular clump and dilating the anastomosis, the distal clump is removed, and threads are finally tied without providing a growth

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factor. Simultaneous resection of the portal vein and hepatic artery is mainly performed in left sided hepatectomy. The left hepatic vein is divided at the final step of liver transection before resecting the hepatic artery, portal vein and right hepatic ducts to prevent unexpected congestion of the left liver. And portal vein reconstruction is performed first to shorten the ischemic time of the right liver.

After completing the portal reconstruction, hepatic arterial reconstruction is carried out with a running suture of 6-0 prolene. However, since the 21st century microsurgical techniques have been used by plastic surgeons. Although heparinized saline is used to flash the lumen of the anastomosis, systemic heparinization is not used perioperatively.

2020 TDDW

Symposium (V) TRADITION AND INNOVATION OF MANAGEMENT OF CHOLANGIOCARCINOMA

GENE LANDSCAPE OF INTRAHEPATIC CHOLANGIOCARCINOMA Ren-Chin Wu Department of Anatomic Pathology, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan School of Medicine, Chang Gung University, Taoyuan, Taiwan Genomic studies on cholangiocarcinoma have yielded divergent results by different investigators, leading to realization that cholangiocarcinoma is vastly heterogeneous, attributable at least to differences in ethnicity, etiology (fluke vs non-fluke), and anatomy (extrahepatic vs intrahepatic). In general, mutations in ARID1A, BAP1, IDH1/2, KRAS, PBRM1, TP53 and rearrangement in FGFR2 are frequently identified in intrahepatic cholangiocarcinoma (iCCC) in most literatures. As compared to iCCC, extrahepatic cholangiocarcinoma (eCCC) more commonly harbors KRAS, SMAD4 and STK11 mutations.

As the distinction between iCCC and eCCC (perihilar) is arbitrarily made at the second-order biliary branches, it is not surprising that a subgroup of iCCC, presumably arising from biliary epithelium of second-order bile duct or beyond, has molecular characteristics resembling that of eCCC. This subgroup of iCCC, now termed “large duct type” according to recent WHO classification, has distinct histology characterized by large glandular structures lined by tall columnar, mucin-containing cells. Another subtype, termed “small duct type”, is presumably derived from hepatic progenitor cells

and histologically characterized by small tubular structures composed of cuboidal cells with a higher nuclear-tocytoplasmic ratio. Similar to eCCC, large duct type iCCC is associated with lithiasis, worse prognosis and mutations in KRAS and SMAD4. In contrast, small duct type iCCC is associated with more favorable outcomes and IDH1/2 mutation.

Applying molecular profiling in iCCC may help provide prognostic prediction and guide therapy in patients with advanced disease.

IDH1/2 mutation was associated with prolonged disease-free survival in small duct type iCCC, whereas BAP1 loss with better clinical outcomes in large duct type iCCC. CDKN2A/B deletion and ERBB2 amplification are associated with shorter progression-free survival. Actionable genetic alterations were identified in near half of patients with advanced cholangiocarcinoma. The most common actionable findings in iCCC are IDH1 mutation and FGFR2 fusion, for which several targeted agents are undergoing clinical trials.

Notably, pemigatinib, an FGFR inhibitor, was recently approved by FDA for cholangiocarcinoma with FGFR2 fusion.

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2020 TDDW

Symposium (V) TRADITION AND INNOVATION OF MANAGEMENT OF CHOLANGIOCARCINOMA

PROTON THERAPY FOR CHOLANGIOCARCINOMA Bing-Shen Huang Department of Radiation Oncology, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan Cholangiocarcinoma (CC) is one of the second most common primary liver cancers. Only approximately 30% of patients are candidates for resection and the 5-year overall survival rates are 11% to 44%.

The main advantage of proton therapy for liver cancers is that it can increase the radiation dose of tumor and reduce the dose of normal liver.

This advantage mainly comes from the physical characteristics of proton different from photonBragg peak.

From November 2015 to December 2017, total 30 patients were treated with PBT at Chang-

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Gung Memorial Hospital Linkou. The median tumor size was 7 cm. Seventeen (56.7%) patients had regional lymph node metastases. The 1-year local control, regional control, and distant metastasesfree rates were 88%, 86%, and 68%, respectively.

The median overall survival and progression-free survival were 19.3 and 10.4 months, respectively.

The median jaundice-free survival was 13 months, with a 1-year biliary tract infection-free rate of 58%.

According to previous clinical results and our experiences, PBT can be a useful alternative treatment for patients unsuitable for surgery.

2020 TDDW

Symposium (VI) NEW AND ALTERNATIVE TREATMENT FOR FGID

PSYCHOLOGICAL THERAPY FOR FUNCTIONAL GASTROINTESTINAL DISORDERS Chia-Fen Tsai Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan Institute of Neuroscience & Institute of Radiological Science, National Yang-Ming University, Taipei, Taiwan Many researches have revealed the complex interactions of environmental, psychological, and biological factors contribute to the development and maintenance of the functional gastrointestinal disorders (FGIDs) such as irritable bowel syndrome, functional constipation, functional dyspepsia and others.

The FGIDs show inadequate response to usual medical care and psychological treatments can help improve functional gastrointestinal disorder patient outcomes. Effective psychological treatments, which are based on multiple randomized controlled trials, include cognitive behavioral therapy, hypnosis, and biofeedback therapy.

In this speech, we will collate an overview of what is currently known about how each of these factors—the environment, including the influence of those in an individual’s family, the individual’s own psychological states and traits, and the individual’s neuropsychological makeup—interact to ultimately result in the generation of FGID symptoms. Second, we will summarize an overview of commonly used assessment tools that can assist clinicians in obtaining a more comprehensive assessment of psychological factors in their patients and psychological treatment which have been shown to be efficacious to manage FGIDs.

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2020 TDDW

Symposium (VI) NEW AND ALTERNATIVE TREATMENT FOR FGID

CONSTIPATION IN OLDER ADULTS Ching-Liang Lu Endoscopy Center for Diagnosis and Treatment, Taipei Veterans General Hospital, Taipei, Taiwan Institute of Brain Science, National Yang-Ming Univerisity, Taipei, Taiwan Chronic constipation is a common gastrointestinal disorder with a prevalence around 10-20 in the general population. The incidence is even disproportionately high among the elderly, which might be from the immobility, poly-medications, and aging process in the population. Though chronic constipation is not life-threatening, it does bring a significantly negative impact on quality of life, individual healthcare costs, and a large economic burden. In Western countries, it is estimated that there are approximately 7 million physician visits per year with 2.5 million of these made by persons over the age of 65. To explore detailed clinical history and physical examination (including rectal examination) is important to unmask the primary and secondary forms of constipation as well as to guide the subsequent diagnostic and therapeutic considerations. With the application of anorectal manometry, defecography, and transit

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study, we can then distinguish from pelvic floor dysfunction, slow and normal transit constipation.

Non-pharmacologic treatment for constipation would include bowel training and biofeedback as well as fiber addition. Laxatives are still the mainstay of therapy. Newer agents targeting at chloride channel, serotonin receptor, guanylate cyclase-C receptor, bile acid, Ghrelin receptor, and opioid receptors have shown to be effective in adults with chronic constipation. However, the safety data of these new agents in the elderly are still lacking. Surgery can be considered after a complete evaluation and deep discussion with in medically refractory patients. Neuromodulation or Botulinum toxin is not ready for routine use in constipation at this time. It is imperative to identify the etiology of chronic constipation in the elderly and the appropriate treatment should be based on the patient’s overall clinical status and capabilities.

2020 TDDW

Symposium (VI) NEW AND ALTERNATIVE TREATMENT FOR FGID

HERB MEDICINE FOR FGID Chien-Lin Chen Department of Medicine, Hualien Tzu Chi Hospital and Tzu Chi University, Hualien, Taiwan Herbal medicine becomes an important therapeutic option in functional gastrointestinal disorders (FGIDs). FGIDs can be chronic unexplained disorders with unfavorable therapeutic response. Herbal medicine is based on different kinds of herbal extracts from single or multiple plants in the history of mankind. Some herbal therapies provide significant benefits for patients with FGIDs, although safety profiles and side effects needs further investigation. Combining herbs can achieve optimal therapeutic response.

They may relieve GI symptoms by significant influence on sensorimotor, accommodation aspects of GI tracts, such as Rikkunshi-to (RKT) and STW-5 which may help alleviate symptoms of functional dyspepsia and irritable bowel syndrome with low side effects profile. Current evidence from systemic meta-analysis has suggested that herbal medicine emerges as a useful and well-tolerated treatment for FGIDs. This review will give an overview on clinical benefits of herbal extracts in the treatments of FGIDs.

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2020 TDDW

Symposium (VI) NEW AND ALTERNATIVE TREATMENT FOR FGID

MEDICAL FOOD AND FODMAP FOR IBS William D. Chey Division of Gastroenterology, Departments of Internal Medicine and Nutritional Sciences, Michigan Medicine, Ann Arbor, MI, USA Over the past 15 years, diet therapies have become an increasingly important treatment for IBS patients. The vast majority of the available clinical research addresses elimination diets for IBS such as the low FODMAP diet, a gluten free diet, and avoidance of common food triggers such as lactose and spicy foods. Of these options, the low FODMAP diet is currently the most evidencebased diet intervention. The literature would suggest that approximately half of IBS patients report adequate relief of their symptoms with the low FODMAP diet. Though this is similar to currently available medical therapies for IBS, this response rate leaves much room for improvement. Elimination diets have made clear the potential of diet therapies for IBS patients.

However, more work is needed to validate the

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efficacy and safety of existing elimination diets.

There are many other elimination diets being utilized by IBS patients including the paleo diet, ketogenic diet, and diets based upon mediator release testing and IgG antibody testing. Given the pathophysiologic and clinical heterogeneity of IBS, it is possible that a number of different diet strategies will prove effective in subgroups of IBS patients. Diet therapies, like any other therapy for IBS, require adequate validation in appropriately designed clinical trials. In addition to validating elimination diets, focus should also be placed on the identification of functional foods which might be used alone or in combination with elimination diets. It is going to also be critically important to identify biomarkers which can help providers to choose the right intervention for the right patient.

2020 TDDW

Symposium (VII) COLORECTAL CANCER SCREENING ON THE CROSS ROAD

ECONOMICAL IMPACT OF COLORECTAL CANCER SCREENING Ming-Fang Yen School of Oral Hygiene, College of Oral Medicine, Taipei Medical University, Taipei, Taiwan From the viewpoint of economics, populationbased screening has pros and cons. The greatest merit of population-based screening is the ability to reduce a large proportion of deaths from colorectal cancer (CRC) through early detection and to potentially reduce the incidence of CRC through the removal of advanced adenoma. However, the benefit accrued from screening occurs later than the cost incurred at the inception of screening.

This aspect is more crucial in determining costs for the comparison of the screened group with the unscreened group, particularly when there is a long disease natural history of colorectal neoplasms.

Neglecting such a time preference reflected in

time-stamped disease natural history between the two groups may lead to a biased result of cost-effectiveness/utility analysis and cost-benefit analysis. In this speech, we first proposed the framework of economic evaluation for populationbased screening for CRC and then reviewed the results in literature on various screening methods.

We also demonstrate a case study with the application of the analytical Markov decision model to evaluating different screening strategies with particularly emphasis on fecal immunochemical test (FIT), in a universal approach or personalized approach.

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2020 TDDW

Symposium (VII) COLORECTAL CANCER SCREENING ON THE CROSS ROAD

SCREENING FOR YOUNG POPULATION Yu-Min Lin Department of Gastroenterology, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan School of Medicine, Fu-Jen Catholic University, New Taipei City, Taiwan

Colorectal Cancer in Taiwan Colorectal cancer (CRC) accounts for the highest number of newly diagnosed cancer cases in Taiwan since 2006. Accordingly, Ministry of Health and Welfare of Taiwan extended the population-based CRC screening program in 2010 from out-reach to in-reach for average-risk individuals aged between 50 and 69 y (extended to 75 y since 2011). The effectiveness of the program appeared encouraging as more than 50% of CRCs were detected in the early stages and a significant reduction of CRC-related mortality was observed in the screened population.1,2 Even so, several issues remained unclear including the CRC burden of the younger generation (age <50y) in Taiwan.

CRC Incidence of Young Generation The generation-X usually refers to those who were born between 1966 and 1980. These 35-50 y individuals are highly productive and are key breadwinners of their family. Preventing illness and disability of the Gen-X is not only important for individual but also for their families and the society.

Recent reports from US suggest that the incidence of CRC is raising significantly in the Gen-X.3 What is the situation in Taiwan? To understand the cancer incidence of the Gen-X in Taiwan, we analyzed the information obtained from the cancer registration database. The CRC incidence rate increased from 17.43 per 100,000 in 2001 to 27.80 per 100,000 in 2013 among age of 35-50.

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Understanding risk factors of the increasing trend and developing effective strategies to decrease the disease burden are the emerging issues.

Colorectal Neoplasm (CRN) Screening for Young Generation The reason for the increased incidence is likely multifactorial. Several reports suggested that unhealthy lifestyle such as smoking, physical inactivity and obesity are significantly associated with colorectal neoplasm in the young adults.4 Currently, most guidelines are lacking of clear recommendations of CRN screening for younger generations. The American Cancer Society is the first organization to recommend starting screening at age 45 for average-risk adults based on the increased incidence of CRC in U.S. adults younger than age 55.5 Physicians may offer choices of screening and patients should engage in shared decision making regarding the type of screening to be used.

Reference: 1. Application of quantitative estimates of fecal hemoglobin concentration for risk prediction of colorectal neoplasia. Chao-Sheng Liao, Yu-Min Lin, Hung-Chuen Chang, et al. World J Gastroenterol. 2013 Dec 7; 19(45): 8366– 8372.

2. Effectiveness of fecal immunochemical testing in reducing colorectal cancer mortality from the One Million Taiwanese Screening

2020 TDDW

3.

4.

Program. Han-Mo Chiu, Sam Li-Sheng Chen, Amy Ming-Fang Yen, et al. Cancer. 2015 Sep 15; 121(18): 3221–3229.

Colorectal Cancer Incidence Patterns in the United States, 1974-2013. Siegel RL, Fedewa SA, Anderson WF, et al. J Natl Cancer Inst.

2017 Aug 1;109(8).

Stepwise relationship between components of metabolic syndrome and risk of colorectal

5.

adenoma in a Taiwanese population receiving screening colonoscopy. Hu NC, Chen JD, Lin YM, et al. J Formos Med Assoc. 2011 Feb;110(2):100-8.

Colorectal cancer screening for averagerisk adults: 2018 guideline update from the American Cancer Society. Wolf AMD, Fontham ETH, Church TR, et al. CA Cancer J Clin. 2018 Jul;68(4):250-281.

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2020 TDDW

Symposium (VII) COLORECTAL CANCER SCREENING ON THE CROSS ROAD

STRATIFIED SCREENING: IS IT NECESSARY AND WHAT ARE THE CHALLENGES? Han-Mo Chiu Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan Colorectal cancer (CRC) screening has proven effective in reducing CRC incidence and its related death. Many countries and regions with moderate to high incidence of CRC have launched population CRC screening program.

Some countries like U.S, Germany and Poland provide primary colonoscopy screening whereas in most EU and Asia-Pacific countries, stratified screening mainly with fecal immunochemical test (FIT) is used to identify people at higher risk of CRC or advanced adenoma to make the most efficient use of constrained healthcare resources and endoscopy manpower.

Though direct comparison study of the effectiveness by colonoscopy or FIT-based screening is still ongoing, accumulating body of evidences demonstrated that stratified screening with FIT is able to reduce CRC mortality by cohort studies and as cost-effective as colonoscopybased screening given good compliance to periodic FIT screening and colonoscopy after positive FIT by modelling studies. Considering the healthcare resources, disease burden of other GI cancers, and endoscopy manpower, FIT screening is a rather practical and affordable CRC screening strategy in the Asia-Pacific counties.

Although CRC screening is effective in

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reducing incidence of advanced stage CRC and CRC related death, interval cancer still exists, which largely affects the effectiveness of the screening program. Previous studies have also shown that FIT screening is less effective in detecting proximal neoplasm, especially the sessile serrated adenoma, and less extent of prevention of proximal colon cancers. Whether we are able to further adopt precision medicine in CRC screening is an intriguing issue. A recent cost-effectiveness study by EGAPP (Evaluation of Genomic Applications in Practice and Prevention Working Group) suggest that CRC screening based on polygenic risk prediction is not ready for widespread implementation. As a matter of fact, in such polygenic testing, only genomic but other lifestyle risk factors or metagenomics were taken into consideration therefore may not be able to accurately predict individual CRC risk. A recent study from U.S. used models accommodating lifestyle, environmental, and genetic factors and it showed greater accuracy in determining risk of CRC and starting ages for screening than the family history only model, which is based on the current screening guideline. Further effort is necessary in this aspect.

2020 TDDW

Symposium (VIII) ADVANCE IN SYSTEMIC TREATMENT FOR HCC

MOLECULAR TARGET THERAPIES: SORAFENIB, LENVATINIB, REGORAFENIB, RAMUCIRUMAB, CABOZANTINIB Chen-Chun Lin Division of Hepatology, Liver Research Unit, Department of Gastroenterology and Hepatology, LinKuo Chang Gung Memorial Hospital; Chang Gung University, Taoyuan, Taiwan Hepatocellular carcinoma (HCC) is the fifth common cancer and the second cancer death in the world. The prognosis is dismal if the tumor in the advanced stage or not suitable for resection or locoregional treatment. Before 2017, sorafenib was the only approved drug based on the two pivotal randomized clinical trials (SHARP and Asia-Pacific), to show survival benefit over placebo for the advanced HCC patients who did not receive any systemic treatments. In 2018, lenvatinib was one of the multiple tyrosine inhibitors and was approved as an alternative to sorafenib for the first-line treatment of advanced or unresectable HCC according to a phase 3 randomized clinical trial (REFLECT) showing non-inferiority to sorafenib in the first-line setting.

Regorafenib is an orally administered multi-kinase inhibitor with a very similar structure to sorafenib but with a significantly lower IC50 concentration for VEGFR-2. Regorafenib was the first drug to prolong overall survival vs. placebo in patients progressing on sorafenib and has been approved since 2017 for the advanced HCC patients who have been previously treated with sorafenib based on the phase 3 RESORCE trial. Cabozantinib is an oral tyrosine kinase, majorly inhibiting VEGFR-2, c-MET, and AXL, and has been approved since 2018 in the EU and 2019 in the USA for the

treatment of patients with advanced HCC who have been previously treated with sorafenib based on the results of phase 3 CELESTIAl trial, which included 72% of patients as the second line and had received only prior sorafenib treatment.

Ramucirumab, administrated by intravenous infusion, is an immunoglobulin G1 monoclonal antibody that targets the VEGFR-2. In a previous phase 3 randomized trial (REACH), the survival benefit was only seen in the subgroup of patients with AFP ≥400 ng/ml. The following data from the double-blind phase 3 trial REACH-2, only included AFP ≥400 ng/ml at baseline, have confirmed the survival benefit over placebo for the advanced HCC with previously treated by sorafenib.

Ramucirumab has been approved since 2019 in the USA and EU. Nowadays, a total of 5 molecular target agents have been approved for patients with advanced HCC. Two of them, sorafenib and lenvatinib, could serve as the first-line treatment, while the other three approved the second-line treatment. The increase in treatment options has created complexity in the therapeutic landscape and timing/sequencing of switches. There is limited evidence to support clinicians in choosing between approved second-line treatments for these patients.

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2020 TDDW

Symposium (VIII) ADVANCE IN SYSTEMIC TREATMENT FOR HCC

IMMUNE CHECKPOINT INHIBITORS MONO-THERAPY FOR HCC Yi-Hsiang Huang Division of Gastroenterology & Hepatology, Taipei Veterans General Hospital, Taipei, Taiwan Institute of Clinical Medicine, National Yang-Ming University, Taipei, Taiwan Despite improvement in surveillance and hepatitis B vaccination, hepatitis C treatment, a large number of HCC patients still present with unresectable, advanced-stage disease and require systemic therapy. Recently, several promising results from the phase 2/3 trials of first or second line settings enable HCC patients access to more treatment options. Manipulation of immune checkpoints (ICI) by targeted antibodies against programmed cell death-1 (PD-1), or programmed death-ligand 1 (PD-L1) axis, have recently emerged as an effective anticancer strategy for many types of cancers, including HCC. Nivolumab is the first FDA-approved immune checkpoint inhibitor for HCC, yielded an objective response rate (ORR) of 14% and 9-month survival rate of 74% in second line setting. Pembrolizumab,

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another antibody against PD1, showed a similar response rate as nivolumab in phase 2 (Keynote 224) and phase 3 (Keynote 240) trials of HCC patients for second line treatment. The real-world experience of immunotherapy for unresectable HCC from Taiwan showed an ORR of 24.4%. A 1010 rule of early AFP response can predict objective response and survival to immune checkpoint inhibitor (ICI) treatment in unresectable HCC. ALBI grade and Child-Pugh class determines survival

by ICI treatment. A recent multicenter postregistration study by collecting 219 HCC patient receiving nivolumab monotherapy revealed an ORR of 22.4% and DCR of 52.1%. Nivolumab had tried to expand its role in the first line setting, unfortunately, it did not reach statistically difference to sorafenib in a phase 3 CheckMate 459 trial.

2020 TDDW

Symposium (VIII) ADVANCE IN SYSTEMIC TREATMENT FOR HCC

LANDSCAPE IN THE FUTURE Ann-Lii Cheng National Taiwan University Cancer Center and National Taiwan University Hospital, Taipei, Taiwan The past decade has witnessed a booming development of systemic treatment for hepatocellular carcinoma (HCC). The paradigm has rapidly shifted from chemotherapy to molecular targeted therapy, immunotherapy, and now to combination of molecular targeted and immune therapy. The current first-line treatment includes sorafenib, Lenvatinib, and combination of atezolizumab (anti-PDL1) and bevacizumab (antiVEGF); and second-line regorafenib, cabozantinib, ramucirumab, plus two anti-PD1 checkpoint inhibitors, nivolumab and pembrolizumab.

Although the tumor response rate of singleagent anti-PD1 is around a modest 15-20%, the quality of response appears to be superior, with many remitted tumors remain under control for a prolonged period of time. Further, peri-operative

administration of immune checkpoint inhibitors (ICIs) may enhance the host immunity against tumors. Several ongoing trials are testing the efficacy of adjuvant or neoadjuvant immunotherapy in HCC. Preliminary results of several combinations of ICIs with multi-target TKIs suggest that this new modality of treatment may further improve tumor response to 30-50%. Final results of these trials are eagerly awaited. On the other hand, the progress of the combinations of two ICIs is also promising.

A major problem of these new treatments, either anti-PD1 plus anti-CTLA 4 or anti-PD1 plus multitarget TKIs, is the significantly increased toxicities.

Possible measures that help alleviate toxicity while maintain treatment efficacy will be discussed.

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2020 TDDW

Symposium (IX) CUTTING EDGES OF MULTIDISCIPLINARY MANAGEMENT OF PANCREATIC CANCER

THE MOLECULAR CARCINOGENESIS OF PANCREATIC CANCER Li-Yuan Bai Division of Hematology and Oncology, China Medical University Hospital, Taichung, Taiwan Clinical Trial Center, China Medical University Hospital, Taichung, Taiwan Pancreatic cancer is the leading 4th cause of cancer death globally and 8th in Taiwan. The incidence and mortality of pancreatic cancer also increase gradually in Taiwan in recent years.

Although the estimated time for pancreatic cancer formation is more than 20 years, most patients with pancreatic cancer are diagnosed at advanced or metastatic stage. Basic studies have shed light on acknowledging the cell of origin of pancreatic cancer. KRAS is believed to be the most important and initiating factor for the development of pancreatic cancer. However, other factors are

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implicated in the cooperative, consecutive events which facilitate the formation of pancreatic cancer, including acquisition of additional mutations, chronic inflammation, obesity, smoking and inflammatory macrophages. The NGS technology does not find more recurrent mutation beyond the classic four (KRAS, TP53, CDKN2A and SMAD4) but help to classify the pancreatic cancer into subtypes which bear the significance in selecting treatment of choices. In this meeting, we will discuss the present situation and problems of molecular carcinogenesis for pancreatic cancer.

2020 TDDW

Symposium (IX) CUTTING EDGES OF MULTIDISCIPLINARY MANAGEMENT OF PANCREATIC CANCER

REFINED DIAGNOSTIC MODALITY OF PANCREATIC CANCER Hsiu-Po Wang Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan Pancreatic cancer incidence rate has increased over the last decades. The pancreatic is with aggressive course and with poor prognosis.

Only 20% of patients are surgical candidates and <10% undergo complete surgical resection.

Among the non-surgical cases (80%), 50% with spreading to distant lymphnodes or organs and 30% with the cancer encases crucial arteries.

The 5-year overall survival (OS) rate is less than 20%. Although many agents have demonstrated initial promise for PC therapy, further investigation almost uniformly reveals no survival benefit. The only possibility to increases the outcome of the patients is to detect the pre-cancerous or small ones.

CA 19-9 and CEA are the most commonly used biomarkers for diagnosis of pancreatic cancer. Ca199 provides the low positive predictive value for screening asymptomatic populations but with higher sensitivity and specificity in advanced pancreatic cancer. CEA is less useful than CA 199 in diagnosis of pancreatic cancer.

CT scans are often used to diagnose pancreatic cancer because they can show the

pancreas fairly clearly. They can also help show if cancer has spread to organs near the pancreas, as well as to lymph nodes and distant organs.

Multiphase CT scan provides higher detection. CT scans can also be used to guide a biopsy needle into a suspected pancreatic tumor. But if a needle biopsy is needed, endoscopic ultrasound to guide the needle into place is preferred. Special types of MRI scans can also be used in people who might have pancreatic cancer or are at high risk.

Endoscopic procedures for pancreatic cancer include ERCP and endoscopic ultrasound (EUS).

ERCP is less used for diagnosis of pancreatic cancer and is mostly replaced by MRCP. In the other hand, EUS is currently considered with high sensitivity and specificity in diagnosis of pancreatic mass. There are ancillary functions in EUS including elastography, contrast enhanced EUS, EUS-guided fine needle aspiration and biopsy, EUS-guided trans-needle confocal microscopy and molecular-genetic diagnosis. EUS not only can detect the small tumors but also provide the cytopathological diagnosis.

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2020 TDDW

Symposium (IX) CUTTING EDGES OF MULTIDISCIPLINARY MANAGEMENT OF PANCREATIC CANCER

MINIMALLY INVASIVE SURGERY FOR PANCREATIC CANCER Masafumi Nakamura Department of Surgery and Oncology, Graduate School of Medical Sciences, Kyushu University, Fukuoka, Japan Minimally invasive pancreatic surgery (MIPS) is still not a standard surgical treatment for PDAC, although minimally invasive distal pancreatectomy (MIDP) has been reported to show some advantages in short-term outcomes including perioperative morbidity. To safely disseminate MIDP, it is important to disseminate the knowledge of critical anatomy which is seen in surgical views specialized for PDAC. In addition, I’d like to show our method (PFC; Peri-Firing Compression) to prevent post-operative pancreatic fistula. We

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use Echelon stapler to well compress pancreatic parenchyma before and during firing to prevent damage of pancreatic capsule. Meanwhile, perioperative morbidity of minimally invasive pancratoduodenectomy (MIPD) has been often reported as even or more than that of open pancreatoduodenectomy (OPD). As well as MIDP, it is important to know specialized approach and anatomy for MIPD for safely performing MIPD. In this session, I’d like to show surgical anatomy for MIPS and how to perform PFC.

2020 TDDW

Symposium (IX) CUTTING EDGES OF MULTIDISCIPLINARY MANAGEMENT OF PANCREATIC CANCER

UPDATE OF (NEO)CHEMO- AND ICI-THERAPY FOR PANCREATIC CANCER Nai-Jung Chiang National Institute of Cancer Research, National Health Research Institutes, Miaoli, Taiwan Department of Oncology, National Cheng Kung University Hospital, Tainan, Taiwan Pancreatic adenocarcinoma (PDAC) is associated with dismal prognosis. Only 2030% of patients had the operable disease at the time of diagnosis. The main cure for PDAC remains surgical resection. With the development of intensive combination chemotherapy of FOLFIRINOX (oxaliplatin, irinotecan, 5-flurouracil plus leucovorin) and gemcitabine plus nabpaclitaxel, patients with unresectable locally advanced and metastatic disease receiving combination therapy had better response rate and longer median overall survival than those receiving monotherapy.

Immunotherapy alone in unresectable PAC confers poor responses. Recently, many clinical

trials are initiated to assess the efficacy of immunotherapy in PDAC, including monotherapy of immune checkpoint inhibitors (ICIs), cancer vaccines, adoptive cell transfer, combinations with other immunotherapeutic agents, chemoradiotherapy or other molecularly targeted agents. ICI monotherapy is highly suggested in only PDAC with mismatch repair deficiency, or microsatellite instability-high. There seems to be a synergistic effect with higher response rates under the combination treatment of immunotherapy with other modalities than monotherapy. In this meeting, I will review the literature about the update of chemotherapy and ICIs applied in the treatment of PDAC.

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2020 TDDW

Symposium (X) BARIATRIC AND METABOLIC ENDOSCOPY: HOW AND WHEN?

INTRAGASTRIC BALLOONS Chi-Ming Tai Division of Gastroenterology and Hepatology, Department of Internal Medicine, E-Da Hospital, Kaohsiung, Taiwan Obesity represents a growing public health threat. Bariatric surgery was the primary means for treating morbidly obese patients. Endoscopic bariatric therapy (EBT) can bridge the gap in patients who do not fit the BMI criteria for surgery and fail conservative or medical therapy. EBTs include devices that are placed or removed via flexible endoscopy, and procedures that utilize instruments that require flexible endoscopy for the indications of weight loss.

Intragastric balloons (IGBs) are the most widely available EBT. Currently, there are eight IGBs in the world market. The Orbera intragastric balloon,

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previously known as the BioEnterics Intragastric Balloon is the most commonly used IGBs. The low invasiveness and relative safety of the IGBs have resulted in broad acceptance of its use. However, they are temporary measures and should be removed six months after placement. These devices may help patients initiate the important first steps in weight loss maintenance but weight regain is an expected result after their removal. To optimize the effect of the IGBs, they should be used in conjunction with a multidisciplinary program that includes lifestyle intervention, dietary support, and physician supervision.

2020 TDDW

Symposium (X) BARIATRIC AND METABOLIC ENDOSCOPY: HOW AND WHEN?

GASTROPLASTY AND ASPIRATION THERAPY FOR OBESITY Tun-Jen Hsiao Superintendent, Charity Clinic, Taoyuan, Taiwan Obesity is a global emerging public health threat. The prevalence of obesity in Taiwan (defined as BMI ≧ 27) was increasing gradually in the past decades. Obesity is associated with many health adverse effects, including diabetes, hypertension, hyperlipidemia, gout, gall bladder disease, NAFLD, GERD, etc. Additionally, people with high BMI was found to have high medical expenditure in NHI reimbursement system. Prevention and treatment of obesity are highly appreciatedly in all counties all over the world. Traditionally, the treatment of obesity is based on some steps as below: 1st Eat less, exercise more, and therapeutical lifestyle change 2nd Pharmacotherapy 3rd Bariatric therapy But in recent years, Endoscopic Bariatric and Metabolic Therapies (EBMT) are a new addition to the treatment arsenal for obesity, including intragastric balloon (IGB), endoscopic sleeve gastroplasty (ESG), aspiration therapy (AT), and duodenal mucosal resurfacing, etc. EBMT poses a position just between pharmacotherapy and bariatric therapy. Till 27, September, 2020, only IGB was proved by TFDA for the treatment of obesity in Taiwan.

Aspiration therapy with the AspireAssist

System removes a portion gastric contents after a meal through a tube similar to a percutaneous endoscopic gastrostomy tube (PEG), reducing the amount of chyme reaching the small bowel for absorption. The A-Tube is placed endoscopically with a standard pull technique. This device was approved for use in the US in patients with a BMI between 35-55 kg/m2.

The Overstitch (Apollo Endosurgery, Austin, TX), is a suturing device that fits on the end of a double channel endoscope, inserting into the larger channel, with a curved needle driver which allows for full thickness sutures to be placed in an interrupted or running fashion. Using This device, endoscopist could suture from internal side to reduce the volume of stomach just like lararoscopic sleeve gastrectomy.

To optimize the effect of the EBMTs, they should be used in conjunction with a multidisciplinary program that includes lifestyle intervention, dietary support, exercise program and physician supervision. Furthermore, there are some promising and outstanding pharmacotherapy is developed recently. Physician would make treatment option considerately for the obese patients.

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2020 TDDW

Symposium (X) BARIATRIC AND METABOLIC ENDOSCOPY: HOW AND WHEN?

BYPASS INTERVENTION AND DUODENAL MUCOSAL RESURFACING Kuan-Chieh Fang Division of Gastroenterology and Hepatology, Taipei Medical University Hospital, Taipei, Taiwan Institute of Clinical Medicine, School of Medicine, Taipei Medical University, Taipei, Taiwan During a period of procedural development to treat obesity since decades ago, surgeon and physician found that bariatric surgery, such as Roux-en-Y gastric bypass (RYGB) and the biliopancreatic diversion (BPD), are effective treatments not only for body weight control but also for the glycemic control. In the field of bariatric bypass intervention, we found the procedure has outstanding results in normalization of concentrations of plasma glucose, insulin, and HbA1c among morbidly obese patients.

Duodenal mucosal resurfacing (DMR), also known by the brand name Revita (DMR), is a novel, minimally invasive, catheter-based upper endoscopic procedure that applying circumferential hydrothermal ablation of the duodenal mucosa and subsequent mucosal healing. The procedure results in the mucosal cell regeneration without the need for incisions, stitches or implants. DMR has been shown to treat the lining of the duodenum, leading to improve glycemic control in people with

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type 2 diabetes mellitus (T2DM) irrespective of body mass index (BMI) changes.

DMR is an insulin-sensitizing intervention which can be complementary to lifestyle intervention approaches and pharmacological treatments aimed at preserving the pancreas and liver from failure. DMR is a potential therapeutic solution for patients with type 2 diabetes and fatty liver disease. It has great impact on reversing dysmetabolic status in patients with T2DM and nonalcoholic fatty liver disease/nonalcoholic steatohepatitis, highlighting the important role of the duodenum in regulating systemic metabolism, insulin sensitivity, and hepatic inflammation.

Although DMR reveals a clinically significant improvement in hyperglycemia in patients with type 2 diabetes in the short-term, with acceptable safety and tolerability. Long-term safety, efficacy, and durability and possible mechanisms of action require further investigation.

2020 TDDW

Symposium (X) BARIATRIC AND METABOLIC ENDOSCOPY: HOW AND WHEN?

GUIDELINES, COMPLIANCE AND TRAINING ISSUES Allison R. Schulman Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, MI, USA Obesity is becoming a world-wide pandemic.

As bariatric endoscopy continues to emerge as a subspecialty for patients who are not candidates for bariatric surgery or who desire less-invasive options, an increasing number of gastroenterologists and surgeons are interested in offering endoscopic bariatric and metabolic therapy as their institutions. There are several important elements for training in bariatric endoscopy and obtaining the tools needed to be able to establish an effective, comprehensive, multidisciplinary bariatric program. This lecture

will review the important elements including how to develop technical endoscopic expertise and the necessary cognitive components required for a successful program. I will review guidelines and compliance issues related to bariatric endoscopy, focusing on important training goals required to establish a program including obesity physiology, interdisciplinary team management, cognitive and technical proficiency in endoscopic bariatric and metabolic therapies, and the importance of individualizing therapy.

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2020 TDDW

Symposium (XI) MULTI-CENTERED CLINICAL TRIALS, EXAMPLES OF HBV AND HELICOBACTER PYLORI INFECTION

MULTI-CENTERED STUDY FOR HP TREATMENT IN TAIWAN Jyh-Ming Liou Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan Eradication of Helicobacter pylori (H. pylori) reduces the risk of gastric cancer peptic ulcer disease, and cures 70% of patients with gastric mucosal associated lymphoid tissue lymphoma. Therefore, we organized the Taiwan Gastrointestinal Disease and Helicobacter Consortium and conducted multicenter clinical trials and studies in the management of H. pylori infection and its associated diseases. The updated prevalence of H. pylori infection is 30% in adults and 8-10% in children and adolescents in our nationwide survey in 2019-2020 in Taiwan. The prevalence of antibiotic resistance of clarithromycin, levofloxacin, metronidazole, amoxicillin, and tetracycline in adults are 16%, 18%, 24%, 2%, and 5%, respectively. In our multicenter clinical trials, we showed that bismuth quadruple therapy for 10 days and sequential therapy for 14 days were superior to triple therapy for 14 days in Taiwan. Levofloxacin-based therapy should be reserved for second-line and third-line

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rescue therapies. Bismuth quadruple therapy and 14-day levofloxacin containing sequential therapy are similarly effective in the second-line treatment of H. pylori infection. Susceptibility testing or genotypic resistance-guided therapy is the preferred treatment for refractory H. pylori infection, but empirical therapy may be an acceptable alternative. Eradication of H. pylori leads to short-term perturbation of gut microbiota. We further showed that the diversity of gut microbiota can be restored months after eradication therapy, but the speed of recovery varies with regimens.

The short-term increases of antibiotic resistance of Escherichia coli and Klebsiella pneumoniae may be restored to basal states months after H. pylori eradication. Future studies that apply in-depth sequencing, such as shotgun metagenomics sequencing, are needed to clarify whether the compositions of gut microbiota at the species level and the resistome of gut microbiota are fully restored long-term after H. pylori eradication.

2020 TDDW

Symposium (XI) MULTI-CENTERED CLINICAL TRIALS, EXAMPLES OF HBV AND HELICOBACTER PYLORI INFECTION

TREATMENT AND PREVENTION OF PEDIATRICS H. PYLORI INFECTION IN TAIWAN Yao-Jong Yang Department of Pediatrics, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan H. pylori primarily infected since childhood.

The transmission route is favored by person-toperson transmission. The socioeconomics, familial transmission, ethics, and other factors determine the prevalence rate of infection. Although we have approached more and more knowledge to this microorganism, the prevalence of H. pylori infection is only a little bit decrease in the past three decades. The consensus of treatment is well established in adult patients in the world. However, the guideline for pediatric H. pylori therapy is still limit due to lack of large-scald multicenter studies. This topic will investigate the evidences for treatment and prevention of pediatric H. pylori infection in Taiwan and the world.

The NASPGHAN/ESPGHAN consensus for pediatric H. pylori eradication suggests the antibiotics choice should be tailored according to susceptibility testing with a strict adherence.

However, only few hospitals can offer the H. pylori culture and sensitivity tests in real-world practice in Taiwan. Moreover, is the cost-effectiveness of culture-based strategy superior than test-to-treat method still unproved. In the recent, Kori et al have reported a registered result from 23 hospitals in Europe from 2013 to 2016, primary resistance to clarithromycin and metronidazole were 25% and

21%, respectively. A 7 to 14-day triple therapy tailored to antibiotic susceptibility only researched 79.8% of successful rate in the naïve patients.

Therefore, new combined reagents and optimal duration for pediatric H. pylori treatment needs further randomized clinical trials.

To prevent H. pylori infection in children needs to understand the transmission route of this microorganism. Person-to-person transmission (fecal-oral, oral-oral, and gastro-oral) is the main transmission route in recent concepts. Methods to block the infectious route such as improving socioecnomic condition and environment hygiene, avoiding contaminant food and water, and contacting infectious pets are highly suggested.

Breastfeeding in middle- and low-income nations provides a protective effect to decrease H. pylori prevalence in infants and young children.

In conclusion, H. pylori eradication in pediatric population based on the culture/susceptibility test is highly recommended. If culture-based strategy is not available, treatment according to the local epidemiological data of antibiotic-resistant rate of H. pylori is required. The effective methods for prevention of H. pylori transmission desires further strong evidence.

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2020 TDDW

Symposium (XI) MULTI-CENTERED CLINICAL TRIALS, EXAMPLES OF HBV AND HELICOBACTER PYLORI INFECTION

THE PREMIT STUDY: PREVENTING MOTHER-TO-INFANT TRANSMISSION OF HBV Huey-Ling Chen Division of Pediatric Gastroenterology, Hepatology and Nutrition, Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan Since the implementation of universal neonatal HBV immunization using HBV vaccines and hepatitis B immunoglobulin (HBIG) in 1984, the chronic HBV infection rate in Taiwan has decreased from 15-20% to <1% in the immunized population. However, immunized children with HBV related chronic hepatitis and hepatocellular carcinoma still occur. Maternal HBeAg positivity and high levels of maternal HBV DNA are the most important risk factors for transmission. The Taiwan Study Group for the Prevention of Mother-to-Infant Transmission of HBV (PreMIT Study) started in 2011 to conduct a multi-centered clinical trial for maternal antiviral therapy in pregnancy. The study group included experts from Obstetrician, Hepatologist, and Pediatrician, aiming to develop better care for HBV-infected mothers and children.

This clinical trial recruited chronic HBV-infected pregnant women seropositive for both HBsAg and HBeAg during routine pregnancy test. Women were tested for HBV DNA; those with high viral load were given tenofovir disoproxil fumarate (TDF) since third trimester until postpartum. From the collaborative work of 14 hospitals, we found shortterm antiviral therapy for pregnant women starting

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since the third trimester is effective to further reduce 90% of children with vaccine failure, and maternal liver health is not affected by this treatment course.

Further long-term follow-up of these children had comparable long-term growth, renal function, and bone development up to 6–7 years. The Taiwan National Health Insurance has incorporated this pregnant women short-term treatment course into reimbursement since 2018. Recently, tenofovir alafenamide fumarate (TAF) has been used for chronic hepatitis B treatment with better safety profile in renal and bone function. Our study group continues to investigate the safety and efficacy of TAF in preventing mother-to-infant transmission.

More information regarding the long-term effect in mother receiving antiviral therapy in pregnancy will provide better care for this population.

In conclusion, pregnant women screening and targeted antiviral treatment, universal neonatal immunization, postnatal surveillance has effectively interrupting mother-to-infant HBV infection and decreased HBV infection in the population. Better care of women and children is anticipated.

2020 TDDW

Symposium (XI) MULTI-CENTERED CLINICAL TRIALS, EXAMPLES OF HBV AND HELICOBACTER PYLORI INFECTION

HOW TO ESTABLISH A COLLABORATIVE TEAM FOR MULTICENTERED CLINICAL TRIALS, EXAMPLE FROM HBV TRANSMISSION STUDY IN SOUTHEAST ASIA Gonzague Jourdain French National Research Institute for Sustainable Development (IRD) The Program for Health, Prevention and Treatment (PHPT) is conducted by the French National Research Institute for Sustainable Development and Chiang Mai University in Chiang Mai, Thailand. Researchers from these institutions and others in Thailand, Laos, Europe and the USA join their efforts to address major public health issues caused infectious diseases. Starting from scratch in 1996, it has needed the initial effort was develop a “Clinical Trial Unit” able to implement clinical trials following international standards for good clinical Practice, human subjects protection, data management and statistical analysis. This required the input of experts in several fields: medicine, clinical epidemiology and statistics, public health, nursing, pharmacy, biology, but also information technology (IT), logistics, quality systems, finance and administration. As academic training in clinical research was very limited in Thailand, specific training was provided to technicians from various backgrounds. In addition to the CTU, the clinical research infrastructure includes a large network

of hospital practitioners (clinical research sites) who have been trained and have experience in clinical research implementation to recruit and follow patients in clinical studies. The coordination between several hospital departments is also a challenge for example between maternity units, pediatrics, hepatology when evaluating strategies to prevent mother to child transmission (MTCT) of hepatitis B virus (HBV). The program has contributed to the field of MTCT of viruses as well as to the design of strategies for HIV prevention and treatment in adults, as evidenced by publications in high impact factor journals and the use of research results in national and international guidelines. Among several factors for success, the most important ones may have been the focus on public health issues, the enthusiasm for collaboration, communication between partners, quality management systems, continuous training, diversity of the team, ability to successfully apply to competitive funding opportunities from public entities internationally.

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2020 TDDW

Symposium (XII) NAFLD/NASH SYMPOSIUM

EXPERIMENTAL MODELS OF NAFLD/NASH Ying-Ying Yang Division of Gastroenterology and Hepatology & General Medicine, Department of Medicine, Division of Clinical Skill Training, Department of Medical Education, Taipei Veteran General Hospital, Taipei, Taiwan Institute of Clinical Medicine, Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan Non-alcoholic steatohepatitis (NASH) is a major cause of chronic liver disease. Liver fibrosis and portal hypertension are the strongest prognostic markers in advanced NASH. In fact, its prevalence has been estimated to be as high as 25% in the general population and even higher (>70%) in patients with other metabolic risk factors like obesity and diabetes. Additionally, it is well known than up to 30% of the Non-alcoholic fatty liver disease (NAFLD) population will further progress and develop NASH, the more severe form of fatty liver disease, cirrhosis and hepatocellular carcinoma (HCC).

Animal models are an essential tool for the identification of the mechanisms driving the pathogenesis and progression of NAFLD to NASH. Ideally, experimental models should reflect the etiology, disease progression, and pathology of human NAFLD. Rats seem to be more susceptible to highfat diet (HFD) than mice. Sprague-Dawley rats susceptible to steatohepatitis development when fed with HFD. Whereas hepatic steatosis and NASH were not induced in Wistar rats with long-term high saturated fat feeding. Moreover, it was reported that BALB/c male mice had more severe hepatic lipid deposition than C57BL/6J male mice when fed an HFD. Adding high fructose to an overfed diet can promote liver fibrosis, hepatocellular ballooning, and adipose tissue inflammation. By

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comparing the effects of MCD diet between male and female Wistar, Long-Evans, Sprague-Dawley, and C57/BL6 mice rats, it had been reported that discovered that the male gender and Wistar strain were related to the greatest degree of steatosis in rats. Moreover, male C57/BL6 mice showed the maximum lipid peroxidation, ultrastructural injury, inflammation, and necrosis and the most similar characteristics of NASH. It was reported that CDAA diet combined with HFD can bring about rapid development of NASH with fibrosis (6–9 weeks), without substantial weight loss, but it still fails to elicit features of the metabolic syndrome. Highly similar to ob/ob mice, db/db mice are inactive, hyperphagic, overly obese, and display hyperlipidemia, hyperglycemia, hyperinsulinemia, and IR and develop hepatic steatosis but no steatohepatitis and fibrosis. An analogous mutation exists in rats and is described as fa/fa (also known as Zucker rats). Fa/fa rats display similar features to both ob/ob and db/ db mice. They also need additional stimulus such as MCD diet to develop the symptoms of steatohepatitis.

As a tumor suppressor gene, phosphatase and tensin homolog (PTEN) negatively regulates several signaling cascades, which regulate apoptosis, cell proliferation, and tumor formation.

PTEN knockout mice spontaneously develop steatosis, steatohepatitis, and fibrosis, which are

2020 TDDW similar to human NASH. Sterol Regulatory ElementBinding Protein 1c transgenic Mice develop IR and marked hepatic steatosis (8-day-age). Besides steatosis, they also spontaneously develop steatohepatitis manifests as lobular inflammation, ballooned hepatocytes, and pericellular fibrosis at 20 weeks. These mice seem to be suitable for the lipodystrophy-associated steatohepatitis model.

KKAy/a mice are established by crossing KK mice with yellow obese mice (Ay) mouse. These mice carry a heterozygous mutation in the agouti gene, which impairs hypothalamic appetite and results in hyperphagia and obesity. Although they develop hyperglycemia, hyperinsulinemia, IR, and liver steatosis, significant steatohepatitis does not occur spontaneously. Additional stimulus such as MCD diet can induce steatohepatitis.

There was also a similar model that mice were given streptozotocin followed by HFD. Compared

to exclusively HFD-fed mice, streptozotocintreated group shows more fibrosis in central vein, portal tract areas, and perisinusoidal space, although there is no significant differences in levels of transaminase, degree of steatosis, or inflammation, accompanied by weight loss.

HFD-fed obese mice combined with multiple administration of CCl4 develop inflammation, apoptosis, and fibrosis in the liver. Under these circumstances, CCl4 potentiates the effect of HFD on NASH and fibrosis development. Low-dose intraperitoneal injections of CCl4 to CDAA diet-fed C57BL/6 mice induce marked features of NASH compared with CDAA diet alone and develop HCC. To date, no single rodent model can display the whole disease spectrum and metabolic features associated with human NASH, but can imitate particular characteristics.

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2020 TDDW

Symposium (XII) NAFLD/NASH SYMPOSIUM

FROM GENETICS TO EPIGENETICS IN NAFLD/NASH Chung-Feng Huang Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan Genetics and epigenetics play a key role in the development of several diseases, including nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH). Family studies demonstrate that first degree relatives of patients with NAFLD are at a much higher risk of the disease than the general population. The development of the Genome Wide Association Study (GWAS) technology and consequent candidate gene studies have allowed the identification of numerous genetic polymorphisms involved in the evolution of diseases (e.g., PNPLA3, MBOAT7, TM6SF2, HSD17B13). On the other hand, epigenetic changes including histone modifications, DNA

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methylation and microRNAs may interact with inherited risk factors to determine an individual’s susceptibility to NAFLD. Several genetic variants are associate with disease progression in NAFLD. Meanwhile, The SNPs accompanied with other seromarkers have been disclosed as predictive tool NASH. Meanwhile, patients who carry different genetic variants may be associated with different treatment outcome after life style modification or therapeutic intervention. Future goal may target on the drug development in treating NASH on the basis of the pathophysiological role of the genetics.

2020 TDDW

Symposium (XII) NAFLD/NASH SYMPOSIUM

INSIGHTS OF MICROBIOTA IN NASH Kuei-Chuan Lee Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan Department of Medicine, National Yang-Ming University, Taipei, Taiwan Non-alcoholic fatty liver disease (NAFLD) has become the most common chronic liver disease in the world. Fatty liver can progress to non-alcoholic steatohepatitis (NASH), liver cirrhosis and hepatocellular carcinoma. Animal and human studies have found that gut microbiota imbalance is one of the important pathological mechanisms of fatty liver and NASH. At present, the evidences of the playing roles of gut microbiota in NASH mainly come from animal experiments, using methods to change the intestinal flora, such as antibiotics, probiotics, fecal bacteria transplantation or sterile animals. Gut micriobiota imbalance can increase intestinal permeability, allowing bacteria and their products to enter the

liver and cause liver inflammation; in addition, the intestinal bacterial dysbiosis would change the production of metabolites and further affect the body’s metabolism. Exploring the relationship between gut micriobiota and fatty liver disease can enable us to better understand the role of the gut liver axis and improve the treatment of fatty liver. With the rapid development of research tools (next-generation sequencing, transcriptome, metabolome), in the future, long-term generation tracking studies are needed to understand the gut microbiota more comprehensively to develop individualized gut microbiota targeted treatments to achieve personalized care.

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2020 TDDW

Symposium (XII) NAFLD/NASH SYMPOSIUM

MANAGEMENT AND THERAPEUTIC APPROACH IN NASH Shiv Chitturi Department of Gastroenterology and Hepatology, The Canberra Hospital, Canberra, Australia Nonalcoholic fatty liver disease (NAFLD) comprises a spectrum of disorders ranging from hepatic steatosis and nonalcoholic steatohepatitis (NASH) through to cirrhosis. The global prevalence of NAFLD has increased considerably and approaches 30% in several Asian countries.

The overall prognosis of NAFLD is dictated by the histologic severity of the disease, with the fibrosis stage being the key determinant. Liver-related mortality is highest among patients with bridging fibrosis (F3) and cirrhosis (F4). Patients with NASH and significant liver fibrosis (F≥2) are also likely to progress and are now targeted in ongoing clinical trials. Noninvasive tests to assess fibrosis stage are being increasingly used instead of liver biopsy.

Serial testing using simple noninvasive tests (FIB4, NAFLD fibrosis score) can be considered for

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assessing NAFLD in the community. Those with abnormal results from these tests can undergo 2nd line screening using more specialised blood tests that combine standard and nonstandard biomarkers (Fibrotest, Enhanced liver fibrosis score) or by elastographic assessment methods of liver stiffness (Fibroscan™, shear wave elastography). This strategy can reduce the need for liver biopsies (20%-30%). Lifestyle measures are the key to managing NASH. Loss of up to 10% baseline body weight can lead to resolution of NASH and reduction in liver fibrosis. Current drug options include pioglitazine and vitamin E along with several new drug classes such as PPAR agonists, thyromimetics, glucagon-like peptide 1 agonists and sodium/glucose transporter 2 inhibitors. Their efficacy and safety will be discussed.

2020 TDDW

Symposium (XIII) GEST-KASID SYMPOSIUM BIG DEBATE ON CONTROVERSY IN COLONOSCOPY PRACTICE

PROS: IS POST-COLONOSCOPY SURVEILLANCE GUIDELINES APPLICABLE IN ASIA? Chang Mo Moon Ewha Womans University College of Medicine, Seoul, Korea According to world cancer statistics, colon cancer in 2018 was the third most common malignant tumor in the world and the fourth leading cause of cancer deaths.1 In the same year, domestic statistics released by the National Statistical Office showed that the incidence rate was 54.9 per 100,000 population, second only to gastric cancer, which was 57.9. It is the third with 17.1, after lung cancer (34.8) and liver cancer (20.7). Compared to 13.9% 10 years ago, it is on the rise.2 In the large intestine, adenoma progresses to colorectal cancer through the process of carcinogenesis, and it is known to reduce the incidence and prevalence of colorectal cancer by blocking the carcinogenesis process by removing the adenoma using colonoscopy.

According to The National Polyp Study, The incidence of colorectal cancer decreased by 90%, 88%, and 76%, respectively, in the three cohorts of the National Cancer Institute in the U.S.3 In subsequent studies, the incidence of colorectal cancer as well as the resulting mortality was 5367%, depending on the study. It has been reported to decrease.

Some Asian countries such as China, Japan, Korea, Malaysia, Singapore and Turkey had higher 5-year prevalence rates than that in other Asian countries. Asian countries, such as Japan and Korea, the 5-year prevalence and agestandardized incidence were higher than that

reported in Western countries. A higher crude incidence and crude mortality was reported for Hong Kong from the latest report of its local Cancer Registry.

The increased risk of subsequent neoplasia occurs because of polypectomy of three or more adenomas, any adenomas larger than 10 mm, any tubulovillous or villous adenoma, any adenoma with high-grade dysplasia, or any serrated polyp larger than 10 mm. Patients with any of these findings are defined as a high-risk group, and colonoscopy 3 years after complete removal is recommended. In addition, the surveillance period can be reduced based on previous colonoscopy findings, completeness of removal, health status, family history, and past medical history.

References: 1. Bray F, Ferlay J, Soerjomataram I, Siegel RL, Torre LA, Jemal A. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2018;68:394-424.

2. Causes of Death Statistics in 2018. [Internet].

Daejeon: Korean Statistical Information Service; 2019 Sep 23 [cited 2020 May 8].

Available from: http://www.index.go.kr/potal/ main/EachDtlPa geDetail.do?idx_cd=2770 3. Winawer SJ, Zauber AG, Ho MN, et al. Prevention of colorectal cancer by

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4.

5.

6.

7.

8.

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colonoscopic polypectomy. The National Polyp Study Workgroup. N Engl J Med 1993;329:1977-1981.

Zauber AG, Winawer SJ, O’Brien MJ, et al.

Colonoscopic polypectomy and long-term prevention of colorectal-cancer deaths. N Engl J Med 2012;366:687-696.

Doubeni CA, Corley DA, Quinn VP, et al.

Effectiveness of screening colonoscopy in reducing the risk of death from right and left colon cancer: a large community-based study.

Gut 2018;67:291-298.

Rabeneck L, Paszat LF, Saskin R, Stukel TA. Association between colonoscopy rates and colorectal cancer mortality. Am J Gastroenterol 2010;105:1627-1632.

Citarda F, Tomaselli G, Capocaccia R, Barcherini S, Crespi M, Italian Multicentre Study Group. Efficacy in standard clinical practice of colonoscopic polypectomy in reducing colorectal cancer incidence. Gut 2001;48:812-815.

International Agency for Research on Cancer

WHO. Cancer today. IARC Web site. https:// gco.iarc.fr/today/. Accessed January 21, 2019.

9. World Cancer Research Fund International.

Diet, nutrition, physical activity and cancer. https://www.wcrf.org/sites/de¬fault/files/ Summary-third-expert-report.pdf. Accessed May 10, 2019.

10. Hong Kong Cancer Registry. Overview of Hong Kong cancer statistics of 2016. Hospital Authority Web site. http://www3.ha.org.hk/ cancereg/pdf/overview/Summary of CanStat 2016. pdf. Updated October 2018. Accessed February 12, 2019.

11. Martin Cs Wong 1, Hanyue Ding 1, Jingxuan Wang 1, Paul Sf Chan 1, Junjie Huang 1Martin Cs Wong, Prevalence and risk factors of colorectal cancer in Asia. Intest Res. 2019 Jul;17(3):317-329.

12. Kim TO, Optimal Colonoscopy Surveillance Interval after Polypectomy. Clin Endosc. 2016 Jul;49(4):359-63.

2020 TDDW

Symposium (XIII) GEST-KASID SYMPOSIUM BIG DEBATE ON CONTROVERSY IN COLONOSCOPY PRACTICE

CONS: IS POST-COLONOSCOPY SURVEILLANCE GUIDELINES APPLICABLE IN ASIA? Wei-Yuan Chang Department of Internal Medicine, National Taiwan University Hospital Hsin-Chu Branch, Hsinchu, Taiwan CRC screening program had already showed its efficacy on reducing CRC prevalence and mortality. The core idea of the CRC screening program was to remove all pre-cancerous adenoma during screening colonoscopy to prevent subsequent CRC development. However, because of the inevitable risk of missed and metachronous lesions, a surveillance colonoscopy after polypectomy was mandatory to keep the protective power of colonoscopy. Therefore, many clinical guidelines had been published to guide colonoscopist to tailor each subject’s surveillance interval.

In Taiwan, most endoscopists followed the consensus guideline update by the US MultiSociety Task Force on designing each subject’s

surveillance plan. However, there are three major difference between Taiwan and USA. First, our CRC screening program used FITtest as screening program whereas USA used colonoscopy as first-line screening tool. This difference led to distinct population on entering the screening program. Second, our colonoscopy quality varied among physician and service unit, whether a universal guideline application in unit with different colonoscopy quality remain unknown.

Last but not the least, the cost of colonoscopy in Taiwan and USA had great difference thus the cost-effectiviness would be very different under the same surveillance guideline. Therefore, a new surveillance guideline designs for Taiwan is needed.

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Symposium (XIII) GEST-KASID SYMPOSIUM BIG DEBATE ON CONTROVERSY IN COLONOSCOPY PRACTICE

CONS: COLONOSCOPY SHOULD BE REPEATED SHORTLY FOR THOSE WITH POOR BOWEL PREP Hyun Jung Lee Department of Internal Medicine, Department of Gastroenterology, Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea The effectiveness of colonoscopy is critically dependent on an adequate bowel preparation.

Despite the importance of bowel cleanliness, suboptimal bowel preparation occurs in upto 30% of cases1 which is associated with decreased ADR, increased costs and adverse events, and the need for repeat procedures at accelerated interval.2 In addition, missed lesions during colonoscopy and incomplete colonoscopy are known to be risk factors for the development of interval colorectal cancer.3 Current guidelines suggest documenting the quality of bowel preparation and recommend early repeat colonoscopy within 1 year when bowel preparation quality for a screening or surveillance colonoscopy is inadequate, defined as the inability to identify lesions > 5 mm.4-6 However, these guidelines have not been supported by data linking scores on a specific rating scale with ability to detect lesions > 5 mm and little is known about outcomes caused by the suboptimal bowel preparation.

Colonoscopies with suboptimal bowel preparations have been shown to have an adenoma miss rate of 42% and an advanced adenoma miss rate of 27%.7 In clinical practice, various scoring systems have been used to rate the quality of colonoscopy preparation including the Aronchick Scale, Ottawa Bowel Preparation Scale, and Boston Bowel Prep Score. However,

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no data are available to determine whether the bowel preparation is adequate to identify polyps > 5 mm and perfect cleaning is clinically necessary. A meta-analysis revealed there was no significant difference in ADR between those patients determined to have intermediate vs highquality cleansing.2 Another study found that for colonoscopy with overall BBPS 3-5 (fair bowel preparation), segmental bowel assessment might be useful to further decide the followup colonoscopy interval.8 Besides poor bowel preparation, endoscopists’ concern about missed polyps could be possible explanations for nonadherence to surveillance guidelines.9 Regardless of the scoring system used, endoscopists should assess the quality of bowel preparation based on the ability to identify polyps after retained fluid or stool has been suctioned and recommend the next colonoscopy.

Meanwhile, a meta-analysis about the effect of bowel preparation on adenoma detection reported suboptimal bowel preparation affected detection of early colonic lesions stronger than advanced lesions.10 In addition, a subgroup analysis of patients in a large Dutch trial evaluating the accuracy of CT colonography for CRC screening demonstrated that the majority of 6-9 mm polyps did not progress to advanced neoplasia within 3 years.11 Based on these results, as recommended

2020 TDDW in USMSTF, if the bowel preparation is fair but adequate (to detect lesions > 5 mm) and if small (≤ 10 mm) tubular adenomas are detected, follow-up at 5 years should be considered.5 Identification of risk factors for inadequate bowel cleaning would have the potential benefit to improve the quality of bowel preparation.

Patients’ characteristics, clinical conditions, and medication use were defined as predictors for colonoscopy preparation failure12 and several models were developed to predict adequate bowel cleansing. Predictive models based on independent predictors of compliance or efficacy may help to better identify at risk candidates and to recommend tailored strategies.

References: 1. Froehlich F, Wietlisbach V, Gonvers JJ, et al.

Impact of colonic cleansing on quality and diagnostic yield of colonoscopy: the European Panel of Appropriateness of Gastrointestinal Endoscopy European multicenter study.

Gastrointest Endosc 2005;61:378-84.

2. Clark BT, Rustagi T, Laine L. What level of bowel prep quality requires early repeat colonoscopy: systematic review and metaanalysis of the impact of preparation quality on adenoma detection rate. Am J Gastroenterol 2014;109:1714-23; quiz 1724.

3. Singh S, Singh PP, Murad MH, et al.

Prevalence, risk factors, and outcomes of interval colorectal cancers: a systematic review and meta-analysis. Am J Gastroenterol 2014;109:1375-89.

4. Rex DK, Schoenfeld PS, Cohen J, et al.

Quality indicators for colonoscopy. Am J Gastroenterol 2015;110:72-90.

5. Lieberman DA, Rex DK, Winawer SJ, et al.

Guidelines for colonoscopy surveillance after

screening and polypectomy: a consensus update by the US Multi-Society Task Force on Colorectal Cancer. Gastroenterology 2012;143:844-857.

6. Hassan C, East J, Radaelli F, et al. Bowel preparation for colonoscopy: European Society of Gastrointestinal Endoscopy (ESGE) Guideline - Update 2019. Endoscopy 2019;51:775-794.

7. Lebwohl B, Kastrinos F, Glick M, et al. The impact of suboptimal bowel preparation on adenoma miss rates and the factors associated with early repeat colonoscopy.

Gastrointest Endosc 2011;73:1207-14.

8. Clark BT, Protiva P, Nagar A, et al.

Quantification of Adequate Bowel Preparation for Screening or Surveillance Colonoscopy in Men. Gastroenterology 2016;150:396-405; quiz e14-5.

9. Djinbachian R, Dubé AJ, Durand M, et al.

Adherence to post-polypectomy surveillance guidelines: a systematic review and metaanalysis. Endoscopy 2019;51:673-683.

10. Sulz MC, Kröger A, Prakash M, et al. MetaAnalysis of the Effect of Bowel Preparation on Adenoma Detection: Early Adenomas Affected Stronger than Advanced Adenomas.

PLoS One 2016;11:e0154149.

11. Tutein Nolthenius CJ, Boellaard TN, de Haan MC, et al. Evolution of Screen-Detected Small (6-9 mm) Polyps After a 3-Year Surveillance Interval: Assessment of Growth With CT Colonography Compared With Histopathology.

Am J Gastroenterol 2015;110:1682-90.

12. Gandhi K, Tofani C, Sokach C, et al. Patient Characteristics Associated With Quality of Colonoscopy Preparation: A Systematic Review and Meta-analysis. Clin Gastroenterol Hepatol 2018;16:357-369.e10.

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2020 TDDW

Symposium (XIII) GEST-KASID SYMPOSIUM BIG DEBATE ON CONTROVERSY IN COLONOSCOPY PRACTICE

PROS: IS ESD JUSTIFIED FOR LARGE SSA/P Su Young Kim Divison of Gastroenterology, Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea The sessile serrated adenomas/polyps (SSA/P) pathway accounts for 20-30% of sporadic colorectal cancer (CRC). SSA/P are difficult to detect and often incompletely removed. Because of these characteristics, SSA/Ps are often considered one of the main reasons for interval CRC. Also, these lesions can rapidly become dysplastic or invasive carcinoma, so active diagnosis and treatment for SSA/P are required.

Generally, SSA/Ps with and without dysplasia should be removed except the diminutive hyperplastic polyps in the rectum or sigmoid colon. Cold snare polypectomy is a good method for the removal of small SSA/Ps without dysplasia up to 10mm size. Endoscopic mucosal resection (EMR) also is a useful therapeutic technique for small SSA/Ps with dysplasia. Most SSA/Ps can be successfully removed using EMR. However, large SSA/Ps with dysplasia or carcinoma, EMR (or endoscopic piecemeal mucosal resection [EPMR]) remains challenging because of its method has the

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disadvantage such as risk of residual dysplastic lesion, recurrence, and problematical pathological assessment.

Endoscopic submucosal dissection (ESD) has recently attracted attention as an alternative that can successfully treat large SSA/Ps. ESD enables complete resection of the lesion by enabling en bloc resection, and improves the initial cure rate through accurate pathological evaluation of resected large SSA/Ps. Previous study showed that ESD demonstrated that no recurrence compared with the high recurrence related with EPMR. However, ESD has a disadvantage in that it takes a relatively longer procedure time than EMR, and is likely to cause complications such as perforation. These shortcomings can be solved by improving the proficiency of the ESD operator and having the ability to cope with complications.

Thus, ESD is expected to be a helpful endoscopic technique for large SSA/Ps with dysplasia or carcinoma.

2020 TDDW

Symposium (XIII) GEST-KASID SYMPOSIUM BIG DEBATE ON CONTROVERSY IN COLONOSCOPY PRACTICE

CONS: IS ESD JUSTIFIED FOR LARGE SSA/P Chen-Ya Kuo Division of Gastroenterology, Fu-Jen Catholic University Hospital, New Taipei City, Taiwan SSA/P is nowadays considered as a precursor lesion of colorectal cancer (CRC) via distinct carcinogensis pathway and contributes to 25% of sporadic CRCs. The prevalence of SSA/P was reported around 1-15% in average-risk patients undergoing colonoscopy. Currently, the most accurate diagnostic and therapeutic modality for SSA/P is colonoscopy.

The biological nature of SSA/P is very different from conventional adenomatous polyp. Around 7590% of SSA/Ps occur at proximal colon and 95% are less than 2 cm and have a very long dwelling time before they become dysplastic. As SSA/ Ps rarely harbor submucosal fibrosis, cold snare polypectomy is currently the preferred endoscopic resection method for SSA/Ps smaller than 1 cm, which carry very low rate of high-grade dysplasia or invasive cancers. For SSA/Ps larger than 1

cm, endoscopic mucosal resection (EMR) is recommended for en bloc resection and piecemeal EMR is also feasible if en bloc resection is difficult.

In a recent meta-analysis, residual polyp rate after hot EMR for large SSA/Ps was low at 5% with low rate of adverse events. In recent years, due to high efficacy and safety of cold snare polypectomy in sub-centimeter colon polyps, several pilot studies had started conducting cold snare endoscopic resection on large SSA/P (≧1 cm) and pooled analysis showed excellent results in terms of postpolypectomy bleeding, complete resection, and residual polyp rates. There is growing evidence that cold EMR is also a good modality for removal of non-dysplastic large SSA/Ps but further randomized controlled trials with larger sample size are needed.

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2020 TDDW

Symposium (XIII) GEST-KASID SYMPOSIUM BIG DEBATE ON CONTROVERSY IN COLONOSCOPY PRACTICE

CONS: PIECEMEAL COLD SNARE POLYPECTOMY FOR LARGE LESION Hyun Gun Kim Department of Internal Medicine, Soonchunhyang University College of Medicine, Seoul, Korea Cold snare polypectomy (CSP) has recently been in the spotlight as the primary procedure for removing colon polyps. A recent survey from the UK showed a high preference for CSP in removing small sessile polyps. CSP is now a standard procedure for removing small polyps less than 1 cm in size in the recent guideline. However, piecemeal CSP still has the controversy of treatment of choice for removal of a large lesion. The guideline recommends that further prospective studies are required to determine the clinical relevance of the piecemeal CSP technique, and its efficacy for completeness of resection for sessile polyps sized 10-19 mm.

Piecemeal CSP has several limitations to be performed on the large lesion. The evidence for the treatment results of piecemeal CSP for the large lesion is still lacking, besides the long-term follow-

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up results for recurrence are also very insufficient.

Theoretically, a large colorectal lesion has a higher possibility of containing cancer compared to a small lesion. Conventional piecemeal resection is known as a procedure with an increased risk of recurrence and is not recommended on the cancerous lesion. CSP does not use electric current, hence resects shallower in-depth than conventional hot method. Therefore, piecemeal CSP may have a higher risk of incomplete resection than conventional piecemeal resection due to vertical residue. Repetitive colonoscopy with short term interval may be an inconvenience to both patients and physicians.

It is important to derive more accurate indications of piecemeal CSP based on prospective long-term follow-up studies after resection of large lesions.

2020 TDDW

Symposium (XIV) HIPEC AND CONVERSION SURGERY FOR GASTRIC CANCER

NATIONWIDE DATA OF HIPEC FOR GASTRIC CANCER Mao-Chih Hsieh Department of Surgery, Wan-Fang Hospital, Taipei Medical University, Taipei, Taiwan There were 3,134 newly diagnosed gastric adenocarcinoma patients in Taiwan at 2017, about 31.4% was found at stage IV when gastric cancer was diagnosed. In stage IV patients, 74.2% received non-surgical treatment. Stage IV gastric cancer was considered as “unresectable” and terminal condition. Peritoneal metastasis (PM) is the most common form of metastasis in gastric cancer.

HIPEC in Taiwan was first developed to treat gastric cancer with PM. National Taiwan University Hospital and Taipei Veterans General Hospital performed HIPEC early since 1992. Both published their data at 1996. Wan-Fang Hospital was the only hospital to start HIPEC since 2000 and persisted till now. After 2014, a new medical equipment for HIPEC was adopted in Taiwan and several hospitals started to perform HIPEC later for patients with PM. Till now, there are at least 13 hospitals are performing HIPEC. However, during this period, HIPEC for PM of colorectal cancers became the major portion.

There is no registration platform for HIPEC in Taiwan. The exact patient numbers of gastric cancer received HIPEC are unknown. The purpose of HIPEC for gastric cancer can be

salvage, palliative, curative intent, prophylactic or for conversion surgery. A recent survey to the members of Taiwan Peritoneal Oncological Association revealed only a few hospitals are performing conversion surgery with HIPEC in recent years, with a total of 72 patients.

The treatment strategies from HIPEC for gastric cancer were changing for the past 20 years in Wan-Fang Hospital. There are 179 gastric cancer patients received HIPEC at Wan-Fang Hospital, most with curative intent and 36 EPIC, 45 NIPS, 34 conversion surgeries. The average PCI was 19.2 and CC score-0/1 can be achieved in 47% (82% when PCI < 19). The overall 5-year survival was 15.1% (median 13.3 months). In CC score-0/1 group, the overall 5-year survival was 27.1% (median 26.5 months).

HIPEC history is short in Taiwan as compared to Japan or Western countries. We use data from Wan-Fang Hospital as an example to discuss what nationwide data should be obtained. To establish a HIPEC guideline or consensus as well as a nationwide registration platform are important to improve survival of gastric cancer patients with PM.

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Symposium (XIV) HIPEC AND CONVERSION SURGERY FOR GASTRIC CANCER

PROPHYLACTIC HIPEC FOR LOCALLY ADVANCED GASTRIC CANCER Ting-Jung Wu Department of General Surgery, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan Department of Medical Science, Chang Gung University, Taoyuan, Taiwan Although the incidence of gastric cancer (GC) was decreased in Taiwan, the GC was still the sixth leading cause of cancer death. GC disseminates principally through the hematogenous torrent or through the peritoneal fluids. It has been demonstrated as peritoneal dissemination is more frequent than hematogenous metastases.

The 40% of patients died for GC have hepatic metastases, while the 53% to 60% showed a disease progression and died with peritoneal carcinomatosis (PC). The two most important factors affecting prognosis in GC are the serosal invasion and the lymphatic spread. When gastric serosa is infiltrated, PC could be considered practically unavoidable. As a consequence, up to half of the patients with advanced GC will develop PC in spite even radical surgery. Since important component of treatment failure on GC is cancer dissemination within the peritoneal cavity and nodal metastasis. In contrast to lymphatic and hematogenous dissemination, peritoneal spread

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should be regarded as a locoregional disease extension rather than systemic metastasis. Taking the natural history of GC into account, the use of hyperthermic intraperitoneal chemotherapy (HIPC) as a targeted adjuvant treatment after surgery may be considered a rational prophylactic/ therapeutic approach. HIPEC allows to reach an high intraperitoneal drug concentration and allows the drugs to directly act on the free-tumor-cells and peritoneal nodules. Drugs absorbed through the peritoneum enter the portal vein, and also have a chemotherapeutic effect on the liver. There were several clinical trials, reports and metaanalysis which support beneficial survival effects resulting from the HIPEC procedure after radical gastrectomy. At this presentation, I summarized the current evidence of prophylactic HIPEC for locally advanced GC and preliminary results in Chang Gung Memorial Hospital Linkou Medical Center.

2020 TDDW

Symposium (XIV) HIPEC AND CONVERSION SURGERY FOR GASTRIC CANCER

CONVERSION SURGERY FOR PATIENTS WITH ADVANCED GASTRIC CANCER WITH PERITONEAL CARCINOMATOSIS Ting-Ying Lee Division of General Surgery, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan Patients with advanced gastric cancer with peritoneal carcinomatosis (AGC with PC) usually has poor outcome and high risk for mortality, even undergone cytoreductive surgery plus HIPEC (Hyperthermic intraperitoneal chemotherapy).

This study is evaluated the prognostic factors of AGC with PC and utilized laparoscopic HIPEC plus neoadjuvant intraperitoneal and systemic chemotherapy (NIPS) as a conversion surgery for the patients with initially high PCI (Peritoneal cancer index) score, and positive peritoneal cytological gastric cancer. Here we retrospect 127 patients with advanced gastric cancer with peritoneal carcinomatosis from January 1st, 2012 to March 1st, 2020. There were 34 patients in conversion group underwent LHIPEC + NIPS as a conversion surgery, then received cytoreductive surgery (CRS) plus HIPEC. The CRS+HIPEC group had 15 patients that undergone cytoreductive surgerty

with HIPEC alone. There were also 23 patients received systemic chemotherapy (C/T) in C/T group and 23 patients in palliative group only conservative therapy or palliative gastrectomy.

The conversion group had significantly better mean survival time than CRS+HIPEC alone group, C/T group, and palliative group.(p < 0.001) The patients in conversion group that undergone LHIPEC + NIPS had significantly decreased PCI score (p < 0.001) and ascites amount (p < 0.001).

The malignant ascites also significantly turn over negative finding after treatment in LHIPEC + NIPS group (p < 0.001). LHIPEC + NIPS can significantly improve the overall survival, PCI score, malignant ascites for initially high PCI score and positive peritoneal cytological gastric cancer with peritoneal carcinomatosis. It can be a reasonable and feasible conversion strategy for patients with AGC with PC.

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2020 TDDW

Young Investigator Award (YIA) ①

DESENSITIZATION OF SMALL HETERODIMER PARTNER (SHP) SIGNALING PATHWAY IN PATIENTS WITH NASH WITH DIFFERENT FIBROSIS STAGES Chin-Fang Chen1, Shih-Chieh Chien1, Chiung-Yu Chen1, Yau-Sheng Tsaia4, Pin-Nan Cheng1, Hung-Wen Tsai2, Yih-Jyh Lin3, Shu-Chu Shiesh5, Yen-Cheng Chiu1, Chiu Hung-Chih1 Department of Internal Medicine, National Cheng Kung University Hospital, Tainan, Taiwan1 Departments of Pathology, National Cheng Kung University Hospital, Tainan, Taiwan2 Departments of Surgery, National Cheng Kung University Hospital, Tainan, Taiwan3 Institute of clinical medicine, National Cheng Kung University, Tainan, Taiwan4 Department of Medical Laboratory Science and Biotechnolog National Cheng Kung University Hospital, Tainan, Taiwan5

非酒精性脂肪性肝炎病人之微小異源 二聚體夥伴（SHP）訊息傳遞隨著肝 纖維化進展而異常 陳鏡方1 簡世杰1 陳炯瑜1 蔡曜聲4 鄭斌男1 蔡弘文2 林毅志3 謝淑珠5 邱彥程1 邱宏智1 國立成功大學醫學院附設醫院內科部1 國立成功大學醫學院附設醫院病理部2 國立成功大學醫學院附設醫院外科部3 國立成功大學臨床醫學研究所4 國立成功大學醫學院附設醫院醫學技術與檢驗部5 Background: Non-alcoholic steatohepatitis (NASH) means hepatic lipid accumulation plus inflammation, result in hepatocellular damage and fibrosis. Bile acid (BAs), synthesized from cholesterol, can control hepatic metabolism and it own homeostasis by FXR signaling pathway.

Activation of FXR signaling pathway can alleviate fat accumulation and prevent NASH. However, how dose FXR signaling pathway changed as the NASH-related fibrosis progressed is still an area of uncertainty. In this study we try to elucidate how FXR signaling pathway is changed in different fibrosis stages of NASH. We found that as fibrosis stage worse in NASH, the FXR directed major

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inhibitory signal SHP is desensitized.

Aims: To dissect the relationship of FXR signaling pathway between normal and different fibrosis stages of NASH. Methods: We collected patients with biopsy proven NASH prospectively in NCKU hospital, healthy controls from NCKU-biobank, and living liver donor preparing for transplant. We used quantitative PCR for BAs related signaling gene expression. The detail algorism was shown in Figure 1. The NASH was scored by NASH-CRN scoring system and staged according to fibrosis severity. Statistical comparison between health control and different fibrosis stages was performed

by Kruskal Wallis test with post-hoc analysis.

Results: NASH patients are frequently to having metabolic syndromes. We collected 94 patients for liver tissue analysis. Histologically, 42.6% of the NASH patients belongs to advanced fibrosis (F3 or F4), and the median NASH score is 4 (range: 3-7) (Table 1). Comparing with health subject, the NASH patients was heavier, with higher BMI, and more frequently to having characteristics of metabolic syndromes (including DM, HTN, and hyperlipidemia, their serum AST and ALT were also higher than controls. (Table 2), SHP, not FXR, signaling pathway is desensitized as the fibrosis worse in NASH patients. We found that the FRX and FXR direct-target genes, including major inhibitory nuclear receptor SHP, alternative BAs transporter-OSTα/β, BAs conjugating enzymesBACS and BAAT were significantly up-regulated as fibrosis stage progressed in NASH. However, despite the up-regulation of SHP, the target genes of SHP, including BAs synthetic enzymes- Cyp7A1, Cyp7B1, Cyp8B1 and hepatic glucose and lipid metabolism genes- including G6pc, Pck1, Srebp, were not down-regulated, and instead up-regulated as the fibrosis stage of NASH progressed.

Conclusions: FXR mediated signaling pathway is still preserved as NASH related fibrosis stage progressed. But the SHP mediated inhibitory effect on hepatic glucose and lipid synthesis, as well as BAs synthesis are disturbed as NASH related fibrosis stage progressed. They were not down-regulated by SHP.

2020 TDDW

②

SARCOPENIA AND INTRAMUSCULAR FAT DEPOSITION INDEPENDENTLY PREDICT THE OUTCOMES OF HEPATOCELLULAR CARCINOMA AFTER SURGICAL RESECTION Tsung-Yi Cheng1,2, Pei-Chang Lee1,2, Gar-Yang Chau1,2, Chien-Wei Su1,2, Yee Chao1,2, Yi-Hsiang Huang1,2, Han-Chieh Lin1,2, Ming-Chih Hou1,2 Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taipei Veterans General Hospital, Taipei, Taiwan1 Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan2

肌少症與肌肉內脂肪堆積可以預測肝 癌病人手術後之預後

Results: No significant change of body composition was observed from the images before and after surgical resection of HCC (median PMI: 7.11 vs. 7.30 cm2/m2, p=0.586; SMI: 44.03 vs. 46.19 cm2/m2, p=0.615; IMATI: 3.58 vs. 3.44 cm2/m2, p=0.680). Patients with pre-operative sarcopenia (SMI < 52.14 cm2/m2) and those with more intramuscular adipose tissue (IMATI > 3.96 cm2/ m2) had a significantly shorter overall survival (OS) after surgery (hazard ratio [HR]: 4.080, p=0.021 and HR: 4.249, p<0.01, respectively). In patients without cirrhosis, SMI remained significant predictors of OS (HR: 4.314, p=0.05).

Conclusions: Sarcopenia independently predicts mortality in HCC patients after surgical resection, especially in those without cirrhosis. In patients with more intramuscular fat deposition also determines post-surgical outcomes significantly.

鄭琮譯1,2 李沛璋1,2 周嘉揚1,2 蘇建維1,2 趙毅1,2 黃怡翔1,2 林漢傑1,2 侯明志1,2 臺北榮民總醫院內科部胃腸肝膽科1 國立陽明大學醫學系內科學科2 Background: Body composition assessments are objective surrogates reflecting nutrition status and severity of liver diseases. Sarcopenia has been reported to predict mortality in patients with hepatocellular carcinoma (HCC). However, the roles of muscle mass and adipose tissue in HCC after resection are still uncertain and diverse.

Aims: In this study, we aimed to assess and investigate the impacts of muscle and adipose tissues on outcomes of HCC after surgical resection.

Methods: From January 2013 to June 2015, 100 consecutive patients who receive surgical resection of HCC in Taipei Veterans General Hospital were retrospectively reviewed. All patients had received computed tomography (CT) for diagnosis and post-operative follow-up. Cross areas of adipose tissue and muscle mass were measured from CT scan by SliceOmatic software at L3 vertebra level; and body composition indices (cm2/m2), including intramuscular adipose tissue index (IMATI), skeletal muscle index (SMI) and psoas muscle index (PMI) were calculated.

Optimal cut-off values were defined by area under receiver operating characteristic curve (AUROC), and survival analyses were performed.

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2020 TDDW

③

DERANGEMENT OF ESOPHAGEAL ANATOMY AND MOTILITY IN MORBIDLY OBESE PATIENTS: A PROSPECTIVE STUDY BASED ON HIGH-RESOLUTION IMPEDANCE MANOMETRY Hung-Hsuan Yen1, Ming-Chieh Shih2, Po-Jen Yang1, Ming-Tsan Lin1, Po-Chu Lee1, Ping-Huei Tseng3 Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan1 Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan2 Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan3

病態性肥胖病患之食道解剖及功能異 常：運用高解析度食道阻抗壓力檢查之 前瞻性研究 顏宏軒1 施銘杰2 楊博仁1 林明燦1 李柏居1 曾屏輝3 臺灣大學醫學院附設醫院外科部1 臺灣大學公共衛生學院流行病學與預防醫學研究 所2 臺灣大學醫學院附設醫院內科部3 Background: Morbidly obese patients often suffer from gastroesophageal reflux disease (GERD). High-resolution impedance manometry (HRIM) allows a comprehensive evaluation of esophageal motility and esophagogastric junction (EGJ) morphology and helps to clarify GERD pathophysiology.

Aims: To evaluate the esophageal function and EGJ anatomy in morbid obesity by HRIM. Methods: We consecutively enrolled 57 morbidly obese patients planning to undergo bariatric surgery and 58 healthy volunteers in this prospective study. All patients responded to validated symptom questionnaires and underwent fasting blood tests, HRIM, and esophagogastroduodenoscopy. We compared anthropometric and HRIM parameters between the two groups, and analyzed correlations between the GERD symptom scores and clinical variables in the obese patients.

Results: The obese patients, comprising 30 males (53%), had a median age of 35 years and body mass index of 40.5 kg/m2. The four-second

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integrated relaxation pressure (IRP-4s) in the lower esophageal sphincter (LES) was significantly higher in the patients than the volunteers (median: 10.8 versus 5.6 mmHg; p < 0.001). EGJ outflow obstruction (EGJOO) and ineffective esophageal motility were diagnosed in 16% and 11% of the patients, respectively, versus 5% and 28% of the volunteers (p = 0.022). Manometric hiatal hernia (m-HH) was present in 19 (33%) of the patients and none of the volunteers; all m-HH were associated with erosive esophagitis (EE). Most of the patients were considered as no GERD by the validated questionnaires, regardless of the presence of m-HH and EE. Conclusions: The obese patients had a higher LES IRP-4s and higher prevalence of EGJOO and m-HH than the healthy volunteers. The presence of m-HH was strongly associated with EE. The absence of GERD symptoms in morbid obesity was not necessarily suggestive of negative esophagogastroduodenoscopy and HRIM findings, and the discrepancy existed between esophagogastroduodenoscopy and HRIM for diagnosing HH. A comprehensive evaluation of the EGJ anatomy and esophageal function may be considered before bariatric surgery.

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PROGRAMMED DEATHLIGAND 1 EXPRESSION LEVEL ASSOCIATES WITH RESPONSE TO IMMUNE CHECKPOINT INHIBITORS IN UNRESECTABLE HEPATOCELLULAR CARCINOMA Chi-Jung Wu1, Ya-Wen Hung1, Pei-Chang Lee1, Chieh-Ju Lee1, Ming-Chih Hou1, Yi-Hsiang Huang1,2 Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan1 Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan2

Programmed Death-Ligand 1 表現量 與免疫檢查點抑制劑用於不可手術切 除肝細胞癌治療成效相關性分析 吳啟榮1 洪雅文1 李沛璋1 李杰如1 侯明志1 黃怡翔1,2

archival HCC tissues or tumor biopsy. The antiPD-L1 antibodies 28-8 and 22C3 were used for nivolumab or pembrolizumab-treated HCC, respectively. High PD-L1 expression was defined as a tumor proportion score (TPS) or combined positive score (CPS) ≧1%. The tumor response was assessed by modified RECIST (mRECIST).

Results: Till the end of June. 2020, 100 cases received ICIs treatment, and the ORR was 38%, DCR was 55% by mRECIST criteria. Fortynine patients had assessable PD-L1 expression specimens and evaluable image after ICIs treatment. Of them, 14 (28.6%) showed high PDL1 expression. For patients with high PD-L1 level, 10 (71.4%) achieved objective response and 13 (92.9%) had disease controlled; while for the other 35 cases of low PD-L1 expression level, 13 (37.1%) had objective response (p = 0.030) and 20 (57.1%) got disease controlled (p = 0.019). The differences in ORR and DCR were both significant.

Conclusions: High PD-L1 expression could predict objective response and disease control of ICIs treatment in unresectable HCC. Which could help decision making in ICIs treatment for HCC.

臺北榮民總醫院內科部胃腸肝膽科1 國立陽明大學臨床醫學研究所2 Background: Immune checkpoint inhibitors (ICIs) are promising systemic therapy for unresectable hepatocellular carcinoma (HCC). However, there is no effective biomarker to predict the treatment response. Given the expansive cost and potential risk of immune-related adverse effects, a biomarker to predict response to ICIs for HCC is in urgent unmet need. Tumor Programmed Death Ligand 1 (PD-L1) expression could predict ICIs treatment response in other cancer types. A numerically higher response was observed in HCC patients with >1% PD-L1 expression in clinical trials, but significance was not reached.

Aims: This study aims to evaluate the association between PD-L1 and treatment response to ICIs in HCC in real-world setting.

Methods: This is a retrospective prospective design to enroll unresectable HCC patients who received pembrolizumab or nivolumab with or without targeted treatment in Taipei Veteran General Hospital. The status of HCC was either in advanced HCC or failed by prior locoregional or systemic therapy. PD-L1 expression was measured by immunohistochemistry assay on

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EFFICACY OF PROPHYLACTIC CLIPPING IN PREVENTION OF DELAYED BLEEDING AFTER ENDOSCOPIC MUCOSAL RESECTION OF LARGE NONPEDUNCULATED COLORECTAL LESIONS: A METAANALYSIS Tsung-Chieh Yang1,2, Yi-Hui Wu2,3, Pei-Chang Lee1,2,4, Chung-Yu Chang5, Hsiao-Sheng Lu1, Yu-Jen Chen1, Yi-Hsiang Huang1,2,6, Fa-Yauh Lee1,2, Ming-Chih Hou1,2 Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan1 Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan2 Center for Geriatrics and Gerontology, Taipei Veterans General Hospital, Taipei, Taiwan3 Institute of Pharmacology, School of Medicine, National Yang-Ming University, Taipei, Taiwan4 Healthcare and Services Center, Taipei Veterans General Hospital, Taipei, Taiwan5 Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan6

大型無柄大腸病灶經內視鏡黏膜切除 術後以預防性止血夾避免延遲出血的 效果：一個統合分析 楊宗杰1,2 吳怡慧2,3 李沛璋1,2,4 張重昱5 呂學聖1 陳宥任1 黃怡翔1,2,6 李發耀1,2 侯明志1,2 臺北榮民總醫院內科部胃腸肝膽科1 陽明大學醫學院醫學系2 臺北榮民總醫院高齡醫學中心3 陽明大學醫學院藥理學研究所4 臺北榮民總醫院健康管理中心5 陽明大學醫學院臨床醫學研究所6 Background: Endoscopic mucosal resection (EMR) is the standard treatment for large nonpedunculated colorectal lesions (LNPCLs).

Delayed bleeding (DB) is the most frequent complication. Previous studies showed conflicting results on the efficacy of prophylactic clipping in prevention of DB after EMR.

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Aims: To conduct a meta-analysis to clarify the efficacy of prophylactic clipping in prevention of DB following EMR of LNPCLs. Methods: We searched PubMed, EMBASE, Web of Science, ScienceDirect, Cochrane Library databases, ClinicalTrials.gov and other relevant sources for studies that examined the effect of prophylactic clipping versus no clipping for the prevention of DB following EMR of LNPCLs. Pooled odds ratio (OR) was determined using a random effects model. The pooled OR of DB in the prophylactic clipping group compared with non-clipping group comprised the primary outcome, and the pooled OR of perforation and post-polypectomy syndrome between two groups comprised the secondary outcome. Subgroup analyses based on study design, polyp location and complete versus partial closure of wound defect were also performed.

Results: A total of 2148 citations were initially screened. Five studies with a total of 2954 patients undergoing EMR for 3112 LNPCLs were extracted.

Prophylactic clipping showed superior efficacy for preventing DB (2.8%) when compared to nonclipping (6.2%) (pooled OR: 0.394, 95% confidence interval [CI]: 0.261-0.595). In subgroup analysis, prophylactic clipping reduced DB following EMR of LNPCLs at proximal location (3.9% in the clipping group, 9.5% in the non-clipping group, pooled OR: 0.415, 95% CI: 0.188-0.916), but not of them at distal location (3.5% in the clipping group, 2.9% in the non-clipping group, pooled OR: 1.162, 95% CI: 0.295-4.571). Complete clip closure showed superior efficacy to prevent DB compared with partial clip closure (2.0% versus 5.4%, pooled OR: 0.359, 95% CI: 0.179-0.718). No benefit of prophylactic clipping for preventing perforation or post-polypectomy syndrome was observed.

Conclusions: Prophylactic endoscopic clipping can reduce DB following EMR of LNPCLs at proximal location. Furthermore, complete clip closure showed superior efficacy to prevent DB compared with partial clip closure. Further trials are needed to focus on the subgroups with periprocedural antithrombotic agents and implement a cost-effective strategy.

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IMPACT OF SUSTAINED VIROLOGICAL RESPONSE ON HEPATIC DECOMPENSATION AFTER CURATIVE RESECTION IN PATIENTS WITH HCV-RELATED HEPATOCELLULAR CARCINOMA Kuo-Cheng Wu1, I-Cheng Lee1,2, Chen-Ta Chi1, Gar-Yang Chau3, Ming-Chih Hou1,2, Yi-Hsiang Huang1,2,4 Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan1 Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan2 Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan3 Institute of Clinical Medicine, National YangMing University, Taipei, Taiwan4

hepatic encephalopathy) and overall survival (OS) were evaluated.

Results: Seventy-three (75.3%) and 63 (95.5%) of patients treated with IFN-based and DAA achieved SVR, respectively. During a median follow-up period of 50.1 months, 64 (24.4%) patients developed hepatic decompensation and 98 (34.4%) patients died. By multivariate analysis, achieving SVR by either interferonbased treatment (HR = 0.436, p = 0.010) or DAA (HR = 0.276, p = 0.015), BCLC stage B or C (HR 2.481, p = 0.004), ALBI grade > 1 (HR = 1.924, p = 0.015), and serum aspartate aminotransferase > 40 U/L (HR = 2.071, p = 0.012) were independent predictors of decompensation-free survival.

Conclusions: The achievement of SVR by either IFN-based or DAA therapy was associated with a significant reduction in hepatic decompensation among patients with HCV-related HCC after curative surgery.

C 型肝炎抗病毒治療反應對肝癌手術切 除後肝代償不全的影響 胡果正1 李懿宬1,2 齊振達1 周嘉揚3 侯明志1,2 黃怡翔1,2,4 臺北榮民總醫院胃腸肝膽科1 國立陽明大學醫學系2 臺北榮民總醫院外科部3 國立陽明大學臨床醫學研究所4 Background: Achieving sustained virological response (SVR) by either interferon-based (IFNbased) or direct-acting antivirals (DAAs) therapy has been shown to improve overall survival (OS) in patients with HCV-related HCC receiving hepatic resection. Whether the survival benefit brought by antiviral therapy was due to a reduction in hepatic decompensation remains to be clarified.

Aims: We aim to evaluate the incidence and predictors of hepatic decompensation after curative resection of HCV-related HCC. Methods: Consecutive 285 patients receiving curative resection for HCV-related HCC were retrospectively enrolled, including 97 (34.0%) and 66 (23.2%) patients with interferon and directacting antivirals (DAA) treatment, respectively, either before or after surgery. The SVR status, hepatic decompensation (defined as the occurrence of total bilirubin above 2 mg/dL, ascites, gastroesophageal variceal bleeding, or

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CLINICOPATHOLOGICAL CHARACTERISTICS OF FIT INTERVAL CANCERS IN THE POPULATION COLORECTAL CANCER SCREENING PROGRAM: ANALYSIS OF CASES IN FOUR INSTITUTES Wei-Yuan Chang1, Wen-Feng Hsu2, Chu-Kuang Chou3, An-Ti Chang4, Meng-Yu Chen5, Yu-Ming Lin5, Li-Ju Lin6, Chun-Mei Fang6, Ming-Shiang Wu2, Han-Mo Chiu2,7 Department of Internal Medicine, National Taiwan University Hospital Hsinchu Branch, Hsinchu, Taiwan1 Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan2 Division of Gastroenterology and Hepatology, Chia-Yi Christian Hospital, Chiayi, Taiwan3 Gastroenterology and Hepatology Medicine, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan4 Department of Internal Medicine, Shin Kong Wu Ho Su Memorial hospital, Taipei, Taiwan5 Health Promotion Administration, Ministry of Health and Welfare, Taipei, Taiwan6 Health Management Center, National Taiwan University Hospital, Taipei, Taiwan7

FIT 陰性間隔癌其臨床及病理特徵分析 張為淵1 許文峰2 周莒光3 張安迪4 陳孟瑜5 林裕民5 林莉茹6 方春媚6 吳明賢2 邱瀚模2,7 國立台灣大學醫學院附設醫院新竹分院內科部1 國立台灣大學醫學院附設醫院內科部2 嘉義基督教醫院消化內科3 中國醫藥大學附設醫院消化內科4 新光吳火獅紀念醫院消化內科5 衛生福利部國民健康署6 國立台灣大學醫學院附設醫院健康管理中心7 Background: Fecal immunochemical test (FIT) is one of the most widely used tests for population colorectal cancer (CRC) screening. FIT interval cancers (FIT ICs), however, exit in the FITbased screening program, and may affect the effectiveness of the screening program.

Aims: The aim of this study was to investigate the

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clinical and pathological characteristics of FIT ICs within Taiwan CRC Screening Program Methods: We conducted a retrospective analyses of Taiwan CRC Screening Program database from 2010 to 2016. We linked the database to the National Cancer Registry and the National Death Registry databases. FIT IC was defined as CRCs that diagnosed due to symptoms within 2 years after a negative FIT screening test. In this study, FIT ICs diagnosed in the National Taiwan University Hospital, Shin Kong Wo HoSu Memorial Hospital, China Medical University Hospital, and Chia-Yi Christian Hospital were retrieved from the database and comprised the study cohort. “Proximal IC” was defined as FIT IC was diagnosed proximal to the splenic flexure, and “distal IC” was defined as FIT IC was diagnosed at splenic flexure to rectum. The clinical and pathological characteristics of proximal ICs and distal ICs were compared.

Results: During 2010-2016, totally of 310 FIT ICs were identified in these four institutes. Eightyfive (27.4%) FIT ICs were proximal ICs and 225 (72.6%) were distal ICs. Among distal ICs, 120 (53.3%) patients were diagnosed due to bleeding symptoms, and 28 (32.9%) patients among proximal ICs. (P < 0.01) Proximal ICs presented at a more advanced (stage III/IV was 51.8%) compared with distal ICs (29.9%) (P = 0.026).

Mucinous colorectal adenocarcinoma was more frequent in the proximal ICs (P < 0.01).

Conclusions: Distal ICs were more common than proximal ones. Proximal ICs were associated with more mucinous histology and diagnosed at more advanced stages.

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REMARKABLE DIFFERENCES IN HBSAG CHANGES DURING RETREATMENT IN HEPATITIS B FLARES WITH DIFFERENT PRERETREATMENT HBSAG/ALT KINETICS Wen-Juei Jeng1,2, Yen-Chun Liu1,2, 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

停藥後 B 肝發炎時的表面抗原定量與 麩胺酸丙酮酸轉氨基酵素動力變化差 異顯著影響再次治療後的表面抗原定 量下降表現 鄭文睿1,2 劉彥君1,2 彭建維1,2 簡榮南1,2,3 廖運範1,3

greater HBsAg decline (-1.0 vs. -0.01 log10 IU/ mL, P < 0.0001) with more frequent rapid decline (69.8 vs 8.3%; P < 0.0001) by month 12 and achieving HBsAg <100 IU/mL by year 3 (33 vs 13%, P = 0.039) during entecavir or tenofovir retreatment. Notably, 33.3% of patients with hostdominating flare showed on-retreatment HBsAg rebound over pre-retreatment level (vs 1.4%; P < 0.0001). Compared with un-retreated controls, HBsAg decline was greater (-1.0 vs -0.47 log10 IU/mL; P < 0.0001) in anti-HBV retreated patients with virus-dominating flare. Conversely, HBsAg decline (-0.01 vs -0.16 log10 IU/mL) and 3-year HBsAg loss rate (0 vs 21%; P = 0.009) were lower in retreated than un-retreated patients with hostdominating flare.

Conclusions: Judging by HBsAg changes, antiHBV retreatment is effective in patients with virusdominating flare but ineffective or even worsen in patients with host-dominating flare. These results support using combined HBsAg/ALT kinetic for retreatment decision that is to retreat patients with virus-dominating flare timely whereas to hold retreatment and watch carefully in patients with host-dominating flare.

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 Background: Hepatitis B flares with deceasing HBsAg reflect effective immune clearance of HBV (“host-dominating flare”) that antiviral treatment may be held or unnecessary. In contrast, flares with increasing HBsAg reflect ineffective immune response (“virus-dominating flare”) that timely retreatment is required.

Aims: To investigate differences in on-retreatment HBsAg changes between patients with different types of hepatitis flare.

Methods: A nested case-control study was conducted in 336 retreated and 105 un-retreated HBeAg-negative patients with hepatitis flare.

HBsAg was quantified before and during flare, at ALT peak or retreatment start, months 6 and 12. Hepatitis flare with increasing HBsAg prior to retreatment or ALT peak was classified as “virusdominating flare” whereas flare with decreasing HBsAg as “host-dominating flare”.

Results: Of the retreated patients, 85.7% showed virus-dominating flare and 14.3% host-dominating flare. Patients with virus-dominating flare showed

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Free Paper Section：HCV

①

IMPACT OF SOFOSBUVIR-BASED VERSUS NON-SOFOSBUVIRBASED DIRECT-ACTING ANTIVIRALS ON RENAL FUNCTION IN CHRONIC HEPATITIS C PATIENTS WITH IMPAIRED RENAL FUNCTION ‒ A LARGE COHORT STUDY FROM THE NATIONWIDE REAL-WORLD HCV REGISTRY PROGRAM (TACR) Ming-Lung Yu1, Chi-Yi Chen2, Pin-Nan Cheng3, Kuo-Chih Tseng4, Ching-Chu Lo5, Chao-Hung Hung6, Chi-Ming Tai7, Hsing-Tao Kuo8, Chun-Yen Lin9, Chien-Hung Chen6, Cheng-Yuan Peng10, Ming-Jong Bair11, Tsai-Yuan Hsieh12, Pei-Lun Lee13, Lee-Won Chong14, Chi-Chieh Yang15, Chih-Lang Lin16, Chun-Ting Chen17, Sih-Ren,Wang18, Lein-Ray Mo19, Chih-Wen Lin20, Jui-Ting Hu21, Chia-Chi Wang22, Chih-Lin Lin23, Wei-Wen Su24, Cheng-Hsin Chu25, Sheng-Shun Yang26, Chien-Yu Cheng27, Wei-Lun Tsai28, Chun-Chao Chang29, Guei-Ying Chen30, Tzong-His Lee31, Chun-Che Lin32, Wen-Chih Wu33, Jia-Sheng,Huang34, Guo-Xiong Zhou35, Jian-Neng,Gao36, Shih-Jer Hsu37, Shiuh-Nan Chang38, Yung-Fa Chen39, Chung-Feng Huang1, Chia-Yen Dai1, Pei-Chien Tsai1, Jia-Horng Kao37, Chun-Jen Liu37, Mei-Hsuan Lee40, Rong-Nan Chien9 Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan1 Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi, Taiwan2 National Cheng Kung University Hospital, Tainan, Taiwan3 Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi, Taiwan4 Martin De Porres Hospital, Chiayi, Taiwan5 Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan6 E-Da Hospital, Kaohsiung, Taiwan7 Chi Mei Medical Center, Tainan, Taiwan8

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Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan9 China Medical University Hospital, Taichung, Taiwan10 Taitung MacKay Memorial Hospital, Taitung, Taiwan11 Tri-Service General Hospital, Taipei, Taiwan12 Chi Mei Hospital, Liouying, Tainan, Taiwan13 Shin Kong Wu Ho Su Memorial Hospital, Taipei, Taiwan14 Show Chwan Memorial Hospital, Changhua, Taiwan15 Keelung Chang Gung Memorial Hospital, Keelung, Taiwan16 Tri-Service General Hospital Penghu Branch, Penghu , Taiwan17 Yuan’s General Hospital, Kaohsiung, Taiwan18 Tainan Municipal Hostipal, Tainan, Taiwan19 E-Da Dachang Hospital and School of Medicine, College of Medicine, I-Shou University, Kaohsiung, Taiwan20 Cathay General Hospital, Taipei, Taiwan21 Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taipei, Taiwan22 Taipei City Hospital RenAi Branch, Taipei, Taiwan23 Changhua Christian Hospital, Changhua, Taiwan24 MacKay Memorial Hospital, Taipei, Taiwan25 Taichung Veterans General Hospital, Taichung, Taiwan26 Tao Yuan Hospital, Ministry of Health and Welfare, Taoyuan, Taiwan27 Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan28 Taipei Medical University Hospital, Taipei, Taiwan29 PenGhu Hospital, Ministry of Health and Welfare, Penghu, Taiwan30 Far Eastern Memorial Hospital, New Taipei, Taiwan31 Chung Shan Medical University Hospital, Taichung, Taiwan32 Wu Wen-Chih Clinic, Kaohsiung, Taiwan33 Yang Ming Hospital, Chiayi, Taiwan34 Zhou Guoxiong Clinic, Penghu , Taiwan35 National Taiwan University Hospital Hsin-Chu Branch, Hsinchu, Taiwan36

2020 TDDW

National Taiwan University Hospital, Taipei, Taiwan37 JIU DA Digestive Medical Alliance, Kaohsiung, Taiwan38 Taipei Municipal Wanfang Hospital, Taipei, Taiwan39 Taipei Veterans General Hospital, Taipei, Taiwan40

慢性Ｃ型肝炎患者接受小分子抗病毒 藥物系列腎功能變化─全國多中心 TACR 註冊系統報告 余明隆1 陳啟益2 鄭斌男3 曾國枝4 羅清池5 洪肇宏6 戴啟明7 郭行道8 林俊彥9 陳建宏6 彭成元10 白明忠11 謝財源12 李佩倫13 張麗文14 楊基滐15 林志郎16 陳軍廷17 王嗣仁18 牟聯瑞19 林志文20 胡瑞庭21 王嘉齊22 林志陵23 蘇維文24 朱正心25 楊勝舜26 鄭健禹27 蔡維倫28 張君照29 陳桂英30 李宗熙31 林俊哲32 吳文誌33 黃嘉生34 周國雄35 高健能36 徐士哲37 張旭男38 陳永發39 黃釧峰1 戴嘉言1 蔡佩倩1 高嘉宏37 劉俊人37 李美璇40 簡榮南9 高雄醫學大學附設中和紀念醫院肝膽胰內科1 戴德森醫療財團法人嘉義基督教醫院2 成功大學醫學院附設醫院3 佛教慈濟醫療財團法人大林慈濟醫院4 天主教聖馬爾定醫院5 高雄長庚紀念醫院6 義大醫院7 財團法人奇美醫院8 林口長庚紀念醫院9 中國醫藥大學附設醫院10 台東馬偕紀念醫院11 三軍總醫院12 柳營奇美醫院13 新光吳火獅紀念醫院14 彰化秀傳紀念醫院15 基隆長庚紀念醫院16 三軍總醫院澎湖分院17 阮綜合醫院18 台南市立醫院19 義大大昌醫院20 國泰綜合醫院21 台北慈濟醫院22 臺北市立聯合醫院仁愛院區23 彰化基督教醫院24 馬偕紀念醫院25

臺中榮民總醫院26 桃園醫院27 高雄榮民總醫院28 台北醫學大學附設醫院29 衛生福利部澎湖醫院30 亞東紀念醫院31 中山醫學大學附設醫院32 吳文誌診所33 嘉義陽明醫院34 周國雄診所35 台大新竹分院36 台大醫院37 九大消化系專科聯盟38 臺北市立萬芳醫院39 臺北榮民總醫院40 Background: Sofosbuvir (SOF) has been approved to be used in chronic hepatitis C (CHC) patients with severe renal impairment. However, the impact of DAA therapy on renal function in CHC patients with impaired renal function has not been well elucidated in large real-world cohorts.

Aims: We aimed to address the impact of SOFvs. non-SOF-based DAAs on serial change of renal function in CHC patients.

Methods: CHC patients receiving DAAs were retrieved from the Taiwan nationwide real-world HCV Registry Program (TACR). Patients under regular dialysis were excluded. Serial eGFR levels were measured at baseline (BL), end-of-treatment (EOT), and end-of-follow-up (EOF, 3 months post EOT).

Results: 11,376 patients were enrolled (mean age, 63.0 years, female 56.1 %, HCV GT1 58.3%, and cirrhosis 40.4%). Of which, 5,740 (50.5%) patients had eGFR < 90 ml/min/1.73m2 (mean 68.9 ± 18.1, Group A), while the other 5,636 (49.5%) had eGFR ≥ 90 ml/min/1.73m2 (mean, 113.1 ± 22.2, Group B). The Group A were significantly older, with higher proportion of co-morbidity and severe liver diseases. The DAA treatment adherence and responses were comparable between the two groups. In Group A, the eGFR continuous significantly increased from BL to EOT and EOF (68.9 ± 18.4, 70.0 ± 21.5, and 70.4 ± 21.9, respectively, BL vs. EOT, and BL vs. EOF: P < 0.001). The trend was similar between patients treated with SOF-based (n = 2,665, eGFR: 71.3 ± 15.0, 72.5 ± 19.0 and 72.6 ± 19.7, respectively) and non-SOF-based (n = 3,075, eGFR: 66.8 ± 20.3, 67.9 ± 23.3 and 68.5 ± 23.4, respectively)

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DAA regimens. When breaking down the patients into eGFR < 30, 30-60, 60-90 ml/min/1.73m2 the trend remained in both subgroups (Fig 1a, 1b and 1c). The increased eGFR between EOF and BL was significantly higher in SOF-based than nonSOF-based subgroups in patients with eGFR < 30 ml/min/1.73m2 (18.3 ± 37.0 vs. 4.1 ± 20.2, P = 0.001, Fig 1a). By contract, in Group B, the eGFR significantly decreased from BL to EOT (P < 0.0001), and substantially recovered at EOF, but not to the extent of BL levels (eGFR: 113.1 ± 22.2, 105.6 ± 23.3 and 106.2 ± 23.8, respectively). A similar trend was observed in both SOF-based (eGFR: 113.9 ± 22.6, 106.1 ± 23.2 and 107.0 ± 25.0, respectively) and non-SOF-based (eGFR: 112.4 ± 27.1, 105.1 ± 23.4 and 105.5 ± 22.6, respectively) regimens.

Conclusions: Both of SOF-based and non-SOFbased DAA regimens restored renal function in CHC patients with chronic kidney diseases, especially in those with significant renal function impairment.

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HEPATIC HCV-RNA IDENTIFICATION IN NATIVE LIVER OF CHRONIC HEPATITIS C RECIPIENTS WHO UNDERWENT LIVING DONOR LIVER TRANSPLANTATION King-Wah Chiu, Tsung-Hui, Hu, Kuang-Den Chen, Kuang-Tzu Huang, Shigeru Goto, Toshiaki Nakano, Li-Wen Hsu, Chao-Long Chen Liver transplantation program, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan

接受活體肝移植的慢性 C 型肝炎患者 原生肝臟內 HCV-RNA 之鑒定 趙景華 胡琮輝 陳廣典 黃廣慈 後藤茂 中野明敏 許麗文 陳肇隆 高雄長庚紀念醫院肝臟移植中心 Background: Chronic hepatitis C virus (HCV) infection leading to liver cirrhosis and hepatocellular carcinoma (HCC), is a worldwide health problem.

Even direct-acting antiviral agents (DAA) are commonly used, living liver transplantation (LDLT) still plays an important role in advanced end stage liver disease.

Aims: For the significance of negative serum HCV-RNA before liver transplantation (LT), we would like to explore the hepatic HCV-RNA in the native liver underwent LDLT. Methods: From February 2016 to August 2019, 80 serum anti-HCV positive recipients were consecutively collected in our LDLT setting. RNA extracted from each specimen was performed one step reverse-transcribed qPCR using the TopScript One Step qRT-PCR Probe Kit with HCV qPCR probe assay and human GAPDH qPCR probe assay on ViiA7 Real-Time PCR System. Fisher’s Exact test was used to compare the difference in serum HCV-RNA before and after LDLT. Results: Among 80 HCV related recipients, 85% (68/80) positive HCV-RNA was significantly higher in the native liver tissues than in the serum before (29/80, 36.3%; p = 0.000) and after LDLT (3/80, 4.4%; p = 0.000). Liver functional enzymes were not statistically significance between before and after LDLT. Conclusions: After LT, high positive HCV-RNA was found in the removed native liver, which

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proved that HCV-RNA in the serum of pretransplant patients should be underestimated in the real status of HCV activity. After the removal of the native liver as a target organ for HCV infection, the liver transplant itself should be considered as a benefit in controlling HCV infection.

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SEVERE ACUTE EXACERBATION OF HCV INFECTION IN CANCER PATIENTS WHO UNDERGO CHEMOTHERAPY WITHOUT ANTIVIRAL PROPHYLAXIS Yuan-Rung Li1,3, Wen-Chi Chen1,3, Wei-Lun Tsai1,3, Jin-Shiung Cheng1,3, Hsien-Chung Yu1,3, Kung-Hung Lin1,3, Ping-I Hsu2 Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan1 Division of Gastroenterology and Hepatology, Department of Internal Medicine, An Nan Hospital, China Medical University, Tainan, Taiwan2 National Yan-Ming University, Taipei, Taiwan3

C 型肝炎癌症病患接受化療後未使用抗 病毒藥物，急性發作之狀況探討 李沅融1,3 陳文誌1,3 蔡維倫1,3 鄭錦祥1,3 余憲忠1,3 林恭弘1,3 許秉毅2 高雄榮民總醫院內科部肝膽胃腸科1 台南安南醫院內科部肝膽胃腸科2 陽明大學3 Background: No guideline has been developed for the management of HCV-infected cancer patients receiving chemotherapy.

Aims: To investigate the incidence of severe acute exacerbation of HCV infection in cancer patients receiving chemotherapy and to search the risk factors predicting severe acute exacerbation of HCV infection.

Methods: This retrospective cohort study reviewed the clinical data of the cancer patients receiving chemotherapy in our institute from August 2012 to December 2017. Incidences of severe acute exacerbation of HCV infection in different kinds of cancers were assessed, and risk factors were analyzed.

Results: Cancer patients with HCV infection (n = 306) had a higher frequency of severe acute liver injury (2.3% vs 0.7%; P = 0.003) than those without HCV infection (n = 4419). The incidence of severe acute exacerbation in HCV-infected hematological cancer patients was higher than that in those with

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HCC and non-HCC solid tumors (9.4% vs 1.9% and 1.1%). Rituximab-containing chemotherapy and hematological malignancy were the risk factors related to the acute exacerbation (P < 0.001 and P = 0.004, respectively). None of patients with severe acute HCV flare developed hepatic decompensation or mortality. However, 57.1% of them discontinued chemotherapy due to liver dysfunction.

Conclusions: HCV infection increases risk of acute severe liver injury in cancer patients undergoing chemotherapy. Rituximab-containing chemotherapy and hematological malignancy are the risk factors related to severe acute exacerbation of HCV infection in cancer patients undergoing chemotherapy. Pre-chemotherapy HCV testing is therefore mandatory before rituximab-containing chemotherapy for the treatment of hematological malignancy.

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THERAPEUTIC EFFICACY OF DIRECT-ACTING ANTIVIRALS IN HCV INFECTED PRISONERS IN TAIWAN Tsung-Yu Tsai, Wang-De Hsiao, Hung-Yao Chen, Chia-Sheng Chu, Yu-Chuan Hsu, Wei-Fan Hsu, Chun-Che Lin, Guan-Tarn Huang, Jaw-Town Lin, Cheng-Yuan Peng Center for Digestive Medicine, Department of Internal Medicine, China Medical University Hospital, China Medical University, Taichung, Taiwan

患有 C 型肝炎的台灣受刑人接受抗病 毒藥物的治療成效 蔡宗佑 蕭望德 陳浤耀 朱家聲 許鈺銓 許偉帆 林俊哲 黃冠棠 林肇堂 彭成元 中國醫藥大學附設醫院消化系中心 Background: Prisoners often have a history of intravenous drug use and/or tattooing, which imposes a higher risk of acquiring blood-borne infectious diseases such as hepatitis C virus (HCV), hepatitis B virus (HBV) or human immunodeficiency virus (HIV). Therefore, the pattern of HCV genotypes, proportion with HBV/HIV co-infections are different between HCV-infected prisoners and HCV-infected non-prisoners. Direct-acting antivirals (DAAs) have been rapidly developed in recent years, and become the first choice of HCV therapy. However, studies on the efficacy of DAA therapy in HCV-infected prisoners are limited in Taiwan.

Aims: To investigate the clinical and virological features and efficacy of DAA therapy in HCVinfected prisoners in Taiwan.

Methods: We enrolled 268 HCV-infected prisoners who received anti-HCV therapy with DAA ± ribavirin regimens between August 1, 2015 and December 31, 2019 at the Ministry of Justice, Agency of Corrections, Prison Pei-De Hospital, Taichung. We followed up these patients until 12 weeks after the completion of DAA therapy. Baseline characteristics including age, gender, FIB-4 and comorbidities (such as hypertension, diabetes cancer, liver cirrhosis, and HBV/HIV co-infection.) were recorded. Laboratory tests including HCV genotype, viral loads, alanine aminotransferase

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(ALT), aspartate aminotransferase (AST), total bilirubin, and AFP levels and platelet count were collected at baseline.

Results: The mean age was 44.3 years and 85.8% (n=230) were men. 6.0% (n=16) patients had HCV/HBV co-infection, 20.5% (n=55) had HCV/ HIV co-infection, 17.9% (n=48) had liver cirrhosis and 2.6% (n=7) had hepatocellular carcinoma.

The major genotypes were genotype 6 (31.7%), followed by 1a (24.6%), 3 (15.7%), 1b (14.2%), 2 (10.5%), and mixed type (3.4%). Baseline albumin level: 4.61 ± 0.45 g/dL, total bilirubin level: 0.84 ± 0.43 mg/dL, AST level: 49.45 ± 34.76 U/L, ALT level: 66.43 ± 63.61 U/L, creatinine level: 1.24 ± 2.14 mg/dL, platelet count: 200.73 ± 70.70 109/L), AFP level: 11.38 ± 59.66 ng/mL and HCV viral load: 5.09 ± 7.50 x106 IU/mL. Patients were mostly treated with Maviret (53.7%, n=144), followed by Harvoni (32.8%, n=88), Zepatier (10.1%, n=27) and others (3.4%, n=7). The sustained virological response (SVR12) rates at 12 weeks off therapy were 98.1%, 96.4% and 98.5% in all, HCV/HBV co-infected and HCV/HIV co-infected patients, respectively. There were 5 patients with virological treatment failure. One was treatment-experienced genotype 6 patient with liver cirrhosis under Harvoni therapy. The others were treatment-naïve patients, with two non-cirrhotic genotype 3 patients under Maviret therapy, one non-cirrhotic genotype 1a and one cirrhotic genotype 6 patients under Harvoni therapy.

Conclusions: The major HCV genotypes in prisoners were genotypes 6, 1a and 3. A high SVR12 rate was achieved with DAA therapy in prisoners with HCV infection. Genotype 3 and liver cirrhosis were the main factors associated with virological treatment failures.

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ONE YEAR METABOLIC PROFILE CHANGE IN CHRONIC HEPATITIS C PATIENTS TAKING DIRECT ANTIVIRAL AGENTS AND SUSTAIN VIROLOGIC RESPONSE Wei-Chu Tsai, Yen-Cheng Chiu, Shih-Chieh Chien, Pin-Nan Cheng, Hung-Chih Chiu Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan

C 型肝炎患者經全口服抗病毒藥物治癒 一年後代謝指標之變化 蔡惟竹 邱彥程 簡世杰 鄭斌男 邱宏智 成功大學附設醫院內科部 Background: Chronic hepatitis C (CHC) infection is associated with increased insulin resistance and relative hypolipidemia. Long-term changes of glycemic and lipid profile after direct antiviral agents (DAA) induced sustained virologic response (SVR) is interesting and warrants further investigation.

Aims: To evaluate the glycemia and lipid profile changes one year after DAA-induced SVR in CHC patients.

Methods: Patients with CHC who received DAA therapy and achieved SVR were enrolled.

Baseline characteristics, medical history, and metabolic factors including fasting glucose, glycated hemoglobin (HbA1C), insulin, total cholesterol, triglyceride, low-density lipoprotein (LDL), and high-density lipoprotein (HDL) at baseline, SVR12, and one year after SVR12 were recorded. Homeostasis model assessment of insulin resistance (HOMA-IR) and homeostasis model assessment of beta cell (HOMA-β) were calculated.

Results: A total of 125 patients receiving DAAs were enrolled, including genotype 1 of 74 patients, genotype 2 of 44 patients, genotype 6 of 5 patients and mixed genotype of 3 patients. The average age was 65.5 years and baseline BMI was 25.3.

Forty patients (31.0%) were male, 51 (40.5%) had cirrhosis, and thirty-three patients (26.2%) took diabetic medications. When comparing with baseline values, Cholesterol increased from 165.8 mg/dL to 180.6 mg/dL, triglyceride from 100.7 mg/

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Section：LGI dL to 112.7 mg/dL, LDL from 101.1 mg/dL to 107.1 mg/dL but HDL decreased from 57.2 mg/dL to 52.9 mg/dL at 1 year after SVR12. After excluding patients taking diabetic medications, fasting glucose increased at 1 year after SVR (98.9 mg/ dL vs 101.2 mg/dL, p=0.030). HbA1C was also stable at SVR12 but increased at 1 year (5.42 vs 5.66, p<0.001). Both HOMA-IR and HOMA-beta decreased at 1 year after SVR12 (HOMA-IR: 3.65 vs 2.77, p<0.001; HOMA-β: 164.9 vs 104.4, p<0.001). BW change ≥2 kg was a independent factor to predict worse HbA1C ≥0.5% at 1 year after SVR12 in multivariate analysis (OR: 3.323, 95% CI: 1.073-10.290, p=0.037).

Conclusions: Worsening of lipid profile and improved insulin resistance was observed at 1 year after DAA-induced SVR12. Increased body weight predicted worsening HbA1C at 1 year after SVR12. The impact of metabolic changes on clinical outcomes needs further investigation.

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NEW ARTIFICIAL INTELLIGENCE SYSTEM FOR COLORECTAL POLYP DETECTION: A PRELIMINARY STUDY Chih-Wei Yang1, Tien-Yu Huang1, Yu-Lueng Shih1, Henry Horng-Shing Lu2, Vincent S. Tseng3, Peng-Jen Chen1 Division of Gastroenterology, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan1 Big Data Research Center and Institute of Statistics, National Chiao Tung University, Hsinchu, Taiwan2 Department of Computer Science, National Chiao Tung University, Hsinchu, Taiwan3

新型人工智能大腸瘜肉偵測系統 楊志偉1 黃天祐1 施宇隆1 盧鴻興2 曾新穆3 陳鵬仁1 三軍總醫院腸胃科1 交通大學大數據研究中心2 交通大學電腦科學所3 Background: Colonoscopy is a primary screening and follow-up tool to detect colorectal cancer (CRC), the third leading cause of cancer death in Taiwan. The removal of adenomatous polyps lowers the incidence of and results in reduced mortality from CRCs. 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. Artificial intelligence (AI) is increasingly applied in GI endoscopy. Using AI to detect colorectal polyps might be promising to increase the polyp detection and reduce the endoscopist’s fatigue.

Aims: We validated a new AI system (GI-CAD v.0.1, TIMS) with 477 still images of polyps.

Methods: A new AI system (GI-CAD v.0.1, TIMS) was trained using a series of videos of 2015 histologically confirmed polyps from 740 patients who underwent high-definition white-light colonoscopy as part of a previous study (MOST107-2314-B-016-011-MY2). A total of 458738 frames showing these polyps from different perspectives were extracted from videos. These frames were manually annotated by educated annotator and reviewed by expert endoscopists.

The image validation set comprised of 477 still

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images of 477 different polyps from 312 patients.

The video validation set included 30 video clips of polyps. To assess sensitivity of video clips, a truepositive per lesion was defined when the target polyp, irrespective of the histology, was detected

by AI in at least one frame.

Results: The sensitivity of each image in the still image validation set was 92.5% and the sensitivity per lesion in the video validation set was 100%.

The mean inference time of each image using the GI-CAD system was 25.7 ms.

Conclusions: Colonoscopy is a real-time procedures requiring complex analysis of millions of frames, and the GI-CAD colon system can afford fast real-time computation with minimal delay. GICAD with high sensitivity might be promising in clinical practice to improve polyp detection and reduce endoscopist’s fatigue.

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INCIDENCE AND LONG-TERM OUTCOMES OF COLONOSCOPY INTERVAL CANCERS IN TAIWAN COLORECTAL CANCER SCREENING PROGRAM Wen-Feng Hsu1, Li-Chun Chang2, Tsui-Hsia Hsu3, Li-Ju Lin3, Ming-Shiang Wu2, Hsiu-Hsi Chen4, Han-Mo Chiu2 Department of Medicine, National Taiwan University Cancer Center, Taipei, Taiwan1 Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan2 Health Promotion Administration, Ministry of Health and Welfare, Taipei, Taiwan3 Graduate Institute of Epidemiology and Preventive Medicine, College of Public Health, National Taiwan University, Taipei, Taiwan4

台灣大腸直腸癌篩檢計劃中大腸鏡間 隔癌的發生率與長期存活 許文峰1 張立群2 徐翠霞3 林莉茹3 吳明賢2 陳秀熙4 邱瀚模2 國立臺灣大學醫學院附設癌醫中心醫院綜合內科 部1 台大醫院內科部2 衛生福利部國民健康署3 台灣大學公衛學院流行病學與預防醫學研究所4 Background: Survival of colorectal cancer (CRC) detected within a screening program may largely affect the effectiveness of screening.

Aims: In this study, we aim to elucidate and compare the long-term outcomes of fecal immunochemical test (FIT) interval cancers (ICs) and colonoscopy ICs within FIT screening program.

Methods: Interval CRCs within a Taiwan CRC Screening Program during 2004 to 2012 comprised the study cohort and were followed up till 2016.

The definitions of FIT IC and colonoscopy IC were based on the definition by World Endoscopy Organization. Hospital level adenoma detection rates (ADR) were categorized into 3 groups: ADR <20 (low ADR group), 20≤ADR<40 (middle ADR group), and ADR ≥40 (high ADR group). The incidence of colonoscopy ICs were compared stratified by different ADR group. Survival status of FIT ICs and each category of colonoscopy ICs were compared. Cox proportional hazards

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regression model was conducted for multivariable analysis.

Results: Totally 2125 ICs were identified from the screening database during the study period.

Of them, 1837 (86.4%) were FIT IC and 288 (13.6%) were colonoscopy ICs. Hospitals with low ADR level had significantly higher incidence of colonoscopy ICs (0.93 per 1000 person-year) than middle and high ADR groups (0.702 per 1000 person-year and 0.584 per 1000 personyear, respectively) (p < 0.001). Colonoscopy ICs in high ADR group presented at a more advanced stage (stage III/IV was 48%) compared with that in the middle and low ADR groups, and FIT ICs (44.0%, 41.18%, and 46.91%, respectively). The survival of colonoscopy ICs in high ADR groups were significantly worse than that of the middle and low ADR groups, and FIT ICs (p = 0.004). In the multivariable analysis, when compared with colonoscopy ICs in middle ADR group, hazard ratio (HR) of CRC death was 1.07 (95% CI=0.60– 2.26) for colonoscopy IC in low ADR group, 1.64 (1.19–2.26) for FIT IC, and 1.94 (1.01–3.80) for colonoscopy ICs in high ADR group.

Conclusions: High ADR group had the lowest incidence of colonoscopy IC, but colonoscopy IC in this group had worse survival than middle and lower ADR groups, and even than FIT ICs.

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COMPARING RIGHT COLON ADENOMA DETECTION RATE DURING WATER EXCHANGE AND AIR INSUFFLATION: A DOUBLE-BLINDED RANDOMIZED CONTROLLED TRIAL Yu-Hsi Hsieh1,2, Chih-Wei Tseng1,2, Malcolm Koo3, Felix W. Leung4 Division of Gastroenterology, Department of Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi, Taiwan1 School of Medicine, Buddhist Tzu Chi University, Hualien, Taiwan2 Graduate Institute of Long-term Care, Tzu Chi University of Science and Technology, 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右側大 腸腺瘤發現率：一雙盲隨機對照試驗 謝毓錫1,2 曾志偉1,2 辜美安3 梁永亨4 大林慈濟醫院腸胃科1 慈濟大學醫學系2 慈濟科技大學長期照護研究所3 加州大學洛杉磯分校4 Background: Missed adenomas and hyperplastic polyps contributed to the occurrence of interval cancers in the right colon. Randomized controlled trials showed increased adenoma detection with water exchange (WE) compared with air insufflation (AI). None of them used right colon adenoma detection rate (rADR) as the primary outcome.

Aims: We hypothesize that in the right colon, compared with AI, WE significantly increases rADR and hyperplastic polyp detection rate (rHPDR) and decreases adenoma miss rate (rAMR).

Methods: Usual WE and AI were performed. After cecal intubation, the second blinded endoscopist examined the right colon. Then, the first colonoscopist reinserted the scope to the cecum with WE in both groups and performed a tandem examination of the right colon and completed the withdrawal. The primary outcome was rADR obtained by the blinded colonoscopist.

Results: Patients were randomized to AI (n=140)

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or WE (n=144). The baseline characteristics were similar. The rADR obtained by the blinded endoscopist was significantly higher with WE than AI (34.7% vs. 22.3%, P=0.025). The WE group had a better Boston Bowel Preparation Scale score in the right colon compared with the AI group (mean [standard deviation], 2.6 [0.6] vs.

2.2 [0.6], P<0.001). The amount of water aspirated was 103% of infused on arrival to the cecum. WE showed a significantly lower rAMR than AI (31.5% vs. 45.2%, P=0.038) and higher rHPDR (18.1% vs. 7.1%, P=0.007).

Conclusions: The data support the proposed hypothesis. The significantly increased rADR and rHPDR and decreased rAMR indicated WE has the potential to prevent interval cancers.

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2-LNCRNA PROGNOSTIC SIGNATURE OF RECTAL CANCER FROM TCGA DATABASE Szu-Jen Wang1,2, Meng-Shun Sun2, Hsi-Jung Chen2, Ching-Yang Tsai2 Graduate Institute of Clinical Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan1 Division of Gastroenterology, Department of Internal Medicine, Yuan’s General Hospital, Kaohsiung, Taiwan2

TCGA 直腸癌資料庫中評估二個長鏈非 編碼 RNA (lncRNA) 的臨床預後效益 王嗣仁1,2 孫盟舜2 陳錫榮2 蔡青陽2 高雄醫學大學臨床醫學研究所1 阮綜合醫院消化內科2 Background: Recent studies demonstrated that the dysregulated long non-coding RNAs (lncRNAs) expression profiles were related to the progression and survival in patients with various cancers including rectal cancer.

Aims: This study aimed to find out a long noncoding RNA (lncRNA) signature for predicting the prognosis of rectal cancer prognosis from The Cancer Genome Atlas (TCGA) database.

Methods: 1. LncRNAs expression profiles and corresponding clinicopathological data for 167 patients with rectal cancer were obtained from The Cancer Genome Atlas (TCGA), including 167 tumor-part specimens and 10 non-tumor-part specimens. 2. Differentially expressed lncRNAs (DELs) between tumor-part and non-tumor-part specimens of rectal cancer were identified using the edgeR package, using an false discovery rate (FDR) < 0.05 and log2 |fold change (FC)| > 2. 3. The least absolute shrinkage and selection operator Cox (LASSO Cox) regression model was used to narrow down the candidates of lncRNA. 4. Next, the key lncRNAs in Lasso Cox regression were further analyzed with a stepwise multivariate Cox regression model. The lncRNAs fitted in the multivariate Cox regression model and independently associated with overall survival were selected to construct a prognostic risk formula. 5.

The R software version 3.6.1 and the “edgeR”, “glmnet”, “survival”, “timeROC” and “survminer” package were utilized to analyze.

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6. The risk scores were calculated based on the formula generated through the multivariate Cox regression model. Using the median risk score as the cutoff value, patients in the dataset were divided into low-risk or high-risk groups correspondingly.

7. The efficiency of the predictive model was estimated by the Receiver operating characteristic curve (ROC curve) and Harrell’s C-index statistic.

Results: Based on lncRNA expression profiling of 167 patients with rectal cancer from the TCGA database, a total of 899 DELs were selected out including 337 down-regulated DELs and 562 up-regulated DELs (Fig. 1). 23 lncRNAs were identified using LASSO Cox. Finally, 2 lncRNAs (AC100803.3 and GATA2-AS1) were confirmed in the multivariate Cox regression model (Fig. 2). The risk score was calculated by the formula as follows: Risk score = 0.1574132*AC100803.3 – 0.4323343*GATA2-AS1. According to this 2-lncRNAs signature, the corresponding AUC for the predictive model of 3-year and 5-year survival was 0.915 and 0.989, respectively (Fig. 3). It had a Harrell’s C-index statistic of 0.9 (95%CI: 0.860.94), indicating a high predictive ability for survival time of rectal cancer. Kaplan-Meier analysis also revealed that for the TCGA cohort, the high-risk group had significantly poorer survival than the low-risk group (Log-Rank test p<0.001) (Fig. 4).

Conclusions: Our data-mining survey constructed the 2-lncRNA model can be a biomarker to predict the prognosis of rectal cancer. Further studies were needed to confirm this signature model.

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IMMUNE FECAL OCCULT BLOOD TEST IS SUPERIOR TO SYSTEMIC INFLAMMATORY MARKERS FOR PREDICTING MUCOSAL HEALING AMONG PATIENTS WITH ULCERATIVE COLITIS Hsu-Heng Yen, Tsui-Chun Hsu, Mei-Wen Chen, Ya-Huei Zeng, Yang-Yuan Chen Division of Gastroenterology, Changhua Christian Hospital, Changhua, Taiwan

糞便潛血免疫學檢查比血液學檢測更 能預測潰瘍性結腸炎病患黏膜癒合之 情形 顏旭亨 許翠純 陳美文 曾雅惠 陳洋源 彰化基督教醫院胃腸科 Background: Ulcerative colitis (UC) has emerged in the Asia–Pacific area over the past two decades. The treatment goal for UC has shifted from symptom relief to endoscopic remission.

Endoscopy is the gold standard for the diagnosis of mucosal healing for the patients; however, it is expensive and invasive.

Aims: The present study evaluated the use of immune fecal occult blood test (iFOBT) as a marker to predict mucosal healing among patients with UC. Methods: A total of 54 patients with UC were retrospectively enrolled from the electronic clinical database of Changhua Christian Hospital, Taiwan, from January 2019 to July 2019. Stool samples for iFOBT, blood samples [hemoglobin level, C-reactive protein (CRP) level, erythrocyte sedimentation rate, albumin level], and Mayo disease activity scores were reviewed and analyzed. Colonic mucosa was assessed using a Mayo endoscopic subscore.

Results: The mean age of the patients was 46.67 years, and 65% of the patients were male. The disease distribution was as follows: E1 (24.07%), E2 (37.04%), and E3 (37.89%). Complete mucosal healing occurred in 25.9% of patients.

Patients with and without mucosal healing were compared, and they had similar age, white blood cell count, hemoglobin level, CRP level, erythrocyte sedimentation rate, and drug use.

Patients with complete mucosal healing exhibited lower platelet counts (226,000/μL vs 287,000/μL,

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Section：HBV p = 0.033), iFOBT values (7.0 ng/mL vs 105 ng/ mL, p = 0.001), neutrophil-to-lymphocyte ratio (1.93 vs 2.34, p = 0.004), and partial Mayo score (1 vs 3, p = 0.001). Predictive cutoff values were analyzed using receiver operating characteristics (ROC). iFOBT showed the highest area under the curve using ROC analysis compared with other parameters. Using an iFOBT criterion of ≤30 ng/ mL, the sensitivity and specificity were 100% and 69.44%, respectively, for predicting complete mucosal healing.

Conclusions: iFOBT may be a useful marker to predict endoscopic healing of colon mucosa among patients with UC in daily clinical practice.

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A COMBINATION OF THE ONEYEAR CHANGES IN FIB-4 AND MODIFIED FIB-4 VALUES HELPS TO IDENTIFY CIRRHOTIC HBV PATIENTS WITH THE MINIMAL ANNUAL RISK OF HEPATOCELLULAR CARCINOMA BEYOND YEAR 5 OF ENTECAVIR THERAPY Hung-Wei Wang1, Chien-Hung Chen2, Hsueh-Chou Lai1, Tsung-Hui Hu2, Jing-Houng Wang2, Cheng-Yuan Peng1 Center for Digestive Medicine, China Medical University Hospital, Taichung, Taiwan1 Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan2

結 合 FIB-4 和 Modified FIB-4 的 一 年 指標變化可識別接受貝樂克治療 5 年 後具有極低肝癌年發生率之肝硬化 B 型肝炎患者 王鴻偉1 陳建宏2 賴學洲1 胡琮輝2 王景弘2 彭成元1 中國醫藥大學附設醫院消化醫學中心1 高雄長庚紀念醫院內科部胃腸肝膽科系2 Background: Long-term nucleos(t)ide analogue (NA) therapy reduces the cumulative incidence of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB). However, HCC risk stratification through the dynamic changes of noninvasive fibrosis index remains unclear in cirrhotic patients.

Aims: We aimed to investigate the annual incidence of HCC stratified by the dynamic changes of fibrosis index in cirrhotic patients with CHB who received NA therapy.

Methods: A total of 481 prior NA-naïve cirrhotic patients with CHB receiving entecavir therapy were enrolled from January 2007 to August 2012.

Baseline clinical characteristics and laboratory data were collected. The dynamic change of fibrosis index was defined as the one-year change in index values (index at 1 year – index at baseline shown as △index). The areas under the receiver operating characteristic (AUROC) curve of △FIB4 and △mFIB-4 in predicting HCC risks were

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analyzed and compared by using the DeLong test.

The Kaplan-Meier method with the log-rank test was used to evaluate the cumulative HCC risks in the 3 subgroups stratified by the combination of △FIB-4 and △mFIB-4. The annual HCC incidence was calculated and compared between within and beyond 5 years of treatment in each subgroup by using the Fisher exact test.

Results: A total of 93 patients developed HCC during treatment. △FIB-4 and △mFIB-4 had similar predictive performance for HCC in cirrhotic patients (AUC: 0.67 vs. 0.72, P = 0.18). Patients with both increased △FIB-4 and △mFIB-4 have the highest cumulative HCC incidence compared to those with both decreased △FIB-4 and △mFIB4 or those with decreased △FIB-4/increased △mFIB-4 and increased △FIB-4/decreased △mFIB-4 (5-yr: 32.7% vs. 10.3% and 32.7% vs.

15.9%, respectively, both P < 0.001). Moreover, this subgroup also continued to exhibit numerically or significantly higher annual HCC incidence up to 7 years of treatment compared with those with both decreased △FIB-4 and △mFIB-4 (1-2 yr: 8.03% vs. 3.10%, P = 0.11; 2-3 yr: 5.69% vs. 3.60%, P = 0.55; 3-4 yr: 12.96% vs. 3.23%, P = 0.02; 4-5 yr: 8.43% vs. 0%, P = 0.01; 5-6 yr: 8.33% vs. 0%, P = 0.05; 6-7 yr: 12.9% vs. 0%, P = 0.03). Patients with both increased △FIB-4 and △mFIB-4 exhibited insignificantly decreased annual HCC incidence over Year 5 to 9 compared with that over Year 1 to 5 (1-5 yr vs. 5-9 yr: 7.12% vs. 4.17%, P = 0.11).

By contrast, patients with both decreased △FIB4 and △mFIB-4 or decreased △FIB-4/increased △mFIB-4 and increased △FIB-4/decreased △mFIB-4 exhibited significantly decreased annual HCC incidence over Year 5 to 9 compared with that over Year 1 to 5 (1-5 yr vs. 5-9 yr: 2.13% vs. 0%, P = 0.02; 1-5 yr vs. 5-9 yr: 3.37% vs. 0.94%, P = 0.01, respectively).

Conclusions: A combination of the one-year changes in FIB-4 and mFIB-4 values could identify the subgroup of cirrhotic patients with CHB undergoing long-term entecavir therapy at minimal annual risk of HCC beyond year 5 of treatment.

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EFFICACY AND RISK OF RENAL EVENTS DURING TENOFOVIR ALAFENAMIDE ANTIVIRAL PROPHYLAXIS IN HBSAGPOSITIVE CANCER PATIENTS UNDERGOING CHEMOTHERAPY I-Cheng Lee1, Keng-Hsin Lan1, Chien-Wei Su1, Yee Chao2, Ming-Chih Hou1, Yi-Hsiang Huang1 Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan1 Cancer Center, Taipei Veterans General Hospital, Taipei, Taiwan2

B 型肝炎帶原之癌症病人接受化學治療 期間使用韋立得抗病毒治療之療效與 腎臟安全性分析 李懿宬1 藍耿欣1 蘇建維1 趙毅2 侯明志1 黃怡翔1 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 Background: Tenofovir alafenamide (TAF) was shown to have better renal safety while comparable efficacy than the older tenofovir disoproxil fumarate (TDF). There was no data comparing the safety and efficacy of TAF and TDF in cancer patients undergoing cytotoxic chemotherapy.

Aims: The aim of this study was to assess the antiviral efficacy and risk of renal events in HBsAgpositive cancer patients treated with TAF or TDF during cancer chemotherapy.

Methods: HBsAg-positive cancer patients treated with TAF (n=108) or TDF (n=142) for HBV prophylaxis during chemotherapy were retrospectively enrolled. Serum creatinine levels were monitored during chemotherapy. Estimated glomerular filtration rate (eGFR) was calculated using the Modification of Diet in Renal Disease (MDRD) formula. Virological response was defined as achieving undetectable HBV DNA. Acute kidney injury (AKI) was defined as an increase in SCr by equal or more than 0.3 mg/dL within 48 hours, or an increase in SCr to ≥1.5 times baseline.

Results: Patients in the TDF group had significantly longer follow-up duration (16.1 vs 6.9 months, p<0.001) and lower percentage of baseline eGFR <60 mL/min (0% vs 7%, p=0.004) than the TAF

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group. The virological response rate were 89.5% and 94.4% in TAF and TDF groups, respectively (p=0.450). The overall incidences of AKI at month 3, 6, and 12 were 12.4%, 17.3%, 27.8% and 9.4%, 17.2%, 30.2%, respectively, in TAF and TDF groups (p=0.850). Majority of the renal events were transient and resolved within one month. By multivariate analysis, the only factor associated with AKI during chemotherapy was the use the cisplatin-containing regimen (hazard ratio = 1.724, p=0.045).

Conclusions: AKI may develop in about 30% of HBsAg-positive cancer patients undergoing chemotherapy. The antiviral efficacy and risk of renal function impairment was comparable between patients treated with TAF and TDF during chemotherapy.

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ROLE OF HEPATITIS D VIRUS INFECTION IN DEVELOPMENT OF HEPATOCELLULAR CARCINOMA Tyng-Yuan Jang, Chung-Feng Huang, Chia-Yen Dai, Jee-Fu Huang, Ming-Lung Yu, Wan-Long Chuang Division of Hepatobiliary, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan

D 型肝炎在 HCC 中扮演的角色 張庭遠 黃釧峰 戴嘉言 黃志富 余明隆 莊萬龍 高雄醫學大學附設中和紀念醫院肝膽胰內科 Background: Hepatitis D virus (HDV) infection increases the risk of hepatocellular carcinoma (HCC) in the natural course. Its role in patients treated with nucleotide/nucleoside analogues (NAs) is unclear.

Aims: We aimed to study the role of Hepatitis D in the development of hepatocellular carcinoma in chronic hepatitis B (CHB) patients treated with nucleotide/nucleoside analogues.

Methods: Altogether, 1349 CHB patients treated with NAs were tested for anti-HDV antibody and RNA. Incidence and risk factors of HCC development were analysed.

Results: Rates of anti-HDV and HDV RNA seropositivity were 2.3% and 1.0%, respectively.

The annual incidence of HCC was 1.4 per 100 person-years after a follow-up period of over 5409.5 person-years. The factors with the strongest association with HCC development were liver cirrhosis (hazard ratio [HR]/95% confidence interval [CI]: 11.10/5.54-22.23, P < 0.001), followed by HDV RNA seropositivity (HR/ CI 5.62 /1.33-23.84, P = 0.02), age > 50 years old (HR/CI 3.49/1.94-6.29, P < 0.001), male gender (HR/CI: 2.60/25-5.43, P = 0.01), and body mass index (HR/CI: 1.11/1.03-1.19, P = 0.004). The 5-year cumulative incidence of HCC was 5.0% for patients with HDV RNA seronegativity compared to 18.2% for patients with HDV RNA seropositivity (P = 0.01). Among cirrhotic patients, the only factor associated with HCC development was platelet count (HR/CI: 0.99/0.99-1.00, P = 0.03).

Among non-cirrhotic patients, the strongest factors associated with HCC development was age > 50

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years old (HR/CI: 26.47/3.23-216.59, P < 0.002), followed by anti-HDV seropositivity (HR/CI: 7.86/1.35-45.73, P = 0.02) and platelet count (HR/ CI: 0.99/0.97-1.00, P = 0.03).

Conclusions: HDV infection played an essential role in the development of HCC in CHB patients who underwent NAs therapy. More aggressive management and closer monitoring of patients with HDV infection is mandatory.

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SAFETY AND EFFICACY OF SWITCHING TO TENOFOVIR ALAFENAMIDE (TAF) IN VIRALLY SUPPRESSED CHRONIC HEPATITIS B (CHB) PATIENTS WITH HEPATIC IMPAIRMENT: WEEK 48 RESULTS FROM A PHASE 2 OPEN LABEL STUDY Wan-Long Chuang1, Chi-Yi Chen2, Yi-Hsiang Huang3, Chun-Yen Lin4, Jeong Heo5, Chien-Hung Chen6, Aric Josun Hui7, Magdy Elkhashab8, Shuyuan Mo9, John F. Flaherty9, Vithika Suri9, Anuj Gaggar9, Tak Yin Owen Tsang10, Harry Janssen11, Young-Suk Lim12 Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan1 Chia-Yi Christian Hospital, Chiayi, Taiwan2 Taipei Veterans General Hospital, Taipei, Taiwan3 Chang Gung University College of Medicine, Taoyuan, Taiwan4 College of Medicine, Pusan National University, Division of Gastroenterology and Hepatology, Pusan National University Hospital, Busan, Korea5 Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan6 Alice Ho Miu Ling Nethersole Hospital, Hong Kong7 Toronto Liver Centre, Toronto, Canada8 Gilead Sciences Inc., Foster City, CA, USA9 Princess Margaret Hospital, Hong Kong10 Toronto Centre for Liver Disease, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada11 Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea12 Background: Switching to TAF, a novel tenofovir prodrug, has shown maintenance of viral suppression with stable or improved bone and renal safety at Wk 24 in CHB patients with impaired hepatic function.

Aims: Here we evaluated the efficacy and safety 48 weeks after CHB patients with hepatic

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decompensation were switched to TAF. Methods: In this Phase 2 study (NCT03180619) patients with CHB having a Child-Turcotte-Pugh (CTP) score ≥7 and ≤12 at screening, or by documented history, receiving TDF and/or other OAVs for ≥48 weeks, with HBV DNA <LLOQ for ≥24 weeks and <20 IU/mL at screening were eligible to participate. All patients were switched to TAF 25 mg QD and were to be treated for 96 weeks. Safety assessments including changes in bone (hip and spine BMD) and renal (CrCl by Cockcroft-Gault [eGFRCG], serum creatinine) parameters, viral suppression, and biochemical responses were assessed at Week 48.

Results: 31 patients were enrolled at 18 sites in 7 countries (11 (36%) patients were from Taiwan), and 90% completed 48 weeks of treatment. At baseline, 74% were ≥50 y, 68% male, 81% Asian, 90% HBeAg-negative, with median fibrotest (FT) score 0.81, median CTP and MELD scores of 6 and 10, respectively, median eGFRCG 98 mL/ min, and 19% and had osteoporosis by T score at spine. Prior use of TDF and entecavir was reported by 68% and 45%, respectively. Key efficacy/safety results at Week 48 are summarized in the Table. By missing equals failure analysis, 31 patients (100%) had HBV DNA <20 IU/mL, 81% had normal ALT and CTP/MELD scores were stable. After switching to TAF in this population with liver impairment, CTP, MELD, and FT scores were unchanged while bone and renal parameters were stable. TAF was well tolerated with few having Grade 3 or 4 AEs (4 patients); no serious AEs related to study drug, and 1 patient who discontinued for worsening renal function unrelated to TAF. Conclusions: CHB patients with hepatic impairment who were switched to TAF from TDF or other OAV showed high rates of viral suppression, normal ALT and bone and renal safety were stable at Week 48.

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COMORBIDITIES IN HEPATITIS B AND HEPATITIS C PATIENTS ON HEMODIALYSIS Po-Yao Hsu1, Po-Cheng Liang1, Chung-Feng Huang1,2, Ming-Lun Yeh1,2, Ching-I Huang1,2, Zu-Yau Lin1, Shinn-Cherng Chen1,2, Chia-Yen Dai1,2, Jee-Fu Huang1,2, Wan-Long Chuang1,2, Ming-Lung Yu1,2 Division of Hepatobiliary, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan1 Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan2

接受血液透析之 C 型肝炎和 B 型肝炎 患者之共病研究 許博堯1 梁博程1 黃釧峰1,2 葉明倫1,2 黃駿逸1,2 林子堯1 陳信成1,2 戴嘉言1,2 黃志富1,2 莊萬龍1,2 余明隆1,2 高雄醫學大學附設中和紀念醫院肝膽胰內科1 高雄醫學大學醫學院內科學系2 Background: Hemodialysis patients are at increased risk for hepatitis B virus (HBV) and hepatitis C virus (HCV) infection. Those with HCV infection have demonstrated higher morbidity and mortality rate compared to non-B and non-C (NBNC) patient. In contrary, HBV infection seemed to have little impact in this population.

This phenomenon may be due to their different comorbidities.

Aims: The current study aimed to investigate the comorbidities of hepatitis C patients and hepatitis B patients on hemodialysis.

Methods: The baseline characteristics and comorbidities were analyzed among hemodialysis patients from 23 hemodialysis centers in Taiwan.

Results: A total of 2,016 hemodialysis patients were recruited, including 159 HCV patients (positive HCV RNA), 217 HBV patients (seropositive for HBsAg), and 1629 NBNC patients (negative for both HBsAg and HCV RNA). The number of comorbidities per person was highest in HCV group (3.5 ± 1.7), followed by NBNC group (2.8 ± 1.5), and HBV group (3.1 ± 1.6). Compared to NBNC patients, HCV patients had a higher

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Section：Pancreas / Biliary proportion of ischemic heart diseases (50.9% vs. 38.9%), hepatocellular carcinoma (6.3% vs.

1.0%), peptic ulcer/GERD (22.6% vs. 15.9%), lung diseases (8.8% vs. 2.9%), and mental/behavioural disorders (10.7% vs. 4.1%) but a lower proportion of hyperlipidemia (30.2% vs. 39.7%). Patients with HBV infection exhibited a higher incidence of hepatocellular carcinoma (4.1% vs. 1.0%) but a lower incidence of hyperlipidemia (32.7% vs. 39.7%), peripheral vascular disease (0.5% vs. 4.1%), disorders of thyroid gland (0.9% vs.

4.1%), arrhythmia (2.3% vs. 8.2%), and mental/ behavioural disorders (0.9% vs. 4.1%).

Conclusions: Compared to NBNC patients on hemodialysis, HCV patients had a higher mean number of comedications, which could be attributed to a higher incidence of ischemic heart diseases, hepatocellular carcinoma, peptic ulcer/ GERD, lung diseases, and mental/behavioural disorders. In contrary, patients seropositive for HBsAg on hemodialysis had a lower mean number of comedications than NBNC patients, which may explain the little impact of HBV on mortality in this population.

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THE SAFETY AND EFFICACY OF EUS-GUIDED ETHANOL ABLATION IN PATIENTS WITH NON-FUNCTIONAL PANCREATIC NEUROENDOCRINE TUMOR Kuei-Yu Chen, Yen-Chih Lin, Hsu-Heng Yen Division of Gastroenterology, Changhua Christian Hospital, Changhua, Taiwan

內視鏡超音波導引下酒精燒灼針對非 功能性胰神經內分泌瘤的治療效果與 安全性 陳奎佑 林彥至 顏旭亨 彰化基督教醫院胃腸肝膽科 Background: Pancreatic neuroendocrine tumor (pNET) can be categorized into functional pancreatic neuroendocrine tumor (F-pNET) and non-functional pancreatic neuroendocrine tumor (NF-pNET). According to ENETS Consensus Guidelines of non-functional pNET, surgery was suggested if tumor size was larger than 2 cm. On the contrary, surveillance was suggested when tumor size was less than 2 cm. EUS-guided tumor ablation is emerging as a new treatment modality of small pancreatic tumor, however, the experience of tumor ablation remained limited.

Aims: To evaluate the safety and efficacy of EUS-guided ethanol ablation in patients with nonfunctional pNET. Methods: After tissue proof by EUS-FNA, we enrolled the patients with non-functional pNET that the tumor size was less than 2cm. Before we injected 99.5% alcohol, we calculated the amount of alcohol based on the volume of the pNET. Using EUS-FNA needles, alcohol injection was continued until all the lesions was completely become white on the EUS image. They received EUS-guided alcohol ablation one or more session until no viable tumor was visualized on CT or MRI image. Besides, we also follow-up with contrastenhanced endoscopic ultrasound (CH-EUS) if we obtained the informed consent from the patients.

All of the patients has pre-treatment and post treatment chromogranin-A data.

Results: We total enrolled 5 patients. All the patients has tissue proof by EUS-FNA. All of them received 1 or 2 sessions of EUS-guided alcohol ablation. The tumor diameter was between 1 cm

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to 1.6 cm. No severe complication such as acute pancreatitis was observed in all of the patients.

Complete remission was confirmed in 4 of them in the follow-up CT or MRI. However, one of the patients hesitated for the second session of EUSguided alcohol ablation even though the residual tumor was found at first time followed image.

Residual tumor was visualized in one of the patients in the follow-up CT scan on 12 days post EUS-guided alcohol ablation, but 3 months later, no residual tumor was identified on the follow-up MRI image, suggestive of the possible delayed effect of tumor ablation.

Conclusions: EUS guided alcohol ablation is a safe technique in the treatment toward nonfunctional pNET which was smaller than 2 cm.

However, it is difficult to evaluate the adequacy of alcohol ablation since tiny viable tumor can’t be identified by CT/MRI study. Routinely use of contrast-enhanced EUS (CH-EUS) post EUSguided ethanol ablation may be helpful, but the efficacy of CH-EUS as a follow-up tool require further evaluation.

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A TRAINING PROGRAM OF A NEW CLASSIFICATION OF CONFOCAL LASER ENDOMICORSCOPY FOR PANCREATIC CYSTIC LESION Ming-Lun Han1, Pradermchai Kongkam2, Hsiu-Po Wang3 Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan1 University and King Chulalongkorn University Hospital, Thailand2 Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan3

共聚焦激光內鏡檢查對胰腺囊性病變 新分類的培訓計劃 韓明倫1 Pradermchai Kongkam2 王秀伯3 臺大醫院綜合診療部1 泰國朱拉隆功國王大學醫院2 臺大醫院內科部3 Background: Pancreatic cystic lesions are common and correct diagnosis of pancreatic cystic lesions is vital for further management. We developed a new confocal laser endomicorscopy classification system based on the vascular structure and epithelial structure. However, its remains uncertain.

Aims: To test the effectiveness of a training program for diagnostic pancreatic cystic lesion from video clips of confocal laser endomicorscopy.

Methods: A total of 17 young trainee, 7 first-year fellows (F1) and 10 second-year fellows (F2) joined an endoscopic training program, which was composed of pretest, teaching course and feedback section and post-test. The pretest and post -test section included 47 clips of confocal laser endomicorscopy endoscopic videos from 8 patients (including four intra-ductal mucinous neoplasms, one serous cystic neoplasm, one mucinous cystic neoplasm, one cystic pancreatic neuroendocrine tumor and one pseudocyst).

Every trainee watched each video clip and made a diagnosis of the lesion in 2 minutes.

Results: The diagnostic accurate rates before and after training program were 55.3% and 63.6% for mucinous lesions; 78.7% and 78.8 % for mucinous lesions. No significant improvement of diagnostic accuracy after the training program was noted both in definite lesions and mucinous lesions. Subgroup

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analysis revealed totally the performance of F2 is better than that of F1 both in pretest and post test.

However, great variation within each subgroup was noted; some F1’s performance are much better than other F1 and even better than F2.

Conclusions: In spite of our training program, it’s still difficult for some fellow doctors in discriminating pancreatic cystic lesions from video clips. Further artificial intelligence (AI) technique maybe could overcome this weak point (high variation between fellow doctors).

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CLINICAL CHARACTERISTICS AND ENDOSCOPIC FEATURES OF NON-AMPULLARY DUODENAL EPITHELIAL LESIONS Wei-Ru Cho, Chih-Chien Yao, Cheng-Kun Wu, Lung-Sheng Lu, Chih-Ming Liang, Ming-Luen Hu, Wei-Chen Tai, Yeh-Pin Chou, Yi-Chun Chiu, Keng-Liang Wu, 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

非壺腹十二指腸上皮病灶的臨床和內 視鏡表徵 卓韋儒 姚志謙 吳鎭琨 盧龍生 梁志明 胡銘倫 戴維震 周業彬 邱逸群 吳耿良 蔡成枝 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: Sporadic superficial non-ampullary duodenal epithelial lesions (SNADELs) are usually benign neoplastic or non-neoplastic origins, asymptomatic and found incidentally by esophagogastrodudenoscopy (EGD) screening.

However, some of the neoplastic lesions such as adenoma may progress to adenocarcinoma overtimes. Although the prevalence of duodenal adenocarcinoma is less than 5% of gastrointestinal malignancies, the prognosis is dismal when it is diagnosed at the advanced stages.

Aims: To evaluate the clinical characteristics and endoscopic features of patients with SNADELs. Methods: This is retrospective chart review study on 104945 patients who underwent EGD in Kaohsiung Chang Gung Memorial hospital, Taiwan between January 2013 to May 2020. A total of 625 patients with histologically confirmed SNADELs were recruited and analyzed by dividing them into two groups according to the pathologist reports: (1) non-neoplastic group (n = 467, 74.7%) and (2) neoplastic group (n = 158, 25.3%).

Results: Among the 467 non-neoplastic SNADELs, 301 wereinflammatory polyps (64.5%), 138 heterotrophic gastric mucosa (29.6%), 41 hyperplastic polyp (8.8%), 1 lymphagiectasia (0.2%) and 1 Brunner’s gland (0.2%). For the

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other 158 neoplastic SNADELs, 124 of them were adenomatous lesions: low to moderate grade dysplasia (LMGD) (n = 78, 49.3%), high grade dysplasia (HGD) (n = 11, 6.96%), and superficial adenocarcinoma (SAC) (n = 35, 22.2%).The other 34 non-adenomatous were all malignant lesion: Gastrointestinal stromal tumor (n = 2, 1.27%), lymphoma (n = 9, 5.70%), neuroendocrine tumors (n = 9, 5.70%), and metastatic carcinoma (n = 14, 8.86%). All together there were a total of 69 malignant neoplastic lesions (n = 35 in the adenomatous subgroup and n = 34 in the nonadematous subgroup). There were significant differences between neoplastic SNADELs and non-neoplastic SNADELs for Helicobacter pylori infection, size, multiple lesions, colors of lesions, locations and growth (p < 0.05). Among the 124 adenomatous lesions, a significantly greater number of HGD and SAC were found in the older patients (p = 0.017), tumor diameter >5 mm (p = 0.001), solitary (p = 0.005), as well as predominantly red color (p < 0.001) and macroscopic appearance of depressed type (p = 0.047). Multivariate logistic regression analysis revealed that tumor size (OR = 5.811; 95% CI: 1.220 – 27.676; p = 0.027), redcolor (OR = 5.306; 95% CI: 2.102 – 13.391; p < 0.001) were the independent risk factors for HGD and SAC. Conclusions: This study suggested that nonampullary duodenal epithelial lesions were mostly benign lesions. However, solitary lesion, macroscopic appearance of depressed type, especially reddish color polyp and tumor size >5 mm could imply HGD and SAC in this patient cohort.

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THE INFLUENTIAL FACTORS FOR DEVELOPING LIVER ABSCESS AFTER ENDOSCOPIC RETROGRADE CHOLANGIOPANCREATICOGRAPHY WITH CHOLEDOCHOLITHIASIS Wei-Ru Cho1, Cheng-Kun Wu1, Yi-Chun Chiu1, Chung-Mou Kuo1, Chung-Huang Kuo1, Lung-Sheng Lu1, Chih-Ming Liang1, Seng-Kee Chuah1, Chien-Ning Hsu2 Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan1 Department of Pharmacy, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan2

總膽管結石經內視鏡逆行性膽胰管攝 影術術後產生肝膿瘍的風險 卓韋儒1 吳鎭琨1 邱逸群1 郭仲謀1 郭仲煌1 盧龍生1 梁志明1 蔡成枝1 許茜甯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 長庚醫療財團法人高雄長庚紀念醫院藥劑部2 Background: Pyogenic liver abscesses (PLA) are the most common type of human visceral abscess.

The mechanism may be due to either the leakage of bowel contents or microbes which subsequently spread to the liver via the portal circulation or in the setting of a biliary infection. Endoscopic retrograde cholangiopancreaticography (ERCP) creates a communication of bowel contents to both the biliary system and liver, which implies the risk of PLA after the procedure. Up until now, there has been a lack of data regarding the issue.

Aims: Therefore, we conducted a population based, cohort study to analyze the risk of PLA among patients receiving ERCP with choledocholithiasis.

Methods: This study was based on data from the Chung Gung Research Database (CGRD) between January 1, 2001 and December 31, 2018.

Those who had an International Classification of Diseases, Ninth and Tenth Revision (ICD9 and ICD10) codes of choledocholithiasis and received ERCP were enrolled. After strict exclusions, 11697

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patients were further divided into the endoscopic sphincterotomy (ES) group (n = 7111) and other ERCP group (n = 4586) for analysis.

Results: Baseline data showed ES group is elder, more comorbidities including diabetes, lipid disorders, hypertensive heart disease, and higher percentage of the use of NSAID/COX2 inhibitors, aspirin, clopidogrel, beta blocking agents and calcium channel blockers and statin.

During the following period, the ES group has higher probabilities of liver abscess (p = 0.0177) and in hospital mortality (p = 0.0296) but lower probabilities of acute pancreatitis (p = 0.0002) and cholangitis (p = 0.0102). On multivariate analysis, the procedure of ES increases the risk of liver abscess (HR: 1.49; 95% CI, 1.12-1.98; p = 0.0058), but may be a protective factor for acute pancreatitis (HR: 0.72; 95% CI, 0.60-0.85; p = 0.0002) and cholangitis (HR: 0.91; 95% CI, 0.84-0.99; p = 0.0259) compared with other ERCP group.

Conclusions: The procedure of ES during ERCP for CBD stone removal is a risk factor for liver abscess but reduces the risk of acute pancreatitis and cholangitis. Further prospective studies are necessary to clarify the association of ES and liver abscess after ERCP.

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WHETHER TO PERFORM ERCP IN PATIENTS WITH SUSPECTED CHOLEDOCHOLITHIASIS? ‒ APPLICATION OF EUS IN UNCERTAIN CASES Weng-Fai Wong2, Ming-Lun Han1, Yu-Ting Kuo1, Chieh-Chang Chen2, Hau-Jyun Su2, Yi-Da Chan2, Wei-Chih Liao2, Hsiu-Po Wang1,2 Division of Endoscopy, Department of Integrated Diagnostics & Therapeutics, National Taiwan University Hospital, Taipei, Taiwan1 Departments of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan2

內視鏡超音波在臨床上疑似患有膽道 結石病人上的應用 黃永輝2 韓明倫1 郭雨庭1 陳介章2 蘇浩俊2 詹易達2 廖偉智2 王秀伯1,2 台大醫院綜合診療部內視鏡科1 台大醫院內科部2 Background: For patients with suspected choledocholithiasis, endoscopic retrograde cholangiopancreatography (ERCP) is a useful tool for both diagnostic and therapeutic purpose.

However, in order to prevent unnecessary adverse events and expenditure associated with ERCP, it should be reserved to patients with high probability of CBD stones. Predictors of the presence of CBD stone was published by the American Society Gastrointestinal Endoscopy (ASGE) in 2019, which base on clinical presentations, image findings and laboratory tests. Nevertheless, its accuracy was challenged by subsequent validation studies.

Endoscopic ultrasound (EUS) provides excellent performance in CBD stones detection which was proofed by multiple demonstrations.

Aims: We want to evaluate the application of EUS in patients with suspected CBD stones in aspects of efficacy and cost effectiveness.

Methods: From January, 2011 to August, 2019, patients who received EUS in NUTH for suspected CBD stone were included. Their information, laboratory and image studies were collected retrospectively from the electronic medical records.

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Section：Cirrhosis & HCC Whether ERCP would be performed after EUS depended on the judgement of clinicians. Patients who had received CBD manipulation before EUS (such as PTCD or ERCP) were excluded. Patients whose data were missed or whose abnormal liver tests could be attributed to concomitant ailments were also excluded.

Results: 139 patients received EUS for suspected CBD stone during the study period.

After exclusion, 106 patients were included for analysis. CBD stones were detected by EUS in 51 patients. 45 of the 51 patients received ERCP, all of them had CBD stone during lithotripsy. CBD stone or CBD dilatation on image were the two significant predictors for CBD stones. Laboratory data including total bilirubin and gamma-glutamyl transferase levels were not capable to predict the presence of CBD stone. The positive and negative predicting value of EUS for CBD stone were 90% and 98% respectively. No EUS related adverse event was recorded. Moreover, if EUS was performed first and ERCP was reserved for patients who truly had CBD stones in EUS, the total expenditure could be reduced for 12.3%.

Conclusions: EUS is a reliable tool for detection of choledocholithiasis prior to ERCP in patient with uncertainty on the diagnosis.

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NIVOLUMAB FOR ADVANCED HEPATOCELLULAR CARCINOMA: A SINGLE-CENTER EXPERIENCE Yi-Jie Huang1, Chung-Hsin Chang1, Teng-Yu Lee1,2, Shou-Wu Lee1,2, I-Da Lu1, Hong-Zen Yeh1, Sheng-Shun Yang1,2,3 Division of Gastroenterology & Hepatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan1 School of Medicine, Chung Shan Medical University, Taichung, Taiwan2 Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan3

保疾伏 ® 治療晚期肝癌：單一醫院經驗 黃儀倢1 張崇信1 李騰裕1,2 李少武1,2 呂宜達1 葉宏仁1 楊勝舜1,2,3 臺中榮民總醫院內科部胃腸肝膽科1 中山醫學大學醫學系2 國立中興大學生物醫學研究所3 Background: Treatment for advanced hepatocellular carcinoma (aHCC) has been evolving rapidly since the approval of immune checkpoint inhibitor (ICI) in Sep 2017 and nivolumab (OPDIVO®) was the first reimbursed ICI as 2nd line systemic therapy in Taiwan on 01 Apr 2019.

Aims: We analyzed clinical outcomes and safety on OPDIVO® for aHCC in our hospital.

Methods: Sixty-nine patients with aHCC treated

by OPDIVO® either monotherapy or in combination with other treatment modalities in previous sorafenib-treated or not were consecutively enrolled from Jan 2018 to Apr 2020. Efficacy and adverse events were analyzed retrospectively.

Results: Of the enrolled subjects, 54 (78.3%) had been exposed to sorafenib, 15 (21.7%) were in Child-Pugh B status, 52 (75.4%) were BCLC stage C, 36 (52.1%) had macrovascular invasion, 38 (55.1%) had extrahepatic metastasis, median serum AFP was 209 ng/mL, 30 (43.5%) had serum AFP greater than 400 ng/mL at baseline; median exposure cycle to OPDIVO® was 5, and 20 (29%) adjusted OPDIVO® dosage to less than 3 mg/Kg throughout treatment period due to multiple reasons including financial constraint.

The median overall survival (OS) was 11.9 months (95% CI 7.924-15.929) which differed significantly

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between Child-Pugh A vs. B (18.6, 95% CI 9.37827.878 vs. 2.6, 95% CI 0.290-4.835), and serum AFP responders in the first three months vs. nonresponders (20.5, 95% CI uncalculable vs. 10.9, 95% CI 6.06-15.755). Thirteen (18.8%) patients experienced any grade of immune-related adverse events (irAEs), the most common was skin rash which occurred in 5 (7.2%). Six (8.6%) subjects had greater than grade 3 irAEs, 4 (5.7%) developed hepatitis which was the most common severe irAE and was subsided after timely glucocorticoid treatment. Three patients discontinued OPDIVO® treatment due to intolerance (2) or financial constraint (1). The objective response rate (ORR) was 24% and the disease control rate (DCR) was 44% in 25 patients who received OPDIVO® monotherapy.

Conclusions: OPDIVO® monotherapy or in combination with other treatment modalities was effective for advanced HCC with a manageable safety profile and serum AFP decline in the first three months correlated with a better OS.

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THE 8TH VERSION AMERICAN JOINT COMMITTEE ON CANCER (AJCC) TUMOR-NODE-METASTASIS (TNM) PRIMARY TUMOR CLASSIFICATION T1A IS NOT HOMOGENOUS IN PATIENTS WITH HEPATOCELLULAR CARCINOMA WHO HAVE UNDERGONE LIVER RESECTION Yi-Hao Yen1, Yueh-Wei Liu2, Chih-Chi Wang2, Jing-Houng Wang1 Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan1 Department of General Surgery, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan2

第 8 版美國腫瘤協會肝癌分期在 T1a 的預後是有差異的：肝癌病患接受手術 切除分析 顏毅豪1 劉約維2 王植熙2 王景弘1 高雄長庚紀念醫院胃腸肝膽科系1 高雄長庚紀念醫院一般外科2 Background: The current 8th version of the American Joint Committee on Cancer (AJCC) tumor-node-metastasis (TNM) staging system for hepatocellular carcinoma (HCC) from 2017 contains changes in the primary tumor (T) classification relative to the 7th version: solitary tumors ≤ 2 cm with or without microscopic vascular invasion (MVI) are categorized as T1a Aims: We aim to clarify whether or not MVI has an impact on overall survival (OS) in patients with solitary HCC ≤ 2 cm undergoing liver resection (LR).

Methods: This retrospective study enrolled 172 patients with solitary HCC ≤ 2 cm who underwent LR at Kaohsiung Chang Gung Memorial Hospital from 2007-2017. The impact of MVI on OS was analyzed.

Results: The median follow-up period was 50.5 months (range: 2.8–135.8). Sixty of the patients had MVI and 112 did not. The histologic grade of tumor differentiation was higher in the patients with MVI than in those without it (p=0.048).

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Other pathologic and clinical factors did not differ significantly between the two groups. The 5-year OS rate was significantly lower for the patients with MVI [80.4% (95% CI = 68.8-93.9%)] than for the patients without MVI [91.2% (95% CI = 84.698.2%)] (p=0.036), and the presence of MVI was an independent factor associated with OS in the multivariate analysis (HR=3.1; 95% CI=1.1-8.8; p=0.04).

Conclusions: The presence of MVI was associated with worse OS in patients with solitary HCC ≤ 2 cm who underwent LR. Therefore, the 8th AJCC TNM T1a classification is not homogenous.

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LONG TERM OUTCOMES OF HEPATOCELLULAR CARCINOMA WITH ESOPHAGOGASTRIC VARICES AFTER RADIOFREQUENCY ABLATION Chien-Wei Su1,2, Cheng-Yi Wei1, Chien-An Liu3, Yi-Hsiang Huang1,4, Han-Chieh Lin1,2, Ming-Chih Hou1,2 Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan1 Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan2 Department of Radiology, Taipei Veterans General Hospital, Taipei, Taiwan3 Institute of Clinical Medicine, National YangMing University, Taipei, Taiwan4

併有胃食道靜脈瘤之肝癌患者接受熱 射頻腫瘤滅除術後之長期預後 蘇建維1,2 魏正一1 柳建安3 黃怡翔1,4 林漢傑1,2 侯明志1,2 臺北榮總內科部胃腸肝膽科1 國立陽明大學醫學系2 臺北榮民總醫院放射線部3 國立陽明大學臨床醫學研究所4 Background: The curative treatment modality of hepatocellular carcinoma (HCC) includes surgical resection (SR), radiofrequency ablation (RFA), percutaneous ethanol injection (PEIT) and liver transplantation (LT). Due to the potential risk of post-hepatectomy liver failure, the BCLC and other international guidelines do not suggest SR for HCC patients with portal hypertension. The presence of EGV was recognized as a surrogate of clinically significant portal hypertension (CSPH). Although RFA is safer than SR in these HCC patients with portal hypertension, but long-term survival benefit was not well investigated until now.

Aims: Our goal is to analyze the long-term prognosis of HCC patients with EGV after RFA. Methods: This retrospective study enrolled the patients with treatment-naïve HCC and with EGV who underwent SR as the first-line treatment from 2003 to 2017. EGV was diagnosed by an esophagogastroduodenoscopy at the time of HCC diagnosis. Prognostic factors were analyzed by

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the Cox proportional hazards model.

Results: A total 183 patients were enrolled. After a median follow-up duration of 42.3months, 128 patients died. The 5-year overall survival (OS) rate is 36.8%. The peri-procedure morbidity incidence rate is 8.7%, and major morbidity incidence rate is 4.9%. Univariate analysis showed that Age >65 years (hazard ratio HR 2.132, 95% confidence interval CI 1.456-3.122, p < 0.001, presence of HBsAg (HR 0.670, 95% confidence interval CI 0.462-0.971, p = 0.034), serum albumin level less than 3.5g/dL (HR 1.595, 95% CI 1.105-2.304, p = 0.013), multiple tumors (HR 1.735, 95% CI 1.170-2.574, p = 0.006), developed peri-RFA major morbidity (HR 3.679, 95% CI 1.850-7.315, p < 0.001) and presence of gastric varices (HR 1.570, 95% CI 1.028-2.398, p = 0.037) were poor prognostic factors of OS. The multivariate analyses showed age >65 years (HR 1.900, 95% CI 1.2882.802, p = 0.001), multiple tumors (HR 1.647, 95% CI 1.109-2.448, p = 0.013) and development of peri-RFA major morbidity (HR 2.962, 95% CI 1.4715.966, p = 0.002) were independent prognostic factors for poor OS. Regarding tumor recurrence, the multivariate analysis showed multiple tumors (HR 1.458, 95% CI 1.028-2.066, p = 0.034) and ALBI grade 2 and 3 (HR 1.434, 95% CI 1.0212.015, p = 0.038) were poor prognostic factors for recurrence free survival rate.

Conclusions: RFA is safe treatment modality for HCC patients with EGV. Age older than 65 years, multiple HCC tumors and development of periRFA major morbidity were the risk factors for poor OS. Multiple tumors and ALBI grade 2/3 were the factors associated with poor RFS. Hence, RFA is the relatively safe treatment modality for patients with HCC and with EGV.

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RAMUCIRUMAB FOR PATIENTS WITH ADVANCED HEPATOCELLULAR CARCINOMA AND ELEVATED ALPHAFETOPROTEIN FOLLOWING NONSORAFENIB-BASED SYSTEMIC THERAPY: INTERIM RESULTS FROM AN EXPANSION COHORT OF REACH-2 Richard C Finn1, Enrico N De Toni2, Thomas Chung Cheung Yau3, Chia-Jui Yen4, Chih-Hung Hsu5, Stephen L Chan6, Aiwu Ruth He7, Peter Galle8, Jörg Trojan9, Guido Stirnimann10, Ari Baron11, Mirelis Acosta-Rivera12, Lipika Goyal13, Chunxiao Wang14, Paolo Abada14, Ryan Widau14, Andrew X Zhu13,15 University of California, Los Angeles, CA, USA1 Department of Medicine II, University Hospital, LMU Munich, Germany2 Department of Pediatrics and Adolescent Medicine, The University of Hong Kong, Hong Kong3 Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan4 Department of Oncology, National Taiwan University Hospital, Taipei, Taiwan5 Department of Clinical Oncology, State Key Laboratory of Translational Oncology, The Chinese University of Hong Kong, Shatin, Hong Kong6 Lombardi Cancer Center, Georgetown University Hospital, Georgetown University, Washington, DC, US7 University Medical Center, Mainz, Germany8 Goethe University Hospital and Cancer Center, Frankfurt, Germany9 University Hospital Inselspital and University of Bern, Bern, Switzerland10 Sutter Health California Pacific Medical Center, San Francisco, CA, USA11 FDI Clinical Research, San Juan, Puerto Rico12 Massachusetts General Hospital Cancer

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Center, Boston, MA, USA Eli Lilly and Company, Indianapolis, IN, USA14 Jiahui International Cancer Center, Shanghai, China15 Background: Ramucirumab (IgG1 VEGFR-2 antagonist) is the first and only treatment approved in a biomarker-selected population with advanced hepatocellular carcinoma (HCC) population. The approval was based on data from the phase 3 REACH (NCT01140347) and REACH-2 (NCT02435433) trials. Similar to other contemporary trials, REACH/REACH-2 did not include patients who received first-line therapy other than sorafenib, which was the only treatment with demonstrated overall survival (OS) when the trials were designed.

Aims: This global open-label expansion (OLE), single-arm REACH-2 cohort was initiated to study ramucirumab in patients with advanced HCC and baseline alpha fetoprotein (AFP) ≥400 ng/mL following a non-sorafenib based systemic therapy.

Methods: Eligible patients have advanced HCC (BCLC stage C or B disease), Child-Pugh (CP) A, ECOG PS 0/1, baseline AFP ≥400 ng/mL, and 1-2 prior systemic regimens for HCC, excluding sorafenib or chemotherapy. Liver transplant patients are eligible. ~44 patients will receive ramucirumab 8mg/kg IV Q2W. Primary endpoint: safety; secondary endpoints include OS, progression-free survival (PFS), objective response rate (ORR), and patient-reported outcomes. Final analysis will occur after all patients have completed ≥3 cycles ramucirumab or discontinued.

Results: As of interim data cutoff (31-January-2020), 24 patients were enrolled: 96% male, median baseline AFP = 2094 ng/mL (IQR: 854, 7981), 50% ECOG-PS 0, 96% CP-A, 67% ALBI grade 1, and 92% BCLC stage C. Most common prior systemic therapies were lenvatinib (n = 8), monotherapy PD-1/PD-L1 inhibitor (n = 9), PD-1 inhibitor + lenvatinib (n = 3), and atezolizumab + bevacizumab (n = 3). Grade ≥3 TEAEs (≥10%) were hypertension (n = 4), proteinuria (n = 3), and pneumonia (n = 3). No deaths due to AEs occurred.

With median follow-up = 6.5 months, median PFS was 5.5 months (18 events; 95% CI 1.3-7.5). ORR was 16.7% (95% CI 1.8-31.6). Median OS was immature (10 events).

Conclusions: Safety and efficacy of ramucirumab following non-sorafenib-based systemic therapy was consistent with that observed in patients who received prior sorafenib in ITT REACH-2 population. Previously presented at ILCA 2020.

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IDENTIFICATION OF KEY GENES IN THE TUMOR MICROENVIRONMENT (TME) OF HEPATOCELLULAR CARCINOMA Szu-Jen Wang1,2, Ching-Yang Tsai2, Chia-Yang Dai3, Ming-Lung Yu3 Graduate Institute of Clinical Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan1 Division of Gastroenterology, Department of Internal Medicine, Yuan’s General Hospital, Kaohsiung, Taiwan2 Division of Hepatobiliary, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan3

肝細胞癌腫瘤微環境關鍵基因的鑒定 王嗣仁1,2 蔡青陽2 戴嘉言3 余明隆3 高雄醫學大學臨床醫學研究所1 阮綜合醫院消化內科2 高雄醫學大學附設中和紀念醫院肝膽胰內科3 Background: Hepatocellular carcinoma (HCC) is the 2nd leading cause of cancer-related deaths worldwide. Even though multiple therapeutic strategies including curative and non-curative treatment and predictive biomarkers, the heterogeneous prognosis was still unanswered.

Therefore, a novel treatment strategy with different mechanisms from those of conventional treatments is needed to improve the prognosis of HCC. Tumor microenvironment (TME), one of the hallmarks of cancer, is defined as the cellular and physical environment surrounding the primary tumor. There are many kinds of cells and molecules in TME including inflammatory and immune cells, extracellular matrix proteins, soluble factors, and so on. Tumor microenvironment (TME) plays an important role in the development of cancer including proliferate, invade, and metastasize.

Multiple immune cells coexist and interact in a complex series of pathways that ultimately lead to tumor carcinogenesis. However, the roles of TME in HCC are not well studied. In this study, we aimed to identify genes related to the tumor microenvironment of hepatocellular carcinoma.

Aims: This study aimed to identify key genes related to the tumor microenvironment of hepatocellular carcinoma from The Cancer

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Section：UGI Genome Atlas (TCGA)-LIHC database.

Methods: We combined The Cancer Genome Atlas (TCGA) and Estimation of STromal and Immune cells in Malignant Tumor tissues using Expression data (ESTIMATE) datasets to identify differentially expressed genes (DEG) between high immune score group and low immune score group. Likewise, the differentially expressed genes between the high stromal score group, and the low stromal score group were analyzed in the same method. Then, we identified the consensus of differentially expressed genes in both groups.

Then, using the STRING database to construct the protein-protein interaction (PPI) network of the consensus gene. We selected 30 hub genes ranked by a degree in Cytoscape (version 3.8.0).

Next, functional enrichment analysis including gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of 30 hub genes were analyzed. GO terms of biological process (BP), cellular components (CC) and molecular functions (MF), and KEGG pathways with FDR < 0.05 were considered to be significant. Finally, we conducted the KaplanMeier curve and log-rank test on these hub genes.

Results: There were 144 differentially expressed genes identified to be associated with immune score and stromal score in the HCC microenvironment (Fig.1). We screened out 30 hub genes by the construction of the PPI network. The functions of these hub genes (Fig. 2) were enriched in immune cell activity, cytokine and chemokine activity, cell adhesion molecules, and extracellular matrix (Fig. 3), which provided further insight into the roles of these genes in the tumor microenvironment.

CXCL8 and MMP9 (Fig. 4), with higher degrees in the PPI network, were negatively related to the overall survival of HCC patients (P = 0.002 and P = 0.008, respectively).

Conclusions: We identified 30 tumor microenvironment related genes in HCC. Among these hub genes, CXCL8 and MMP9 can be regarded as prognostic biomarkers in hepatocellular carcinoma. Further studies are needed to advanced confirm these two markers.

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DISTAL MEAN NOCTURNAL BASELINE IMPEDANCE PREDICTS PATHOLOGICAL ESOPHAGOPHARYNGEAL ACID REFLUX IN PATIENTS WITH SUSPECTED LARYNGOPHARYNGEAL REFLUX Hua-Nong Luo, Han-Chung Lien, Sheng-Shun Yang, Hong-Zen Yeh, Chi-Sen Chang Division of Gastroenterology, Taichung Veterans General Hospital, Taichung, Taiwan

利用遠端食道之平均夜間基礎食道阻 抗值預測喉咽逆流疾患的異常食道咽 喉酸逆流 羅華濃 連漢仲 楊勝舜 葉宏仁 張繼森 臺中榮民總醫院胃腸肝膽科 Background: Mean nocturnal baseline impedance (MNBI) is a novel impedance metric to detect reflux induced impairment of mucosal integrity, and may be a surrogate marker for diagnosis of laryngopharyngeal reflux (LPR).

Aims: To assess MNBI values in non-erosive reflux patients with suspected LPR to predict pathological esophagopharyngeal acid reflux.

Methods: This is a multicenter prospective study conducted in 3 referral hospitals in Taiwan. We used hypopharyngeal pH-impedance catheters to detect pathological esophagopharyngeal reflux, which was defined as pathological reflux in the hypopharynx and/or distal esophagus. Patients were divided into those with concomitant typical reflux symptoms (CRTS, n = 54) and those without, i.e., isolated LPR (ILPR, n = 85) symptoms.

Asymptomatic healthy subjects underwent unsedated transnasal endoscopy to rule out upper gastrointestinal pathology for serving as controls (n = 25). The MNBI values at 3, 5 cm above the squamocolumnar junction (SCJ), and 7 cm below the upper esophageal sphincter were measured to predict pathological reflux.

Results: Median MNBI values were significantly lower in the patients with objective evidence of reflux (i.e., impedance pH(+) lower than impedance pH(-) groups) in both CTRS and ILPR patients. In CTRS patients, median MNBI is 1494Ω (range: 919-1848Ω) and 1632Ω (range:

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514-2630) at 3cm and 5cm above SCJ in pH(+) group (n = 19); whereas median MNBI is 2367Ω (range: 1961-3076Ω) (P = 0.009) and 2355Ω (range: 1863-3063Ω) (P < 0.0001) in pH(-) groups (n = 35). In ILPR patients, median MNBI is 1770Ω (range: 1231-2605Ω) and 2217Ω (range: 7742641) at 3cm and 5cm above SCJ in pH(+) group (n = 27) ; whereas median MNBI is 2556Ω (range: 1796-3186Ω) (P = 0.004) and 259Ω (range: 1818-3323Ω) (P = 0.054) in pH(-) groups (n = 58). In receiver operating characteristic analysis, the area under curve of the MNBI with the best cutoff value of 2019Ω is 0.888, with sensitivity 88% and specificity 84% in CTRS patients; AUC is 0.742 with sensitivity 88% and specificity 56% in ILPR patients. There was a graded increase in median MNBI values along the axis of the distal to proximal esophagus in the pH+ groups in both CTRS and ILPR patients.

Conclusions: Distal MNBI may predict pathological esophagopharyngeal reflux in nonerosive reflux patients with suspected LPR.

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THE ROLE OF CONTRAST ENHANCED HARMONIC EUS IN THE EVALUATION OF GASTRIC SUBEPITHELIAL LESION Jiann-Hwa Chen1,2, Wei-Chih Su1, Tsung-Hsien Hsiao1, Chih-Hsiang Chen1, Lung-Yuan Hsu1,2, You-Chen Chao1,2 Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taipei Tzu Chi Hospital, Taipei, Taiwan1 School of Medicine, Tzu Chi university, Hualien, Taiwan2

對比劑內視鏡超音波對於胃黏膜下病 灶的角色評估 陳建華1,2 蘇偉志1 蕭宗賢1 陳至翔1 徐榮源1,2 趙有誠1,2 台北慈濟醫院肝膽腸胃科1 慈濟大學醫學院2 Background: Subepithelial tumors are divided into benign subepithelial and potentially malignant gastrointestinal stromal tumors. It is difficult to distinguish benignancy from malignancy between these tumor types.

Aims: To evaluate the diagnostic value of endoscopic ultrasonography (EUS) and contrastenhanced harmonic (CEH) EUS in patients with gastric subepithelial tumor (GSET) larger than 2 cm in diameter.

Methods: A total of 5 patients with suspected GSET underwent EUS and CEH-EUS before histological evaluation. We use Sonazoid 0.015ml/Kg for contrast-enhanced hormonic EUS assessment.

One patient received EUS guided fine needle biopsy (FNB) and followed by operation, another received endoscopic biopsy and then surgical removal and the other three patients underwent EUS/FNB only. The puncture needle used is EchoTip ProCore 20G, Cook Co., Salem, USA. The malignant potential was assessed according to the modified Fletcher classification system.

The clinical characteristics and EUS/CEH-EUS features were recorded.

Results: The gender ratio of male to female is 1:4. The tumor size is 27.6 ± 4.7 mm in diameter.

Hyper-enhancement vascular pattern is observed in the four SETs from the 4th layer of stomach wall. Heterogeneous perfusion echogenicity

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was also observed in the four SETs from the 4th layer of stomach wall. The malignant potential of all three gastrointestinal stromal tumors is low risk. The CEH-EUS of aberrant pancreas is isoenhancement and homogeneous echogenicity.

Conclusions: The hyper-enhancement and heterogenicity are observed in the SET derived from the muscular layer of gastric wall. Aberrant pancreas reveals iso-enhancement and homogeneous echogenicity.

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TWO KINDS OF 14-DAY BISMUTH QUADRUPLE THERAPIES ARE EFFECTIVE FOR FIRST LINE HELICOBACTER PYLORI ERADICATION Feng-Woei Tsay1, Deng-Chyang Wu2, Ping-I Hsu1,3, Wen-Chi Chen1, Jin-Chiung Cheng1 Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Veterans General Hospital and National Yang-Ming University, Kaohsiung, Taiwan1 Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan2 Division of Gastroenterology and Hepatology, Department of Internal Medicine, An Nan Hospital, China Medical University, Tainan, Taiwan3

二種 14 天鉍劑 4 合療法對於第一線胃 幽門桿菌之除菌效益 蔡峯偉1 吳登強2 許秉毅1,3 陳文誌1 鄭錦翔1 高雄榮民總醫院胃腸肝膽科1 高雄醫學大學附設中和紀念醫院內科部2 台南市立安南醫院胃腸肝膽科3

Background: Bismuth quadruple therapy is recommended as an alternative therapy in high clarithromycin-resistant area for eradication of Helicobacter pylori. Traditionally, bismuth quadruple therapy (PBTM) with PPI, bismuth, tetracycline and metronidazole is used. The addition of bismuth to triple therapy (PBCA) with PPI, bismuth, clarithromycin and amoxicillin also can improve cure rates despite a high prevalence of antimicrobial resistance. Currently, whether PBTM therapy achieves a higher eradication rate than PBCA therapy remains unanswered.

Aims: To compare the efficacies of 14-day bismuth quadruple (PBCA) reverse 14-day bismuth quadruple (PBTM) therapy.

Methods: Consecutive H. pylori-infected subjects were randomly assigned to receive either a 14day PBCA therapy (pantoprazole 40 mg b.i.d, bismuth 240 mg b.i.d, clarithromycin 500 mg b.i.d, and amoxicillin 1 g b.i.d, for 14 days) or a

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14-day PBTM therapy (pantoprazole 40 mg b.i.d, bismuth 120 mg q.i.d, tetracycline 500 mg q.i.d, and metronidazole 250 mg q.i.d for 14 days). H. pylori status was examined 6 weeks after the end of treatment by rapid urease and histology or urea breath test.

Results: Retrospectively, 392 H. pylori-infected participants were randomized to receive a 14day PBCA therapy (n = 196) or a 14-day PBTM therapy (n = 196) therapy. The eradication rates by intention-to-treat analysis were similar: 94.9% vs 95.9%. Per-protocol analysis yielded similar results (95.3% vs 96.2%). 14-day PBCA therapy had a less frequency of adverse events as 14-day PBTM therapy (12.2% vs 54.1%; P = 0.00). 14day PBCA therapy also had good drug compliance than 14-day PBTM therapy (98.5% vs 92.9%; P = 0.01).

Conclusions: Both 14-day PBCA and 14-day PBTM therapies cure most patients with H. pylori infection in southern Taiwan. However, the former has fewer adverse effects than the latter.

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EFFICACIES OF HYBRID, HIGHDOSE DUAL AND BISMUTH QUADRUPLE THERAPIES IN THE FIRST-LINE TREATMENT OF H. PYLORI INFECTION─A MULTICENTER RANDOMIZED CONTROLLED TRIAL Ping-I Hsu1,10, Jyh-Chin Yang2,10, Seng-Kee Chuah3,10, Kuan-Yang Chen4,10, Yu-Hwa Liu5,10, Feng-Woey Tsai6,10, Chia-Long Lee7,10, Hong-Zen Yeh8,10, Chao-Hung Kuo9,10, Hsi-Chang Lee4,10, Deng-Chyang Wu9,10 Division of Gastroenterology, Department of Medicine, An Nan Hospital, China Medical University, Taichung, Taiwan1 Division of Gastroenterology, Department of Internal Medicine, National Taiwan Univeristy Hospital, Taipei, Taiwan2 Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan3 Division of Gastroenterology and Hepatology, Department of Internal Medicine, Renai Branch, Taipei City Hospital, Taipei, Taiwan4 Division of Gastroenterology, Department of Internal Medicine, Shin Kong Wu Ho-Su Memorial 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, Taipei, Taiwan8 Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan9 Taiwan Acid-Related Disease & Microbiota Consortium10

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混合療法、高劑量二合療法與鉍劑四合 療法在幽門螺旋桿菌感染第一線治療 上之療效比較─一多中心隨機控制試 驗 許秉毅1,10 楊智欽2,10 蔡成枝3,10 陳冠仰4,10 劉玉華5,10 蔡峯偉6,10 李嘉龍7,10 葉宏仁8,10 郭昭宏9,10 李熹昌4,10 吳登強9,10 中國醫藥大學安南醫院消化內科1 國立台灣大學醫學院附設醫院胃腸科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胃腸肝膽科4 新光吳火獅紀念醫院胃腸科5 高雄榮民總醫院胃腸肝膽科6 國泰綜合醫院胃腸肝膽科7 臺中榮民總醫院胃腸肝膽科8 高雄醫學大學附設醫院胃腸科9 台灣胃酸相關疾病暨微菌叢聯盟10 Background: Bismuth quadruple therapy is the treatment of choice for the first-line therapy of H. pylori infection in areas of high clarithromycin resistance in several important international consensuses. However, it is associated with a high frequency of adverse events. Both hybrid and highdose dual therapies have great potential to replace bismuth quadruple therapy in the treatment of H. pylori infection.

Aims: To investigate whether 14-day hybrid and 14-day high-dose dual therapies have a higher eradication rate and a lower frequency of adverse events than 10-day bismuth quadruple therapy in the first-line treatment of H. pylori infection.

Methods: For this multi-center, randomized, open-label, superiority trial, patients with H. pylori infection were randomly to receive (1) 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), (2) 14-day hybrid therapy (rabeprazole 20 mg b.i.d. plus amoxicillin 1 g, b.i.d. for 14 days, and clarithromycin 500 mg plus metronidazole 500 mg b.i.d. for final 7 days) or (3) 14-day high-dose dual therapy (rabeprazole 20 mg and amoxicillin 750 mg q.i.d for 14 days). H. pylori status was assessed 6 weeks after the end of treatment.

Results: 437 H. pylori-infected participants were randomized to receive bismuth quadruple (n = 143), hybrid (n = 146) or high-dose dual therapy

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(n =148). Intention-to-treat analysis showed that hybrid and bismuth quadruple therapies had equivalent eradication rates (95.2% vs 92.3%), and the former had a lower frequency of adverse effect than the latter (24.0% vs 35.7%; P = 0.030). High-dose dual therapy achieved a lower eradication rate (84.5% vs 92.3%; P = 0.037) than bismuth quadruple therapy, but it had a lower frequency of adverse effect than bismuth quadruple therapy (12.5% vs 35.7%; P < 0.001).

Further analysis showed hybrid therapy achieved a higher eradication rate than high-dose dual therapy (95.2% vs 84.5%; P = 0.002).

Conclusions: 14-day reverse hybrid therapy and 10-day bismuth quadruple therapy are equivalent in efficacy for the first-line treatment of H. pylori infection. However, 14-day high-dose dual therapy has a lower eradication rate than 10-day bismuth quadruple therapy. Both hybrid and high-dose dual therapies have a lower frequency of adverse events than bismuth quadruple therapy.

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A NEW TOOL OF MAGNETICASSISTED CAPSULE ENDOSCOPE FOR UPPER GASTROINTESTINAL EXMINATION Yi-Lun Hsieh1, Chen-Hsun Chen1, Meng-Chieh Wu2, Chun-Sheng Shen1, Wen-Hung Hsu1,3, Deng-Chyang Wu1,3, Jeng-Yih Wu1,3 Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan1 Division of Internal Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan2 Department of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan3

磁力導引膠囊胃鏡：一上消化道診斷新 工具 謝易倫1 陳震勳1 吳孟杰2 沈群勝1 許文鴻1,3 吳登強1,3 吳政毅1,3 高雄醫學大學附設中和紀念醫院胃腸內科1 高雄巿立大同醫院內科2 高雄醫學大學醫學系3

Results: Totally, 40 subjects including 18 females and 22 males, mean aged 39.2 ± 12.9 were enrolled in this study. Among 40 enrolled subjects, GERD were found in 26 cases at EGD while 27 cases had GERD at MACE exam. In term of peptic ulcers (including shallow ulcers) were diagnosed in 16 cases at EGD and 15 cases at MACE. 10 cases by EGD were found to have gastric polyps and 11 cases by MACE. For MACE exam, the choking, sore-throat sensation was significant less than EGD exam. Seventy-three percent of cases (29/40) suffered from nausea/retch when EGD were performed, while only 45% cases suffered from nausea/retch at MACE was swallowing and no more during the procedure. In considering which method when needed in the future, 78% subjects prefer MACE than EGD in term of satisfactions.

Conclusions: From the results of this study, the findings of magnetic guidance capsule gastroscopy were not significantly different compared to EGD. From the view of the satisfaction questionnaire, magnetically guided capsule gastroscopy was better than gastroscopy. Although magnetically guided capsule gastroscopy requires more clinical practice to have a more definite result, it provides another option for the examination of upper gastrointestinal diseases.

Background: Esophagogastroduodenoscopy (EGD) is a clinical common tool for upper gastrointestinal lesions. Although high-risk adverse events were rarely reported when performing EGD, some of serious events such as cardiopulmonary adverse events, perforations, and hemorrhage were still noted in an incidence of 1/200-1/10,000.

Aims: Another important key issue is infection.

Recently a novel single use magnetic-assisted capsule endoscope (MACE) system to visualize the entire upper GI tract was proved by TFDA, however, its clinical use yet to be validated.

Methods: Subjects met the inclusion/exclusion criteria were invited into this study. After inform consent was sign, a questionnaire including demographic data, past medical history and systematic review was queried. MACE was performed and then following by EGD exam. Each examination was performed by a physician who was blind to the other’s results. After each exam, satisfaction questionnaire was recorded. And the findings of both exams were compared.

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Poster Section：Liver P.001

SERUM HEPATITIS B CORERELATED ANTIGEN LEVELS STRATIFIES RISK OF DISEASE PROGRESSION IN CHB PATIENTS WITH INTERMEDIATE VIRAL LOADS Tai-Chung Tseng1,2,7, Chun-Jen Liu1,2,5, Wan-Ting Yang2, Chun-Ming Hong1,4, Tung-Hung Su1,2, Cheng-Hsueh Tsai2, Chi-Ling Chen5, Hung-Chih Yang1,5,6, Chen-Hua Liu1,2, Pei-Jer Chen1,2,5, Jia-Horng Kao1,2,3,5 Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan1 Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan2 Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan3 Division of Hospital Medicine, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan4 Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan5 Department of Microbiology, National Taiwan University College of Medicine, Taipei, Taiwan6 Department of Medicine, National Taiwan University Hospital Cancer Center, Taipei, Taiwan7

B 型肝炎之核心相關抗原的血清濃 度，可用來區分慢性 B 型肝炎中病毒 量患者的疾病進展之風險 曾岱宗1,2,7 劉俊人1,2,5 楊菀婷2 洪俊銘1,4 蘇東弘1,2 蔡承學2 陳祈玲5 楊宏志1,5,6 劉振驊1,2 陳培哲1,2,5 高嘉宏1,2,3,5 國立台灣大學醫學院附設醫院胃腸肝膽內科1 國立台灣大學醫學院附設醫院肝炎研究中心2 國立台灣大學醫學院附設醫院醫學研究部3 國立台灣大學醫學院附設醫院整合醫學內科4 國立台灣大學醫學院臨床醫學研究所5 國立台灣大學醫學院微生物所6 國立台灣大學癌醫中心醫院綜合內科7 Background: Patients with chronic hepatitis B virus (HBV) infection are at risk of developing

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adverse liver events. Serum hepatitis B corerelated antigen (HBcrAg) is a surrogate biomarker for viral replication templates in liver.

Aims: It remains unclear whether a high HBcrAg level predicts the risk of cirrhosis, especially in patients with intermediate viral load (IVL, HBV DNA 2000-19,999 IU/mL), who have a moderate risk of disease progression.

Methods: A total of 1673 treatment-naïve, noncirrhotic patients with negative hepatitis B e antigen (HBeAg) and ALT level < 40 U/L at baseline were enrolled. We explored the relationship between baseline levels of HBcrAg and development of cirrhosis in the overall cohort, and whether a higher HBcrAg level (<10 vs ≥10 KU/mL) was associated with an increased risk of cirrhosis and its leading events in those with IVL. Results: Of the 1673 patients, 104 developed cirrhosis after a mean follow-up of 15.92 years. A higher HBcrAg level was not only associated with increased incidence of cirrhosis but also cirrhosisrelated complications and liver-related death. In the subgroup of 445 patients with IVL, the cirrhosis risk stratified by HBcrAg level of 10 KU/mL yielded a hazard ratio of 3.22 (95% CI: 1.61-6.47). The risk stratification remained significant when exploring other leading endpoints, including HBV-associated hepatitis, and HBV DNA > 20,000 IU/mL after 3 years of follow-up.

Conclusions: In HBeAg-negative patients with normal ALT levels, higher HBcrAg levels are associated with an increased risk of cirrhosis.

HBcrAg < 10 KU/mL can define a lower risk of disease progression in patients with IVL.

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P.002

MICRO-ELIMINATION OF HEPATITIS C FOR HEMODIALYSIS POPULATION IN AN COUNTY OF TAIWAN ‒ AN INNOVATIVE COLLABORATIVE CARE MODEL Tsung-Hui Hu1, Wei-Wen Su2, Chi-Chao Yang3, Chi-Chieh Yang4, Wu-Hsien Kuo5, Yen-Po Yeh6, Hsiu-Hsi Chen7 Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gang Memorial Hospital, Kaohsiung, Taiwan1 Division of Gastroenterology, Changhua Christian Hospital, Changhua, Taiwan2 Division of Gastroenterology, Chang-Hua Hospital, Ministry of Health and Welfare, Changhua, Taiwan3 Division of Gastroenterology, Department of Internal Medicine, Show Chwan Memorial Hospital, Changhua, Taiwan4 Division of Gastroenterology, Department of Internal Medicine, Yuan-Sheng Hospital, Changhua, Taiwan5 Changhua County Public Health Bureau, Changhua, Taiwan6 College of Public Health, National Taiwan University, Taipei, Taiwan7

彰化縣透析中心 C 型肝炎之微根除： 一個創新的合作照護模式 胡琮輝1 蘇維文2 楊智超3 楊基傑4 郭武憲5 葉彥伯6 陳秀熙7 高雄長庚紀念醫院胃腸肝膽科系1 彰化基督教醫院胃腸肝膽科2 衛生福利部彰化醫院胃腸科3 秀傳紀念醫院胃腸肝膽科4 員生醫院胃腸肝膽科5 彰化縣衛生局6 國立臺灣大學公共衛生學院7 Background: HCV micro-elimination, which focuses on smaller, targeted high-risk subpopulations, has been proposed for achieving global elimination of HCV. Patients with end stage renal disease (ESRD) had a high incidence of HCV infection (8-12%). However, there are several barriers to treat HCV patients in dialysis centers due to unawareness, unwillingness,

and difficulty of referral due to long journey and patients’ disability.

Aims: The objective of this study is to demonstrate the efficiency of the novel delivery model in achieving the elimination of HCV among hemodialysis patients in 31 dialysis centers in the jurisdiction area under a Public Health Bureau of Changhua County in Taiwan.

Methods: A total of 31 hemodialysis (HD) centers are managed and the micro-elimination program was implemented (led by the public authority). To overcome the barrier of HCV treatment, mobile clinics were set up at HD centers that did not have a hepatologist/gastroenterologist. This team was responsible for delivering a continuum of care from screening, diagnosis, treatment, and follow-up on site. The treatment regimen included either grazoprevir/elbasvir (GZP/EBV; Merck) or glecaprevir/pibrentasvir (GLE/PIB; AbbVie). The primary outcome includes the achievement of HCV micro-elimination, which was defined as per WHO criteria and sustained virological response rates at 12 weeks after treatment (SVR12).

Results: A total of 3,657 patients visiting Changhua County HD and peritoneal dialysis (PD) centers from Jan 2019 to Jun 2019 were screened.

Among the patients, 403 (11.0%) patients were seropositive for HCV. Finally, a total of 184 viremic patients received treatment (coverage rate 89.3%).

The flow chart of diagnosis and treatment is shown figure. The mean age is 66 years, ranged from 40 to 90 years old, and the longest dialysis period is 30 years. Genotype (GT)-1 patients made up 50%, and GT-2 made up about 40% of patients. Finally, 83% of patients were treatedwith the GLE/PIB, the others were GZP/EBV and LDV/SOF. Among the treated patients, 173 patients (94%) completed the course of treatment. Seven patients died during treatment, and 7 patients died after EOT and before SVR12. None of the death was considered to be related to DAA therapies. The response rate at EOT and SVR12 are all 100% according to per protocol analysis. Notably, we also surveyed the incidence of HCV for the 619 staff at HD centers with a coverage rate of 98.7%. Only 5 patients were positive for anti-HCV (0.82%) in which 4 patients have been already treated. Only 1 patient was viremic but has since completed DAA therapy under this program.

Conclusions: Our study has demonstrated that the novel treatment-delivery approach with mobile

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clinics can achieve elimination of HCV in ESRD subpopulation in a very short period of time. We hope that the success of this program would encourage the implementation of methods to accelerate HCV eradication globally.

P.003

THE DYNAMICS OF CYTOKINE PROFILES PREDICTS RISK OF HCC AMONG HCV PATIENTS WITH ADVANCED FIBROSIS AFTER SUCCESSFUL ANTIVIRAL THERAPY Ming-Ying Lu2, Chung-Feng Huang1,2, Shu-Chi Wang3, Ching-I Huang1,2, Ming-Yen Hsieh1,2, Po-Cheng Liang1,2, Yi-Hung Lin1,2, Nai-Jen Hou1,2, Ming-Lun Yeh1,2, Zu-Yau Lin1,2, Shinn-Cherng Chen1,2, Jee-Fu Huang1,2, Chia-Yen Dai1,2, Wan-Long Chuang1,2, Ming-Lung Yu1,2 Division of Hepatobiliary, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan1 Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan2 Department of Medical Laboratory Science and Biotechnology, Kaohsiung Medical University, Kaohsiung, Taiwan3

利用細胞激素之動態表現預測抗病毒 藥物治療成功後之 C 型肝炎患者之肝 癌發生 呂明穎2 黃釧峰1,2 王述綺3 黃駿逸1,2 謝明彥1,2 梁博程1,2 林宜竑1,2 侯乃仁1,2 葉明倫1,2 林子堯1,2 陳信成1,2 黃志富1,2 戴嘉言1,2 莊萬龍1,2 余明隆1,2 高雄醫學大學附設中和紀念醫院肝膽胰內科1 高雄醫學大學醫院院內科學科2 高雄醫學大學醫學檢驗生物技術學系3 Background: Successful HCV eradication did not eliminate hepatocellular carcinoma (HCC) development. Clearance of HCV by direct-acting antiviral agents (DAA) or interferon (IFN) result in reconstitution of immune surveillance. It is unclear whether the host immunological modification after viral eradication may influence the development of HCC. Aims: To investigate the impact of differential cytokine expression on the development of HCC following antiviral therapy.

Methods: A total of 100 treatment naïve chronic hepatitis C patients with advanced fibrosis treated either by pegIFN/ribavirin or DAA who achieved

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sustained virologic response (SVR) were enrolled in this study. The primary endpoint was the development of HCC. The cytokine profiles were measured at baseline and SVR12 or SVR24 follow-up. A total of 64 cytokines was detected by the multiplex immunoassay.

Results: HCC developed in 12 (IFN group n=11, DAA group n=1) of the 97 patients over 459 person-years of follow-up after HCV eradication.

In univariate analysis, the Fibrosis-4 index (FIB4), HbA1c, the variation of tumor necrosis factors (TNF)-α and TWEAK (TNF-like weak inducer of apoptosis) after antiviral therapy were significantly associated with the development of HCC. The multivariate Cox regression model showed the reduction of TNF-α (△≦-5.7 pg/ml) was the independent risk factor of HCC (HR=11.54, 95% C.I. =2.27-58.72, p=0.003). We established an HCC predictive model as follows: Score = 4xFIB4 (≧9, yes=1, no=0) + 5xHbA1c (≧7, yes=1, no=0) + 11x△TNF (≦-5.7, yes=1, no=0) + 4x△TWEAK (≦-70, yes=1, no=0). Time-dependent ROC analysis revealed the 3-year, 5-year, 10-year, and 13-year AUC were 0.882, 0.864, 0.903 and 1.000, respectively.

Conclusions: Reduction of serum TNF-α predicts HCC development in chronic hepatitis C patients with advanced fibrosis after successful viral eradication.

P.004

COMBINING IMMUNE CHECKPOINT INHIBITOR WITH LENVATINIB PROLONGS SURVIVAL THAN LENVATINIB ALONE IN SORAFENIB-EXPERIENCED HEPATOCELLULAR CARCINOMA PATIENTS Po-Ting Lin1,2, Wei Teng1,2, Wen-Juei Jeng1,2, Chun-Yen Lin1,2, Shi-Ming Lin1,2, I-Shyan Sheen1,2 Department of Gastroenterology and Hepatology, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan1 College of Medicine, Chang Gung University, Taoyuan, Taiwan2

在有 Sorafenib 使用經驗的肝癌病人 族群，使用 Lenvatinib 加上免疫檢查 點抑制劑比單用 Lenvatinib，更可以 延長病人的存活率 林伯庭1,2 滕威1,2 鄭文睿1,2 林俊彥1,2 林錫銘1,2 沈一嫻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 Background: Lenvatinib and immune checkpoint inhibitors (ICIs) were approved as the promising agents for unresectable hepatocellular carcinoma (HCC). Nevertheless, the benefits of combing ICI with lenvatinib in sorafenib-experienced patients remain uncertain.

Aims: We aimed to investigate whether the combination use of ICI and lenvatinib provides better survival than lenvatinib alone in advanced stage HCC patients.

Methods: From March 2018 to August 2019, a total of 53 unresectable HCC patients receiving lenvatinib were recruited. Treatment response was evaluated by dynamic image including CT or MRI every 2-3 months using the modified RECIST criteria. Overall survival (OS), progression-free survival (PFS) and predictors for survival were analyzed.

Results: Among the 53 patients, the median age was 67.2 years old, and 66.4 % were male.

Twenty-one patients had sorafenib experienced history. Eighteen patients (34 %) died with median follow-up duration of 8.1 months. Patient receiving

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lenvatinib had median OS of 16.9 [95% CI: 10.123.7] months, and progression-free survival (PFS) of 7.23 [95% CI: 4.8-9.7] months. In multivariate Cox regression analysis, ALBI grade III (adjusted HR: 6.699, P = 0.0039) and the history of sorafenib treatment (adjusted HR: 4.476, P = 0.0457) were the independent predictive factor for OS. In sorafenib-experienced patients, those combined treated with ICI (N =14) showed significantly better survival than monotherapy with lenvatinib (median: 12.8 vs. 4.1 months, log-rank P = 0.008).

Conclusions: The ALBI grade and sorafenib treatment history were predictors for OS in HCC patients receiving lenvatinib. For sorafenibexperienced patients, combining ICI with lenvatinib achieved better OS than lenvatinib alone.

P.005

LIPOPOLYSACCHARIDE IS CRITICAL TO PROPRANOLOLINDUCED RENAL ARTERY FLOW REDUCTION IN RATS WITH ADVANCED CIRRHOSIS Shao-Jung Hsu1,2, Hui-Chun Huang2,3, Fa-Yauh Lee1,2, Ming-Chih Hou1,2, Yi-Hsiang Huang1,2 Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan1 Faculty of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan2 Division of General Medicine, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan3

內毒素在嚴重肝硬化大鼠因乙型交感 神經抑制劑引發之腎臟血流下降中具 關鍵角色 許劭榮1,2 黃惠君2,3 李發耀1,2 侯明志1,2 黃怡翔1,2 臺北榮民總醫院內科部胃腸肝膽科1 陽明大學醫學院2 臺北榮民總醫院內科部一般內科3 Background: Propranolol is used to control complications of liver cirrhosis, but recent studies showed that propranolol may increase mortality rate in patients with end-stage liver cirrhosis.

Propranolol attenuates portal hypertension by decreasing cardiac output. However, in end-stage cirrhosis, impaired compensatory response of the heart to stresses such as infection may decrease kidney perfusion and lead to death. Nevertheless, the role of propranolol under the setting of liver cirrhosis facing infection is unknown.

Aims: To evaluate the effects of propranolol on renal artery (RA) blood flow and heart compensatory capability to stress in rats with early or late stage liver cirrhosis.

Methods: Liver cirrhosis was induced by common bile duct ligation in Sprague-Dawley rats. Early or advanced cirrhosis was induced 4 or 6 weeks after operation, respectively. Sham operation was surgical control. The rats randomly received a single dose of propranolol or vehicle as control.

Then, escalated doses of lipopolysaccharide (LPS) were given sequentially with the dosage of

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1, 1 and 2 mg/kg. Hemodynamic changes after each injection were recorded.

Results: Rats with late cirrhosis had higher baseline RA flow. Propranolol alone increased RA flow in sham rats without affecting cirrhotic rats.

Interestingly, LPS dose dependently decreased RA flow only in advanced cirrhotic rats with propranolol. The protein expressions related to β1 receptor signaling pathway of the heart, including the Gαs, Gαi1/2 and Gαi3 were not significantly different among the groups. The inhibitory protein GRK2 of β1 receptor pathway was activated in cirrhosis. Furthermore, the PKA activity decreased markedly in advanced cirrhotic rats treated with propranolol.

Conclusions: Acute propranolol administration decreased RA flow only when there are severe liver cirrhosis and sepsis at the same time. The increased cardiac contractility inhibitory protein GRK2 and decreased PKA activity may play certain roles.

P.006

SIGNIFICANT AMELIORATION OF HEPATITIS C VIRUS INFECTION IN A HYPER-ENDEMIC AREA ‒ LONGITUDINAL EVIDENCE FROM THE COMPACT STUDY IN TAIWAN Pei-Chien Tsai1, Ching-I Huang1,2, Ming-Lun Yeh1,2, Chung-Feng Huang1,2, Meng-Hsuan Hsieh1,2, Jeng-Fu Yang1,2, Po-Yao Hsu1, Po-Cheng Liang1, Yi-Hung Lin1, Tyng-Yuan Jang1, Ming-Yen Hsieh1, Chia-Yen Dai1,2, Shinn-Chern Chen1,2, Jee-Fu Huang1,2, Ming-Lung Yu1,2, Wan-Long Chuang1,2, Wen-Yu Chang1 Division of Hepatobiliary, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan1 Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan2

從 COMPACT 經驗證實台灣高盛行區 C 肝感染之顯著改善 蔡佩倩1 黃駿逸1,2 葉明倫1,2 黃釧峰1,2 謝孟軒1,2 楊正甫1,2 許博堯1 梁博程1 林宜紘1 張庭遠1 謝明彥1 戴嘉言1,2 陳信成1,2 黃志富1,2 余明隆1,2 莊萬龍1,2 張文宇1 高雄醫學大學附設中和紀念醫院肝膽胰內科1 高雄醫學大學附設中和紀念醫院內科部2 Background: Hepatitis C virus (HCV) infection is the leading cause of cirrhosis and hepatocellular carcinoma worldwide. Tzukuan, located in the southwestern area of Taiwan, is an HCV hyperendemic area (>30%).

Aims: This study aimed to assess the changing epidemiological characteristics of HCV infection and to evaluate the long-term outcomes after the implementation of public health strategies for two decades.

Methods: The residents were recruited into HCV surveillance in a community-based COMPACT program. Their HCV status, demographic and clinical profiles were recorded and validated annually.

Results: From 2000 through 2019, a total of 10,714 residents received the screening. Among them, 1,614 underwent repeated tests during the followup period. The HCV infection prevalence rates

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were 21.1% (1,076/5099) in 2000-2004, 18.8% (239/1,269) in 2005-2009, 14.1% (292/2,071) in 2010-2014, and 10.3% (234/2,275) in 2015-2019 (p for trend test <0.0001). The annual incidence rates were 0.54% in 2005-2009, 0.4% in 20102014, and 0.22% in 2015-2019 (p=0.01). In addition to old age, lower education level was a major risk factor for HCV infection across different periods. HCV infection prevalence rate among those illiterates reached 40.9%, followed by 28.5% in those with elementary school level, and <10% in those with high school or higher levels. The major risk factor has shifted from iatrogenic exposure in 2000-2009 to household transmission after 2010.

Conclusions: HCV infection has been decreasing and the epidemiological features are changing in the hyper-endemic area.

P.007

CLINICAL OUTCOMES IN PATIENTS WITH ACUTE ABDOMEN AND HEPATIC PORTAL VEIN GAS Wen-Shan Chao1, Cheng-Chung Wu2,4, Chih-Chiang Hung3, Chuan-Hsun Chang4 Division of General Surgery, Tung’s Taichung Metro Harbor Hospital, Taichung, Taiwan1 Department of Surgery, Taichung Veterans General Hospital, Taichung, Taiwan2 Division of Breast Surgery, Department of Surgery, Taichung Veterans General Hospital, Taichung, Taiwan3 Department of Surgery, Cheng-Hsing General Hospital, Taipei, Taiwan4

急性腹痛合併肝門靜脈氣體之病人臨 床預後 趙玟珊1 吳誠中2,4 洪志強3 常傳訓4 童綜合醫院一般外科1 臺中榮民總醫院外科部2 臺中榮民總醫院乳房外科3 振興醫院外科部4 Background: Hepatic Portal Venous Gas (HPVG) is a well-known, rare, but ominous radiological sign in patients with acute abdomen. The outcomes of the patients with HPVG is uncertain.

Aims: The purpose of this study is to review our experiences and establish an appropriate clinical decision in patients with acute abdomen and HPVG. Methods: We retrospective searched the patient with the key words: HPVG, bowel ischemia, acute abdomen at tertiary care academic medical centers. 20 patients were obtained from February 2008 to March 2018. The early and long-term outcomes were studies and analyzed.

Results: The patients included eleven males and nine females, with an age range of 40-87 years old.

Sixteen patients underwent surgical intervention, and 6 of them died of severe ischemic bowel.

The other four patients did not have surgery, 2 of them died of moribund status secondary to severe bowel ischemia; the other 2 survivors received conservative treatment because of equivocal clinical presentation. Preoperative shock was the only impact factor for mortality in this series.

No recurrent HPVG in the twelve survivors after followed-up period 12-120 months.

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Conclusions: HPVG is an episodic presentation in acute abdomen but not an indication for surgical intervention. The mortality rate in patients with both HPVG and bowel ischemia was high but sometimes with equivocal presentation. Thus, for patients with acute abdomen, negative laboratory findings and physical examinations (PE), and CTproven presence of portal venous gas still need for further investigations.

P.008

FACTORS PREDICTING OUTCOMES OF HEPATITIS B-RELATED CIRRHOSIS PATIENTS WITH LONG-TERM ANTIVIRAL THERAPY Yi-Lin Chen1, Chih-Lin Lin1, Kuo-Chih Tseng2, Kuan-Yng Chen1, Li-Ying Liao1, Jia-Horng Kao3 Department of Gastroenterology, Taipei City Hospital, Ren-Ai branch, Taipei, Taiwan1 Department of Internal Medicine, Dalin Tzu Chi Hospital, Chiayi, Taiwan2 Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan3

B 肝相關肝硬化患者接受長期抗病毒 藥物治療預後之相關因子 陳奕霖1 林志陵1 曾國枝2 陳冠仰1 廖麗瑛1 高嘉宏3 臺北市立聯合醫院仁愛院區消化內科1 大林慈濟醫院內科部2 台大醫院內科部胃腸肝膽科3 Background: Long-term nucleos(t)ide analogues (NA) therapy has been shown to improve the survival in patients with HBV-related cirrhosis.

Aims: The aim of this study was to evaluate the clinical outcomes and factors associated with survival in HBV-related cirrhotic patients receiving long-term NA treatment. In addition, the impact of HCC development on the survival of HBV-related cirrhotic patients with antiviral therapy was also examined.

Methods: A total of 126 HBV-related cirrhosis, treatment naive patients with serum levels of HBV DNA more than 2000 IU, including 67 compensated cirrhosis and 59 decompensated cirrhosis, were retrospectively enrolled. Patients who had hepatitis C or D virus, or human immunodeficiency virus co-infection, had a history of heavy alcohol use, had hepatocellular carcinoma and other causes of liver disease were also excluded from this study.

The effectiveness of treatment, survival and risk factors of mortality were determined. Baseline data of biochemical tests were collected before the day of NA administration and the survival time was confirmed through the end of 2018.

Results: Patients with decompensated cirrhosis had significantly lower baseline serum HBV DNA

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levels than compensated cirrhotic patients (4.98 ± 1.91 vs. 5.67 ± 1.26 log10 IU/ml, P = 0.031). The mean follow-up duration was 84 and 42 months in compensated cirrhotic and decompensated cirrhotic patients (P < 0.0001), respectively. For 59 decompensated cirrhotic patients, 27.1% (16/59) of patients achieved CTP class A and 23.7% (14/59) showed improvement in the CTP score of ≧ 2 points after 2 years of NA treatment. The 1, 2 and 3-year cumulative survival rates were significantly higher in compensated cirrhotic patients than those with decompensated cirrhosis (100%, 98.5%, 98.5% vs. 81.2%, 75.6%, 69.5%; P < 0.0001).

Multivariate analysis for risk factors of mortality in cirrhotic patients showed that older age (hazard ratio: 3.28, 95% CI: 1.25-8.62, P = 0.016) and decompensated cirrhosis (hazard ratio: 8.30, 95% CI: 2.45-28.06, P = 0.0007) were independently associated with liver-related mortality. A total of 31 patients, 37.3% of compensated cirrhotic and 10.2% of decompensated cirrhotic patients, developed HCC during the follow-up. The 1, 2 and 3-year cumulative survival rates were not different between compensated cirrhotic patients with and without HCC development (96%, 96%, 96% vs.

100%, 100%, 100%; P = 0.577) (Figure 2). Similarly, the 1, 2 and 3-year cumulated survival rates were comparable between decompensated cirrhotic patients with and without HCC development (83.3%, 83.3%, 66.7% vs. 81%, 74.7%, 69.8%; P = 0.528). Among patients with HCC, 70.9% were at the earlier stages of BCLC system, and 83.8% received potentially curative treatment.

Conclusions: Antiviral therapy improves liver function of HBV-related cirrhotic patients and provides a better chance of curative treatment in those with HCC development. Decompensated cirrhosis is a risk factor for liver-related mortality in this special clinical setting.

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P.009

SAFETY AND EFFICACY OF SWITCHING TO TENOFOVIR ALAFENAMIDE (TAF) IN VIRALLY SUPPRESSED CHRONIC HEPATITIS B (CHB) PATIENTS WITH RENAL IMPAIRMENT: WEEK 48 RESULTS FROM A PHASE 2 OPEN LABEL STUDY Yi-Hsiang Huang1, Chi-Yi Chen2, Wei-Wen Su3, Chien-Hung Chen4, Harry Janssen5, Pietro Lampertico6, Jeong Heo7, Sang Hoon Ahn8, Tak Yin Owen Tsang9, Aric Josun Hui10, Magdy Elkhashab11, Syed Mohammed Raza Jafri12, Susanna Tan13, Shuyuan Mo13, John F. Flaherty13, Anuj Gaggar13, Kosh Agarwal14, Edward Gane15, Young-Suk Lim16, Wan-Long Chuang17 Taipei Veterans General Hospital, Taipei, Taiwan1 Chia-Yi Christian Hospital, Chiayi, Taiwan2 Changhua Christian Hospital, Changhua, Taiwan3 Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan4 Toronto Centre for Liver Disease, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada5 Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Università degliStudi di Milano, Italy6 College of Medicine, Pusan National University, Division of Gastroenterology and Hepatology, Pusan National University Hospital, Busan, Korea7 Yonsei Liver Center, Severance Hospital, Seoul, Korea8 Princess Margaret Hospital, Hong Kong9 Alice Ho Miu Ling Nethersole Hospital, Hong Kong10 Toronto Liver Centre, Toronto11 Henry Ford Hospital, Detroit, MI, USA12 Gilead Sciences, Inc., Foster City, CA, USA13 Institute of Liver Sciences, King’s College Hospital, London, UK14 Auckland Clinical Studies, Auckland, New

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Zealand15 Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea16 Kaohsiung Medical University Chung-Ho Memorial Hospital, Kaohsiung, Taiwan17 Background: Switching to TAF, a novel tenofovir prodrug, has shown maintenance of viral suppression with stable or improved bone and renal safety at Wk 24 in CHB patients with moderate to severe renal impairment (eGFR by Cockcroft-Gault [eGFRCG] <60 mL/min) and ESRD patients on HD. Aims: We evaluated the safety and efficacy in these virally suppressed patients with renal impairment 1 year after switching to TAF in a Phase 2 study.

Methods: CHB patients with renal impairment receiving TDF and/or other OAVs for ≥48 weeks and virally suppressed for ≥6 months with HBV DNA <20 IU/mL at screening were enrolled into 2 cohorts: 1) moderate-severe renal impairment (eGFRCG 15 to <60 mL/min) and 2) ESRD (eGFRCG <15 mL/min) on chronic HD. All patients were switched to TAF 25 mg QD for 96 weeks (given post-HD on days of dialysis for ESRD patients). Safety assessments including changes in bone (hip and spine BMD) and renal (CrCl by Cockcroft-Gault [eGFRCG], serum creatinine) parameters, viral suppression, and biochemical responses were assessed in all patients at Week 48.

Results: 93 patients (mod-severe impairment 78; ESRD 15) were enrolled from 26 sites in 8 countries, and 22 patients (24%) were from Taiwan; 89% of patients remained on study at Week 48. At baseline, 74% were male, 77% Asian, 68% ≥60 y, 83% HBeAg-negative and median ALT was 17 U/L. Up to 25% overall (both cohorts) had osteoporosis at hip and/or spine, and a high proportion had comorbidities (60% HTN, 24% DM). Key efficacy/safety results at Week 48 are summarized in the Table. Efficacy (HBV DNA <20 IU/mL) was maintained in nearly all patients on treatment at Week 48 and a high proportion had normal ALT levels. Five patients discontinued study drug early (withdrew consent) with last available HBV DNA <20 IU/mL; 1 patient had HBV DNA ≥20 IU/mL and 1 patient died. Relative to baseline levels, switching to TAF resulted in stable hip/spine BMD in moderate to severe renal impairment patients, with a slight decrease in hip

BMD in ESRD patients. Slight improvements were observed in renal parameters including eGFRCG and markers of renal tubular function in moderate to severely impaired patients. TAF was well tolerated, with no Grade 3/4 or serious adverse events related to study drug.

Conclusions: In renally-impaired CHB patients, including ESRD patients on HD, viral suppression was well maintained, and the bone and renal safety were stable or improved 48 weeks after switching to TAF.

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P.010

48-WEEK SAFETY AND EFFICACY OF SWITCHING TO TENOFOVIR ALAFENAMIDE (TAF) FROM TENOFOVIR DISOPROXIL FUMARATE (TDF) IN CHRONIC HBV ASIAN PATIENTS WITH TDF RISK FACTORS (RF) Jia-Horng Kao1, Ahn Sang Hoon2, Hann Hie-Won3, Fung Scott4, Trinh Huy5, Nguyen Tuan Trong6, Paik Seung Woon7, Gaggar Anuj8, Flaherty John8, Yee Leland J8, Jump Belinda8, Sethi Shalini8, Wu George8, Wan-Long Chuang9 Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan1 Severance Hospital, Seoul, Korea2 Thomas Jefferson University Hospital, Philadelphia, PA, USA3 Toronto Centre for Liver Disease, Toronto General Hospital, University Health Network, Toronto, Ontario, Canada4 San Jose Gastroenterology, San Jose, USA5 Research and Education, Inc.,San Diego, CA, USA6 Department of Internal Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea7 Gilead Sciences, Foster City, CA, USA8 Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan9 Background: In a recent Phase 3 study (Study 4018) in HBV patients suppressed on TDF treatment, switching to TAF demonstrated noninferior efficacy to continued TDF with superior bone and renal safety at Week 48.

Aims: To assess the safety and efficacy of switching to TAF from TDF in patients of Asian descent with risk factors for TDF toxicity as per current EASL and AASLD guidelines.

Methods: Virally suppressed patients (HBV DNA <20 IU/mL at screening) on TDF were randomized (1:1) to switch to TAF or continue TDF for 48 weeks in a double-blind fashion. Viral suppression and changes in bone (BMD by DXA) and renal (creatinine clearance [eGFRCG]) parameters were assessed over 48 weeks.

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Results: Among the 400 Asian patients enrolled, 288 (72%) had at least 1 TDF RF. At Week 48, similar proportions with ≥1 RF had HBV-DNA <20IU/mL (TAF 97%; TDF 97%) and normal ALT by 2018 AASLD criteria (TAF 76%; TDF 73%). TAF subjects with ≥1 RF had increases in eGFRCG compared to decreases on TDF [median (Q1, Q3) change; TAF: +2.6 (-2.01, 7.34); TDF: -2.7 (-7.56, +15.79); p<0.0001)]. Among patients with ≥1 RF, improvements were seen in BMD for TAF vs. continued declines in TDF patients at both spine (p<0.0001) and hip (p<0.0001).

Conclusions: Virally suppressed Asian patients with CHB and risk factors for TDF who switched to TAF showed improved bone and renal safety while efficacy was well-maintained.

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P.011

A PHASE 3 STUDY COMPARING SWITCHING FROM TENOFOVIR DISOPROXIL FUMARATE (TDF) TO TENOFOVIR ALAFENAMIDE (TAF) WITH CONTINUED TDF TREATMENT IN VIROLOGICALLYSUPPRESSED PATIENTS WITH CHRONIC HEPATITIS B (CHB): FINAL WEEK 96 EFFICACY AND SAFETY RESULTS Jia-Horng Kao1, Wan-Long Chuang2, Chi-Yi Chen3, Maria Buti4, Alnoor Ramji5, Scott Fung6, Sang Hoon Ahn7, Edward Tam8, Mandana Khalili9, Ho Bae10, Won Young Tak11, Kris Mar12, John F. Flaherty12, Anuj Gaggar12, Leland Yee12, Yang Liu12, Gulan Zhang12, Kosh Agarwal14, Young-Suk Lim14, Henry Chan15, Pietro Lampertico16 Division of Gastroenterology and Hepatology, National Taiwan University Hospital, Taipei, Taiwan1 Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan2 Chia-Yi Christian Hospital, Chiayi, Taiwan3 Hospital General Universitario Valle Hebron and Ciberehd, Barcelona4 Division of Gastroenterology, University of British Columbia5 Toronto Centre for Liver Disease, Toronto General Hospital, University Health Network6 Department of Internal Medicine, Institute of Gastroenterology, Yonsei University, College of Medicine, Seoul, Korea7 LAIR Centre, Vancouver, Canada8 University of California San Francisco9 Saint Vincent Medical Center, Los Angeles, United States10 Kyungpook National University College of Medicine11 Gilead Sciences Inc., Foster City, CA, USA12 Institute of Liver Studies, King’s College Hospital13 Department of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Ulsan, Korea14 Institute of Digestive Disease, Department of

Medicine and Therapeutics, and State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong15 Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Università di Milano, Milan, Italy16 Background: We have previously demonstrated at Week 48 that switching to TAF vs continued TDF treatment in CHB patients who were virally suppressed on long-term TDF has shown noninferior efficacy of TAF to TDF with superior bone and renal safety.

Aims: Here we report the final, efficacy and safety results from this study at Week 96.

Methods: In this Phase 3 study (NCT02979613), CHB patients taking TDF for ≥48 weeks with HBV DNA <LLOQ (local lab) for ≥12 weeks and <20 IU/mL at screening were randomized (1:1) to TAF 25 mg QD or TDF 300 mg QD, each with matching placebo, and treated for 48 weeks in a double-blind (DB) fashion. At Week 48, all patients received open-label (OL) TAF 25 mg once daily for an additional 48 weeks. Safety assessments including changes in bone (hip and spine BMD) and renal (CrCl by Cockcroft-Gault [eGFRCG], serum creatinine) parameters; viral suppression, and serological and biochemical responses were also assessed in all patients.

Results: Of 488 (TAF 243, TDF 245) patients randomized and treated, 472 (97%; TAF 235, TDF 237) completed 48 weeks of DB treatment, and 465 (95%; TAF 233, TDF 232) completed study treatment through Week 96. Key efficacy/safety results are summarized in the Table. Virologic suppression (HBV DNA <20 IU/mL) was similarly maintained at Wk96 in patients switched to TAF treatment at BL vs those switched to TAF after 48 weeks of DB TDF treatment; rates of ALT normalization were increased in both groups at Wk 96. In patients switched to TAF at BL vs those switched at Wk48, similar increases in spine BMD were seen while increases in hip BMD were smaller. In the TDF group, eGFRCG decreased at Wk48 (-2.7 mL/min); an improvement was seen after switching to TAF at Wk96 (-0.39 mL/min).

Conclusions: In CHB patients on long-term TDF treatment, viral suppression was maintained, ALT normalization increased, and bone and renal safety parameters were improved at Wk96.

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P.012

CLINICAL RELAPSE PATTERN IN HBEAG NEGATIVE CHRONIC HEPATITIS B CAN BE CHANGED

BY SWITCHING TO ANOTHER NUCLEOS(T)IDE ANALOGUES BEFORE CESSATION Chien-Wei Peng1,2, Wen-Juei Jeng1,2, Yun-Fan Liaw2,3 Department of Gastroenterology and Hepatology, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan1 College of Medicine, Chang Gung University, Taoyuan, Taiwan2 Liver Research Unit, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan3

e 抗原陰性慢性 B 型肝炎患者於核苷∕ 核苷酸類似物停藥後之臨床復發型態可 藉由換藥改變 彭建維1,2 鄭文睿1,2 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: Finite nucleos(t)ide analogue (Nuc) therapy in HBeAg negative chronic hepatitis B (CHB) patients has been proved to be feasible and reasonably safe. The main safety concern is the clinical relapse (CR), which occurs much earlier in patients stopping tenofovir (TDF) and other Nuc(s) than after stopping entecavir (ETV).

Aims: It is unknown whether the timing of relapse can be modified by switching from one Nuc to another. This study was conducted to address this issue.

Methods: This study was derived from the OffNuc Cohort in Chang Gung Memorial Hospital (CGMH-off-Nuc cohort). All these patients stopped Nuc by APASL stopping rule and were followed for a minimum of 48 weeks after Nuc cessation.

The HBeAg negative CHB patients were classified into four groups: ETV monotherapy (mono-ETV), TDF monotherapy (mono-TDF), switched to ETV (switch-ETV), and switched to non-ETV (switchnon-ETV). Patients in the “switch-Nuc” group were excluded if the duration of initial Nuc (startNuc) or switched Nuc (end-Nuc) was < 12 weeks.

Propensity score weighting was performed to

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minimize baseline and post-therapy confounders.

Adjusted cox regression analysis and KaplanMeier curve were used to compare the CR risks in the four groups.

Results: A total 1255 patients (972 mono-ETV, 186 mono-TDF, 50 switch-ETV and 48 switchnon-ETV) were enrolled. The median time to CR was 39, 13, 34 and 16 weeks in mono-ETV, mono-TDF, switch-ETV and switch-non-ETV respectively (P < 0.0001). The start-Nuc treatment duration was 46(14-206) and 65 (14-385) weeks in switch-ETV and switch-non-ETV respectively. The end-Nuc treatment duration was 82 (17-415) and 100 (39-365) weeks in switch-ETV and switchnon-ETV respectively. Before propensity score weighting, age (adjusted HR: 1.01, 95% CI: 1.011.21, P < 0.001), male (adjusted HR: 1.25, 95% CI: 1.02-1.52, P = 0.031), cirrhosis (adjusted HR: 1.21, 95% CI: 1.04-1.40, P = 0.013) and end of treatment HBsAg > 100 IU/mL (adjusted HR: 1.76, 95% CI: 1.41-2.20, P < 0.001) were independent factors for higher CR risk. Comparing to monoTDF patients, mono-ETV (adjusted HR: 0.56, 95% CI: 0.46-0.68, P < 0.001) and switch-ETV patients (adjusted HR: 0.63, 95% CI: 0.43-0.91, P = 0.015) had lower CR risk. After propensity score weighting, the mono-ETV (adjusted HR: 0.60, 95% CI: 0.47-0.75, P < 0.001) and switch-ETV patients (adjusted HR: 0.65, 95% CI: 0.44-0.97, P = 0.035) had significantly lower CR risks.

Conclusions: Patients treated with TDF or other Nuc switched to ETV >12 weeks prior to Nuc cessation may postpone the timing of CR to that after stopping mono-ETV. Switching to ETV >12 weeks prior to cessation of therapy may be a good strategy to avoid early onset of CR. The optimal duration of switching therapy is to be determined by further studies.

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P.013

A COMPARISON STUDY OF ENTECAVIR VS TENOFOVIR DISOPROXIL FUMARATE ON REDUCING HEPATOCELLULAR CARCINOMA RISK IN CHRONIC HEPATITIS B VIRUS RELATED CIRRHOTIC PATIENTS: A RETROSPECTIVE COHORT STUDY

= 201) developed HCC in ETV group and 12 patients (13.6%, n = 88) developed HCC in TDF group. There was no significant difference of the cumulative HCC incidence between ETV and TDF groups (p = 0.23).

Conclusions: This study suggests that ETV and TDF long-term treatment is associated with similar risks of HCC.

Huang-Lun Lai, Yu-Hung Lin, Chun-Hsiang Wang, Ming-Jeng Kuo, Kuo-Kuan Chang, Ruey-Chang Lin, Jen-Juan Kuo, Keh-Cherng Wey, Yuan-Chi Mao, I-I Chen, Lein-Ray Mo Department of Hepatogastroenterology, Tainan Municipal Hospital (Managed by Show Chwan Medical Care Corporation), Tainan, Taiwan

於慢性乙型肝炎病毒相關肝硬化的患者 中，Entecavir 與 Tenofovir Disoproxil Fumarate 降低肝細胞癌風險的比較研 究：回溯式世代研究 賴皝綸 林裕鴻 王俊雄 郭明正 張國寬 林瑞昌 郭振源 魏克承 毛元治 陳一毅 牟聯瑞 台南市立醫院肝膽胃腸科 Background: Chronic hepatitis B virus (HBV) related cirrhosis is a major risk factor of hepatocellular carcinoma (HCC). Little is known about the efficacy of reducing HCC risks in different nucleos(t)ide analogue treatments.

Aims: This study aimed to compare the efficacy of decreasing HCC risk in patients with chronic HBV related cirrhosis who received long-term entecavir (ETV) or tenofovir disoproxil fumarate (TDF) therapy.

Methods: We performed a retrospective study of HBV related cirrhotic patients who treated with ETV or TDF for at least 6 months from December 2007 through May 2020. The occurrence of HCC in different regimens was evaluated. The KaplanMeier method with a log-rank test was used to compare the cumulative incidence of HCC development in the two treatment groups.

Results: A total of 289 patients (male: 206 (71.28%), female: 83 (28.72%), average age: 61 ± 10.7 years old) were enrolled. During a median follow-up of 62 months, 25 patients (12.4%, n

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P.014

CHRONIC HEPATITIS B PATIENTS TREATED WITH GENERIC ENTECAVIR (ENVIR): REAL-WORLD EXPERIENCE OF ONE SINGLE MEDICAL CENTER Chung-Hsin Chang, Hong-Zen Yeh, Yi-Jie Huang, Sheng-Shun Yang Devision of Gastroenterology and Hepatology, Taichung Veterans General Hospital, Taichung, Taiwan

中部某醫學中心使用欣苷治療慢性 B 肝患者的經驗 張崇信 葉宏仁 黃儀倢 楊勝舜 臺中榮民總醫院胃腸肝膽科 Background: Entecavir is recommended as firstline therapy for chronic hepatitis B (CHB). The efficacy and safety of generic entecavir (Envir) in routine practice is uncertain.

Aims: We conduct the study to evaluate the efficacy of Envir in CHB patients.

Methods: From June 2016 to Jan 2020, 81 patients who received Envir in Taichung veterans general hospital were enrolled for analysis and patients were divided into three groups: naïve, brand name nucleos(t)ide analogs (NUC)- Envir switch and retreated with Envir group. We evaluated the virological and biochemical responses.

Results: The median age of 53.16 ± 11.67 and 60.5% male, treated with a median duration of 19.54 ± 11.58 months. 32 were treated with Envir initially, 37 were NUC-Envir switch and 12 were-retreated with Envir (Table 1). The median HBV DNA level was 0.66 ± 2.87 log IU/mL; the median qHBsAg was 3.02 ± 0.8 log IU/mL, and the median ALT was 28.5 ± 82.05 U/L in all patients. The 12-month virological response rate is 90%, and ALT normalization rate is 91% in naïve group and retreated Envir group (figure 1 & 2). The dynamic change in HBsAg level from baseline to month 12 is significant decline in all patients (p = 0.016, figure 3). No virological breakthrough and no adverse effect were noted during treatment.

Conclusions: Envir provided favorable efficacy and safety for chronic hepatitis B patients and is a feasible alternative choice to brand name prescription drug for CHB patients.

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P.015

COMPARISON OF HEPATITIS B VIRUS RELAPSE RATES BETWEEN HBEAG-POSITIVE CHRONIC HEPATITIS B PATIENTS WHO DISCONTINUE ENTECAVIR AND TENOFOVIR TREATMENT Chien-Hung Chen, Jing-Houng Wang, Chao-Hung Hung, Sheng-Nan Lu, Tsung-Hui Hu Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan

慢性 B 型肝炎 e 抗原陽性病人停止貝 樂克或惠立妥治療 B 型肝炎病毒復發 率的比較 陳建宏 王景弘 洪肇宏 盧勝男 胡琮輝 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: The incidence and predictors of HBV relapse remains unclear in HBeAg-positive patients who discontinued entecavir or tenofovir disoproxil fumarate (TDF) therapy Aims: To compare HBV relapse rates between HBeAg-positive CHB patients without cirrhosis who discontinued entecavir and TDF treatment.

Methods: A retrospective-prospective study was conducted in 222 HBeAg-positive CHB patients who received entecavir (n=147) and TDF (n=75) therapy. The patients all had post-treatment followup for at least 6 months. All patients fulfilled the stopping criteria of the Asia-Pacific Association for the Study of the Liver of 2016.

Results: In the entecavir group, the incidence of virological relapse at 6, 12, 36 months were 16.3%, 36.8% and 52.4%, and clinical relapse were 6.1%, 27.4% and 43.3%, respectively. In the TDF group, the incidence of virological relapse at 6, 12, 36 months were 61.3%, 72.4% and 77.4%, and clinical relapse were 26%, 56.5% and 68.5%, respectively. Patients who discontinued TDF therapy had significantly higher rates and earlier times of virological and clinical relapse than those who discontinued entecavir therapy in all patients and propensity score-matched patients.

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Multivariate analysis showed that being in the TDF group, old age, male gender, NA-experienced status, higher HBsAg at base and end of treatment were independent factors of virological and clinical relapse in all patients and PS-matched HBeAgpositive patients. The severity of ALT flare was no difference in TDF group compared to entecavir group. In patients with virological or clinical relapse, there were no significant difference in HBeAg seroreversion between entecavir and TDF group.

Two patients in entecavir group experienced hepatic decompensation upon clinical relapse, and one died even with timely retreatment.

Conclusions: HBV relapse rate was significantly higher after the cessation of TDF therapy than that after the cessation of ETV therapy in HBeAgpositive patients without cirrhosis.

P.016

ALBUMIN‒BILIRUBIN (ALBI) GRADE PREDICT HEPATOCELLULAR CARCINOMA AND MORTALITY IN CHRONIC HEPATITIS B PATIENTS WITH CIRRHOSIS TREATED WITH ENTECAVIR OR TENOFOVIR Fai-Meng Sou1, Cheng-Yuan Peng2, Chi-Yi Chen3, Sheng-Nan Lu1, Tsung-Hui Hu1, Chien-Hung Chen1 Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan1 Division of Gastroenterology, Department of Internal Medicine, China Medical University Hospital and School of Medicine, China Medical University, Taichung, Taiwan2 Division of Hepatogastroenterology, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi, Taiwan3

ALBI Grade 預測慢性 B 型肝炎肝硬化 病人接受貝樂克或惠立妥治療發生肝 癌和死亡 蘇輝明1 彭成元2 陳啟益3 盧勝男1 胡琮輝1 陳建宏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 中國醫藥大學附設醫院胃腸肝膽科暨中國醫藥大 學醫學系2 戴德森醫療財團法人嘉義基督教醫院胃腸肝膽科3 Background: It remains unclear whether the Albumin–Bilirubin (ALBI) grade could predict hepatocellular carcinoma (HCC) development in chronic hepatitis B (CHB) patients with cirrhosis treated with entecavir or tenofovir disoproxil fumarate (TDF).

Aims: To investigate whether ALBI grade could predict HCC and mortality in CHB patients with cirrhosis treated with entecavir or TDF. Methods: A total of 1560 CHB patients with cirrhosis who received entecavir or TDF for at least 12 months were recruited.

Results: In the entire cohort, the cumulative incidences of HCC at 3, 5, and 10 years were

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9.5%, 15.2%, and 25.4%, respectively. ALBI (HR: 1.424, 95% CI: 1.111-1.824, P = 0.005) or modified ALBI (mALBI) grade (HR: 1.255, 95% CI: 1.070-1.471, P = 0.005) was an independent predictors of HCC after adjusting for other factors.

In addition, ALBI (HR: 1.746, 95% CI: 1.206-2.528, P = 0.003) or mALBI grade (HR: 1.599, 95% CI: 1.251-2.042, P < 0.001) were also an independent predictors of liver-related mortality. Compared with Child-Pugh (A, B, C) and PAGE-B (≤9, 10–17, ≥18) classification, ALBI or mALBI grade (C-index: 0.600 and 0.604) was similar to PAGE-B (C-index: 0.619, P = 0.41 and 0.52, respectively) and was superior to Child-Pugh classification (C-index: 0.564, P = 0.02 and 0.008, respectively) for predicting HCC development. ALBI or mALBI grade (C-index: 0.677 and 0.695) was superior to PAGE-B (C-index: 0.575, P = 0.003 and 0.007, respectively) and Child-Pugh classification (C-index: 0.641, P = 0.121 and 0.018, respectively) for predicting liver-related mortality.

Conclusions: ALBI grade or modified ALBI grade could predict HCC and liver-related mortality in CHB patients with cirrhosis treated with entecavir or TDF.

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P.017

EARLIER AND MORE SEVERE OFFTENOFOVIR HEPATITIS FLARES THAN OFF-ENTECAVIR FLARES IN HEPATITIS B E ANTIGEN-NEGATIVE PATIENTS Yen-Chun Liu1,2, Wen-Juei Jeng1,2, 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

e 抗原陰性肝炎惠立妥停藥後復發較貝 樂克停藥後復發嚴重且發生時間較早 劉彥君1,2 鄭文睿1,2 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 Background: It has been recognized that clinical relapse occurs much earlier and more frequently after cessation of therapy with tenofovir (TDF) than entecavir (ETV). However, it remains undetermined whether the severity of hepatitis flare after cessation of TDF and ETV is also different.

Aims: This study aims to compare the severity and timing of off-ETV and off-TDF hepatitis flare.

Methods: The retrospective-prospective cohort (CGMH off-Nuc cohort) composed of hepatitis B e antigen-negative chronic hepatitis B patients who discontinuing TDF or ETV by APASL stopping rule. Serum ALT level of these patients were monitored every 1 to 1.5 months after cessation of Nuc for first 3 months, and followed up with 1 to 3 months interval afterwards. Clinical relapse was defined as serum ALT level greater than 2 times (x) the upper limit of normal (ULN) plus HBV DNA more than 2000 IU/mL. Hepatitis flare was defined as ALT level ≥ 5x ULN. Once ALT was rising or above 5x ULN, ALT, total bilirubin and INR were monitored weekly to biweekly until ALT was normalizing. Hepatic decompensation was defined as total bilirubin > 2 mg/dL and INR ≥ 1.5 with symptoms related to severe hepatitis. Time from end-of-treatment to flare, severity of flare

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and liver adverse events were compared between patients who stopped ETV and TDF. Results: Among 1066 off-Nuc patients in this cohort, 717 patients encountered clinical relapse with 469 developing hepatitis flare (362 off-ETV and 107 off TDF). The 2-year cumulative incidence of off-Nuc flare was significantly higher in offTDF than off-ETV patients (58.6% vs. 37.6%, p < 0.001). Compared to off-ETV flares, off-TDF flares showed shorter time to flare (12 vs. 39 weeks, p < 0.001; cirrhosis: 12 vs. 35 weeks, p < 0.001; noncirrhosis: 12 vs. 45 weeks, p < 0.001), greater ALT peak level (563 vs. 434 U/L, p = 0.005), higher proportion of ALT ≥ 20x ULN (38.3% vs. 23.5%, p = 0.002), ALT ≥ 1000 U/L (24.3% vs. 13.5%, p = 0.008), INR ≥ 1.5 (6.5% vs. 1.9%, p = 0.007) and hepatic decompensation (6.5% vs. 1.9%, p = 0.007). Among non-cirrhotic patients, higher proportion of ALT ≥ 20x ULN was observed in those off-TDF than those off-ETV (40.6% vs. 20.5%, p < 0.001). On the other hand, higher proportion of ALT ≥ 1000 U/L was observed in cirrhotic patients off TDF than off ETV (27.9% vs. 14.8%, p = 0.045).

All five patients (2/162 in ETV, 3/43 in TDF, p = 0.063) who died or received transplantation due to liver disease had liver cirrhosis.

Conclusions: Hepatitis flare occurred earlier, more frequent and more severe in patients discontinuing tenofovir than in patients stopping entecavir. Different strategy of post therapy monitoring is necessary for different Nuc.

P.018

INVESTIGATE THE EFFICACY AND SAFETY OF TENOFOVIR ALAFENAMIDE (TAF) IN REALWORLD TREATMENT NA&IUML;VE CHRONIC HEPATITIS B PATIENTS IN TAIWAN: 24-48 WEEK RESULTS FROM A SINGLE-CENTER COHORT Tsung-Hui Hu, Pao-Yuan Huang, Ming-Chao Tsai, Kuo-Chin Chang, Chien-Hung Chen, Kwong-Ming Kee Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gang Memorial Hospital, Kaohsiung, Taiwan

Tenofovir Alafenamide（TAF）初治 病人之 6-12 個月實務經驗 胡琮輝 黃寳源 蔡明釗 張國欽 陳建宏 紀廣明 高雄長庚紀念醫院胃腸肝膽科 Background: Tenofovir Alafenamide (TAF) is a novel tenofovir prodrug, and it has demonstrated noninferior efficacy to TDF with superior bone and renal safety in chronic hepatitis B (CHB) patients in phase 3 clinical studies. In Taiwan, TAF was reimbursed from May, 2019. The evidences of TAF in local real-world CHB patients are still limited.

Aims: We aim to determine the efficacy and safety of TAF in naïve CHB patients in Taiwan real-world cohort.

Methods: Data of naïve CHB patients were retrospectively analyzed. All patients were treated with TAF 25 mg QD. The primary endpoint is proportion with HBV DNA <20 IU/mL at Week 24.

Key secondary endpoints were changes in alanine aminotransferase (ALT), estimated glomerular filtration rate as per Cockcroft-Gault (eGFRCG), and serum creatinine. All laboratory data were collected as per the standard of care practice every 6-12 month.

Results: In total, data of 30 naïve CHB patients treated with TAF for at least 6 months were analyzed. Median age was 60 years, 73.3% of patients were male, 83% HBeAg-negative, 63.3 % of patients were cirrhotic, and 13.3% and 26.7% of patients had a history of DM and/or HTN, respectively. 29 patients have baseline and 6-month HBV DNA data. After 24-week treatment of TAF, 26/29 (89.7%) patients achieved DNA

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viral suppression. Meanwhile, the median ALT level was changed from 64 U/L to 31 U/L after 6-month of TAF treatment. For the renal safety, the median eGFRCG changed from 89.45 to 88.4, and serum creatinine changed from 0.865 mg/dL to 0.82 mg/dL 5/30 (16.7%) of patients have ≥ 1 stage CKD stage improvement. At 48 weeks, there is no difference of change in eGFRCG between TAF and ETV (historical control), but a borderline difference (p=0.09) between TAF (better) and TDF (worse) (historical control). Overall, TAF was well tolerated; no serious AEs related to study drug and no discontinuations due to AEs. Conclusions: In this real-world cohort, the preliminary results demonstrated that TAF is effective and safe for naïve CHB patients. After 6-12 month of treatment, most of the patients achieved DNA viral suppression; median ALT level was improved, and renal function was stably maintained.

P.019

THE EPIDEMIOLOGY OF HEPATITIS B, C, D IN THE INMATES OF PENGHU PRISON Ming-Ying Lu3,4, Chun-Ting Chen1,2, Pei-Chien Tsai4, Chung-Feng Huang4,5, Meng-Hsuan Hsieh4,5, Jee-Fu Huang4,5, Chia-Yen Dai4,5, Wan-Long Chuang4,5, Ming-Lung Yu4,5 Division of Gastroenterology and Hepatology, Department of Internal Medicine, Tri-Service General Hospital Penghu Branch, National Defense Medical Center, Taipei, Taiwan1 Division of Gastroenterology and Hepatology, Department of Internal Medicine, Tri-Service General Hospital, Penghu Branch, National Defense Medical Center, Penghu, Taiwan2 Shi-Yu Township Public Health Center, Penghu, Taiwan3 Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan4 Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan5

澎湖監獄受刑人族群 B、C、D 型肝炎 之流行病學研究 呂明穎3,4 陳軍廷1,2 蔡佩倩4 黃釧峰4,5 謝孟軒4,5 黃志富4,5 戴嘉言4,5 莊萬龍4,5 余明隆4,5 三軍總醫院胃腸肝膽科1 三軍總醫院澎湖分院胃腸肝膽科2 澎湖縣西嶼鄉衛生所3 高雄醫學大學附設醫院肝膽胰內科4 高雄醫學大學醫學院內科學科5 Background: Although the prevalence of viral hepatitis has significantly diminished over the past years, the transmission of hepatitis B, C and D among intravenous drug users (IDU) has been an emerging public health concern in Taiwan.

Nevertheless, only sporadic domestic studies were conducted on the epidemiological trends of viral hepatitis among this population yet.

Aims: To explore the prevalence of hepatitis B, C and D and analyze the risk factors of viral hepatitis among IDUs in Penghu Prison.

Methods: A total of 1138 (67.1%) participants

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among 1697 inmates of Penghu Prison received the screening for viral hepatitis B, C and D in September 2019. 1015 (89.2%) study subjects were IDUs. The hepatitis makers (i.e. HBsAg, HBeAg, anti-HBe, anti-HBc IgG, anti-HCV, and anti-HDV) were detected using commercially available enzyme-linked immunosorbent assay.

Serum HBV DNA, HCV RNA, HDV RNA and HCV genotypes were identified by real-time PCR. Results: The prevalence of hepatitis B, C, and D in Penghu Prison was 13.6%, 34.9%, 4.7%, respectively. The superinfection rate of HCV and HDV among HBV carriers were 36.1% and 25.2%.

The predominant HCV genotypes were GT6 (40.8%), followed by GT1a (23.7%), GT3 (10.9%), GT1b (10.4%), and GT2 (10.0%). The risk of HBV viremia was significantly reduced in the presence of anti-HCV positive (OR = 0.29, 95% CI = 0.110.78, p = 0.014). HCV viremia among treatment naïve HCV patients was negatively correlated with anti-HDV seropositivity (OR = 0.33, 95% CI = 0.12-0.89, p = 0.028) and body mass index (OR = 0.87, 95% CI = 0.79-0.95, p = 0.002). Anti-HCV seropositivity (OR = 6.52, 95% CI = 3.12-13.60, p = 5.9x10-7) and fibrosis-4 index (OR = 1.39, 95% CI = 1.01-1.91, p = 0.043) were independent risk factors of anti-HDV seropositivity.

Conclusions: IDUs have emerged as a reservoir for viral hepatitis in Taiwan. More effective public health policy is required to control the epidemic in these high-risk groups.

P.020

REAL CLINICAL PRACTICE OF DIRECT-ACTING ANTIVIRAL THERAPY FOR HEPATITIS C‒ RELATED HEPATOCELLULAR CARCINOMA Wei-Chen Lin, Yang-Sheng Lin, Chen-Wang Chang, Ching-Wei Chang, Tsang-En Wang, Horng-Yuan Wang, Ming-Jen Chen Division of Gastroenterology, Department of Internal Medicine, Mackay Memorial Hospital, Taipei, Taiwan

直接作用抗病毒藥物在 C 型肝炎之肝 癌患者的實際臨床狀況 林煒晟 林揚笙 章振旺 張經緯 王蒼恩 王鴻源 陳銘仁 台北馬偕紀念醫院胃腸肝膽科 Background: With the introduction of direct-acting antiviral (DAA) agents, hepatitis C virus (HCV) treatment has dramatically improved. Since 2017, the DAA was reimbursed by the Taiwan National Health Insurance for HCV patients, and there was no prohibition for using DAA in patients with hepatocellular carcinoma (HCC). However, there are insufficient data on the benefits of DAA therapy in HCC. Aims: The purpose of this study was to investigate the outcome of patients who received DAA therapy after HCC diagnosis.

Methods: We retrospectively reviewed patients with HCV-related HCC in a single medical center between January 2010 and December 2019, and the outcome of patients with DAA therapy was analyzed.

Results: In total, 60 had received DAA therapy after treatment for HCC. The most common genotype was genotype 1b (60.0%), followed by genotype 2 (36.7%). Harvoni was the most commonly used DAA regimen in 35% of patients, followed by Sovaldi (16.6%). The sustained virologic response at 12 weeks posttreatment was 93.3%. Thirty-five patients (58.3%) received DAA after curative HCC therapy. There were four patients who failed DAA treatment. Among them, three patients belonged to genotype 2, and three patients (75%) only had a partial response to HCC therapy before DAA use. In all, 13 (37.1%) patients had recurrent HCC

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after curative therapy, and the median follow-up period was 20 months. The cumulative incidences of recurrence-free survival at 1 and 2 years were 85.1% and 73.2%, respectively.

Conclusions: With a higher rate of HCC in patients with HCV than in patients with other causes of cirrhosis, realizing the impact of DAA therapy on long-term outcomes in this population is vital.

P.021

POST-TREATMENT LIVER STIFFNESS MEASUREMENT USING ACOUSTIC RADIATION FORCE IMPULSE PREDICTS INCIDENT HEPATOCELLULAR CARCINOMA IN CHRONIC HEPATITIS C PATIENTS WITH ADVANCED LIVER FIBROSIS Wei-Fan Hsu1,2, Sheng-Hung Chen1,3, Hsueh-Chou Lai1,4, Hung-Wei Wang1, Chun-Che Lin1,3, Guan-Tarn Huang1,3, Guan-Tarn Huang1,3, 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

口服抗病毒藥物治療後肝臟硬度測試 預測慢性 C 型肝炎重度肝臟纖維化病 患肝細胞癌發生 許偉帆1,2 陳昇弘1,3 賴學洲1,4 王鴻偉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 Background: Hepatocellular carcinoma (HCC) is a significant health problem worldwide. Chronic hepatitis C (CHC) is a well-known etiology for HCC, and direct-acting antiviral agents (DAAs) have been the standard of care for CHC. Several studies have demonstrated that patients with CHC who achieved sustained virological response (SVR) after DAA therapy had a lower incidence of liver-related events, including de novo HCC. Noninvasive factors predictive of incident HCC in patients with CHC after DAA therapy are still unknown.

Aims: To evaluate noninvasive factors predictive of incident HCC in patients with CHC after DAA therapy.

Methods: From September 2012 to April 2020, 720 patients with CHC who had received liver

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stiffness measurement (LSM) using acoustic radiation force impulse (ARFI) and a complete course of DAA therapy were screened. Of them, 134 patients were excluded due to HCC before or during DAA therapy (n = 88), hepatitis B virus (n = 55), or human immunodeficiency virus (n = 2) co-infection (more than one exclusion criteria could exist in a patient). Among 586 patients, 236 patients with advanced liver fibrosis, defined as an LSM using ARFI of ≥1.81 m/s according to the reimbursement guidelines of National Health Insurance, were enrolled. Demographic data, clinical and virological features associated with HCC occurrence recorded at baseline, end of therapy (EOT), 3, and 6 months after DAA therapy were collected.

Results: Of 236 patients, 92 (39 %) were male, and 109 (46.2%), 68 (28.8%), and 80 (33.9%) had liver cirrhosis, diabetes mellitus, and hypertension, respectively. The median age was 61 (54–68) years (first quartile–third quartile). The median ALT, total bilirubin, albumin, AFP, AST-to-platelet ratio index (APRI), FIB-4, and LSM using ARFI were 80 (49–123) U/L, 0.9 (0.7–1.2) mg/dL, 4.1 (3.9–4.4) g/dL, 8.59 (4.27–17.99) ng/mL, 1.70 (0.94–3.15), 4.07 (2.34–6.70), and 2.26 (2.05– 2.62) m/s, respectively. 166, 55, 2, and 11 had genotype 1, 2, 3, and 6 hepatitis C virus (HCV) infections, respectively, and two patients had mixed genotype HCV infection. The median follow-up duration after DAA therapy was 21.3 (10.6–29.8) months, and the median time to the onset of HCC was 17.1 (8.9–25.0) months in 14 patients with de novo HCC after DAA therapy, with a calculated incidence rate of 4.16 per 100 person-years. Of 14 patients with de novo HCC after DAA therapy, 7, 3, 3, and 1 patient belonged to Barcelona Clinic Liver Cancer stages A, B, C, and D, respectively.

A univariate Cox regression analysis identified albumin, total bilirubin, platelet count, FIB-4, HCV RNA at baseline; albumin, platelet count, and FIB4 at EOT; albumin, total bilirubin, international normalized ratio, platelet count, APRI, FIB-4, SVR, and LSM using ARFI >1.90 m/s at 3 or 6 months after DAA therapy as the significantly associated factors. Only LSM using ARFI >1.9 m/s at 3 or 6 months after DAA (Hazard ratio: 5.947, 95% confidence interval: 1.295–27.309, p = 0.022) was an independent predictor of incident HCC in multivariate Cox regression analysis.

Conclusions: Of 236 patients, 92 (39 %) were male, and 109 (46.2%), 68 (28.8%), and 80

(33.9%) had liver cirrhosis, diabetes mellitus, and hypertension, respectively. The median age was 61 (54–68) years (first quartile–third quartile). The median ALT, total bilirubin, albumin, AFP, ASTto-platelet ratio index (APRI), FIB-4, and LSM using ARFI were 80 (49–123) U/L, 0.9 (0.7–1.2) mg/dL, 4.1 (3.9–4.4) g/dL, 8.59 (4.27–17.99) ng/ mL, 1.70 (0.94–3.15), 4.07 (2.34–6.70), and 2.26 (2.05–2.62) m/s, respectively. 166, 55, 2, and 11 had genotype 1, 2, 3, and 6 hepatitis C virus (HCV) infections, respectively, and two patients had mixed genotype HCV infection. The median follow-up duration after DAA therapy was 21.3 (10.6–29.8) months, and the median time to the onset of HCC was 17.1 (8.9–25.0) months in 14 patients with de novo HCC after DAA therapy, with a calculated incidence rate of 4.16 per 100 person-years. Of 14 patients with de novo HCC after DAA therapy, 7, 3, 3, and 1 patient belonged to Barcelona Clinic Liver Cancer stages A, B, C, and D, respectively.

A univariate Cox regression analysis identified albumin, total bilirubin, platelet count, FIB-4, HCV RNA at baseline; albumin, platelet count, and FIB4 at EOT; albumin, total bilirubin, international normalized ratio, platelet count, APRI, FIB-4, SVR, and LSM using ARFI >1.90 m/s at 3 or 6 months after DAA therapy as the significantly associated factors. Only LSM using ARFI >1.9 m/s at 3 or 6 months after DAA (Hazard ratio: 5.947, 95% confidence interval: 1.295–27.309, p = 0.022) was an independent predictor of incident HCC in multivariate Cox regression analysis.

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P.022

NO IDENTIFIED ASSOCIATION BETWEEN GLECAPREVIR/ PIBRENTASVIR USE AND RISK OF HEPATIC DECOMPENSATION IN HCV-INFECTED PATIENTS WITH COMPENSATED CIRRHOSIS AT BASELINE: AN ACTIVE COMPARATOR COHORT STUDY Lani R. Wegrzyn1,2, Carrie Huisingh1,2, Ariel Porcalla2, Lino Rodrigues3, Margaret Burroughs3, Meenal Patwardhan2, Andrew Campbell3, Ryan D. Kilpatrick1,2 AbbVie Global Epidemiology1 AbbVie Pharmacovigilance and Patient Safety2 AbbVie Clinical Development3 Background: Glecaprevir/pibrentasvir (G/P) is a direct-acting antiviral (DAA) combination for treating HCV patients without liver cirrhosis or with compensated cirrhosis. Cirrhotic patients are at risk for hepatic decompensation due to the natural disease progression, and early generation protease inhibitors (PIs) have been associated with these events.

Aims: To assess the relative risk of hepatic decompensation in patients with compensated cirrhosis receiving G/P, compared with PI-free regimens.

Methods: A comparative cohort study was conducted within a US administrative claims database (Optum CDM) over 16 weeks after treatment initiation in patients with compensated cirrhosis receiving G/P (n=240), compared to those receiving PI-free regimens (sofosbuvir/ velpatasvir, ledipasvir/sofosbuvir, sofosbuvir, daclatasvir; n=4,185), during 2014 through 2018.

A Cox regression model was specified based on known risk factors and potential confounders of G/P and decompensation association.

Results: Six hepatic decompensation events in the G/P-treated group (6/240; 2.5%) and 133 events in the comparator group (133/4,185; 3.2%).

In the multivariable-adjusted regression model, no association between G/P use and hepatic decompensation was identified (HR=0.78), while portal hypertension was associated with an increased risk of hepatic decompensation

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(HR=2.75).

Conclusions: In this study, no association was observed between use of G/P compared with nonPI regimens and risk of hepatic decompensation. A 2-3-fold increased risk of hepatic decompensation was observed with baseline portal hypertension, consistent with the natural history of disease.

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P.023

IMPACT OF PRESCRIBED TREATMENT DURATION ON HEPATITIS C TREATMENT ADHERENCE: COMPARISON OF 8AND 12-WEEK TREATMENT WITH GLECAPREVIR/PIBRENTASVIR Ira M. Jacobson1, Tania Welzel2, Douglas E. Dylla3, Annie Luetkemeyer4, Jordan J. Feld5, Christophe Moreno6, David Nelson7, Georgios Papatheodoridis8, Juergen K. Rockstroh9, Eric Crown3, Sandra S. Lovell3, Ashley Brown10 NYU Langone Medical Health, New York, NY, USA1 J.W. Goethe University Hospital, Frankfurt, Germany2 AbbVie Inc3 Zuckerberg San Francisco General, University of California at San Francisco, San Francisco, CA, USA4 Toronto Centre for Liver Disease, University Health Network, University of Toronto, Ontario, Canada5 Département de Gastroenterologie, d’Hépatopancréatologie et Cancérologie Digestive, CUB Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium6 Department of Medicine, University of Florida, Gainesville, FL, USA7 Medical School of National and Kapodistrian University of Athens, Athens, Greece8 Medizinische Klinik und Poliklinik I, Universitätsklinikum Bonn, Bonn, Germany9 Imperial College Healthcare NHS Trust, London, UK10

HCV GT1–6 without cirrhosis or with compensated cirrhosis, prescribed G/P for 8 or 12 weeks across 10 Phase 3 trials. Adherence was calculated using percentage of pills taken relative to total number expected for each treatment interval, excluding any patient with missing data.

Results: Of 2086 patients included, 1634 were non-cirrhotic (8-week [n = 961], 12-week [n = 673]) and 452 had cirrhosis (8-week [n = 280], 12-week [n = 172]). Mean treatment adherence for the overall treatment period was 99.4%. Statistically significant decreases in mean adherence were seen between 4-week intervals 1–4 (101.6%), 4–8 (98.4%), and 8–12 (97.1%). The proportion of patients with ≥90% adherence was 98.4%, 94.5%, and 91.0% (P<0.001) during Weeks 1–4, 4–8, and 8–12, respectively and the proportion with ≥80% adherence was 99.4%, 98.6%, and 97.4% (P<0.001). Results were similar regardless of cirrhosis status (Table). Intention-to-treat sustained virologic response at post-treatment Week 12 (SVR12) was 98% overall and was not impacted by non-adherence.

Conclusions: Overall adherence to G/P is high regardless of treatment duration, although a modest decline in adherence was observed with longer treatment duration. SVR12 rates remained high (>98%) with 8- or 12-week G/P therapy. The study suggests that suboptimal adherence may not compromise treatment outcomes and should give reassurance to those initiating treatment in special patient populations.

Background: Adherence to direct-acting antiviral (DAA) for hepatitis C virus (HCV) has been shown to decline with longer treatment durations. Shorter treatment duration may be a key to facilitate the World Health Organization HCV elimination goal.

DAA combination of glecaprevir/pibrentasvir (G/P) has been studied in treatment-naïve (TN) patients with and without compensated cirrhosis for 8 and 12 weeks.

Aims: This analysis compared adherence over time for G/P, prescribed for 8 or 12 weeks.

Methods: Data were pooled from TN patients with

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P.024

CHARACTERISTICS OF PATIENTS WITH HEPATITIS C VIRUS INFECTION AND ANTI-VIRAL TREATMENT INITIATION IN TAIWAN ‒ THE MOSAIC STUDY Ming-Lung Yu1,2, Wei-Lun Tsai3, Chi-Jen Chu4, Jia-Horng Kao5,6 Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan1 School of Medicine and Hepatitis Research Center, College of Medicine, and Center for Cancer Research and Center for Liquid Biopsy, Kaohsiung Medical University, Kaohsiung, Taiwan2 Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan3 Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan4 Department of Internal Medicine and Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan5 Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan6

台灣Ｃ型肝炎患者特徵及使用抗病毒 治療 ─ MOSAIC 研究 余明隆1,2 蔡維倫3 朱啟仁4 高嘉宏5,6 高雄醫學大學附設中和紀念醫院肝膽胰內科1 高雄醫學大學醫學院癌症研究中心／液態生物檢 體研究中心／醫學系／肝炎研究中心2 高雄榮民總醫院內科部胃腸肝膽科3 臺北榮民總醫院內科部胃腸肝膽科4 國立台灣大學醫學院附設醫院內科部／肝炎研究 中心5 國立台灣大學醫學院臨床醫學研究所6 Background: Hepatitis C virus (HCV) infection is the leading cause of chronic liver diseases worldwide. Monitoring the epidemiology, diagnosis and treatment patterns is important for the management of patients with chronic HCV infection

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from both individual and public health perspective.

Aims: To describe epidemiology and treatment initiation patterns in patients seeking HCV care.

Methods: The MOSAIC study was an observational study conducted in 20 countries, including Taiwan.

Results: Of the 111 chronic HCV patients enrolled form Taiwan, 58 (52.3%) were treatment-naïve.

HCV genotype 1 was reported in 58 (52.3%) patients of whom the majority (n=47; 81.0%) were subtype 1b. Sixty-two (55.9%) patients had HCV RNA level >800,000 IU/mL. Liver cirrhosis was found in 35 (29.3%) patients and more prevalent in treatment-experienced patients (71.0%).

Interferon-based treatment was started within 12 weeks from study inclusion in 12 (10.8%) patients of whom 11 (91.7%) were treatmentnaïve. Anti-HCV treatment was not recommended by physician in 70 (71.4%) s and refused by 23 (23.5%) patients.

Conclusions: The MOSAIC study provides data on epidemiology of HCV infection and interferonbased treatment decision pattern in Taiwan.

Further studies are needed to observe the impact of interferon-free treatment on the treatment selection pattern.

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P.025

RELATIONSHIPS BETWEEN SERUM VITAMIN D STATUS AND CYTOKINE: RESULTS FROM INTERFERON-BASED THERAPY IN PATIENTS WITH CHRONIC HEPATITIS C INFECTION WITHOUT CIRRHOSIS Jung-Chun Lin1, Hsuan-Wei Chen1, Yi-Lin Chiu2, Tsai-Yuan Hsieh1, Peng-Jen Chen1, Tien-Yu Huang1, Hsuan-Hwai Lin1, Yu-Lueng Shih1 Division of Gastroenterology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan1 Department of Biochemistry, National Defense Medical Center, Taipei, Taiwan2

at end-of-treatment and decreased markedly at the 24-week follow-up period. In non-SVR group, this treatment-dependent change was lost. In gene expression analysis, vitamin D biosynthesis process was activated in subjects with SVR, but not in patients without SVR. Furthermore, vitamin D receptor (VDR) signaling in peripheral blood mononuclear cells (PBMCs) was triggered in marked responders, but not in poor responsders.

Conclusions: Taken together, these data suggest that interferon has regulatory influence on vitamin D status that can contribute to VDR signaling in PBMCs.

血清維生素 D 狀態與細胞激素之間的 關係：從干擾素治療非肝硬化之慢性 C 型肝炎病人結果的分析 林榮鈞1 陳宣位1 邱奕霖2 謝財源1 陳鵬仁1 黃天祐1 林煊淮1 施宇隆1 國防醫學院三軍總醫院內科部胃腸科1 國防醫學院生物化學科2 Background: Vitamin D contributes to bone health and extra-skeletal effects. The mechanisms underlying the vitamin D metabolism have not been extensively evaluated. The relationships between vitamin D and inflammatory cytokines are debated.

Aims: Our objective was to investigate whether supplemental interferon is associated with longitudinal change of vitamin D status in humans.

Methods: A total of 48 patients with 24 or 48 weeks of pegylated interferon-α plus ribavirin therapy were tested for serum 25-hydroxyvitamin D [25(OH)D] level before treatment, end of treatment, and 24 weeks after treatment. In addition, we analyzed publicly available RNA sequencing data from accession GSE42697 and GSE7123 in Gene Expression Omnibus.

Results: The overall sustained virologic response (SVR) rate was 62.5%. There was no statistically significant association between baseline 25(OH) D concentrations and liver fibrosis. In patients with SVR, serum 25(OH)D increased markedly

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P.026

SOFOSBUBIR/VELPATASVIR IS EFFEVTIVE AND TOLERABLE FOR TREATMENT OF HCV PATIENTS WITH CKD OR HEMODIALYSIS: A REAL WORLD OBSERVATORY STUDY Chi-Yi Chen, Chang-Chao Su, C hou-Chu Kuang, Li-Jen Chang, Po-Yueh Chen, Tsung-Jung Tsai Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chia-Yi Christian Hospital, Chiayi, Taiwan

宜譜莎（Epclusa）於 2020 年 1 月使 用在 C 肝合併腎功能不全或洗腎病人 的療效及安全性 陳啟益 蘇昶昭 周莒光 張力仁 陳柏岳 蔡崇榮 嘉義基督醫院胃腸肝膽科 Background: Hepatitis C virus (HCV) infection remains challenging health problem in the world. Sofosbuvir/velpatasvir (SFO/VEL) is a pangenotypic direct-acting antiviral agent for treatment of chronic hepatitis C virus (HCV) infection. Real-world data of SFO/VEL in HCV patients with CKD or hemodialysis are limited.

Aims: We investigated the effectiveness and safety profile of SFO/VEL in HCV patients with CKD or hemodialysis.

Methods: CHC patients with CKD or hemodialysis received SFO/VEL between Jan and Feb 2020 were consecutively enrolled. According the reimbursement of the Taiwan government, only one DAA regimen of SFO/VEL was available.

The primary endpoint was sustained virological response at week 12 off therapy (SVR12). The safety profiles were also assessed.

Results: There were total 14 CHC patients with history of CKD or hemodialysis. There were 5 male and 7 female. There were 8 CKD and 6 hemodialysis with median age 72 years. There were 7 genotype 1b and 7 genotype 2. The EOT success rate and SVR12 rate were 100%. EGFR of CKD was not significant change after SFO/VEL. There was no morbidity or mortality during and after SFO/VEL. Conclusions: Pangenotypic SFO/VEL regiment is highly effective and safe for chronic hepatitis C patients with CKD or hemodialysis.

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P.027

REAL-WORLD EFFECTIVENESS AND SAFETY OF SOFOSBUVIR/ VELPATASVIR FOR THE TREATMENT OF HCV PATIENTS WITH HEPATIC DECOMPENSATION Chi-Yi Chen, Po-Yueh Chen, Chou-Chu Kuang, Li-Jen Chang, Chang-Chao Su, Ming-Tse Hsu Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chia-Yi Christian Hospital, Chiayi, Taiwan

宜譜莎（Epclusa）治療 C 肝肝硬化 合併肝代償失調的療效及安全性 陳啟益 陳柏岳 周莒光 張力仁 蘇昶昭 許銘澤 嘉義基督醫院胃腸肝膽科 Background: Sofosbuvir/velpatasvir (SFO/VEL) is a pangenotypic direct-acting antiviral agent for the treatment of chronic hepatitis C virus (HCV) infection. Real-word data of SFO/VEL in HCV patients with hepatic decompensation are limited.

Aims: We investigaged the effectiveness and safety profiles of SFO /VEL in hepatic decompensation patients with chronic hepatitis C (CHC).

Methods: 22 CHC patients with hepatic decompensation who received 12 weeks of SFO/ VEL and Ribavirin between August 2019 and June 2020 were consecutively enrolled. There were 395 CHC patients received SFO/VEL DAA therapy.

The primary endpoint was sustained virological response at week 12 after therapy (SVR12).

The withdrawal rate and mortality rate were alos assessed.

Results: A total of 22 CHC patients with hepatic decompensation were enrolled. The median age was 71 years. A majority (19/22) of patients were infected with HCV genotype 2. The overall SVR rates of 395 CHC received SFO/VEL were 94%.

The SVR12 rate of hepatic decompensation were 17/22 (77%). The withdrawal rates were 6/22 (27%). During the 6 CHC patients withdraw from SFO/VEL, 5/6 (83%) were death and 1/6 (17%) achieved SVR12. There were one withdraw with SVR but died from heaptic failure. There was also one withdraw without SVR but survived. The mortality rate were 5/22 (22%). The per protocol

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SVR12 rates were 94% (16/17).

Conclusions: The pangenotypic SFO/VEL regimen is effective with per protocol SVR12 rate 94% in CHC patients with hepatic decompensation.

However, the mortality rates were as high as 22%.

P.028

HEPATITIS D VIRUS MIGHT FLARE AFTER DDA TREATMENT FOR HEPATITIS C VIRUS IN HEPATITIS B, C, D TRIPLE-INFECTED PATIENTS Cheng-Heng Lin, Hung-Da Tung, Pei-Lun Lee, Jyh-Jou Chen, Yu-Hsun Wu, Mai-Gio Pang Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chimei Medical Center, Liouying, Tainan, Taiwan

以 DAA 治療 B、C、D 型肝炎三重感 染病患之 C 型肝炎可能引起 D 型肝炎 發作 林政衡 董宏達 李佩倫 陳志州 吳昱勳 彭美杰 奇美醫學中心柳營院區胃腸肝膽科 Background: Hepatitis B could flare in patients with hepatitis B and C dual infection treated with DAAs. The risk of HDV flare in hepatitis B, C and D triple infection treated with DAAs has not been reported yet.

Aims: To evaluate the risk of HDV flare in hepatitis B, C, D triple-infected patients treated with DAA for HCV. Methods: Seven patients with hepatitis B, C, D triple-infection were enrolled in Taiwan Second Jail GI clinic from Jan. to Dec. 2019. HCV RNA was undetectable in one patient, hence 6 of them were treated with DAAs, including Sofosbuvir/Ledipasvir (Harvoni) 12w in 1, and Glycaprevir/Pibrentasvir (Maviret) 8w in 5. The biochemical, serological and virological responses were analyzed.

Results: All 7 patients with injection drug use (IDU) history and tattoo, among 6 patients treated with DAA, HCV genotype 1b, 3 and 6 were detected in 3, 1 and 2 patients respectively. All 6 patients achieved SVR12. Transaminase flare (ALT > 7x ULN) was observed in one patient with GT1b treated with Maviret. The HBsAg titer and HBV DNA were both in stationary condition, suggestive of HDV rather than HBV flare.

Conclusions: Currently there is no effective antiviral regiment for HDV. Although the HDV previously reported in Taiwan posed a minor role in cirrhosis/HCC, the possibility of HDV flare after DAA treatment for hepatitis B, C and D tripleinfection should be kept in mind.

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P.029

LONG-TERM BIOMARKER EVALUATION AND CLINICAL RELEVANCE OF OXIDATIVE STRESS IN CHRONIC HEPATITIS C PATIENTS RECEIVING DIRECT ACTING ANTIVIRALS I-Che Feng1, Pin-Nan Cheng2, Kung-Chia Young3, Hsing-Tao Kuo1, Ming-Jen Hsu1 Division of Gastroenterology & Hepatology, Department of Internal Medicine, Chi Mei Medical Center, Tainan, Taiwan1 Division of Gastroenterology & Hepatology, Department of Internal Medicine, National Cheng Kung University Hospital, Tainan, Taiwan2 The Institute of Basic Medical Sciences, National Cheng Kung University, Tainan, Taiwan3

慢性 C 型肝炎病患接受直接抗病毒藥 物治療對於氧化壓力之長期生物標記 評估與臨床相關性 馮意哲1 鄭斌男2 楊孔嘉3 郭行道1 許銘仁1 奇美醫學中心永康總院胃腸肝膽科1 國立成功大學醫學院附設醫院內科部胃腸肝膽科2 國立成功大學醫學院基礎醫學研究所3 Background: Chronic hepatitis C represents a burdensome healthcare threat worldwide, including Taiwan. Proved protective vaccines against hepatitis C virus (HCV) infection are not yet available, however, remarkable treatment advances with direct acting antivirals (DAA) nowadays opens a new era approaching more effective, better tolerated and safer therapeutics for chronic hepatitis C patients with nearly all HCV genotypes. Notably, chronic HCV infections may cause not merely liver disease but along with high risks of metabolic syndrome, type II diabetes and cardiovascular disease.

Aims: After complete eradication of HCV by 12 to 24 weeks of various DAA regimens for treatment of chronic hepatitis C patients, the longterm benefits on the development of metabolic and cardiovascular diseases are still worthy to evaluate.

Methods: This retrospective cohort study

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includes forty CHC patients with HCV genotype 1 and 2 infections who received HCV treatment between April 2015 and January 2018 and had a determination of SVR at 12 weeks posttreatment. The patients were classified into two groups according to genotype 1 and 2 equal number of patients in each group. The virological, biochemical, lipoprotein/apoliprotein, plasma or fractioned oxLDL, plasma 8-oxo-dG and plasma IMA (Ischemia-modified albumin) analysis were investigated at times of baseline, follow up 12 weeks and follow up one year in each group.

Since cellular oxidative stress might contribute to a wide spread involvement of pathogenesis, including cardiovascular, metabolic and hepatic diseases. We aim to assess the biological redox status in chronic hepatitis C patients receiving DAA treatment by using a panel of oxidative stress markers.

Results: We further pioneered the investigation on the DAA-induced lipids/lipoproteins dynamics in each lipoprotein particle. The results suggested that the transport of TG and Chol from hepatocytes to blood might be improved as evident by an increase of plasma total Chol, HDL-Chol, TG and Chol loading capacities in per VLDL particle but a reduction TG-to-Chol ratio in LDL in chronic hepatitis C patients with SVR. Although the therapeutic HCV elimination in SVR might induce reversal of disease with reduction of all-cause mortality, our study further revealed a predisposition to CVD by measuring aortic stiffness.

Conclusions: HCV negatively modulating lipoprotein synthesis and secretion that resolves with viral clearance. The DAA treatment change the level of stable ROS (reactive oxygen stress)modified components of DNA, lipids and proteins in genotype 1 patients. The long-term changes of lipid profiles following SVR are now on the way for further investigations.

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P.030

A COMPREHENSIVE AND EFFICIENT MODEL FOR SCREENING HEPATITIS C VIRUS ‒ EXPERIENCE FROM A SOUTHERN LOCAL HOSPITAL CHI MEI MEDICAL CENTER-LIOUYING CAMPUS Pei-Lun Lee1, Jyh-Jou Chen1, Hung-Da Tung1, Chia-Yi Hou2, Chun-Ta Cheng1, Tang-Wei Chuang1, Hsu-Ju Kao1, Yu-Hsun Wu1, Mai-Gio Pang1, Cheng-Heng Lin1 Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chimei Medical Center, Liouying, Tainan, Taiwan1 Department of Clinical Pathology, Chimei Medical Center, Liouying, Tainan, Taiwan2

全面且高效的 C 性肝炎篩檢模式 ─ 台 南市柳營奇美醫院肝膽胃腸科的經驗 分享 李佩倫1 陳志州1 董宏達1 侯佳儀2 鄭俊達1 莊棠惟1 高旭儒1 吳昱勳1 彭美杰1 林政衡1 奇美醫療財團法人柳營奇美醫院肝膽胃腸科1 奇美醫療財團法人柳營奇美醫院臨床病理科2 Background: Direct acting antiviral (DAA) regimens have led the treatment of chronic hepatitis C virus (HCV)-infected patients into a new era. However, the current challenge of HCV elimination remains on how to effectively identify those untreated patients and link them to care.

Aims: The current study demonstrates a comprehensive in-hospital HCV screening model, which includes an interruption-free algorithm to identify untreated patients and effectively link them to treatment.

Methods: Adult patients aged 40 y/o or above who have been instructed to take a blood test at the Out-Patient Departments (OPD) of the Chi Mei Medical Center-Liouying (CM-LY) campus during Dec. 15th, 2019 to Jun. 15th, 2020 were enrolled. Patients that have not been tested for anti-HCV within 5 years at CM-LY were informed by nurses at OPD and encouraged to include additional anti-HCV (Abbott Architect® anti-HCV, a chemiluminsent microparticle immunoassay, CMIA) into their blood tests. Anti-HCV positive

patients were further contacted by department of Gastroenterology (GI) case managers for followup and link them to GI doctors for HCV treatment.

Patients who have already been diagnosed with chronic hepatitis C (ICD-10 code B182) were excluded from this study. Informed consents were collected from all enrolled patients.

Results: A total of 11,564 patients were enrolled during the time period and screened for HCV antibody. Among them, 734 patients were anti-HCV positive. We further categorized these patients based on the titer of their HCV antibody into Titer > 10 S/CO (n = 438, 59.67%), Titer 4 – 10 S/CO (n = 111, 15.12%), and Titer < 4 S/CO (gray zone; n = 185, 25.20%). A total of 330 (60.11%) patients that showed positive anti-HCV antibody returned to the OPD and received HCV RNA testing (Abbott RealTime HCV). According to their HCV antibody titer, the HCV RNA positivity rate were 64.11%, 18.18%, and 0% for Titer > 10 S/CO, Titer 4 – 10 S/CO, and gray zone patients, respectively. 114 (83.09%) patients of those viremic patients were successfully linked to DAA treatment.

Conclusions: The current study identified 330 positive anti-HCV antibody patients from OPD patients that routinely returning to our hospital.

However, none of them have been diagnosed for chronic hepatitis C nor received HCV treatment previously. We have demonstrated that these patients can be successfully linked to treatment and similar results can be achieved in other hospitals using this setting. To the best of our knowledge, this approach is easy to implement and can efficiently identify those potential HCVinfected cases in a way that would not interrupt the daily practice of OPD staffs.

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P.031

REAL WORLD EFFECTIVENESS AND SAFETY OF GLECAPREVIR/ PIBRENTASIVIR IN 537 PATIENTS WITH CHRONIC HEPATITIS C Chi-Yi Chen, Chou- Chu Kuang, Po-Yueh Chen, Chang-Chao Su, Li-Jen Chang, Yu-Min Feng Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chia-Yi Christian Hospital, Chiayi, Taiwan

P.032

WHAT IS YOUR CHOICES BETWEEN 8 WEEKS OF GLECAPREVIR/PIBRENTASVIR AND 12 WEEKS OF SOFOSBUVIR/ VELPATASVIR ACCORDING TO PATIENTS WITH CHRONIC HEPATITIS C? Chi-Yi Chen, Chang-Chao Su, Chou- Chu Kuang, Li-Jen Chang, Po-Yueh Chen, Yu-Ling Lin

艾百樂（GP）治療 537 位慢性 C 肝病 人的成效及安全性

Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chia-Yi Christian Hospital, Chiayi, Taiwan

陳啟益 周莒光 陳柏岳 蘇昶昭 張力仁 酆裕民

全基因型 8 週艾百樂（GP）及 12 週 宜譜莎（EPCLUSA），治療 C 肝病人 會想選擇哪一樣？

嘉義基督醫院胃腸肝膽科 Background: Glecaprevir/pibrentasvir (GLE/PIB) is a pangenotypic direct-acting antiviral agent for the treatment of chronic hepatitis C virus (HCV) infection. Real-world data of GLE/PIB in Taiwan are limited. We thus investigated the effectivenss and safety of GLE/PIB in Chi-Yi patients with chronic hepatitis C (CHC).

Aims: We investigated the effectivenss and safety of GLE/PIB in Chi-Yi patients with chronic hepatitis C (CHC).

Methods: CHC patients who received 8, 12, 16 weekds of GLE/PIB between August 2018 and June 2020 were consecutively enrolled. The treatment duration was determinted according to the reimbursement of the Taiwan government.

The primary endpoint was sustained virological response at week 12 after therapy (SVR12). The safety profiles were also investigated.

Results: A total 537 CHC patients with 57% male were enrolled. The median age was 67 years. A majority (80%) of patients were infected with HCV genotype 2. The overall SVR12 rate were 98.2%.

The common adverse effects (AE) were pruritius (15%) anorexia (8%) and fatigue (6%). Only two serious AEs unrelated to GLE/PIB occurred. Seven patients had Grade 3 elevation of total bilirubin level. None had premature treatment termination, hepatic decompensation or death.

Conclusions: Interferron-free GLE/PIB regimen is highly effective and safe for chronic hepatitis C patients in Chia-Yi.

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陳啟益 蘇昶昭 周莒光 張力仁 陳柏岳 林玉玲 嘉義基督醫院胃腸肝膽科 Background: Glecaprevir/pibrentasvir (GLE/PIB) and sofosbuvir/velpatasvir were pangenotypic direct-acting antiviral agent for the treatment of chronic hepatitis C virus (HCV) infection. What is your choices between 8 weeks of glecaprevir/ pibrentasvir and 12 weeks of sofosbuvir/ velpatasvir was important question from patient’s consideration.

Aims: We investigated the clinical choices between 8 weeks of glecaprevir/pibrentasvir and 12 weeks of sofosbuvir/velpatasvir according to patient’s will.

Methods: CHC patients indicated for DAA therapy were collected between March and June2020.

CKD for GLE/PIB and hepatic decompensation for SFO/VEL were excluded. Drug interaction were also excluded. We collected the choices and made analysis.

Results: A total 86 CHC patients were collected.

The answer were 28 choices for GLE/PIB and 58 choices for SFO/VEL. Young age favored GLE/PIB and old age favored SFO/VEL. IN GLE/PIB group, there were 15/male and 13/female. However, in SFO/VEL group, there were 26 male/32 female.

In HIV patients, there were 4 GLE/PIB and 2 SFO/VEL. Distance from hospital and traffic consideration also favor GLE/PIB. Conclusions: The answer of clinical choices between 8 weeks of glecaprevir/pibrentasvir and 12 weeks of sofosbuvir/velpatasvir according to patient’s will perfered SFO/VEL.

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P.033

FIBROSIS-4 INDEX PREDICTS THE RISK OF HEPATOCELLULAR CARCINOMA IN PATIENTS WITH UNTREATED CHRONIC HEPATITIS C Chang Shan-Han1, Su Tung-Hung1,2, Lee Mei-Hsuan3, Liu Chun-Jen1,2, Chen Pei-Jer1,2,4,5, Yang Hung-Chih1,2, Liu Chen-Hua1,2, Chen Chi-Ling4, Tseng Tai-Chung1,2, Chen Chien-Hung6, Lee Hsuan-Shu1, Chen Ding-Shinn1,2,7, Chen Chien-Jen7, Kao Jia-Horng1,2,4,5 Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan1 Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan2 Institute of Clinical Medicine, National YangMing University, Taipei, Taiwan3 Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan4 Department of Medical Research, National Taiwan University Hospital, Taipei, Taiwan5 Department of Internal Medicine, National Taiwan University Hospital Yunlin Branch, Yunlin, Taiwan6 Genomics Research Center, Academia Sinica, Taipei, Taiwan7

FIB-4 數值在為治療之慢性 C 型肝炎病 患族群能預測肝癌之風險 張善涵1 蘇東弘1,2 李美璇3 劉俊人1,2 陳培哲1,2,4,5 楊宏志1,2 劉振驊1,2 陳祈玲4 曾岱宗1,2 陳健弘6 李宣書1 陳定信1,2,7 陳建仁7 高嘉宏1,2,4,5

carcinoma (HCC) among untreated chronic hepatitis C patients.

Methods: We conducted a retrospective study to include untreated chronic hepatitis C patients who received longitudinal follow-up at the liver clinic of National Taiwan University Hospital during 19862014. Patients were screened if they had positive anti-HCV, HCV RNA or had a diagnosis of chronic hepatitis C. We excluded patients with incomplete medical records, coinfection of HBV or HIV, HCC development in the first year of follow-up, or a follow-up duration less than 3 years.

Results: A total of 1155 patients were included in the ERADICATE-C cohort. After excluding patients without complete data for Fib-4 index calculation, 772 patients were enrolled. The mean age was 55 years, 63% were females and 74 patients had baseline clinical cirrhosis. After 12 years of followup, 163 patients developed HCC. The median baseline Fib-4 level was 2.1. The Fib-4 index < 1.45 (n = 225), 1.45-3.25 (n = 289) and > 3.25 (n = 258) stratified the risk of HCC (log rank P < 0.0001) over time. Multivariable cox regression analysis showed that male (hazard ratio [HR]: 1.943, 95% confidence interval [CI]: 1.378-2.740), AFP ≥ 20 ng/mL vs. < 20 ng/mL (HR: 3.396, 95% CI: 2.2875.045) and higher Fib-4 index had a greater risk of HCC. Compared with patients with Fib-4 < 1.45, patients with Fib-4 between 1.45 and 3.25 had HR: 6.860, 95% CI: 3.032-15.522), and those with Fib-4 > 3.25 had the highest risk (HR: 8.627, 95% CI: 3.530-21.083).

Conclusions: Baseline Fib-4 index can stratify the risk of HCC in patients of chronic hepatitis C without antiviral therapy and thus prioritize the usage of anti-viral therapy in resource-constrained countries.

國立台灣大學醫學院附設醫院胃腸肝膽科1 國立台灣大學醫學院附設醫院肝炎研究中心2 國立陽明大學臨床醫學研究所3 國立台灣大學臨床醫學研究所4 國立台灣大學醫學院附設醫院醫學研究部5 國立台灣大學醫學院附設醫院雲林分院6 國立中央研究院7 Background: The fibrosis-4 index (Fib-4) is a useful noninvasive marker for severity of liver fibrosis in patients with chronic hepatitis C. Aims: To investigate the predictive role of baseline Fib-4 index in the development of hepatocellular

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P.034

THE PREVALENCE AND TREATMENT STATUS OF HCV INFECTION IN INJECTING DRUG USERS IN A MUNICIPAL HOSPITAL IN SOUTHERN TAIWAN Sheng-Yeh Tang, Wen-Wei Huang, Chang-Bih Shie, I-Ting Wu, Li-Fu Kuo, Kun-Feng Tsai, Ping-I Hsu Department of Division of Gastroenterology, Department of Medicine, An Nan Hospital, China Medical University, Tainan, Taiwan

於南臺灣一所市立醫院中注射毒品者 C 型肝炎病毒感染情形及接受抗病毒 藥物治療狀況 湯昇曄 黃文威 施長碧 吳奕霆 郭立夫 蔡坤峰 許秉毅 台南市立安南醫院消化內科 Background: The prevalence of HCV infection in injecting drug users is higher than that in general population.

Aims: (1) to assess the prevalence of HCV infection in injecting drug users in a municipal hospital in southern Taiwan, and (2) to investigate whether HCV-infected injecting drug users receive adequate anti-HCV treatment.

Methods: In this retrospective study, we reviewed the medical records of the patients receiving methadone therapy in a municipal hospital from October 2014 to December 2019, and checked the data of anti-HCV antibody and HCV viral loads of these patients. Additionally, the percentage of the HCV-infected subjects receiving anti-HCV therapy was assessed.

Results: Among the 262 patients undergoing methadone therapy in this study period, 118 (45.4%) receiving anti-HCV testing. One hundred and fourteen (96.6%) out of 118 patients were antiHCV (+). In the 114 anti-HCV (+) patients, only 25 (21.9%) received anti-HCV treatment by direct acting agent therapies.

Conclusions: A very high percentage of the subjects receiving methadone therapy in the municipal hospital in southern Taiwan have HCV infection. Less than half of the subjects with methadone are tested HCV infection, and only a small percentage of the HCV-infected methadone users in this hospital receive adequate anti-HCV therapy.

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P.035

TREATMENT EFFICACY AND SAFETY OF SOFOSBUVIR/ VELPATASVIR FOR CHRONIC HEPATITIS C AMONG UREMIC PATIENTS UNDER MAINTENANCE HEMODIALYSIS-ERASE-C FINAL REPORT Chung-Feng Huang, Yu-Ju Wei, Ming-Lun Yeh, Ching-I Huang, Wen-Yi Lin, Yi-Hung Lin, Po-Cheng Liang, Ta-Wei Liu, Chia-Yen Dai, Jee-Fu Huang, Wan-Long Chuang, Ming-Lung Yu Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan

Sofosbuvir/Velpatasvir 於洗腎慢性Ｃ 型肝炎患者治療療效及安全性研究 黃釧峰 魏鈺儒 葉明倫 黃駿逸 林文一 林宜竑 梁博程 劉大維 戴嘉言 黃志富 莊萬龍 余明隆 高雄醫學大學附設中和紀念醫院肝膽胰內科 Background: Hepatitis C virus (HCV) prevails in uremic patients in Taiwan. However, treatment uptake is underappreciated in the special population.

Aims: The current study aimed to address the efficacy and safety of sofosbuvir/velpatasvir in treating chronic hepatitis C (CHC) patients underwent hemodialysis Methods: An outreach, group treatment strategy using 12-week SOF/VEL was adopted in 18 hemodialysis units. The primary objectives were sustained virological response (SVR12, defined as undetectable HCV RNA throughout 12 weeks of the post-treatment follow-up period) and safety.

Results: A total of 105 uremic patients with CHC were included (mean age 66.2 years, female 48.6%, hepatitis B virus dual infection 7.6%, preexisting hepatocellular carcinoma 6.7%, liver cirrhosis 35.2%, HCV GT-1 43.8%, GT2 50.5%, GT6 4.8%). By full-analysis-set (FAS) population, the rate of undetectable HCV RNA at treatment week 1, week 2, week 4, end-of-treatment (EOT), post-treatment week 4 (SVR4) and post-treatment week 12 (SVR12) was 46.7% (49/105), 72.4 % (76/105), 90.5 % (95/105), 93.3 % (98/105), 91.4 % (96/105) and 89.5 % (94/105), respectively. Ten patients discontinued treatment early, 5 due to

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treatment-related adverse events (AE: dizziness [n=1], nausea/vomiting [n=2], epigastric pain [n=2]) and 5 due to treatment-unrelated serious adverse events (SAEs: sepsis [n=3], acute myocardial infarction [n=1] and pneumonia [n=1]). Seven patients experienced mortality: 2 during treatment, 5 after EOT; none were treatment-related. Of the 10 patients who discontinued treatment early, 8 had available HCV RNA 12 weeks after treatment discontinuation, and four achieved SVR12.

Therefore, the SVR12 rate was 95.9% (94/98) and 100% (86/86) in modified FAS and per-protocol analysis, respectively. The most common adverse event was fatigue (9.5%), followed by pruritus (8.6%). A total of 45 SAE events were noted: 23 during treatment, 22 after treatment; none were treatment-related.

Conclusions: Twelve weeks of SOF/VEL was highly effective and safe in Asian uremic CHC patients, which meticulously validated the earlier phase-2 study in the West.

P.036

GENOTYPE DISTRIBUTION, CLINICAL CHARACTERISTICS, AND RACIAL DIFFERENCES OBSERVED IN CHRONIC HEPATITIS C PATIENTS IN PINGTUNG, TAIWAN Tyng-Yuan Jang, Chia-Yen Dai Division of Hepatobiliary, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan

屏東 C 肝臨床表徵及基因型表現 張庭遠 戴嘉言 高雄醫學大學附設中和紀念醫院肝膽胰內科 Background: The World Health Organization (WHO) set out to eliminate hepatitis C virus (HCV) infection by 2030, a goal Taiwan might achieve before 2025. Using effective direct antiviral agents (DAAs) against chronic hepatitis C (CHC) in Taiwan, the treatment of CHC has been initiated in rural areas.

Aims: We aimed to elucidate the clinical and virological characteristics of HCV infection, and the treatment efficacy of DAAs in patients from Pingtung county in southern Taiwan.

Methods: A total of 152 chronic hepatitis patients treated with DAAs were consecutively enrolled.

Baseline characteristics and therapeutic efficacy were evaluated.

Results: HCV genotype 2 was the most common viral genotype (39.5 %), followed by 1b (36.8%), 6 (10.5%), and 1a (9.2%). The sustained virological response (SVR) rate was 99.2%. Hakka patients accounted for 22.4 % of the study cohort, of which 14.7% had HCV genotype 6. There were no differences in clinical characteristics between Hakka and non-Hakka patients. Patients with HCV genotype 6 were younger in age (OR/CI: 0.95/0.91-1.00, P = 0.04) and comprised of more people who inject drugs (PWID) (OR/CI: 17.6/3.685.5, P < 0.001), when compared to other patients.

Conclusions: We demonstrated that DAA therapy can achieve a 99.2% SVR rate among CHC patients in Pingtung county of southern Taiwan, with a relative higher prevalence of genotype 6.

The most important factor attributed to genotype 6 infection was PWID.

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P.037

MASS SCREENING AND OUTREACH TREATER TEAM WITH A PANGENOTYPIC DIRECT-ACTING ANTIVIRAL REGIMEN FOR MICROELIMINATION OF HEPATITIS C VIRUS INFECTION IN PRISONERS Chun-Ting Chen1,2, Ming-Ying Lu3,4, Pei-Chien Tsai4, Yu-Lueng Shih2, Tsai-Yuan Hsieh2, Chung-Feng Huang4,5, Jee-Fu Huang4,5, Chia-Yen Dai4,5, Wan-Long Chuang4,5, Fung-Wei Chang6,7, Ming-Lung Yu4,5 Division of Gastroenterology and Hepatology, Department of Internal Medicine, Tri-Service General Hospital Penghu Branch, National Defense Medical Center, Penghu, Taiwan1 Division of Gastroenterology and Hepatology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan2 Xi-Yu Township Public Health Center, Penghu, Taiwan3 Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan4 Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan5 Department of Obstetrics and Gynecology, TriService General Hospital, National Defense Medical Center, Taipei, Taiwan6 Office of Superintendent, Tri-Service General Hospital Penghu Branch, National Defence Medical Center, Penghu, Taiwan7 Department of Health Promotion and Health Education, National Taiwan Normal University, Taipei, Taiwan8

大規模篩檢及使用全基因型直接抗病 毒藥物治療監獄中的 C 型肝炎病人 陳軍廷1,2 呂明穎3,4 蔡佩倩4 施宇隆2 謝財源2 黃釧峰4,5 黃志富4,5 戴嘉言4,5 莊萬龍4,5 張芳維6,7 余明隆4,5 三軍總醫院澎湖分院胃腸肝膽內科1 三軍總醫院胃腸肝膽內科2

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澎湖縣西嶼鄉衛生所3 高雄醫學大學附設中和紀念醫院肝膽胰內科4 高雄醫學大學醫學院醫學系5 三軍總醫院婦產科6 三軍總醫院澎湖分院院本部7 臺灣師範大學健康促進與衛生教育學系8 Background: People who inject drugs (PWID) has became the major route of HCV transmission.

PWID is the most important risk factor of HCV infection in prisoners. Prisoners are the key population of HCV infection. HCV treatment is not frequently administered to prisoners due to multiple factors, including unawareness of HCV infection, difficultly management, easily loss of follow-up, and lack of hepatologist in prison. Physicians should collaborate with prison authorities to carry out strategies to diagnose and treat HCV infection in prisoners.

Aims: Our study aimed to mass screen and treat HCV infected prisoners with pangenotypic directacting antiviral regimen.

Methods: From September 2019 to August 2020, we prospectively recruited prisoners from single jail in Taiwan. All participants filled out the questionnaire. They received laboratory investigations, including anti-hepatitis C antigen antibodies (anti-HCV), hepatitis B surface antigen (HBsAg). HCV ribonucleic acid (HCV RNA) and HCV genotyping were checked if anti-HCV showed positive. At 4 and 12 week of treatment, and 12 week of post-treatment, patients underwent regular laboratory investigations, including HCV RNA viral loads and liver enzymes.

Results: A total of 1138 prisoners were enrolled.

397 (34.9 %) of 1138 participated prisoners were anti-HCV positive. Of those with anti-HCV positive, 209 (52.6 %) were detectable HCV RNA viral loads. Of those with detectable HCV RNA viral loads, 187 prisoners received pangenotypic directacting antiviral (DAA) therapy with sofosbuvir/ velpatasvir. Out of 1138 participated prisoners, 25 prisoners with known detectable HCV RNA viral loads also underwent sofosbuvir/velpatasvir treatment. A total of 212 prisoners received DAA treatment. 3 prisoners did not complete therapeutic regimen due to being released from jail and unpredictable transferring to other jails.

209 prisoners with detectable HCV RNA viral loads completed pangenotypic DAA therapy with sofosbuvir/velpatasvir. The viral response of end of treatment are 100% (209/209). The sustained viral

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response at 12 week of post-treatment (SVR12) will be completed by August 2020.

Conclusions: The prevalence of HCV infection in prisoners is high. Treatment HCV infection in prisoners can be at the start of elimination for HCV infection in countries. Well-designed strategies for mass screening and treatment in prisoners with HCV infection can be implemented successfully by the collaboration between physicians and prison authorities. In our study, pangenotypic DAA regimen with sofosbuvir/velpatasvir can achieve high SVR rate in prisoners with HCV infection.

P.038

HEALTH-RELATED QUALITY OF LIFE IN HEPATITIS B, HEPATITIS C AND NON-ALCOHOLIC FATTY LIVER DISEASE Ming-Chieh Lin1, Chung-Feng Huang1,2, Ming-Lun Yeh1,2, Ching-I Huang1,2, Po-Cheng Liang1, Yi-Hung Lin1, Ming-Yen Hsieh1,3, Meng-Hsuan Hsieh1,2, Chia-Yen Dai1,2, Zu-Yau Lin1,2, Shinn-Cherng Chen1,2, Jee-Fu Huang1,2,3, Ming-Lung Yu1,2, Wan-Long Chuang1,2 Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan1 Hepatitis Research Center, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan2 Department of Internal Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan3

B 型肝炎、C 型肝炎及非酒精性脂肪肝 炎之健康相關生活品質 林明頡1 黃釧峰1,2 葉明倫1,2 黃駿逸1,2 梁博程1 林宜竑1 謝明彥1,3 謝孟軒1,2 戴嘉言1,2 林子堯1,2 陳信成1,2 黃志富1,2,3 余明隆1,2 莊萬龍1,2 高雄醫學大學附設醫院肝膽胰內科1 高雄醫學大學肝炎中心2 高雄市立大同醫院內科部3 Background: The difference of patient-reported health-related quality of life (HRQoL) in hepatitis patients with different etiologies have rarely been investigated in Taiwan due to the conservative culture.

Aims: The study aimed to assess the characteristics and the difference of HRQoL in chronic hepatitis B (CHB), chronic hepatitis C (CHC), and nonalcoholic fatty liver disease (NAFLD) patients.

Methods: A prospective cohort research was conducted among the outpatient clinic in a tertiary referral centre in Southern Taiwan. The 36-Item Short Form Health Survey (SF-36) was completed by the patients upon the initial diagnosis and recruitment for a long-term follow-up purpose.

Results: There were 244 patients (198 males, age = 44.2 ± 11.2 years) of CHB, 54 patients (29 males, age = 55.2 ± 12.7 years) of CHC, and 129

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patients (85 males, age = 50.9 ± 14.8 years) of NAFLD, respectively. CHC patient had the mean score of 67.1 ± 23.3 in physical components of the SF-36 health survey, which was significantly lower than CHB patients (76.4 ± 19.5), and NAFLD patient (77.5 ± 13.7), respectively (p = 0.001).

CHC group had significantly lower performance in physical functioning and bodily pain components of physical component summary than CHB and NAFLD groups. Despite there was no significant difference of mental component summary between groups, NAFLD patients had significantly lower mean mental health scores (63.2 ± 13.8) than CHB (65.1 ± 17.0) patients, and CHC (70.3 ± 21.4) patients, respectively (p = 0.02).

Conclusions: The study demonstrated that there was significant difference of patient-reported HRQoL in hepatitis patients with different etiologies.

P.039

COMEDICATIONS AND POTENTIAL DRUG-DRUG INTERACTIONS WITH DIRECT-ACTING ANTIVIRALS IN HEPATITIS C PATIENTS ON HEMODIALYSIS Po-Yao Hsu1, Po-Cheng Liang1, Chung-Feng Huang1,2, Ming-Lun Yeh1,2, Ching-I Huang1,2, Zu-Yau Lin1, Shinn-Cherng Chen1,2, Jee-Fu Huang1,2, Wan-Long Chuang1,2, Chia-Yen Dai1,2, Ming-Lung Yu1,2 Division of Hepatobiliary, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan1 Faculty of Internal Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan2

洗腎之 C 型肝炎患者之服用藥物與口 服抗病毒藥物可能之藥物交互作用 許博堯1 梁博程1 黃釧峰1,2 葉明倫1,2 黃駿逸1,2 林子堯1 陳信成1,2 黃志富1,2 莊萬龍1,2 戴嘉言1,2 余明隆1,2 高雄醫學大學附設中和紀念醫院肝膽胰內科1 高雄醫學大學醫學院內科學系2 Background: Direct-acting antivirals (DAAs) have been approved for hepatitis C virus (HCV) treatment in patients on hemodialysis.

Nevertheless, the complicated comedications and their potential drug-drug interactions (DDIs) with DAAs might limit the clinical practice.

Aims: This study aimed to investigate the comedications and potential DDIs with DAAs in this special population.

Methods: Number, class, and characteristics of comedications and their potential DDIs with five DAA regimens were analyzed among HCV-viremic patients from 23 hemodialysis centers in Taiwan.

Results: Of 2,015 hemodialysis patients screened in 2019, 169 HCV-viremic patients were enrolled (mean age, 65.6 years; median duration of hemodialysis, 5.8 years). All patients received at least one comedication (median number, 6; mean class number, 3.4). The most common comedication classes were hemodialysisassociated medications (94.1%), cardiovascular drugs (69.8%) and antidiabetic drugs (43.2%).

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Hemodialysis-associated medications were excluded from DDI analysis. Sofosbuvir/ velpatasvir/voxilaprevir had the highest frequency of contraindicated DDIs (red, 5.6%), followed by glecaprevir/pibrentasvir (4.0%), sofosbuvir/ ledipasvir (1.3%), sofosbuvir/velpatasvir (1.3%), and elbasvir/grazoprevir (0.3%). For potential DDIs (orange, requiring close monitoring or dose adjustments), Sofosbuvir/velpatasvir/voxilaprevir had the highest frequency (19.9%), followed by sofosbuvir/ledipasvir (18.2%), glecaprevir/ pibrentasvir (12.6%), sofosbuvir/velpatasvir (12.6%), and elbasvir/grazoprevir (7.3%). Overall, lipid-lowering agents were the most common comedication class with red DDIs to all DAA regimens, followed by cardiovascular agents, and central nervous system agents.

Conclusions: HCV-viremic patients on hemodialysis had a very high prevalence of comedications with a broad spectrum, which had varied DDIs with currently available DAA regimens. Elbasvir/grazoprevir had the fewest and sofosbuvir/velpatasvir/voxilaprevir had the most potential DDIs.

P.040

SAFETY OF SOFOSBUVIR-BASED REGIMENS FOR THE TREATMENT OF CHRONIC HCV INFECTION IN PATIENTS WITH MILD OR MODERATE RENAL IMPAIRMENT Mark Sulkowski1, Francois Durand2, K Rajender Reddy3, Eric Lawitz4, Marc Bourlière5, Nelson Cheinquer6, S tacey Scherbakovsky6, Anand Chokkalingam6, Liyun Ni6, Anuj Gaggar6, Wan-Yi Lu6, Massimo Colombo7 Johns Hopkins University School of Medicine, Baltimore, Maryland, USA1 Hôpital Beaujon, University Paris Diderot, Clichy, France2 Department of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA3 Texas Liver Institute, University of Texas Health Science Center, San Antonio, Texas, USA4 Hépato-Gastro-Entérologie, Hôpital Saint Joseph, Marseille, France5 Gilead Sciences, Inc.6 Fondazione IRCCS Ca’ Granda Osepdale Maggiore Policlinico, Milan, Italy7 Background: The major metabolite of sofosbuvir (SOF), GS-331007, is cleared renally and tends to accumulate in patients with chronic kidney disease (CKD). However, there are a substantial amount of data showing that this accumulation is not clinically significant, even in patients with end stage renal disease. This retrospective analysis of 37 Phase 2 and 38 Phase 3 studies presents the safety profile of SOF-based therapies (LDV/SOF, SOF/VEL and SOF/VEL/VOX) in patients with mild to moderate CKD as well as in patients with normal renal function.

Results: 8,181 patients were included in this analysis. Mean baseline eGFR was 118.2, 69.3, and 43.6 mL/min/1.73 m2 for patients with normal renal function (n = 6,575), mild (n = 1,499), or moderate (n =107) renal impairment, respectively.

The mean eGFR at post-treatment follow-up week 4 was 114.4, 69.9, and 46.3 mL/min/1.73 m2 for patients with normal renal function (n = 5,519), mild (n = 1,285), or moderate (n = 90) renal impairment, respectively. When comparing baseline levels with

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those of post-treatment follow-up week 4, there was no clinical difference observed. Baseline characteristics were generally similar across groups, except patients with impaired renal function were older. Table 1 provides a summary of adverse events (AEs). Rates of Grade 3–4 AEs and discontinuations due to AEs were similar across groups. Patients with moderate renal impairment had higher rates of SAEs but most were not treatment-related.

Conclusions: Sofosbuvir-based regimens were safe and well-tolerated in patients with mild or moderate renal impairment. Renal function remained stable throughout treatment, and similar rates of AEs were observed across all treatment groups.

P.041

LONG-TERM COURSE OF CIRRHOSIS REGRESSION: LESSONS FROM PATIENTS WITH HCV CIRRHOSIS FOLLOWING SUCCESSFUL SOFOSBUVIRBASED TREATMENT Ira Jacobson1, Andrew J. Muir2, Eric Lawitz3, Edward Gane4, Brian Conway5, Peter J. Ruane6, Ziad Younes7, Frances Chen8, Marianne Camargo8, Anand P. Chokkalingam8, Anuj Gaggar8, Robert P. Myers8, Wan-Yi Lu8, Barbara Leggett9, Jose Luis Calleja10, Kosh Agarwal11, K. Rajender Reddy12, Alessandra Mangia13 NYU Langone Health, New York, NY, USA1 Duke University, Durham, NC, USA2 Texas Liver Institute, University of Texas Health San Antonio, TX, USA3 New Zealand Liver Transplant Unit, Auckland City Hospital, Auckland, New Zealand4 Vancouver Infectious Diseases Centre, Vancouver, BC, Canada5 Ruane Medical & Liver Health Institute, Los Angeles, CA, USA6 GastroOne, Germantown, TN, USA7 Gilead Sciences, Inc., Foster City, CA, USA8 School of Medicine, University of Queensland, Brisbane, Australia9 Hospital Universitario Puerta de Hierro, Madrid, Spain10 Kings College Hospital NHS Trust Foundation, London, UK11 University of Pennsylvania, Philadelphia, PA, USA12 Casa Sollievo della Sofferenza Hospital, San Giovanni Rotondo, Italy13 Background: The aim of this study was to evaluate changes in noninvasive tests of fibrosis (NITs) to understand the natural history of cirrhosis regression following removal of the causative exposure.

Methods: In this ongoing, prospective cirrhosis registry study, 1,574 subjects with HCV cirrhosis who achieved SVR via sofosbuvir (SOF)-based regimens were enrolled. Routine assessments included semi-annual Child-Pugh-Turcotte (CPT) scoring and measurement of the Enhanced Liver

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Fibrosis (ELF) test, as well as annual liver stiffness measurement by transient elastography (LS by TE). Logistic regression was used to identify predictors of fibrosis improvement as defined by NITs. Results: As of May 2019, median duration of follow-up was 123 weeks (IQR 96, 168). At week 144, 49% of those with baseline CPT class B/C had improved CPT class, while 98% of those with baseline CPT class A remained in CPT class A. During follow-up, changes in ELF and LS by TE suggested fibrosis improvement in an increasing proportion of patients with both F3 and F4 fibrosis at enrollment (Figure). ELF score improved by ≥ 0.5 units at week 144 in 27% and 47% of patients with baseline F3 (ELF 9.8–11.3) and F4 (ELF > 11.3) fibrosis, respectively. Predictors of ELF improvement included higher ELF (p < 0.001) and AST (p = 0.049), and lower platelets (p = 0.02) and BMI (p = 0.10) at registry baseline. In patients with cirrhosis in whom HCV has been eradicated

by SOF-based therapy, NITs suggest significant fibrosis improvement in 25–50% of patients within 3 years. Associations between reductions in these NITs and improvements in clinical outcomes require evaluation during longer-term follow-up.

P.042

THE SAFETY AND EFFICACY OF SOFOSBUVIR/VELPATASVIR IN PEDIATRIC PATIENTS 6 TO < 18 YEARS OLD WITH CHRONIC HEPATITIS C INFECTION Maureen M. Jonas1, Rene Romero2, Etienne M. Sokal3, Philip Rosenthal4, Gabriella Verucchi5, Chuan-Hao Lin6, Jessica Wen7, Michael R Narkewicz8, Sanjay Bansal9, Jiang Shao10, Sean Hsueh10, Anuj Gaggar10, Kathryn Kersey10, Wan-Yi Lu10, Regino P. Gonzalez-Peralta11, Daniel H. Leung12, William F. Balistreri13, Karen F. Murray14, Kathleen B. Schwarz15 Boston Children’s Hospital, Boston, MA, USA1 Emory University School of Medicine and Children’s Healthcare of Atlanta, Atlanta, GA, USA2 Cliniques Universitaires Saint-Luc, UC Louvain, Brussels, Belgium3 University of California San Francisco, San Francisco, CA, USA4 University of Bologna, Bologna, Italy5 Children’s Hospital Los Angeles, Los Angeles, CA, USA6 University of Pennsylvania and The Children’s Hospital of Philadelphia, Pennsylvania, USA7 University of Colorado School of Medicine and Children’s Hospital of Colorado, Aurora, USA8 Kings College Hospital, London, United Kingdom9 Gilead Sciences, Inc, Foster City, CA, USA10 Pediatric Gastroenterology, Hepatology and Liver Transplant, AdventHealth for Children, Orlando, FL, USA11 Baylor College of Medicine and Texas Children’s Hospital, Houston, TX, USA12 Cincinnati Children’s Hospital Medical Center, Cincinnati, OH, USA13 University of Washington School of Medicine and Seattle Children’s Hospital, Seattle, WA, USA14 Johns Hopkins University School of Medicine, Baltimore, United States, Boston, MA, USA15 Background: Direct-acting antiviral regimens have been approved for the treatment of HCV in adolescents aged 12 to < 18 years, but for younger

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children, the standard of care is still interferonbased therapy. The current study evaluated the safety and efficacy of sofosbuvir (SOF)/velpatasvir (VEL) in children 6 to < 18 years old.

Methods: In this open-label study, patients 6 to < 12 years old received SOF/VEL 200/50 mg and 12 to < 18 years old received SOF/VEL 400/100 mg once daily for 12 weeks. The efficacy endpoint was SVR12. Safety was assessed by adverse events (AEs) and clinical/laboratory data. Intensive pharmacokinetic (PK) was done to confirm the appropriateness of the chosen dose in a subgroup of patients of each age group.

Results: A total of 102 adolescents (12 to < 18 years old) and 73 patients 6 to < 12 years were enrolled and treated. Majority of subjects were GT 1 (75%), female (51%), white (80%), treatmentnaïve (85%), and vertically infected (91%).

Intensive PK confirmed that the doses selected were appropriate. The SVR12 rate among adolescents was 95% (97/102) and among the 6 to < 12 years old was 92% (67/73); one patient in each age group had virologic failure and the remaining 9 patients did not achieve SVR for non-virologic reasons. Most AEs were mild or moderate. Five subjects had a serious AE and 2 discontinued due to AEs, none of which was attributed to treatment.

The most common AEs were headache, fatigue, and nausea in adolescents and vomiting, cough and headache in younger children.

P.043

PROPRANOLOL LOWERS THE INCIDENCE RISK OF HEPATOCELLULAR CARCINOMA IN PATIENTS WITH ALCOHOLIC CIRRHOSIS: A RETROSPECTIVE TERTIARY-CENTER STUDY Tzu-Hao Li1,2,3, Ying-Ying Yang2,3,4,5, Ming-Chih Hou2,5, Han-Chieh Lin2,5 Division of Allergy, Immunology, And Rheumatology, Department of Internal Medicine, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan1 Faculty of Medicine, National Yang-Ming University, Taipei, Taiwan2 Institute of Clinical Medicine, National YangMing University, Taipei, Taiwan3 Division of Clinical Skills Training, Department of Medical Education, Taipei Veterans General Hospital, Taipei, Taiwan4 Division of Gastroenterology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan5

Propranolol 減少酒精性肝硬化病人肝 細胞癌之發生率：一個回顧性醫學中 心研究 黎子豪1,2,3 楊盈盈2,3,4,5 侯明志2,5 林漢傑2,5 新光吳火獅紀念醫院過敏免疫風濕科1 國立陽明大學醫學系2 國立陽明大學臨床醫學研究所3 臺北榮民總醫院臨床技術訓練科4 臺北榮民總醫院內科部肝膽腸胃科5 Background: Alcoholic cirrhosis (AC) leads to enormous disease burden and occupies a substantial proportion in the etiology of hepatocellular carcinoma (HCC), but scarce attention has been paid to this topic. Besides, propranolol has been reported to decrease the rate of HCC in viral hepatitis.

Aims: To investigate the effects of propranolol on incidence of HCC in AC patients.

Methods: We conducted a retrospective tertiarycenter cohort study to identify the HCC incidence in AC patients by reviewing the medical and hospitalization records of AC subjects older than 18 years within the years 2006 and 2017; the primary outcome in our study was the incidence

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of HCC. In comparison with the previous literature, we identified the relevant studies written in English or Chinese, focusing on the incidence of HCC in AC, from the PubMed, EMBASE, Airiti Library, and Cochrane Central Register of Controlled Trials (CENTRAL) databases, which had been published until April 2019, and conducted a meta-analysis for pooled incidence.

Results: A total of 23 AC patients with propranolol and 46 AC patients without propranolol were analyzed after twofold propensity-score matching.

The cumulative incidence of HCC was lower in the propranolol group (log-rank test, P = 0.046).

Besides, the pooled annual incidence derived from meta-analysis of eight studies was 2.41%, which was higher than the calculated annual incidence of HCC in our AC cohort with propranolol (1.45%).

Conclusions: In conclusion, propranolol is associated with decreased risk of HCC incidence in patients with AC.

P.044

SPONTANEOUS BACTERIAL PERITONITIS; SINGLE HOSPITAL EXPERIENCE IN SHUANG-HO HOSPITAL Bo-Jun Wu, Szu-Hao Huang, Bi-Zhen Kao, Ming-Yao Chen Division of Gastroenterology and Hepatology, Department of Internal medicine, Taipei Medical University-Shuang Ho Hospital, New Taipei, Taiwan

自發性腹膜炎之單一醫院臨床經驗： 以雙和醫院為例 吳帛駿 黃思皓 高碧珍 陳明堯 衛生福利部雙和醫院胃腸肝膽科 Background: Spontaneous bacterial peritonitis (SBP) is a severe complication of cirrhotic patients leading to acute kidney injury, hepatic encephalopathy and a high mortality.

Aims: To study risk factors, complications, recurrence and mortality of SBP. Methods: Retrospective study of 50 cirrhotic patients with 68 admissions (by ascitic fluid polymorphonuclear leukocyte count more than 250 cells/mm3) after exclusion of fungal peritonitis (1 patient) and secondary bacterial peritonitis (2 patients).

Results: Mean age was 60.1 ± 11.9 years, alcoholic 58.7%, Child-Pugh (CP) score 11.2 ± 1.8 (CP class C 88% and 12% CP class B), MELD score 25.1 ± 7.6, ascites fluid total protein < 1.0 (35.4%), ascites grade 3 or 4 (54.0%), diabetes mellitus (37.0%), malignancy (22.2%), gastric acid suppressor use (17.6%), steroid use (8.8%), concurrent other infection (27.9%), GI bleeding (29.4%), complicated with acute kidney injury (51.4%), and hepatic encephalopathy (66.1%).

The common presentations were abdomen pain (35.3%), fever (19.1%), abdomen distension, change in mental status and fatigue and shock.

Ascitic culture positive rates were 19.1%, the most common organisms were Gram-negative bacilli (76.9%; E. coli 30.7% and Klebsiella 30.7%) and drugs resistant organism was 23.0%. Persistent SBP occurred in 3 patients (7.3%). Half of recurrent episodes (11 patients, 22.0%) occurred within 1 month. The mortality within 5 days, 1 month and 1 year (10.0%, 36%, 72%, respectively). The cause

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of mortality at 1 month were severe sepsis (50%), acute hepatic failure (38.9%) and hepatorenal syndrome (11.1%). The mortality was determined

by MELD score, bilirubin > 2.5 mg/dL and presence of acute kidney injury (P < 0.005).

Conclusions: The infection-related mortality from SBP is low with appropriate treatment early in the course of infection, however, patient who have liver disease severe enough to develop SBP have poor prognosis, thus liver transplantation should be seriously considered for survival of SBP who are good transplantation candidates.

P.045

COMORBIDITY AND OUTCOME OF HOSPITALIZED CIRRHOTIC PATIENTS Bi-Zhen Kao, Ming-Yao Chen, Chia-Shin Wu, Sheng-Tsai Lin, Yu-Hsin Lai, Po-Wen Lu, Ming-Zhe Tay, Chung-Ying Lee Division of Gastroenterology and Hepatology, Department of Internal medicine, Taipei Medical University-Shuang Ho Hospital, New Taipei, Taiwan

住院肝硬化病人的合併症及臨床結果 高碧珍 陳明堯 巫嘉興 林聖才 賴雨欣 盧柏文 鄭明哲 李宗頴 衛生福利部雙和醫院胃腸肝膽科 Background: Cirrhosis is associated with multiple complications and repeated hospital admissions for as many as 50% of patients in whom it progresses to hepatic decompensation. Chronic liver disease including cirrhosis and hepatocellular carcinoma is currently the 10th leading cause of death in the Taiwan.

Aims: To study characters and outcomes of the hospitalized cirrhotic patients.

Methods: A retrospective study of cirrhotic patients admitted between 2013 to 2018 in Shuang-Ho Hospital.

Results: Among 1716 enrolled patients, 37.6% of patients was in compensated state and 72.4% in decompensated state. The aetiologies of cirrhosis included alcohol use (40.5%), chronic hepatitis B (CHB; 35.2%), chronic hepatitis C (CHC; 19.0%), both CHB&CHC (3.0%), autoimmune hepatitis (AIH; 3.0%), and others (12.0%). The patients’ characters were mean age (61.1 years), male (70.7%), diabetes mellitus (DM; 32.9%), chronic kidney disease stage > 3b (13.5%), hepatocellular carcinoma (HCC; 31.9%) and other malignancy (15.4%). Those patients had high prevalence of bacterial infection (42.6%), acute kidney injury (AKI; 9.3%), Gastrointestinal bleeding (GIB; 22.2%) and sudden cardiac arrest (OHCA/ IHCA; 2.4%). Over-all average age at expire was 65.2 years (alcoholics at 56.9 year, CHB at 63.9 years, CHC at 68.8 years, and AIH at 77 years).

Decompensated patients had higher prevalence of AKI (13.2% vs 2.7%), GI bleeding (34.0% Vs 8.5%) and, high mortality at 1-month and at 1-year

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(9.9% Vs 3.8% and 30.7% Vs 8.6%) with P < 0.0001. Determinants of mortality at - year were hepatic decompensation (Relative risk=RR 1.22), infection (RR 1.3), AKI (RR 2.8), OHCA/IHCA (RR 3.2) and GIB (RR 1.22) with P < 0.05.

Conclusions: The cirrhotic patients had high prevalence of DM, HCC, other malignancy, infection, GI bleeding, AKI and sudden cardiac arrest. Moreover, decompensated cirrhotic patients had higher risk of AKI, GI bleeding and mortality rate.

P.046

NOVEL ORAL GALACTOSE SINGLE POINT TEST AS A SAFE, SIMPLE, HIGHLY-SENSITIVE QUANTITATIVE ASSESSMENT OF LIVER FUNCTION IN HUMANS Tien-Yu Huang1, Ping Yang2, Hsuan-Hwai Lin3, Johnson Yiu-Nam Lau4, Oliver Yoa-Pu Hu5 Division of Gastroenterology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan1 School of Pharmacy, National Defense Medical Center, Taipei, Taiwan2 Division of Gastroenterology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan3 Department of Applied Biology & Chemical Technology, The Hong Kong Polytechnic University, Hong Kong4 Master Program for Clinical Pharmacogenomics and Pharmacoproteomics, Taipei Medical University, Taipei, Taiwan/School of Pharmacy, National Defense Medical Center, Taipei, Taiwan5 Background: A simple, clinically useful quantitative liver function test, called the galactose single point (GSP) method, was recommended by the US FDA and applied in Taiwan to quantitatively measure the residual liver function. This current study was going to translate the traditional GSP method to oral galactose single point (OGSP) that greatly improved the technical simplicity and greatly reduced the burden to patients.

Aims: To evaluate what the OGSP cutoff values to discriminate subjects with different hepatic function.

Methods: A total number of 146 non-diabetic subjects were enrolled into the study and 45, 56, and 45 subjects of them were divided to normal subjects group, mild or moderate impairment group, and severe impairment group, respectively.

All subjects were assigned to two sequences to receive GSP and OGSP measurement with different order. The OGSP method was developed by measurement of galactose concentration 1 h after galactose orally administered (0.5g/kg).

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Subjects’ liver function diagnosed by clinical physician according to the clinical presentation and laboratory data, were available for analysis to determine the clinical utility of the OGSP method.

Results: The test was safe with no complications.

Highly significant galactose blood levels were observed between normal healthy subjects and patients 60, 70, 80 and 90 min after galactose was orally administered (p < 0.0001, n=24). The critical values of OGSP based on the respective mean ± 2*SE in normal subjects, mild or moderate impairment, and severe impairment groups were defined as < 343.2, 343.2~628.8, and > 628.8 μg/ mL, respectively. Highly significant correlations (p < 0.0001, n=146) were obtained between OGSP and GSP. Positive correlations were observed between OGSP and AST (aspartate aminotransferase), ALT (alanine aminotransferase) and total bilirubin.

Conclusion: The OGSP test is a safe, simple, and highly sensitive quantitative measurement of liver function for the determination of a patient’s various degree liver function, the prognosis of liver function for patients with cirrhosis, post-operational follow-up and the timing of a liver transplant.

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P.047

LIVER RESECTION IN ELDERLY PATIENTS WITH HEPATOCELLULAR CARCINOMA: AGE DOES MATTER Yi-Hao Yen1, Yueh-Wei Liu2, Chih-Chi Wang2, Jing-Houng Wang1 Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gang Memorial Hospital, Kaohsiung, Taiwan1 Department of Surgery, Kaohsiung Chang Gang Memorial Hospital, Kaohsiung, Taiwan2

年紀大肝癌病患接受手術切除預後較差 顏毅豪1 劉約維2 王植熙2 王景弘1 高雄長庚紀念醫院胃腸肝膽科系1 高雄長庚紀念醫院一般外科2 Background: Increasing proportions of elderly patients with hepatocellular carcinoma (HCC) requiring oncological treatment have been noted.

Aims: We aim to evaluate the impact of elderly age on outcomes of liver resection (LR) for HCC. Methods: This retrospective study enrolled 1004 patients with HCC who underwent curative LR in our institution from 2007 to 2017, dividing them into three groups according to age (18–59 years, n=461; 60–74 years, n=447; ≥75 years, n=96). Elderly patients were defined as those ≥75 years old. Outcomes were then compared among the three groups, with a multivariate competing risk model used to estimate cause-specific subdistribution hazard ratios (SHRs) for HCC- and non-HCC-related deaths.

Results: The OS was significantly lower in the elderly than younger patients. However, recurrence-free survival was similar among the 3 groups. The cumulative incidence of HCC-related death was similar among the 3 groups; however, the cumulative incidence of non-HCC-related death was significantly higher in the elderly than younger patients. Moreover, the multivariate analysis showed that elderly age was not an independent variable associated with HCC-related death. However, elderly age was an independent variable associated with non-HCC-related death.

The 60-year SHR for non-HCC-related death increased with increasing age.

Conclusions: The elderly patients had

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significantly worse OS after LR than the younger patients, possibly due to the cumulative incidence of non-HCC-related death being significantly higher among the elderly than among the younger patients. Elderly patients should be more stringently selected for LR.

P.048

MICROSCOPIC PORTAL VEIN INVASION IS A POWERFUL PREDICTOR OF PROGNOSIS IN PATIENTS WITH HEPATOCELLULAR CARCINOMA WHO HAVE UNDERGONE LIVER RESECTION Yi-Hao Yen1, Fang-Ying Kuo2, Yueh-Wei Liu3, Chih-Chi Wang3, Jing-Houng Wang1 Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gang Memorial Hospital, Kaohsiung, Taiwan1 Department of Pathology, Kaohsiung Chang Gang Memorial Hospital, Kaohsiung, Taiwan2 Department of Surgery, Kaohsiung Chang Gang Memorial Hospital, Kaohsiung, Taiwan3

肝癌合併顯微鏡下門靜脈血管侵犯是 一個強大的預後因子在手術切除肝癌 病患 顏毅豪1 郭芳穎2 劉約維3 王植熙3 王景弘1 高雄長庚紀念醫院胃腸肝膽科系1 高雄長庚紀念醫院病理科2 高雄長庚紀念醫院一般外科3 Background: A recent study proposed simple classifications of microscopic vascular invasion (MVI): microscopic portal vein invasion (MPVI) and microvessel invasion (MI).

Aims: We aim to validate these classifications of MVI. Methods: This retrospective study consecutively enrolled 514 Barcelona Clinic Liver Cancer (BCLC) stage 0, A, and B hepatocellular carcinoma (HCC) patients who underwent liver resection in our institution from 2011-2017.

Results: Among these 514 patients, 240 patients were classified as having no MVI at all (designated as no vascular invasion, NVI), 157 patients were classified as having MI only, and 117 patients were classified as having MPVI. The 5-year overall survival (OS) rate in the MI-only group was 83.3%, which was not significantly different from that of the NVI group (87.2%), p=0.20. Using NVI as reference, a multivariate analysis showed that MI-only is not an independent variable associated

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with OS. The 5-year OS in the MPVI group was 59.2%, which was significantly lower than those for for MI-only (p<0.001). Using NVI as reference, a multivariate analysis showed that MPVI is an independent variable associated with OS (HR=3.12, 95% CI=1.80-5.40, P<0.001).

Conclusions: The results of this study validate the simple MVI classifications to be clinical useful.

P.049

IL6-STAT3 INDUCES AMPK AND PFKL EXPRESSION FOR REGULATING ENERGY HOMEOSTASIS AND CELL MIGRATION IN LIVER CANCER Bi-Ling Yang1, Ai-Sheng Ho1, Hsin-Chi Lin1, Hsin-Hung Huang1, Chun-Chia Cheng2 Division of Gastroenterology, Cheng Hsin General Hospital, Taipei, Taiwan1 Radiation Biology Research Center, Institute for Radiological Research, Chang Gung University / Chang Gung Memorial Hospital at Linkou, Taiwan2

IL6-STAT3 誘導 AMPK 和 PFKL 表達 以調節肝癌的能量平衡和細胞遷移 楊必玲1 何愛生1 林信吉1 黃信閎1 程俊嘉2 振興醫院胃腸肝膽科1 長庚大學放射醫學研究院2 Background: Metastasis is the main lethal reason for tumor patients. PFKL overexpresses in liver cancer involving in glycolysis-mediated energy production that leads to tumor metastasis. Till now, the mechanism of regulating PFKL expression is unclear completely.

Aims: This study, therefore, intended to uncover the detailed regulation for PFKL expression and to find novel compounds against metastasis in liver cancer.

Methods: Knockdown of PFKL was used to investigate its function in liver cancer cell lines.

IL6-mediated targets, including STAT3 and AMPK were examined as the upstream regulator of PFKL. The inhibitors against STAT3 and AMPK were investigated to be the therapies for liver cancer metastasis. The in vitro cell migration and in vivo metastasis assay in zebrafish were performed to validate the findings.

Results: We found that knockdown of PFKL reduced glycolysis and ATP production, resulting in lower cell migration in vitro. IL6 phosphorylated AMPK which stabilized PFKL expression.

Therefore, knockdown and inhibition of AMPK reduced cell migration in liver PLC5 cells. A compound screening methodology revealed that targeting STAT3 by nafuroxazide specifically reduced cell viability in liver PLC5 cancer cells. We furthermore demonstrated that STAT3 mediated

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AMPK and PFKL transcriptions. The specific inhibitors targeting STAT3 significantly reduced HepG2-mediated cell migration in a zebrafish model.

Conclusions: We uncovered that PFKL enhanced cell migration, and revealed the AMPK stabilized IL6-STAT3-mediated PFKL expression.

We also demonstrated that STAT3 and AMPK were potential targets for liver tumor therapies, their specific inhibitor such nifuroxazide and dosomorphin, respectively, significantly reduced liver tumor metastasis.

P.050

BBI608 IMPROVES RADIATIONMEDIATED THERAPEUTICS AGAINST LIVER CANCER STEMLIKE TUMORSPHERES Ai-Sheng Ho1, Zong-Lin Sie2, Bi-Ling Yang1, Hsin-Chi Lin1, Hsin-Hung Huang1, Chun-Chia Cheng2 Division of Gastroenterology, Cheng Hsin General Hospital, Taipei, Taiwan1 Radiation Biology Research Center, Institute for Radiological Research, Chang Gung University / Chang Gung Memorial Hospital at Linkou, Taoyuan, Taiwan2

BBI608 增進輻射對於肝癌類幹細胞的 抑制 何愛生1 謝宗霖2 楊必玲1 林信吉1 黃信閎1 程俊嘉2 振興醫院胃腸肝膽科1 長庚大學放射醫學研究院2 Background: Cancer stem cells play a vital role against clinical therapeutics, contributing to tumor relapse. However, the mechanism inducing resistance in radiotherapy (radioresistance) in liver cancer is not completely clear.

Aims: There are many oncogenes involving in tumorigenesis and initiation of cancer stemness property, including STAT3. Therefore, we aimed to investigate targeting STAT3 by its specific inhibitor, BBI608, to improve the radiationmediated therapeutics in liver cancer stem-like tumorspheres.

Methods: Flow cytometry was used to analyze the stemness markers, including CD133 and LGR5 in the selective hepatocellular carcinoma (HCC) cell lines, including HepG2 and two HBsAg-positive Hep3B and PLC5. The cells exposed under 0, 2, 4, and 10 Gy were collected for measuring cell viability and migration. Then, BBI608 was used to investigate the synergic effect to radiationmediated therapeutics against HCC cells.

Results: We found that HepG2 was a LGR5positive cell line by 36% population, but Hep3B and PLC5 were negative in CD133 and LGR5. As expect, radiation exposure significantly reduced cell viability and migration against HCC cell lines.

However, we found Hep3B- and PLC5-derived tumorspheres were resistant to radiation, but the cell viabilities were not affected in radiation

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exposure. BBI608 significantly reduced cell viability in Hep3B and PLC5 cells, and inhibited the formation of PLC5-derived tumorspheres.

Moreover, BBI608 significantly reduced growth factors-mediated migration in PLC5 cells, and enhanced radiation effect against PLC5 migration.

Conclusions: This study found that radiation reduced cell viability and migration in HCC cell lines but HCC-derived tumorspheres were resistant in radiation exposure. BBI608, a STAT3 inhibitor, significantly inhibited formation of HCCderived tumorspheres and improved the radiationmediated therapeutics. This study reveals that STAT3 participates in radioresistance in HCC cancer stem cells.

P.051

TAIWAN BARCELONA CLINIC LIVER CANCER SUBSTAGE OF ADVANCED HEPATOCELLULAR CARCINOMA FOR PRECISION MEDICINE Chih-Wen Lin1,2,4,5, Yaw-Sen Chen3,4, Gin-Ho Lo1,2,4, Tsung-Chin Wu1,4, Jen-Hao Yeh1,4, Ming-Lun Yeh6,7, Chia-Yen Dai6,7, Jee-Fu Huang6,7, Wan-Long Chuang6,7, Lewis Roberts8, Dae Won Jun9, Hidenori Toyoda10, Satoshi Yasuda10, Mindie H Nguyen11, Ming-Lung Yu6,7 Division of Gastroenterology and Hepatology, E-Da Dachang Hospital, I-Shou University, Kaohsiung, Taiwan1 Division of Gastroenterology and Hepatology, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan2 Department of Surgery, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan3 School of Medicine, College of Medicine, I-Shou University, Kaohsiung, Taiwan4 School of Chinese Medicine, College of Chinese Medicine, and Research Center for Traditional Chinese Medicine, China Medical University, Taichung, Taiwan5 Hepatobiliary Division, Department of Internal Medicine, and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan6 Hepatitis Research Center, College of Medicine, and Cohort Research Center and Center for Cancer Research, Kaohsiung Medical University, Kaohsiung, Taiwan7 Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA8 Division of Gastroenterology and Hepatology, Department of Internal Medicine, Hanyang University Seoul Hospital, Seoul, Korea9 Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Japan10 Division of Gastroenterology and Hepatology, Stanford University, Palo Alto, CA, USA11

台灣巴塞隆納晚期次分期的精準醫療 林志文1,2,4,5 陳耀森3,4 羅錦河1,2,4 吳宗勤1,4

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葉人豪1,4 葉明倫6,7 戴嘉言6,7 黃志富6,7 莊萬龍6,7 Lewis Roberts8 Dae Won Jun9 Hidenori Toyoda10 Satoshi Yasuda10 Mindie H Nguyen11 余明隆6,7 義大大昌醫院胃腸肝膽科1 義大醫院胃腸肝膽科2 義大醫院外科部3 義守大學醫學院醫學系4 中國醫藥大學附設醫院中醫藥研究中心5 高雄醫學大學附設中和紀念醫院肝膽胰內科6 高雄醫學大學癌症研究中心7 Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, MN, USA8 Division of Gastroenterology and Hepatology, Department of Internal Medicine, Hanyang University Seoul Hospital, Seoul, Korea9 Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Japan10 Division of Gastroenterology and Hepatology, Stanford University, Palo Alto, CA, USA11

cohort as well as the international validation cohort.

The distinction between the substages persisted in subgroup analysis by substage combined with treatment modality. In substage C0-C3, patients receiving HCC curative therapy had a significantly better median OS than those receiving sorafenib or local palliative therapy.

Conclusions: Our new substaging system provides more precise prognosis to better tailor therapy for BCLC-C HCC patients.

Background: Patients with Barcelona Clinic Liver Cancer Stage C (BCLC-C) hepatocellular carcinoma (HCC) can often be markedly heterogeneous with varying prognosis.

Aims: This study aims to establish a new subclassification system for BCLC-C HCC to better predict overall survival (OS) and to tailor therapy.

Methods: We retrospectively studied 1856 BCLC-C HCC patients between 2006 and 2017 from E-Da Hospital, Taiwan (n=622, training cohort), Kaohsiung Medical University Hospital, Taiwan (n=742, Taiwan validation cohort), and Stanford University Medical Center and Mayo Clinic (United States), Hanyang University Hospital (South Korea), and Ogaki Municipal Hospital (Japan) to make up the international validation cohort (n=460).

Results: In the training cohort, significant factors associated with OS were largest tumor size≥10 cm, extrahepatic spread, macrovascular invasion, and Child-Pugh class, which provided the basis, together with aged ≥75 years, for the substaging, through C0 to C4, of BCLC-C HCC patients. The median OS for substages C0, C1, C2, C3, and C4 were 43.8 months (95% confidence interval [CI]: 32.2-53.7), 20.6 months (CI: 14.1-25.9), 11.5 months (CI: 8.02-14.1), 5.7 months (CI: 4.025.98), and 3.2 months (CI: 2.41-3.59), respectively, (P<0.05). OS remained distinct among the proposed substages in the Taiwan validation

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P.052

COMPARISON OF OVERALL SURVIVAL ON SURGICAL RESECTION VERSUS TRANSARTERIAL CHEMOEMBOLIZATION WITH OR WITHOUT RADIOFREQUENCY ABLATION IN INTERMEDIATE STAGE HEPATOCELLULAR CARCINOMA: A PROPENSITY SCORE MATCHING ANALYSIS Po-Jen Hsiao1,6, Yaw-Sen Chen4,6, Gin-Ho Lo1,2,6, Yao-Chun Hsu2,6, Chia-Chang Hsu3,6, Tsung-Chin Wu1,6, Jen-Hao Yeh1,2,6, Pei-Min Hsieh4,5, Hung-Yu Lin4,5,6,7, Chih-Wen Shu5, Chao-Ming Hung4,5,6, Chih-Wen Lin1,2,3,6,7,8,9 Division of Gastroenterology and Hepatology, E-Da Dachang Hospital, I-Shou University, Kaohsiung, Taiwan1 Division of Gastroenterology and Hepatology, Department of Medicine, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan2 Health Examination Center, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan3 Department of Surgery, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan4 Department of Surgery, E-Da Cancer Hospital, I-Shou University, Kaohsiung, Taiwan5 School of Medicine, College of Medicine, I-Shou University, Kaohsiung, Taiwan6 Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan7 School of Chinese Medicine, College of Chinese Medicine, China Medical University, Taichung, Taiwan8 Research Center for Traditional Chinese Medicine, China Medical University Hospital, Taichung, Taiwan9

比較手術切除與動脈栓塞術單一或合 併射頻消融術的總存活率：傾向評分 匹配分析 蕭博仁1,6 陳耀森4,6 羅錦河1,2,6 許耀峻2,6 許家彰3,6 吳宗勤1,6 葉人豪1,2,6 謝沛民4,5 林鴻裕4,5,6,7 徐志文5 洪朝明4,5,6 林志文1,2,3,6,7,8,9

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義大大昌醫院胃腸肝膽科1 義大醫院胃腸肝膽科2 義大醫院健康管理中心3 義大醫院外科部4 義大治療醫院外科部5 義守大學醫學院醫學系6 高雄醫學大學醫學研究所7 中國醫藥大學中醫學系8 中國醫藥大學附設醫院中醫藥研究中心9 Background: Patients with Barcelona Clinic Liver Cancer (BCLC) stage B hepatocellular carcinoma (HCC) are recommended to undergo transcatheter arterial chemoembolization (TACE). However, TACE in combination with radiofrequency ablation (RFA) is not inferior to surgical resection (SR), and the benefits of surgical resection (SR) for BCLC stage B HCC remain unclear.

Aims: This study aims to compare the impact of SR, TACE+RFA, and TACE on analyzing overall survival (OS) in BCLC stage B HCC. Methods: Overall, 428 HCC patients were included in BCLC stage B, and their clinical data and OS were recorded. OS was analyzed by the KaplanMeier method and Cox regression analysis.

Results: One hundred forty (32.7%) patients received SR, 57 (13.3%) received TACE+RFA, and 231 (53.9%) received TACE. The OS was significantly higher in the SR group than that in the TACE+RFA group [hazard ratio (HR): 1.78; 95% confidence incidence (CI): 1.15-2.75, p=0.009].

The OS was significantly higher in the SR group than that in the TACE group (HR: 3.17; 95% CI: 2.31-4.36, p<0.0001). Moreover, the OS was significantly higher in the TACE+RFA group than that in the TACE group (HR: 1.82; 95% CI: 1.212.74, p=0.004). The cumulative OS rates at 1, 3 and 5 years in the SR, TACE+RFA, and TACE groups were 89.2%, 69.4% and 61.2%, 86.0%, 57.9% and 38.2%, and 69.5%, 37.0% and 15.2%, respectively. After propensity score matching, the SR group still had a higher OS than those of the TACE+RFA and TACE groups. The TACE+RFA group had a higher OS than that of the TACE group.

Conclusions: The SR group had higher OS than the TACE+RFA and TACE groups in BCLC stage B HCC. Furthermore, the TACE+RFA group had higher OS than the TACE group.

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P.053

LONGITUDINAL ANALYSES OF THE BIPHASIC KINETICS IN LIVER AND SPLEEN STIFFNESS VALUES IN HEPATITIS C VIRUS-INFECTED PATIENTS ON AND OFF DIRECTACTING ANTIVIRAL THERAPIES Sheng-Hung Chen1,2,3, Hsueh-Chou Lai2,4, Wei-Fan Hsu2,3, Hung-Wei Wang2,3, Chun-Che Lin2,3, Guan-Tarn Huang2,3, Jaw-Town Lin2,3, Cheng-Yuan Peng2,3 Graduate Institute of Clinical Medical Science, School of Medicine, China Medical University, Taichung, Taiwan1 Center for Digestive Medicine, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan2 School of Medicine, China Medical University, Taichung, Taiwan3 College of Chinese Medicine, China Medical University, Taichung, Taiwan4

分析接受 Direct-Acting Antivirals 治 療之 C 型肝炎病患治療中及治療後肝 臟及脾臟硬度跨越時間之雙相變化 陳昇弘1,2,3 賴學洲2,4 許偉帆2,3 王鴻偉2,3 林俊哲2,3 黃冠棠2,3 林肇堂2,3 彭成元2,3 中國醫藥大學臨床醫學研究所1 中國醫藥大學附設醫院內科部消化醫學中心2 中國醫藥大學醫學系3 中國醫藥大學中醫學系4 Background: In real-world practices, the longitudinal measurements of liver stiffness (LS) and spleen stiffness (SS) are characterized by missing visits. To take into considerations the within-subject measurements and especially the follow-up time elapsed, analyses such as generalized linear mixed models (GLMMs) are required; however, relevant studies are limited.

Delineating the stiffness kinetics and the correlates on and off direct-acting antiviral (DAA)-based treatments facilitates the constructions of the prognostic tools for liver-related events (LREs) and portal hypertension-related events (PHREs) using the measurement results changing over time.

Aims: The present prospective study aimed to delineate the within-subject values and slope coefficients in declines across months (mo),

and to estimate the correlates with the values in all the measured LS and SS through GLMMs incorporating the baseline patient characteristics and the time elapsed.

Methods: Consecutive Hepatitis C virus (HCV)infected patients who intended to receive directacting antiviral-based therapy at China Medical University Hospital from July 2014 to May 2020 were prospectively screened. Participants (eligible n = 592) were monitored from the treatment baseline across follow-up visits up to xx weeks after the completion of DAA therapy using LS and SS values (meter per second, m/s) through acoustic radiation force impulse elastography. The slope coefficients of the stiffness changes over a certain time frame were calculated as stiffness changes (m/s) (former minus latter) divided by the time interval (mo).

Results: Through GLMMs, all the LS values measured (visit n = 2154) significantly and negatively correlated with the follow-up time elapsed and positively with the baseline LS (P < 0.001). Post Hoc multiple comparisons revealed that the slope coefficients differed significantly only between baseline (TW0)–treatment Week 4 (TW4) (0.060 [-0.050–0.225] m/s/mo) and TW4– end of treatment (EOT) (0.010 [-0.030–0.075] m/s/mo) (adjusted P < 0.001). All the SS values measured (visit n = 1346) significantly and negatively correlated with the time elapsed only at 24 weeks off treatment (PW24) (P < 0.001) and positively with the baseline SS (P < 0.001) The slopes of SS values differed significantly only between EOT–PW12 (-0.010 [-0.110–0.083] m/s/ mo) and PW12–PW24 (0.043 [-0.063–0.160] m/s/ mo) (adjusted P < 0.001). For the remainders of the patient parameters, from TW0 to PW24, the SS-to-LS ratios changed significantly at TW4, EOT, and PW12 as compared to the baseline. The aspartate aminotransferase (AST)-to-platelet ratio index, Fibrosis-4 index, levels of AST and alanine aminotransferase, and platelet count changed significantly at TW4, EOT, PW12 and PW24.

Conclusions: The biphasic fast-to-slow and slow-to-fast declines developed early on treatment in LS, and off treatment in SS values, respectively, in HCV-infected patients receiving DAA-based therapies. Baseline values also significantly and positively predicted the followup measurement results across the time frames.

The fully delineated stiffness kinetics including the posttreatment LS reflecting the posttreatment

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liver fibrosis burden and the posttreatment SS indicating the posttreatment portal stress might be comprehensively incorporated in establishing nomograms in predicting posttreatment LREs and PHREs in future studies to assist with post-viral eradication surveillance.

P.054

LONG TERM OUTCOMES OF HEPATOCELLULAR CARCINOMA WITH ESOPHAGOGASTRIC VARICES AFTER SURGICAL RESECTION Cheng-Yi Wei1, Chien-Wei Su1,2, Gar-Yang Chau2,3, Yi-Hsiang Huang1,4, Han-Chieh Lin1,2, Ming-Chih Hou1,2 Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan1 Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan2 Division of General Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei, Taiwan3 Institute of Clinical Medicine, National YangMing University, Taipei, Taiwan4

併有胃食道靜脈瘤之肝癌患者接受外 科切除後之長期預後 魏正一1 蘇建維1,2 周嘉揚2,3 黃怡翔1,4 林漢傑1,2 侯明志1,2 臺北榮民總醫院內科部胃腸肝膽科1 國立陽明大學醫學系2 臺北榮民總醫院外科部一般外科3 國立陽明大學臨床醫學研究所4 Background: The curative treatment modality of hepatocellular carcinoma (HCC) includes surgical resection (SR), radiofrequency ablation (RFA), percutaneous ethanol injection (PEIT) and liver transplantation (LT). The international guidelines do not suggest SR for patients with portal hypertension due to the potential risk of post-hepatectomy liver failure. The presence of EGV is a surrogate of clinically significant portal hypertension (CSPH). The efficacy of SR in the population of HCC patients with portal hypertension has not been well investigated until now.

Aims: Our goal is to analyze the long-term prognosis of HCC patients with EGV after SR. Methods: This retrospective study enrolled the patients with treatment-naïve HCC and with EGV who underwent SR as the first-line treatment from 2003 to 2017. EGV was diagnosed by an esophagogastroduodenoscopy at the time of HCC diagnosis. Prognostic factors were analyzed by

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the Cox proportional hazards model.

Results: A total 68 patients were enrolled. After a median follow-up duration of 57.9 months, 23 patients died. The 5-year overall survival (OS) rate is 66.7%. Univariate analysis showed that presence of HBsAg (hazard ratio HR 0.436, 95% confidence interval CI 0.191-0.998, p = 0.049), serum albumin level less than 3.5g/dL (HR 2.482, 95% CI 1.071-5.752, p = 0.034), ALBI grade 2 and 3 (HR 2.607, 95% CI 1.027-6.617, p = 0.044), developed peri-operative major morbidity (HR 4.403, 95% CI 1.477-13.121, p = 0.008) were poor prognostic factors of OS. The multivariate analyses found ALBI grade 2 and 3 (HR 3.237, 95% CI 1.234-8.494, p = 0.017) and development of major morbidity after hepatectomy (HR 6.327, 95% CI 2.012-19.892, p = 0.002) were independent prognostic factors for poor OS. Regarding tumor recurrence, no prognostic factors were associated with poorer recurrence free survival (RFS) after multivariate analysis.

Conclusions: HCC patients with EGV who underwent SR had good long-term survival benefit. ALBI grade 2 and 3, and development of post-operative were poor prognostic factors for OS. Hence, SR could be considered as the firstline treatment modality for patients with HCC and with EGV.

P.055

LONG-TERM EFFECTIVENESS OF POPULATION-WIDE MULTIPLE INTERVENTIONS FOR HEPATOCELLULAR CARCINOMA IN TAIWAN Sih-Han Liao1,2,3, Chi-Ling Chen4, Chen-Yang Hsu3, Kuo-Liong Chien3,5, Jia-Horng Kao2,4, Pei-Jer Chen2,4, Hsiu-Hsi Chen3, Chien-Hung Chen2,6,7 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 Division of Cardiology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan5 Department of Internal Medicine, National Taiwan University Hospital Yunlin Branch, Yunlin, Taiwan6 College of Medicine, National Taiwan University, Taipei, Taiwan7

台灣各種以族群為基礎的肝癌防治對 策的長期效果 廖思涵1,2,3 陳祈玲4 許辰陽3 簡國龍3,5 高嘉宏2,4 陳培哲2,4 陳秀熙3 陳健弘2,6,7 台大癌醫中心醫院綜合內科部1 台大醫院內科部胃腸肝膽科2 台灣大學公衛學院流行病學與預防醫學研究所3 台灣大學醫學院臨床醫學研究所4 台大醫院內科部心臟科5 台大醫院雲林分院內科部6 台灣大學醫學院7 Background: A series of population-wide interventions on hepatocellular carcinoma (HCC) related to hepatitis B and C virus infection have been launched in Taiwan since 1984. Nonetheless, the impacts of these programs have not been systematically elucidated as yet.

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Aims: Here we assessed relative contributions to long-term mortality reduction of HCC between incidence reduction and case-fatality improvement attributed to each intervention program.

Methods: Population-based registry data on HCC mortality and incidence of individuals aged 0 to 84 years between 1979 and 2016 were collected before (period 1) and after intervention with three segmentations, 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 mortality decomposition Poisson regression model was used to estimate respective contributions to incidence and casefatality rate reduction by various age groups.

Results: The mortality trends of children, youngand middle-aged groups substantially declined whereas that of the old age group only declined slightly. The declining mortality trends were partially explained by the reduction of incidence and partially by the remarkable decline in casefatality rate attributed to universal HCC care. The reduction of 35.9% (26.8% to 44.4%) incidence was attributed to hepatitis B vaccination for aged <30 years, and 14.9% (11.8% to 17.9%) and 15.4% (14.1% to 16.6%) for age of 30-49 and 5069 years, respectively, were attributed to anti-viral therapy.

Conclusions: Assessing relative contributions to HCC mortality between incidence and casefatality rate reduction attributed to population-wide multiple interventions provides a new insight into the resource allocation to prevention of HCC from cradle to grave.

P.056

T-ACE BEADS LOADED WITH DOXORUBICIN FOR HEPATOMA TREATMENT ─ A PI INITIATED MULTICENTER CLINICAL TRIAL Yi-Sheng Liu1, Chiung-Yu Chen2, Ping-I Hsu3, Huei-Lung Liang4, Feng-Woei Tsay3, Hung-Wen Tsai5, Yen-Cheng Chiu2, Yih-Jyh Lin6, Jui-Wen Kang2, Xi-Zhang Lin2 Department of Radiology, National Cheng Kung University Hospital, Tainan, Taiwan1 Department of Internal Medicine, National Cheng Kung University Hospital, Tainan, Taiwan2 Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan3 Department of Radiology, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan4 Department of Pathology, National Cheng Kung University Hospital, Tainan, Taiwan5 Department of Surgery, National Cheng Kung University Hospital, Tainan, Taiwan6

載藥大員栓塞微球粒治療肝癌 ─ 計畫 主持人發起之多中心臨床試驗 劉益勝1 陳炯瑜2 許秉毅3 粱慧隆4 蔡峯偉3 蔡弘文5 邱彥程2 林毅志6 康瑞文2 林錫璋2 國立成功大學醫學院附設醫院影像醫學部1 國立成功大學醫學院附設醫院內科部2 高雄榮民總醫院內科部3 高雄榮民總醫院放射線部4 國立成功大學醫學院附設醫院病理部5 國立成功大學醫學院附設醫院外科部6 Background: Transcatheter arterial chemoembolization (TACE) remains an important modality to treat intermediate-stage of hepatoma in many countries. Microsphere differs from conventional iodized oil-based TACE in application method and offers better treatment results. However, it is expensive. T-ACE Bead without drugs has been tested in previous clinical trial (NCT02825550).

Aims: We loaded Doxorubicin with T-ACE Beads to test the safety and effectiveness of the Beads in suitable patients.

Methods: T-ACE Beads are alginate-Gelatinbased amphiphilic microspheres, sized 100- 200 um, made by ITRI pilot plant, Taiwan. Under IRB

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and TFDA, we conducted the clinical trial (NCT 03299036). We recruit 24 suitable hepatoma patients for T-ACE Beads embolization. In brief, all patients were Child-Pugh score less than 8, and tumor size less than 8 cm in diameter. T-ACE Beads loaded with Doxorubicin (20-50 mg). The embolization was performed under angiography.

The end-point was stasis of the tumor blood flow at the second injection. All the possible tumor feeding vessels were embolized. The treatment results were assessed by CT/MRI at one and three months after TACE treatment according to m-RECIST criteria.

Results: All 24 patients received T-ACE Beads loaded with Doxorubicin, 17 M 7 F, aged 71.5 ± 11.3, previous treatment experience in 17 patients.

At one month, images by m-RECIST show CR 20.8%, PR 50.0%, SD 20.8% and PD 4.1%.

There are 9 patients withdraw to receive other treatments: operations, RFA, and HAI. The other 15 patients at 3 months, showed CR 20%, PR 60%, SD 13.3% and PD 6.7%. Biochemical tests, CBC and doxorubicin, and clinical presentations showed that all the 24 patients well tolerated TACE procedure, no significant adverse event occurred.

Conclusions: The study is limited in case number. The coming trials will recruit more patients worldwide. However, current results show T-ACE Beads are comparable with the current commercial available microspheres in safety and effectiveness.

P.057

EARLY RESPONSES OF LENVATINIB FOR UNRESECTABLE HEPATOCELLULAR CARCINOMA: A REAL-WORLD EXPERIENCE FROM ONE CENTER IN TAIWAN Shao-Wu Lee, Teng-Yu Lee, Sheng-Shun Yang, Hong-Zen Yeh, Chi-Sen Chang Division of Gastroenterology, Taichung Veterans General Hospital, Taichung, Taiwan

Lenvatinib 治療於患有無法切除肝癌病 患之早期療效：臺灣中部單一中心研究 李少武 李騰裕 楊勝舜 葉宏仁 張繼森 臺中榮民總醫院胃腸肝膽科 Background: Lenvatinib had been approved as a fist-line systemic therapy for patients with advanced hepatocellular carcinoma (HCC).

Aims: The aim of this study is to investigate the realworld early response of lenvatinib to the patients with unresectable HCC. Methods: Data for the patients with unresectable HCC receiving Lenvatinib at Taichung Veterans General Hospital from April 2019 to February 2020 was evaluated. The inclusion criteria included tolerable to Lenvatinib, BCLC stage B or C, ChildPugh stage A or ≦ 7 scores, survival and take Lenvatinib over two month or until next radiologic examination done.

Results: Amongst a total of 23 subjects enrolled, the mean Lenvatinib using time was 4.52 months, and the mean following time was 5.96 months (313). Within the following period, 9 cases (39.1%) expired. The general data found male predominant (87%), more with hepatitis B infection (HBV/HCV: 65%/35%), Child-Pugh class A (A/B: 82.6%/17.4%), BCLC stage C (B/C: 39.1%/60.9%) and severed as secondary-line therpay (2’/1’: 56.5%/43.5%). The ORR and DCR were 35.8% and 60.9% respectively.

Further analysis disclosed better ORR being noted in BCLC stage B comparing with BCLC stage C (66.7% vs. 14.3%, p=0.023). While comparing with the expired patients and the alive ones, the subjects with low AFP level, BCLC stage B, radiologic documented well tumor disease-control had a better survival rate.

Conclusions: The early radiologic responses of Lenvatinib were acceptable, and the patients with early BCLC stage or lower AFP had a better therapeutic outcome.

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P.058

LIVER RESECTION OF HEPATOCELLULAR CARCINOMA WITHIN AND BEYOND THE BARCELONA CLINIC LIVER CANCER GUIDELINE RECOMMENDATIONS: RESULTS FROM A HIGH-VOLUME LIVER SURGERY CENTER IN EAST ASIA Kuo-Tung Hung1, Yueh-Wei Liu2, Chee-Chien Yong2, Chih-Che Lin2, Chih-Chi Wang2, Chao-Long Chen2, Yu-Fan Cheng3, Jing-Houng Wang1, Yi-Hao Yen1, Chien-Hung Chen1 Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, 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

符合和超出巴塞隆那臨床肝癌指引之 下的肝癌肝切除：來自東亞一間大型 肝手術醫學中心的研究結果 洪國棟1 劉約維2 楊志權2 林志哲2 王植熙2 陳肇隆2 鄭汝汾3 王景弘1 顏毅豪1 陳建宏1 高雄長庚紀念醫院胃腸肝膽科系1 高雄長庚紀念醫院外科部與肝移植中心2 高雄長庚紀念醫院放射診斷科與肝移植中心3 Background: The Barcelona Clinic Liver Cancer (BCLC) guidelines were updated in 2012, and a single large hepatocellular carcinoma (HCC) >5 cm was regarded as BCLC stage A rather than B in the updated version.

Aims: In this study, we sought to re-evaluate the outcomes of patients with HCC who underwent liver resection (LR) within (stage 0 and A) and beyond (stage B and C) the BCLC guideline recommendations of the updated BCLC staging system.

Methods: This retrospective study enrolled 774 consecutive patients with naïve HCC who

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underwent LR from 2011-2018 at our institution.

The overall survival (OS) and recurrence-free survival (RFS) of these patients were examined.

Results: Of the patients, 606 had BCLC stage 0 or A HCC, and 168 had BCLC stage B or C HCC. The 5-year OS and RFS among the patients within the BCLC criteria for LR were 75.2% and 56.1%, respectively, versus 54.9% and 34.0%, respectively, among the patients beyond the BCLC criteria (p < 0.001). Alpha fetoprotein (AFP) >400 ng/dL (HR = 2.06, 95% CI = 1.31-3.26, p = 0.002) was the only independent variable associated with recurrence among the patients beyond the BCLC criteria.

Conclusions: LR provided acceptable outcomes among selected patients with BCLC stage B and C HCC.

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P.059

HEPATIC ARTERIAL INFUSION CHEMOTHERAPY (HAIC) FOR HEPATOCELLULAR CARCINOMA WITH PORTAL VEIN TUMOR THROMBOSIS (PVTT) IN TAINAN MUNICIPAL HOSPITAL Sheng-Hsun Yang, I-I Chen, Huang-Lun Lai, Yu-Hung Lin, Chun-Hsiang Wang, Ming-Jeng Kuo, Kuo-Kuan Chang, Ruey-Chang Lin, Jen-Juan Kuo, Keh-Cherng Wey, Yuan-Chi Mao, Lein-Ray Mo Department of Hepatogastroenterology, Tainan Municipal Hospital (Managed by Show Chwan Medical Care Corporation), Tainan, Taiwan

and PR, respectively (response rate 41%). The 6, 12, 18, 24, 30 and 36-month cumulative survival rates for all the 58 patients were 86%, 48%, 39%, 27%, 22%, and 22%, respectively and while for the twenty-four responders (CR and PR) were 87%, 82%, 67%, 62%, 51%, and 51%, respectively.

Median survival times for the 24 responders and 34 non-responders were 30.7 (range, 24.1-37.2) and 11.1 (range, 3-19.7) months, respectively.

Univariate and multivariate analyses demonstrated that the therapeutic response was significant prognostic factors.

Conclusions: HAIC using low-dose cisplatin and 5-fluorouracil could be a usefully alternative treatment for HCC patients with PVTT. Responders (CR and PR) could certainly have survival benefits.

台南市立醫院肝動脈灌注化療 （HAIC）對肝細胞癌合併門靜脈腫瘤血 栓形成（PVTT）的影響 楊昇勳 陳一毅 賴皝綸 林裕鴻 王俊雄 郭明正 張國寬 林瑞昌 郭振源 魏克承 毛元治 牟聯瑞 台南市立醫院肝膽胃腸科 Background: Hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT) is associated with poor prognosis.

Aims: The aim of this study was to evaluate the efficacy of hepatic arterial infusion chemotherapy (HAIC) for HCC with portal vein tumor thrombosis.

Methods: Fifty-eight HCC patients with PVTT were treated with HAIC via a subcutaneously implanted injection port. Twenty-seven patients had PVTT in the main portal trunk or in the first portal branch, ten patients had PVTT in the second portal branch and twenty-one patients had third or more of the peripheral branch. One course of chemotherapy consisted of cisplatin (15.7 mg/m2 on Day 1–5), 5-fluorouracil (250 mg/m2 on Day 1–5) and epirubicin (30 mg/m2 on Day 1). The patients were scheduled to receive three consecutive courses of HAIC. Responders were defined as complete response (CR) or partial response (PR) and nonresponders were defined as stable disease (ST) or progressive disease (PD). The prognostic factors associated with survival after treatment were analyzed.

Results: Four and twenty patients exhibited CR

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P.060

SURVIVAL OF PATIENTS WITH HEPATOCELLULAR CARCINOMA IN RENAL INSUFFICIENCY: PROGNOSTIC ROLE OF ALBUMINBILIRUBIN GRADE Shu-Yein Ho1, Chih-Chieh Ko2,3, Chien-Wei Su2,3, Ming-Chih Hou2,3, Yi-Hsiang Huang2,3, Teh-Ia Huo4,5 Division of Gastroenterology and Hepatology, Min-Sheng General Hospital, Taoyuan, Taiwan1 Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan2 Division of Gastroenterology and Hepatology, Taipei Veterans General Hospital, Taipei, Taiwan3 Department of Medical Research, Taipei Veterans General Hospital, Taipei, Taiwan4 Institute of Pharmacology, National Yang-Ming University School of Medicine, Taipei, Taiwan5

利用白蛋白 - 膽色素評分預測腎功能不 全的肝癌患者的預後 何樹仁1 柯智傑2,3 蘇建維2,3 侯明志2,3 黃怡翔2,3 霍德義4,5 敏盛綜合醫院胃腸肝膽科1 臺北榮民總醫院內科部2 臺北榮民總醫院胃腸肝膽科3 臺北榮民總醫院研究部4 國立陽明大學藥理研究所5 Background: Renal insufficiency (RI) is commonly seen in patients with hepatocellular carcinoma (HCC). The prognostic role of albumin-bilirubin (ALBI) grade 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.

In multivariate Cox analysis for patients with RI, α-fetoprotein level 20 ng/mL, tumor size >3 cm, vascular invasion, distant metastasis, presence

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of ascites, performance status 1–2, performance status 3–4, and ALBI grade 2 and grade 3 were independent predictors of decreased survival (all p < 0.05). 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 (p < 0.001).

Conclusions: In summary, 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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P.061

COMBINATION THERAPY WITH REGORAFENIB PROLONGS SURVIVAL IN PATIENTS WITH UNRESECTABLE HEPATOCELLULAR CARCINOMA Wei Teng1,5, Cho-Li Yen2,5, Ming-Chin Yu3,5, Ruey-Shyang Soong4,5, Chen-Chun Lin1,5, Shi-Ming Lin1,5 Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan, Taiwan1 Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Keelung Branch, Keelung, Taiwan2 Department of General Surgery, Chang Gung Memorial Hospital, Tucheng Branch, New Taipei City, Taiwan3 Department of General Surgery, Chang Gung Memorial Hospital, Keelung Branch, Keelung, Taiwan4 College of Medicine, Chang Gung University, Taoyuan, Taiwan5

癌瑞格搭配其他治療可延長不適合手 術切除肝癌病患之存活率

survival (PFS) were analyzed.

Results: Among the 51 patients, the median age was 66 years old, and 86% were male. Forty-seven (92%) patients had sorafenib-experienced history.

Most patients were Child-Pugh A (90%) and ABLI grade I (51%) at baseline. Twenty-one (41%) patients died during median follow-up duration of 6.5 months. Regorafenib was used as the second and third lines of therapy in 39 (77%) and 11 (21%) patients respectively. The overall response rate was 7.8% (n = 4), while the median PFS and OS were 3.1 (95% CI: 2.5-3.7) and 17.1 (95% CI: 5.9-28.3) months respectively. A total of 9 patients received regorafenib combined with other therapy including loco-regional therapy (n=6), immune checkpoint inhibitors (n=2) and chemotherapy (n = 1). There were no significant difference including age, gender, tumor burden and preserved liver function between combination and monotherapy group. Patients with combination therapy showed better OS (median: 17.1 vs. 10.6 months, log-rank P = 0.043) and PFS (median: 6.6 vs. 2.7 months, log-rank P = 0.054) than regorafenib alone.

Conclusions: The present study showed the efficacy and side effects of regorafenib in the realworld data. Combination therapy has superior median OS and PFS than regorafenib alone.

滕威1,5 嚴卓立2,5 游明晉3,5 宋睿祥4,5 林成俊1,5 林錫銘1,5 林口長庚紀念醫院胃腸肝膽科1 基隆長庚紀念醫院胃腸肝膽科2 新北市立土城醫院一般外科3 基隆長庚紀念醫院一般外科4 長庚大學醫學院5 Background: Regorafenib demonstrated a clinical benefit for patients with unresectable hepatocellular carcinoma (uHCC) in the phase III RESORCE trial. Nevertheless, the benefits of combination therapy with regorafenib in sorafenibexperienced patients remain uncertain.

Aims: We aimed to investigate whether the combination therapy provides better survival than regorafenib alone in unresectable HCC patients.

Methods: From August 2016 to December 2019, a total of 51 unresectable HCC patients receiving regorafenib were recruited. Treatment response was evaluated by dynamic image including CT or MRI every 2-3 months using the modified RECIST criteria. Overall survival (OS) and progression-free

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P.062

STAIN IS ASSOCIATED WITH LOW RECURRENT RISK IN BCLC STAGE 0-A HEPATOCELLULAR CARCINOMA PATIENTS AFTER CURATIVE RESECTION Shih-Yu Yang1, Chih-Chi Wang2, Yueh-Wei Liu2, Chih-Che Lin2, Chee-Chien Yong2, Tsung-Hui Hu1, 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

Statin 與降低 BCLC 期別 0-A 肝癌病 人手術後復發率相關 楊適宇1 王植熙2 劉約維2 林志哲2 楊志權2 胡琮輝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 心及一般外科暨長庚大學醫學系2 Background: Statin use is associated with reduced risk of hepatocellular carcinoma (HCC).

However, the effect on HCC recurrence is still unclear.

Aims: To evaluate the effect of statin use on HCC recurrence after curative resection in whole general population.

Methods: We enrolled 820 Barcelona Clinic Liver Cancer (BCLC) stage 0 or A HCC patients who received primary resection from January 2001 to June 2016 at Kaohsiung Chang Gung Memorial Hospital. Exposure to statin was defined as the use at least 3 months before HCC recurrence.

Factors influence the overall survival (OS) and recurrence-free survival (RFS) were analyzed by Cox’s proportional hazards models.

Results: Of 820 patients, 46 (5.6%) received statin (statin group) and 774 (94.4%) did not (non-statin group). During a mean 76.5 months of follow-up, 440 (53.7%) patients experienced recurrence,

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and 144 (17.6%) patients died. The cumulative incidence of HCC recurrence in the statin group was significantly lower than that in the non-statin group (p = 0.001), but there was no significant difference on OS. In the multivariate analysis, liver cirrhosis (hazard ratio [HR]: 2.207; p < 0.001), tumor number (HR: 2.657 ; p = 0.001), tumor size (HR: 1.656; p = 0.003) and vascular invasion (HR: 1.570; p = 0.004) were independent risk factors for HCC recurrence, but statin use (HR: 0.382 ; p = 0.005) and nucleos(t)ide analogues (NA) therapy (HR: 0.520 ; p < 0.001) were found to significantly decrease the risk for HCC recurrence.

Conclusions: Statin use may have chemopreventive effect on HCC recurrence in patients after curative resection.

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P.063

NIVOLUMAB FOR UNRESECTABLE HEPATOCELLULAR CARCINOMA: REAL-WORLD EXPERIENCE IN KAOHSIUNG CHANG GUNG MEMORIAL HOSPITAL Yuan-Hung Kuo, Yi-Hao Yen, Chien-Hung Chen, Kong-Ming Kee, Chao-Hung Hung, Tsung-Hui Hu, Sheng-Nan Lu, 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

保疾伏治療無法切除肝細胞癌：高雄 長庚紀念醫院的真實經驗 郭垣宏 顏毅豪 陳建宏 紀廣明 洪肇宏 胡琮輝 盧勝男 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

and 14 (26.9%) in Child B. The median treatment duration of Nivolumab was 5.8 months. The median progression-free survival and overall survival (OS) was 2.6 months and 14 months, respectively.

The OS of Child A patients was superior to that of Child B patients (14 months vs 1.8 months, P < 0.001). Of 36 patients with evaluable images, the objective response rate and disease control rate was 13.9% and 36.1%, respectively. The median duration of treatment durability was 5.2 months.

After excluding 2 patients remained Nivolumab treatment, only 12 (23.1%) patients could still afford following sequential systemic therapies after Nivolumab failure. There were 21 (40.4%) patients died during the follow-up. In multivariate analysis, poorer liver function and not feasible to receiving following therapy were predictors of a miserable prognosis in patients with Nivolumab use.

Conclusions: In real-world clinical practice, Nivolumab was still effective for unresectable HCC patients with an adequate disease control rate as 36.1%. However, patients with good liver function reserve might be eligible to have a survival benefit

by Nivolumab.

Background: Immune check point therapy such as nivolumab has been as evidence-based second-line treatment strategy in patients with unresectable advanced hepatocellular carcinoma (HCC). However, clinical experience of Nivolumab is not often in Taiwan.

Aims: This study aimed to assess the efficacy of Nivolumab in clinical practice.

Methods: From Jul 2013 to Dec 2019, 54 consecutive patients with Barcelona clinical liver cancer (BCLC) HCC stage B or C received Nivolumab in our hospital, and their medical records were collected for further analysis. Two patients were excluded; one lost OPD follow-up after Nivolumab use and another just died the next day after Nivolumab use. All enrolled patients were followed up till May 2020. Radiological responses was evaluated using the Response Evaluation Criteria in Solid Tumors version 1.1.

Results: here were 38 (73.1%) male patients and 14 (26.9%) female patients, with a mean age of 60.8 years old. The distribution of etiology of HCC was hepatitis B virus infection in 31 (59.6%) patients, hepatitis C virus infection in 16 (30.8), B+C in 2 (3.8%) and non-B, non-C in 3 (5.8%), respectively. In clinical practice, there were 38 (73.1%) patients in Child-Pugh class A (Child A)

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P.064

LIVING DONOR LIVER TRANSPLANTATION FOR BCLC INTERMEDIATE-STAGE HEPATOCELLULAR CARCINOMA Ming-Chao Tsai1, Chih-Chi Wang2, Chih-Che Lin2, Yueh-Wei Liu2, Chee-Chien Yong2, Tsung-Hui Hu1, Chao-Long Chen2 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

活體肝移植治療 BCLC 中期肝細胞癌 蔡明釗1 王植熙2 林志哲2 劉約維2 楊志權2 胡琮輝1 陳肇隆2 高雄長庚紀念醫院胃腸肝膽科1 高雄長庚紀念醫院肝臟移植中心2 Background: Intermediate stage hepatocellular carcinoma (HCC) encompasses the largest subgroup of patients with diseases. However, transarterial chemoembolization is the only recommended treatment option according to the Barcelona Clinical Liver Cancer (BCLC) staging.

Aims: To investigate characteristics and outcomes of living donor liver transplantation (LDLT) for BCLC stage B HCC. Methods: From 2004 to 2018, we enrolled 104 BCLC stage B HCC patients who received LDLT in the four institutions constituting the Chang Gung Memorial Hospital (CGMH). Factors influence the overall survival (OS) and recurrence rate were analyzed by Cox’s proportional hazards models.

Results: During a mean 5.3 years of followup after LDLT, 12 (11.5%) patients experienced recurrence, and 18 (17.3%) patients died. One, 3-, and 5-year OS and recurrence rates were 92.3/89.2/84.1% and 4/12/13.5%, respectively.

Kaplan-Meier survival analysis found that age >60 years, neutrophil-to-lymphocyte ratio (NLR)>4.5, and more than 4 times of HCC treatments before LDLT showed significance in both recurrence rate and OS. In the multivariate analysis, age >60

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years (hazard ratio [HR]: 3.135; p < 0.001), HCC treatment before LDLT >3 times (HR: 4.205; p = 0.024), and postoperative HCC recurrence (HR: 4.54; p = 0.007) were independent risk factors for OS. In the HCC recurrence analysis, only NLR >4.5 (HR: 9.869; p = 0.006) and HCC treatment before LT>3 times (HR: 20.22; p < 0.001) were independent risk factors.

Conclusions: LDLT can be a valuable therapeutic option for selected patients in BCLC intermediatestage HCC.

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P.065

ERITORAN ATTENUATES HEPATIC INFLAMMATION AND FIBROSIS IN MICE WITH NONALCOHOLIC STEATOHEPATITIS Yun-Cheng Hsieh, Kuei-Chuan Lee, Pei-Shan Wu, Yi-Hsiang Huang, Han-Chieh Lin, Ming-Chih Hou Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan

Eritoran 改善脂性肝炎小鼠之肝發炎 與纖維化 謝昀蓁 李癸汌 吳佩珊 黃怡翔 林漢傑 侯明志 臺北榮民總醫院肝膽胃腸科 Background: Toll-like receptor (TLR) 4 signaling plays an important role in liver fibrogenesis, which activates hepatic stellate cells (HSCs) and kupffer cells by recognizing lipopolysaccharide.

Aims: We aimed to investigate the effects of eritoran, a TLR-4 antagonist, on liver inflammation and fibrosis in mice with nonalcoholic steatohepatitis (NASH).

Methods: Mice fed with 12-week normal chow or fast food diet (FFD) randomly received eritoran (5 mg/kg) or vehicle intraperitoneally twice a week for further 12 weeks.

Results: In FFD-fed mice, eritoran reduced liver inflammation without altering hepatic steatosis or insulin resistance. Hepatic neutrophil accumulation and monocyte chemoattractant protein-1 expression were decreased by eritoran treatment. In addition, eritoran attenuated liver fibrosis through suppression of HSC activation with downregulation of hepatic α-smooth muscle actin and transforming growth factor-β1. Furthermore, eritoran significantly suppressed hepatic TLR4 downstream signaling pathway by decreasing the expression of myeloid differentiation primary response 88 (MyD88), and the nuclear translocation of NF-kB. Conclusions: Eritoran attenuated hepatic inflammation and fibrosis in mice with NASH through suppression of hepatic TLR-4 signaling.

Targeting TLR-4 pathway may serve as a potential treatment for NASH.

P.066

REPROGRAMMING OF MATERNAL HIGH-FAT DIET-INDUCED FETUS LIVER INJURY VIA BUTYRATE Mao-Meng Tiao, Yu Hsuan Liao, Yi-Ting Lu, Yu-Jyun Huang Department of Pediatrics, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University, Kaohsiung, Taiwan

丁酸重編程產婦高脂飲食誘導的胎兒 肝損傷 刁茂盟 廖祐玄 盧怡庭 黃伃㚬 高雄長庚紀念醫院小兒科暨長庚大學 Background: The maternal high-fat diet can impact offspring rat liver and development of NAFLD. Aims: Our aim is to study the effect of butyrate on fetus liver injury caused by maternal high-fat diet.

Methods: After confirmation of pregnancy on the 14th day after mating, pregnant females SpragueDawley rats are randomly divided for the maternal high-fat diet (MH) group exposure paradigm or normal control diet (NC) until delivery. The other maternal high-fat diet rats were fed with sodium butyrate as MHS group. The fetus was sacrificed at gestation 21 days.

Results: Shortened ileum villi in MH group in both pregnant mother and fetus were recovered in MHS group. Maternal liver histology of lipid accumulation with steatosis in MH group was recovered in MHS group. Fetal liver histology of increased IL6 in MH group was decreased in MHS group. The Western blot of caspase 3 (apoptosis), TNF-alpha (inflammation) in fetus liver was decreased in MHS group compared to MH group (P<0.05). PhosphorAKT (survival), GPX1 (antioxidative stress) was higher in MHS group than MH group (P<0.05).

Conclusions: Oxidative stress with inflammation plays a vital role in the fetus liver after maternal high fat diet, and prenatal butyrate may reprogram this.

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P.067

PERFORMANCE OF ULTRASOUNDGUIDED BIOPSY FOR THE DIAGNOSIS OF FOCAL LIVER LESIONS Shang-Chi Wang1, Yun-Liang Chang1, Lee-Won Chong1,2, Hung-Chuen Chang1,2, Yu-Hwa Liu1, Cheuk-Kay Sun1, Kou-Ching Yang1, Yu-Min Lin1,2 Division of Gastroenterology and Hepatology, Department of Internal Medicine, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan1 School of Medicine, Fu Jen Catholic University, Taipei, Taiwan2

對於診斷局部肝臟病灶超音波導引切 片檢查的表現 王上齊1 張允亮1 張麗文1,2 張鴻俊1,2 劉玉華1 孫灼基1 楊國卿1 林裕民1,2 新光吳火獅紀念醫院胃腸肝膽科1 天主教輔仁大學醫學院2 Background: The diagnosis of hepatic neoplasms was highly dependent on image examination.

However, the role of liver biopsy for liver lesion in the era of dynamic image was not clear.

Aims: We aimed to understand the value of biopsy after dynamic imaging (DI) for the diagnosis of focal liver lesions (FLL).

Methods: We retrospectively evaluated reports from the liver biopsy (LB) database in a single hospital between January 2018 and December 2019. Individuals underwent biopsy with the indication of FLL were enrolled. By reviewing their medical history, patients with a DI (CT or MR) for FLL within 6 months prior to LB were included for analysis. The yields of liver biopsy include conclusive rate, consistency rate and amended rate were determined by comparing the histology results with the diagnosis made by DI. Results: A total of 240 LBs was performed within the periods. There were 198 LBs meet the criteria for diagnosing FLL. Neoplastic, non-neoplastic and inconclusive lesions were 131 (66.2%), 16 (8.1%) and 51 (25.8%) respectively. The conclusive pathology of neoplasms included: HCC (52), intrahepatic cholangiocarcinoma (22), metastatic tumor (45), and others (12). The consistency between LB and DI for diagnosis of primary hepatic tumor, metastatic tumor and others were

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68.3%, 95.5%, and 30.8% respectively (p<0.01).

There were 21 (10.6%) lesions changed their initial diagnosis after LB. Conclusions: The LB was conclusive in 147/198 FLL (74.2%). About 10% of imaging diagnosis for FLL will be amended after LB. The consistency between DI and LB for the diagnosis of FLL were variable among different pathologies. These findings suggest even in the era of advanced imaging techniques, liver biopsy remains an irreplaceable diagnostic tool.

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Section：GI P.068

P.069

Dinesh Kumar Patel, Kanika Patel

Jia-Feng Wu1, Chia-Hsiang Yang2, Ping-Huei Tseng3

THERAPEUTIC BENEFIT AND BIOLOGICAL POTENTIAL OF ASTILBIN IN THE MEDICINE: MEDICINAL IMPORTANCE IN THE NEURODEGENERATIVE DISORDERS Department of Pharmaceutical Science, Sam Higginbottom University of Agriculture, Technology and Sciences, Payagraj, India Background: Herbal medicine have numerous health beneficial aspects in the medicine due to the presence of different phytochemical. Astilbin is an important pure phytochemical belongs to the flavonoidal class chemical compound found to be present in the Smilax and Hypericum perforatum.

Aims: In the modern medicine astilbin has numerous important biological applications as it have anti-inflammatory, antioxidant and free radicals scavenging properties.

Methods: In order to know the biological potential of astilbin in the medicine for their effectiveness against various brain complications, here in the present investigation numerous scientific data have been collected and analyzed for the biological potential of astilbin. Biological importance of astilbin in serotonin (5-HT) and dopamine (DA) level have been investigated through scientific data analysis of different research work.

Results: From the scientific data analysis of different research work in the medicine and other allied field it was found that astilbin has huge biological potential in the medicine due to their biological potential and pharmacological activities.

Scientific data analysis of various research works revealed the biological importance of astilbin in the medicine for the treatment of memory degenerative disorders through effectiveness of astilbin in different behavioral experimental model of animals including forced swimming test, open field test and tail suspension test.

Conclusion: From the scientific data analysis of different research work, it was found that astilbin has beneficial potential for the treatment of numerous memory degenerative disorders.

PRESSURE-IMPEDANCE ANALYSIS ASSISTED THE DIAGNOSIS AND CLASSIFICATION OF INEFFECTIVE ESOPHAGEAL MOTILITY DISORDER Department of Pediatrics, National Taiwan University Hospital, Taipei, Taiwan1 Department of Electrical Engineering, National Taiwan University, Taipei, Taiwan2 Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan3

壓力合併阻抗訊號分析在高解析食道 壓力阻抗檢測能加強無效性食道蠕動 異常的診斷 吳嘉峯1 楊家驤2 曾屏輝3 台大醫院小兒部1 台灣大學電機系2 台大醫院內科部3 Background: Ineffective esophageal motility (IEM) is one of the most common esophageal motility disorders, with an estimated prevalence of approximately 20–30%.

Aims: We elucidated the clinical significance of distal contractile integral-to-esophageal impedance integral (EII) ratio (DCIIR) in ineffective esophageal motility (IEM) adult patients.

Methods: We recruited 101 patients with IEM (48.38 ± 1.58 years) and 42 matched healthy volunteers (44.28 ± 1.85 years) in this case– control study. All subjects underwent esophageal high-resolution impedance manometry from October 2014 to May 2018. The diagnosis of IEM was based on the Chicago Classification version 3.0. The EII, EII ratio, and DCIIR were analyzed by MATLAB software.

Results: The EII, EII ratio, and DCIIR calculated at an impedance threshold of 1500Ω (EII1500, EII ratio1500, and DCIIR1500, respectively) were significantly lower in the IEM group than in healthy controls (P < 0.0001, < 0.0001, and < 0.0001, respectively). Receiver operating characteristic analysis showed that a DCIIR1500 < 0.008 mmHg/Ω, EII1500 > 71000 Ω.s.cm, and EII ratio1500 > 0.43 were all predictive of IEM. Only DCIIR1500 < 0.008 mmHg/Ω remained

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significant in diagnosing IEM in the multivariate logistic regression analysis (odds ratio = 72.13, P < 0.001). The DCIIR1500 is negatively correlated with Eckardt score and the Reflux Disease Questionnaire (correlation coefficient = –0.2844 and –0.3136; P = 0.0006 and 0.0002, respectively).

Receiver operating characteristic analysis further showed that a DCIIR1500 cutoff of 0.002 mmHg/Ω achieved the best differentiation between the IEMalternans and IEM-persistens subtypes among IEM patients (P < 0.001).

Conclusions: The novel pressure-impedance parameter of HRIM, DCIIR1500, may assist in the diagnosis and classification of IEM and correlated with clinical symptoms.

P.070

THE AMINO ACID POLYMORPHISMS OF IMAA OF H. PYLORI CORRELATED TO HOST GASTRIC MUCOSAL INTEGRIN Α5Β1 EXPRESSION AND THE DEVELOPMENT OF OLGA AND OLGIM STAGES III-IV Hsiu-Chi Cheng1,2, Hsiao-Bai Yang3,4, Chung-Tai Wu1,2, Wei-Lun Chang1, Wei-Ying Chen1, Yu-Ching Tsai5, Bor-Shyang Sheu1,6,7 Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan1 Institute of Clinical Medicine, College of Medicine, National Cheng Kung University, Tainan, Taiwan2 Department of Pathology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan3 Department of Pathology, Ton-Yen General Hospital, Hsinchu, Taiwan4 Department of Internal Medicine, Tainan Hospital, Ministry of Health and Welfare, Tainan, Taiwan5 Graduate Institute of Clinical Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan6 Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Chung-Ho Memorial Hospital, Kaohsiung, Taiwan7

幽門桿菌 ImaA 胺基酸多型性與宿主胃 細胞表面接受體 α5β1 的表現，以及進 展成 OLGA 與 OLGIM 第三和第四期 有關 鄭修琦1,2 楊曉白3,4 吳忠泰1,2 張維倫1 陳威穎1 蔡郁清5 許博翔1,6,7 國立成功大學醫學院附設醫院內科部1 國立成功大學醫學院臨床醫學研究所2 國立成功大學醫學院附設醫院病理部3 東元醫院病理科4 衛生福利部台南醫院內科部5 高雄醫學大學臨床醫學研究所6 高雄醫學大學附設中和紀念醫院內科部胃腸內科7

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Background: ImaA, an outer membrane protein of Helicobacter pylori (H. pylori), reduces cag pathogenicity island-dependent inflammation via degrading the host integrin β1 and antagonizing the interaction between H. pylori type-IV secretion system and integrin α5β1. A region between codon 42 and 1008 of ImaA amino acid sequence plays the main regulatory function.

Aims: This study aimed to validate whether amino acid polymorphisms of ImaA prime gastric integrin α5β1 and induce precancerous conditions.

Methods: Subjects who were indicated to receive gastroscopy were enrolled to obtain gastric tissues for H. pylori culture, integrin α5β1 immunohistochemistry staining, and inflammation and precancerous lesion evaluation. The amino acids of ImaA were directly sequenced by polymerase chain reaction.

Results: A total of 145 subjects were enrolled, including 69 females. The mean age of patients was 52.6 years. The amino acid polymorphism of ImaA, 536N>D/S/T, had higher integrin α5β1 supranuclear/apical priming in corpus of all subjects (OR 2.933 [1.081~7.937], P=0.032) and OLGA stages III-IV in subjects ≥ 40 y/o (OR 2.793 [1.070~7.299], P=0.032). There were seven amino acid polymorphisms of ImaA which were correlated with OLGIM stages III-IV in subjects ≥ 40 y/o, including 414G>S/E/N (OR 6.623 [0.847~52.632], P=0.043), 434A/S>T (OR 6.214 [1.384~27.910], P=0.008), 457T/K>Q (OR 5.149 [1.451~18.272], P=0.006), 490H/S/G>N (OR 5.273 [1.168~23.800], P=0.018), 536S>N/ D/T (OR 6.993 [0.890~55.556], P=0.040), 670672GNS/others>DHN (OR 5.892 [1.310~26.496], P=0.011), and 892-893 SD>TN/AN/NN/NS (OR 6.897 [0.878~55.556], P=0.041). Combining these amino acid polymorphisms, the H. pylori strains which ImaA polymorphisms were 414S/E/N, 434T, 457Q, 490N, 536N/D/T, 670-672DHN, and 892893TN/AN/NN/NS induced higher rate of OLGIM stages III-IV in subjects ≥ 40 y/o than those which did not have the polymorphisms (40.0% vs. 10.4%, OR 5.714 [2.262~14.437], P<0.001).

Conclusions: H. pylori ImaA amino acid polymorphisms were correlated with integrin α5β1 supranuclear/apical priming, OLGA stages III-IV, and OLGIM stages III-IV. Combined polymorphisms as 414S/E/N, 434T, 457Q, 490N, 536N/D/T, 670-672DHN, and 892-893TN/AN/NN/ NS, we may predict a ≥40 y/o subject who was infected by such an H. pylori strain to have an OR as high as 5.7 to develop precancerous conditions as OLGIM stages III-IV.

P.071

SHORT-TERM OUTCOMES OF DIFFERENT MODALITIES OF PYLOROMYOTOMY VERSUS GASTRIC ELECTRICAL STIMULATION IN THE TREATMENT OF GASTROPARESIS: A SYSTEMIC REVIEW AND META-ANALYSIS Sz-Iuan Shiu, Shih-hsiung Shen, Hong-Zen Yeh Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan

針對不同術式的幽門切開術和胃電刺 激對於胃輕癱的短期預後之比較：系 統性文獻回顧與統合分析 許斯淵 沈士雄 葉宏仁 臺中榮民總醫院肝膽胃腸科 Background: Current guideline recommends several therapeutic options for gastroparesis after failure of dietary modification and tailored doses of prokinetic medications. However, the optimum intervention of gastroparesis remains elusive.

Aims: The aim of this meta-analysis was to compare the short-term outcomes of efficacy, and complication rate between different modalities of pyloromyotomy and gastric electrical stimulation (GES) in the treatment of gastroparesis.

Methods: Comprehensive, computerized research was performed on PubMed, Embase, and Cochrane Central Register of Controlled Trials, and we reviewed relevant articles published before 15 April 2020 without any language limitations. Metaanalysis was conducted by RevMan 5.3 software.

Results: Three studies totaling 196 participants who received 4 interventions were eligible for analysis including single per-oral pyloromyotomy (POP), double POP, laparoscopic pyloromyotomy (LP), and GES. Compared to single POP, double POP achieved better clinical response with pooled RR of 1.27 (95% CI, 1.01-1.60, p = 0.04) while GES and LP showed no difference with pooled RR of 0.87 (95% CI, 0.73-1.04, p = 0.13) and 0.89 (95% CI, 0.74-1.08, p = 0.23) separately.

As for recurrence and complication rate, only GES had borderline significance of recurrence in comparison to single POP (RR 2.17, 95% CI, 1.004.71, p = 0.05) and there was no difference in the

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rest of comparisons.

Conclusions: We conducted a detailed comparison of three modalities of pyloromyotomy and GES in the treatment of gastroparesis and the results suggest double POP demonstrated better clinical success with similar recurrence and complication rate. In addition, GES might result in more recurrence among these interventions.

P.072

TREND IN ANTIBIOTIC RESISTANCES CHANGES OF HELICOBACTER PYLORI FROM 2013 TO 2019: A MULTICENTER REPORT FROM TAIWAN Chih-Ming Liang1,2, Pin-I Hsu3, Deng-Chyang Wu4, Wei-Chen Tai1,2, Feng-Woey Tsai5, Chia-Long Lee6, Hsi-Chang Lee7, Kuan-Yang Chen7, Seng-Kee Chuah1,2 Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan1 Chang Gung University College of Medicine, Taoyuan, Taiwan2 An Nan Hospital, China Medical University, Tainan, Taiwan3 Kaohsiung Medical University Hospital, Kaohsiung, Taiwan4 Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan5 Cathay General Hospital, Taipei, Taiwan6 Taipei City Hospital, Taipei, Taiwan7

胃幽門螺旋桿菌抗藥性改變的趨勢 （2013-2019 年） ：台灣多中心的報告 梁志明1,2 許秉毅3 吳登強4 戴維震1,2 蔡峯偉5 李嘉龍6 李熹昌7 陳冠仰7 蔡成枝1,2 高雄長庚紀念醫院胃腸肝膽科1 長庚大學醫學系2 台南市立安南醫院消化內科3 高雄醫學大學附設醫院胃腸內科4 高雄榮民總醫院胃腸肝膽科5 國泰綜合醫院胃腸內科6 臺北市立聯合醫院消化內科7 Background: The prevalence of antibiotic resistance of Helicobacter pylori (H. pylori) varies among countries and may be partly determined by geographical factors. The use of first-line H. pylori eradication with standard triple therapy, which consists of a proton pump inhibitor (PPI), clarithromycin and amoxicillin, might lead to a poor outcome (< 80%) due to increase of clarithromycin resistance. However, the eradications rates had been increased to > 90 % by the use of various effect treatment regimens such as high dose dual therapy, hybrid and reverse hybrid therapy, bismuth and non-bismuth quadruple therapies.

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Clearly, antibiotic resistance determines the success of eradication.

Aims: To determine the trend in the primary, secondary and tertiary antibiotic resistances of H. pylori in Taiwan.

Methods: We analyzed H. pylori-infected isolates from patients before first-line eradication therapy (n = 1369), second line eradication therapy (n =196), and third line eradication therapy (n = 184) from January 2013 to December 2019. The H. pylori strains were tested for susceptibility to amoxicillin, clarithromycin, levofloxacin, metronidazole and tetracycline using the E-test method. The minimal inhibitory concentration (MIC) was determined by the agar dilution test. MIC values of ≥ 0.5, ≥ 1, ≥ 1, ≥ 4 and ≥ 8 mg/L were considered to be the resistance breakpoints for amoxicillin, clarithromycin, levofloxacin, tetracycline and metronidazole, respectively.

Results: A progressively higher primary resistance rate was observed for clarithromycin (11.8%-20.4%, p = 0.039 in χ2 test for linear trend), levofloxacin (17.3%-38.8%, p < 0.001) and metronidazole (25.6%-42.3%, p < 0.001) among patients who receiving first-line eradication therapy. The similar upward resistance trends were found for secondary resistance for levofloxacin (30.5%-64.7%, p = 0.006) and (40.5%-77.4%, p < 0.001), and tertiary resistance for metronidazole and tertiary resistance for metronidazole (44.4%88.2%, p = 0.014). The tertiary resistance for levofloxacin increase from 65.9% in year 2013 to 100.0% in year 2019 (p = 0.106). The resistance to amoxicillin and tetracycline remained very low in Taiwan (Amoxicillin: 0.6%-1% for primary resistance, p = 0.800; 0% for secondary resistance; 0-5.6% for tertiary resistance, p = 0.236; Tetracycline: 0% for primary resistance, p = 0.178; 4.3%-7.1%, p = 0.459; 0%-7.7%, p = 0.087).

Conclusions: Primary, secondary and tertiary antibiotics resistance of clarithromycin, levofloxacin and metronidazole for H. pylori has been increasing in the past 7 years in Taiwan.

High clarithromycin resistance (>20%) indicated that more effective treatment options such as high dose dual therapy, hybrid and reverse hybrid therapy, bismuth and non-bismuth quadruple therapies should be prescribed as a first-line H. pylori eradication therapy in Taiwan. Levofloxacinbased triple therapy should also be replaced for second line therapy. Third line treatment should be antibiotic susceptibility based.

P.073

SAFETY OF COLD SNARE POLYPECTOMY FOR COLORECTAL POLYPS ON CONTINUOUS ANTITHROMBOTIC: A SYSTEMATIC REVIEW AND META-ANALYSIS Jen-Hao Yeh1,2, Chih-Wen Lin1,2, Wen-Lun Wang2, Ching-Tai Lee2, Cheng-Hao Tseng2,3, Tsung-Chin Wu1, Po-Jen Hsiao1, Jaw-Yuan Wang4 Division of Gastroenterology and Hepatology, Department of Internal Medicine, E-DA Hospital/I-shou University, Da-Chung Branch, Kaohsiung, Taiwan1 Division of Gastroenterology and Hepatology, Department of Internal Medicine, E-DA Hospital/I-shou University, Kaohsiung, Taiwan2 Division of Gastroenterology and Hepatology, Department of Internal Medicine, E-DA Cancer Hospital/I-shou University, Kaohsiung, Taiwan3 Division of Colorectal Surgery, Department of Surgery, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan4

大腸息肉冷切除於持續服用抗栓劑下 的安全性：系統回顧與統合分析 葉人豪1,2 林志文1,2 王文 吳宗勤1 蕭博仁1 王照元4

2

李青泰2 曾政豪2,3

義大大昌醫院胃腸肝膽科1 義大醫院胃腸肝膽科2 義大癌治療醫院胃腸肝膽科3 高雄醫學大學附設中和紀念醫院大腸直腸外科4 Background: Cold-snare polypectomy (CSP) has replaced hot snare polypectomy (HSP) as the standard for colorectal polyps ≤ 1 cm. However, the safety of CSP for patients on continuous antithrombotics has not been systematically reviewed.

Aims: To investigate the he safety of CSP for patients on continuous antithrombotics.

Methods: We performed a systematic review of the PubMed, Embase, and Cochrane databases through June 2020. Primary outcomes were immediate bleeding, delayed bleeding, and postpolypectomy bleeding rates of CSP on continuous anthrombotics. Meta-analysis was performed to compare the outcomes with HSP or to patients

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without periprocedural antithrombotics by odds ratios (OR) with 95% confidence interval (CI).

Results: Eleven studies including including 5636 patients and 15577 colorectal lesions were enrolled. The meta-analysis showed significantly lower delayed bleeding (4.6% vs. 12.1%, OR 0.35, 95% CI, 0.18 – 0.70) of CSP than that of HSP in patients on antithrombotics, with similar immediate bleeding rates (6.9% vs. 5.9%, OR, 0.70, 95% CI, 0.08 – 6.20). On the other hand, CSP with continuous antithrombotics significantly increased immediate bleeding rate (12.8% vs. 4.4%, OR, 3.04, 95% CI, 2.32 – 3.98), and delayed bleeding rate was also increased with low occurrence (0.48% vs. 0.14%, OR 3.14, 95% CI, 1.22 - 8.05).

Nevertheless, sensitivity analysis suggested antithrombotics was not associated with more delayed bleeding with CSP (risk difference 0.002, 95% CI: -0.001 – 0.005). Post-polypectomy bleeding rate was not influenced by the technique and antithrombotics.

Conclusions: CSP for colorectal polyps ≤ 1cm is safe for patients with continuous antithrombotics, as long as immediate bleeding is properly managed in the earliest time.

P.074

CLINICAL APPLICATION OF ARTIFICIAL INTELLIGENCE TO HELP COLON POLYP DETECTION DURING COLONOSCOPIC EXAMINATION Chih-Sheng Hung1,2,3, Chia-Long Lee1,2, Hsin-Yu Chen1,2, Ting-Chun Huang1,2, Chi-Kun Chiang1,2, Tien-Chien Tu1,2, Ching-Yi Lee4, Joe Yeh4, Allison An1 Division of Gastroenterology, Department of Internal Medicine, Cathay General Hospital, Taipei, Taiwan1 School of Medicine, Fu-Jen Catholic University, New Taipei City, Taiwan2 School of Medicine, Taipei Medical University, Taipei, Taiwan3 Aether AI, Taipei, Taiwan4

以電腦人工智慧學習輔助大腸鏡檢查 時息肉的偵測 洪志聖1,2,3 李嘉龍1,2 陳信佑1,2 黃鼎鈞1,2 江技坤1,2 涂天健1,2 李青怡4 葉肇元4 安貞臻1 國泰綜合醫院胃腸科1 天主教輔仁大學醫學院醫學系2 臺北醫學大學醫學院醫學系3 雲象科技公司4 Background: Computer assisted artificial intelligence (AI) has been widely developed in medical image diagnosis in recent years. AI can help doctors to identify image abnormalities easily from deep neural network learning experiences.

This new computed technology changes the traditional medical science and help physicians to early find abnormalities with the help of artificial intelligence.

Aims: We set up a computer training model and try to use deep neural network learning to help gastroenterologist to mark and identify colon polyps during colonoscopic examination.

Methods: We collected 146397 colon images (3215 subjects received colonoscopic examination and 20543 colonic polyps detected by gastroenterologists) in Cathay General Hospital-Taipei from January 1st -2016 to April 30th -2020. All these images were sent to AI training model (Yolov 4, CSPDarknet53, set up

by Hong-Yuan Mark Liao and Chien-Yao Wang).

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Normal colonic mucosa, small fecal particles, air bubbles, colon cancer and colon polyps were marked by endoscopists previously and we trained computer how to differentiate polyps from other abnormalities (fecal materials, air bubbles, colon malignancy etc) and normal colonic mucosa. After trained computer AI, 17 real time colonoscopic videos (including 2515 images and 724 of them contain colon polyps) were conducted to test the polyp detection rate.

Results: The positive predict rate and sensitivity to identify colon polyps during these real-time colonoscopic examinations are 95.58% and 91.91% individually. The polyp detection rate by AI is not inferior to expert endoscopists. Computer can easily differentiate colon polyps from fecal materials, small air bubble, normal and abnormal colonic mucosa more than 90% accuracy during colonoscopic examination.

Conclusions: Deep neurological network training is a potential new technology to help endoscopists to mark and find colon polyps during colonoscopic examination. It can be used to assist young trainee in endoscopic training and decrease the polyp misdiagnosis during endoscopic examination.

P.075

PERORAL ENDOSCOPIC MYOTOMY (POEM) FOR ACHALASIA: A SINGLE MEDICAL CENTER EXPERIENCE IN KAOHSIUNG Yu-Chi Li1,2, Keng-Liang Wu1,2, Seng-Kee Chuah1,2, Wei-Chen Tai1,2 Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan1 College of Medicine, Chang Gung University, Taoyuan, Taiwan2

經口內視鏡肌肉切開術治療食道弛緩 不能：一個高雄醫學中心的經驗 李育騏1,2 吳耿良1,2 蔡成枝1,2 戴維震1,2 高雄長庚紀念醫院胃腸肝膽內科1 長庚大學醫學院2 Background: Achalasia is a primary esophageal motor disorder of unknown etiology characterized manometrically by insufficient relaxation of the lower esophageal sphincter (LES) and loss of esophageal peristalsis. Achalasia equally affects both sexes and all ethnicities and it is one of the rare primary motility dysfunctions of the esophagus which has no curative treatment.

Peroral endoscopic myotomy (POEM) was a revolutionized treatment of achalasia and was first described in 2010 by Professor Inoue.

Aims: We aimed to evaluate the safety and clinical efficacy of POEM for achalasia patients in Kaohsiung CGMH. Methods: We retrospectively enrolled the patients who received POEM for achalasia between July 2015 and May 2020 from Kaohsiung Chang Gung Memorial Hospital. We recorded the information by chart review, including the patient characteristics (age, sex, body mass index), pre- and post-POEM LES pressure, pre- and post-treatment Eckardt score, procedure time of POEM, and post POEM complication or symptom.

Results: 32 patients (19 female, 59%) who underwent POEM were enrolled into this study.

The mean age is 46.3 years old. The mean BMI is 20.6. There are 10 patients received highresolution manometry (HRM). Six patients were diagnosed as type I achalasia and 4 patients as

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type II according to Chicago classification. The mean pre-POEM LES pressure was 34.8 mmHg and post-POEM 3months LES pressure was 21.5 mmHg. The average POEM time was 47.4mins.

The average Eckardt score improved from 8.3 to 0.7 after POEM. The average postoperative follow up time was 16.5months. There was no POEM related immediate or delayed major bleeding or complication. Three patients had fever and one patient had asthma after POEM during admission.

Seven patients had previous endoscopic-guided pneumatic dilatation for achalasia before POEM. There was only one patient received two times POEM due to recurrent symptom of dysphagia.

Six patients (18%) had Gastroesophageal reflux disease (GERD) after POEM procedure.

Conclusions: Our data showed that the POEM treatment for achalasia was safe and low complication. Besides, the achalasia symptom and Eckardt score also got improved after treatment.

However, there was about 18% of patients had GERD after treatment.

P.076

OPTIMAL TIMING OF SINGLESTAGE RETROGRADE ENDOSCOPIC COMMON BILE DUCT STONE REMOVAL IN MILD AND MODERATE ACUTE CHOLANGITIS: A PROSPECTIVE TRIAL Hsin-Wei Fang, Chih-Ming Liang, Yi-Chun Chiu, Lung-Sheng Lu, Cheng-Kun Wu, Fai-Meng Sou, Pao-Yuan Huang, Te-Ling Ma, Chung-Huang Kuo, Seng-Kee Chuah, Chung-Mou Kuo Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan

輕中度急性膽管炎併有膽管結石進行 一階段內視鏡膽道取石術的適當時機 ─ 一個前瞻性試驗 方信為 梁志明 邱逸群 盧龍生 吳鎮琨 蘇輝明 黃寳源 馬德齡 郭仲煌 蔡成枝 郭仲謀 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: Choledocholithiasis is the most common cause of biliary obstruction leading to cholangitis. The evidence supporting the feasibility of single-stage stone removal in patients with moderate acute cholangitis remains insufficient.

Aims: In this study, we aimed to compare the efficacy and safety of removing a single-stage, retrograde, endoscopic common bile duct stone in patients with mild and moderate acute cholangitis associated with choledocholithiasis.

Methods: We enrolled 196 endoscopic retrograde cholangiopancreatography (ERCP)-naïve patients diagnosed with acute cholangitis and choledocholithiasis between September 2018 and February 2020 at a single hospital. For eligible patients, single-stage treatment involved stone removal at initial ERCP. Early ERCP was defined as ERCP performed ≤ 72 hours following diagnosis in the emergency room.

Results: The final analysis included 138 patients.

The success rate of complete stone extraction was similar in patients with mild and moderate cholangitis (88.5% vs. 91.7%; p = 0. 536).

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Complication rates were also comparable between the two groups. In the moderate cholangitis group, the length of hospitalization declined significantly among patients who underwent early singlestage ERCP (10.6 ± 6.1 vs. 18.7 ± 12.5 days; p = 0.001) compared with patients treated with delayed ERCP. In the multivariate analysis, early ERCP indicated shorter hospitalization times (≤ 10 days) (odds ratio (OR), 7.689; p = 0.030), while endoscopic retrograde biliary drainage, for acute cholangitis only, indicated longer hospitalization times (OR, 0.358; p = 0.030). A stone size larger than 1.5 cm was an independent risk factor for stone extraction failure (OR, 24.507; p = 0.009).

Conclusions: Single-stage, retrograde, endoscopic common bile duct stone removal may be safe and effective for patients with mild and moderate cholangitis. The benefit of early singlestage ERCP (≤ 72 hours) was reflected mainly by reduced hospitalization time and costs.

P.077

PEPTIC ULCERS: A NATIONWIDE POPULATION-BASED STUDY OF TAIWAN (ONE-YEAR DATA) Yu-Hsien Lin1, Ping-Tze Chen1,2, Yuan-Kuei Li1, Hong-Ming Chao1 Department of Surgery, Taoyuan Armed Forces General Hospital, Taoyuan, Taiwan1 Department of Surgery, Ministry of Health and Welfare SinYing Hospital, Tainan, Taiwan2

以健保資料庫探討台灣消化性潰瘍之 盛行率及併發症發生率 林昱賢1 陳秉澤1,2 李元魁1 趙宏明1 國軍桃園總醫院外科部1 衛生福利部新營醫院外科部2 Background: Peptic ulcer disease (PUD) refers to a defect or break in the gastrointestinal mucosa in the stomach or duodenum. The incidence of peptic ulcer disease has decreased in recent decades due to advances in drug treatment; however, it remains a significant cause of morbidity and a major contributor to healthcare costs.

Aims: Our objective in this study was to estimate the incidence of peptic ulcer disease and the complication rates (bleeding and perforation), based on expenditures incurred by medical facilities listed in the National Health Insurance Research Database (NHRID) of Taiwan for 2013.

Methods: Comparisons were conducted between inpatients with peptic ulcers and those who underwent surgery in terms of medical expenses and hospital outcomes. Variables for the length of hospital stay and mortality were characterized using logistic regression.

Results: The 280,167,685 records of inpatients in the nationwide database listed 100,767 patients (0.0359%) hospitalized due to peptic ulcer disease.

Among these, 334 patients underwent surgery due to uncontrolled hemorrhage or perforation. The average medical expenditures were as follows: peptic ulcer patients (48,857 NTD) and peptic ulcer patients who received surgery (199,353 NTD). The average hospital stays were as follows: peptic ulcer patients (8.40 days) and peptic ulcer patients who underwent surgery (16.07 days).

Conclusions: Our results revealed that the incidence of peptic ulcers in 2013 ranged from

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27.87/100,000 to 39.33/100,000. These results are similar to a retrospective cohort study conducted in Finland. The results demonstrated that the accessibility and convenience of Taiwan’s medical care.

P.078

COMPARISONS OF THE EFFICACIES OF NON-BISMUTH CONTAINING QUADRUPLE THERAPIES IN THE TREATMENT OF FIRST-LINE ANTI-HELICOBACTER PYLORI DURING 5-YEAR INTERVAL FROM 2013: A TERTIARY CENTER REPORT Shih-Cheng Yang, Chih-Ming Liang, Lung-Sheng Lu, Wei-Chen Tai, Cheng-Kun Wu, Chih-Chien Yao, Keng-Liang Wu, 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

比較自 2013 年五年期間不含铋四合一 處方在第一線抗幽門桿菌療法治療成 功率的變化：一個醫學中心的研究報 告 楊世正 梁志明 盧龍生 戴維震 吳鎮琨 姚志謙 吳耿良 蔡成枝 高雄長庚紀念醫院暨長庚大學醫學院 Background: The first line eradication rate of standard triple therapy for Helicobacter pylori (H. pylori) infection has declined to < 80% relate to the increasing incidence of clarithromycin-resistant strains of H. pylori and novel therapies are needed.

Other alternatives include non-bismuth containing quadruple therapy (concomitant therapy), high dose dual therapy and hybrid therapy, which provide > or close to 90% eradication rates.

However, in areas with high rates of clarithromycin and metronidazole resistance, we assume the increasing antibiotics resistances may affect the efficacies of these treatment regimens over times.

Aims: To compare the efficacies of concomitant therapy in the treatment of first-line antiHelicobacter Pylori during 5-year interval from 2013 in Taiwan.

Methods: We recruited 197 eligible H. pyloriinfected patients in the intention-to-treat (ITT analysis) after excluding those who had taken antibiotics, bismuth, PPI, within 4 weeks, were allergic to the medications used, had history of

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previous gastric surgery or serious concomitant illness, currently pregnant or those who refused to participate. They were divided into two groups as EACM-A (enrolled from January 2013 to June 2016, N=98) and EACM-B (enrolled from June 2013 to December 2017, N=99). All patients were prescribed with 7-day non-bismuth quadruple therapy (Esomeprazole 40 mg bid., clarithromycin 500 mg bid., amoxicillin 1 g bid. and metronidazole 500 mg bid. for 7 days, EACM group, n=120).

Fourteen patients were lost during follow-up (8 in EACM-A and 6 in EACM-B), resulting in 90 for EACM-A group and 93 in the per protocol (PP) study for EACM-B group. Urea breath tests were followed-up 8 weeks later.

Results: The eradication rates for EACM-A and EACM-B groups were 87.8% (95% confidence interval [CI] = 79.64% to 93.54%) and 84.8% (95% CI = 76.19% to 91.23%) (p = 0.553) in intention-totreat (ITT) analysis; 95.6% (95% CI = 89.07% to 98.80%) and 90.3% (95% CI = 82.40% to 95.46%) (p = 0.168) in per protocol (PP) analysis. The adverse event rates were 16.7% vs. 10.8% in the 2 groups (p = 0. .244). The antibiotic resistance rates between the 2 groups were amoxicillin (0%), tetracycline (0%); clarithromycin (11.8% vs. 17.8%, p = 0.461); metronidazole (32.4% vs. 33.3%, p = 0.927) and levofloxacin (14.7% vs. 37.8%, p = 0.024). The multivariate analysis showed that resistant to metronidazole was the clinical factor for treatment failure.

Conclusions: A 7-days concomitant therapy achieved a > 90% H. pylori eradication rates in the PP analysis despite an increase of clarithromycin resistance rates from 11.8% in 2013 to 17.8% in 2017. However, both groups did not attain either grade A or B success rates. Metronidazole resistance was the clinical factor for treatment failure.

P.079

OPERATION OR NOT? DEVELOPMENT OF A MORTALITY RISK INDEX IN TREATMENT OF PERFORATED PEPTIC ULCER: A POPULATION BASED STUDY IN ASIA Yi-Kai Huang1,2, Jian-Han Chen1,2 Department of General Surgery, E-Da Hospital, Kaohsiung, Taiwan1 School of Medicine, I-Shou University, Kaohsiung, Taiwan2

面對胃腸穿孔的治療選擇：手術與保 守治療 黃羿凱1,2 陳建翰1,2 義大醫院外科部一般外科1 義守大學醫學院2 Background: We start this study is to identify the risk of failure nonoperative treatment, and to generate a reliable risk score system to help surgeon make the decision between nonoperative or surgical treatment to patients with perforated peptic ulcer.

Aims: To build a scoring system helping making decision if surgical treatment or not when perforated peptic ulcer.

Methods: We extracted admission data of adult (≥18 y/o) patients with perforated peptic ulcer disease from NHIRD database from January 1, 1996, to December 31, 2013 for analysis. The perforated peptic ulcer disease was defined by ICD-9 diagnostic code in the leading diagnosis of this admission. Patients were who received ulcer repair, ulcer excision, gastrectomy or laparoscopic procedure were also identified form the procedure codes of this admission. Patients with gastric cancer, with undetermined gender were excluded.

They are randomly divided into an 80% model derivation cohort and 20% validation cohort.

Multivariant analysis with COX regression model was applied to generate score system, PPUMS. Then, the scoring system was applied to validation group.

Results: After multivariant analysis, PPUMS score, range from 0 to 14 points, composite with Renal, Severe Liver Disease, Cancer with Meta score two points. Obese scores three point and Age scores varies of point depending on ages.

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Among these factors, patients who score below 4 points have lowest mortality rate (3.2%), whereas, patients who score between 4-8 points have 18.7% and patients who score over eight points have 40.5% mortality rate. In derivation group, patients with PPUMS beyond 8 points had similar mortality risk between operation group (38.9%) and non-operation group (46.8%) (OR: 0.721, p = 0.128). In validation cohort group, patients with PPUMS beyond 8 points had also similar mortality risk between operation group (38.9%) and nonoperation group (46.8%) (OR: 0.736, p = 0.502).

Conclusions: PPUMS is a good predictor for mortality risk of patients who suffer from PPU and with varies of underlying disease or comorbidities.

When Patients suffering from PPU with PPUMS 0 to 8 points, surgical management is suggested due to lower risk of mortality. However, while it goes to patients with PPUMS over 8 points, operation may do limited benefit due to high mortality rate compared to nonoperative treatment.

P.080

FEASIBILITY AND APPLICATIONS OF PORTABLE MAGNETIC ASSISTED CAPSULE ENDOSCOPY ON HOME CARE PATIENTS Yang-Chao Lin1,3,5, Chen-Ching Lin2, Chih-Kuang Liu2,3, Ming-Chih Chen3 Division of Gastrointestinal and Hepatobiliary, Department of Internal Medicine, Fujen Catholic University Hospital, Taipei, Taiwan1 Department of Administration, Taipei City Hospital, Taipei, Taiwan2 Graduate Institute of Business Administration, College of Management, Fujen Catholic University, Taipei, Taiwan3 Department of Social Welfare, Taipei City Government, Taipei, Taiwan4 Department of Internal Medicine, Zhong-Xing Branch, Taipei City Hospital, Taipei, Taiwan5

可攜式磁控膠囊胃鏡檢查於居家醫療 患者之實用性評估 林暘朝1,3,5 陳靜琳2 劉志光2,3 陳銘芷3 天主教輔仁大學附設醫院胃腸肝膽科1 臺北市立聯合醫院院本部2 天主教輔仁大學管理學院商學研究所3 台北市社會局4 臺北市立聯合醫院中興院區內科部5 Background: Taiwan officially became an aged society with people over 65 years old breaking the 14% mark in 2018, the National Health Insurance Administration (NHIA) launched the National Health Insurance Integrated Home Care Project in February 2016, that allows health care professionals to visit the homes of elderly people with reduced mobility to provide more comprehensive services. Many elderly and disabled patients suffering gastrointestinal symptoms were noticed during home visits without definite endoscopic studies. With the introduction of newly invented Magnetic Assisted Capsule Endoscopy (MACE), InsightEyes EGD system.

Thanks for the compact size and disposable capsules, it becomes possible for endoscopists to perform endoscopic examinations for patients at home. Taipei City Hospital, Zhong-Xing Branch started to provide endoscopic examinations for home care patients in March, 2020. Total 15 patients were enrolled for gastrointestinal

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symptoms at the end of April, 2020.

Aims: We would like to evaluate the diagnostic outcomes and feasibility regarding patient tolerability, examination time and completeness of the procedure for home care patients.

Methods: We retrospectively collect data from HIS regarding patient age, sex, body mass index, major diseases, time to complete study, number of attempts to swallow the capsule, endoscopic landmarks recorded on the report sheets, endoscopic lesions. Microsoft Excel was used for statistical analysis.

Results: Of the 15 patients, 7 females and 8 males, aged from 47 to 99 years old, with mean age of 74, two patients were paralyzed, one had cerebral palsy, two had hearing impairments, others had certain physical impairments, all completed the capsule endoscopy without complications. An average of 2.2 attempts for each patient to successfully swallow the capsule into the esophagus. Mean time for physicians to complete each capsule endoscopy was 23.6 minutes. Average time to reach the duodenum bulb was about 10.2 minutes.

No vomiting or early termination of the procedure was recorded. Regarding the anatomic landmarks recorded during the examination, Fundus: 80%; Cardia: 80%; Body, Antrum, Angle, Pylorus: 100%; Duodenal bulb: 83%; 2nd portion: 80%; Papilla Vater: 27%; Duodenal 3rd portion: 27%. Each patient had been found average of 2.8 endoscopic lesions, mostly Reflux esophagitis, Gastric ulcers, Gastritis, Duodenitis, Pyloric stenosis...etc.

Conclusions: The novel portable magnetic assisted capsule endoscopy provides an access for elderly or disabled patients to receive endoscopic examinations at home. Our study was the first one to applicate this endoscopic system to diagnose patients at their homes, no post procedural complications were noted in this study, and all patients were treated according to the endoscopic findings. However, we had encountered some problems in terms of preendoscopy preparation, limitations in positioning of patients. In our study, cardia and fundus were not clearly observed in 20% of the patients, video clips showed much mucus and bubbles obscured the observation parts; and the disabled or elderly patients were difficult to change positions in our study. We were unable to reach the duodenum and more distal parts in 3 of the 15 patients, one had pyloric stenosis, the other two patients had been

changed positions, and it took over 20 minutes but still failed, might partly due to skill issues, and also partly due to it lacks shaft force to “push” into the duodenum compared to conventional endoscopy. Aside from the problems encountered during procedure, this pioneer study showed well tolerability of the patients, high diagnostic yield, and safety of capsule endoscopy.

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P.081

ANALYSIS OF PATIENTS UNDERGO EMERGENT UPPER GASTROINTESTINAL ENDOSCOPIC PROCEDURES DURING COVID-19 PANDEMIC IN ONE MEDICAL CENTER Meng-Yu Ko, Chia-Wei Yang, Hsu-Heng Yen, Yang-Yuan Chen Division of Gastroenterology and Hepatology, Changhua Christian Hospital, Changhua, Taiwan

在一個醫學中心對於 COVID-19 大流 行期間接受急診上消化道內視鏡檢查 的患者進行分析 柯孟佑 楊佳偉 顏旭亨 陳洋源 彰化基督教醫院胃腸肝膽科 Background: A novel and highly contagious severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) causes Coronavirus disease 2019 (COVID-19) which is currently pandemic worldwide. First appearing of COVID-19 was in Wuhan, China. The COVID-19 has made upper gastrointestinal (GI) endoscopy “high-risk” procedures during this pandemic. To evaluate the impact of COVID-19 on the endoscopic practice, we analyze the patterns of emergent endoscopic procedures during the period.

Aims: The impact that the outbreak of COVID-19 is having on the patients’ attitude to attend the emergency room (ER) in order to undergo endoscopic procedures is not clear. We conducted a retrospective study in our hospital to investigate to what extent the fear of COVID-19 has influenced the patients’ decision to undergo endoscopic procedures during the COVID-19 outbreak though prescribed as relatively emergent by the doctors in ER. Methods: For this retrospective study, we collected data from patients who attend the ER for emergent upper GI endoscopy in February, 01, 2019 to April, 30, 2019 and February, 01, 2020 to April, 30, 2020. Data collection was based on charge codes in our hospital. The inspection items are upper GI panendoscopy, endoscopic treatment in upper GI bleeding, esophageal variceal ligation transendoscopy, panendoscopic polypectomy, histoacryl injection for gastric variceal and upper

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Results: We have performed 365 upper GI endoscopic procedures from February, 01, 2019 to April, 30, 2019 and 245 upper GI endoscopic procedures from February, 01, 2020 to April, 30, 2020. Among them, in the period of 2019, there were 279 (76%) upper GI panendoscopy, 57 (16%) endoscopic treatment in upper GI bleeding, 19 (5%) esophageal variceal ligation transendoscopy, 4 (1%) histoacryl injection for gastric variceal and 4 (1%) upper GI pan-endoscopic foreign body removal, respectively. In the period of 2020, there were 171 (70%) upper GI panendoscopy, 49 (20%) endoscopic treatment in upper GI bleeding, 15 (6%) esophageal variceal ligation transendoscopy, 3 (1%) histoacryl injection for gastric variceal and 7 (3%) upper GI pan-endoscopic foreign body removal, respectively.

Conclusions: During the COVID-19 pandemic in 2020, the total numbers of upper GI endoscopic procedures were decreased and less than in 2019. But the percentage of upper GI bleeding, esophageal variceal ligation and foreign body removal were higher in 2020.

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P.082

THE REVIEW OF ASSOCIATION BETWEEN PSYCHIATRIC COMORBIDITY AND CAUSTIC INGESTION: OUTCOMES OF 396 CASES WITHIN 20 YEARS IN A NORTH TAIWAN MEDICAL CENTER Hao-Tsai Cheng1,2,3, Hsin-Chih Huang1,2, Ming-Yao Su1,2, Sen-Yung Hsieh2, Chen-June Seak4, Shu-Wei Huang1 Division of Gastroenterology and Hepatology, Department of Internal Medicine, New Taipei Municipal TuCheng Hospital, New Taipei, Taiwan1 Department of Gastroenterology and Hepatology, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan2 Graduate Institute of Clinical Medicine, College of Medicine, Chang Gung University, Taoyuan, Taiwan3 Department of Emergency Medicine, Linkou Medical Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan4

evaluation, treatment, and outpatient clinic followup. Statistical analyses were conducted using IBM SPSS, version 22.

Results: The mean age of 396 patients with PCs was 50.0 ± 18.4 at caustic ingestion, with a median follow-up period of 16.6 months. The overall survivals were: 88.6% (6-month), 86.1% (1year), 74.2% (5-year), and 53.2% (10-year). The presence of PCs predicted serious EGD grading, higher rates of admission/surgery/ICU stay, increment of systemic/upper-GI complications, and poor 5-year overall survival rate. Based on the univariate and multivariate analyses, poor overall survivals among patients with PCs were highly consistent with GI and systemic complications.

Conclusions: In our study, PCs changed clinical patterns and played critical roles in survival outcomes of caustic injury victims. Clinical awareness benefits either for mild cases to limit injuries or for severe ones to receive emergent interventions. Future studies based on worldwide populations are essential for realizing geographical differences.

腐蝕性物質在消化道傷害跟精神疾病 相關研究：一北台灣醫學中心 20 年的 經驗 鄭浩材1,2,3 黃欣智1,2 蘇銘堯1,2 謝森永2 薛承君4 黃書偉1 新北市立土城醫院胃腸肝膽科1 林口長庚紀念醫院胃腸肝膽科2 長庚大學臨床醫學研究所3 林口長庚紀念醫院急診科4 Background: Caustic substance ingestion is uncommon but life-threatening. Given the documented high prevalence of psychiatric comorbidities (PCs), how it affects clinical features and prognostic outcomes remain unclear due to scarce discussion.

Aims: This study reported detailed clinical courses with long-term multifaceted outcomes, and reviewed the association between caustic ingestion and each specific PCs. Methods: The retrospective chart review included 396 adult cases with PCs and 377 cases without PCs (control group) treated between January 1999 and December 2018 in Chang Gung Memorial Hospital. Patients received multidisciplinary

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ABO BLOOD GROUPS AND CROHN’S DISEASE: A HOSPITALBASED STUDY IN CENTRAL TAIWAN Yi-Hua Wu1, Hsiang-Chun Lai2, Jen-Wei Chou1, Tsung-Wei Chen3 Center for Digestive Disease, China Medical University Hospital, Taichung, Taiwan1 Department of Chinese Medicine, China Medical University Hospital, Taichung, Taiwan2 Department of Pathology, China Medical University Hospital, Taichung, Taiwan3

ABO 血型與克隆氏症（Crohn’s Disease） ：中台灣一醫學中心之十年 經驗 吳宜樺1 賴香君2 周仁偉1 陳宗偉3 中國醫藥大學附設醫院消化內科1 中國醫藥大學附設醫院中醫內科2 中國醫藥大學附設醫院病理科3 Background: The variations in ABO blood groups are reported to be associated with multiple disorders. Crohn’s disease (CD) is a chronic and relapsing disease of the gastrointestinal tract with unclear etiology.

Aims: The aim of our current study was to investigate the distribution of ABO blood groups in patients with CD in Taiwan and to explore its impact on disease severity.

Methods: From January 2000 to November 2019, we retrospectively collected patients diagnosed as CD in our hospital, a tertiary referral center in central Taiwan. Clinical characteristics of patients with CD including gender, age at diagnosis, ABO blood groups, disease phenotype and behavior, operation rate and baseline laboratory data were collected.

Results: A total of 75 patients with CD were enrolled into our current study (Table 1). We found out male predominance as 77.3% of all patients.

The mean diagnostic age of all CD patients was 40.5 years. Of 75 CD patients, 25 (33.3%) were blood type O, 20 (26.6%) were blood type A, 23 (30.6%) were blood type B, and the remainders 7 (9.3%) were blood type AB. However, there was no significant association between the ABO blood groups and CD patients compared to general population of Taiwanese (p > 0.05) (Table 2). In

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the subgroup analysis of each blood type, there were no significant difference of disease location and operation rate between groups. Furthermore, blood type B CD patients had higher C-Reactive Protein level compared to blood type O patients (p = 0.0491). Blood type O CD patients had the lower C-Reactive Protein level compared to non-O groups (p = 0.0289) (Table 3). We analyzed the characteristics between diagnostic age older or younger than 40 years. There was significant difference between two age groups (Table 4).

Conclusions: ABO blood groups are not associated with the prevalence of Crohn’s disease.

CD patients with blood type O had lower baseline CRP.

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NKX6.1 REPRESSES TUMORIGENESIS, METASTASIS AND CHEMORESISTANCE IN COLORECTAL CANCER Yu-Lueng Shih1, Hsin-Hua Chung2, Je-Ming Hu3, Yu-Ching Chou4, Ya-Wen Lin5 Division of Gastroenterology, Department of Internal Medicine, Tri-Service General Hospital, Taipei, Taiwan1 Graduate Institute of Medical Sciences, National Defense Medical Center, Taipei, Taiwan2 Division of Colorectal Surgery, Department of Surgery, Tri-Service General Hospital, Taipei, Taiwan3 School of Public Health, National Defense Medical Center, Taipei, Taiwan4 Department and Graduate Institute of Microbiology and Immunology, National Defense Medical Center, Taipei, Taiwan5

To further explore how NKX6.1 exerts its tumor suppressive function, we used RNA sequencing technology for comprehensive analysis. The results showed that differentially expressed genes (DEGs) were mainly related to cell migration, response to drug, transcription factor activity and growth factor activity and suggested that these DEGs are involved in the function of NKX6.1 suppressing cancer invasion and metastasis.

Conclusions: Our results demonstrated that NKX6.1 functions as a tumor suppressor partly by repressing EMT and enhancing chemosensitivity in CRC, making it a potential therapeutic target.

大腸直腸癌中 NKX6.1 能抑制腫瘤增 生轉移及化療抗藥性 施宇隆1 鍾新華2 胡哲銘3 周雨青4 林雅雯5 三軍總醫院胃腸肝膽科1 國防醫學院醫學科學研究所2 三軍總醫院大腸直腸外科3 國防醫學院醫學公共衛生學系4 國防醫學院微生物暨免疫學研究所5 Background: Accumulating evidence suggests that NKX6.1 plays a role in various types of cancer. In our previous studies, we identified NKX6.1 hypermethylation as a promising marker and demonstrated that the NKX6.1 gene functions as a metastasis suppressor through epigenetic regulation of the epithelial-to-mesenchymal transition (EMT) in cervical cancer. More recently, we have demonstrated that NKX6.1 methylation is related to the chemotherapy response in colorectal cancer (CRC).

Aims: To study the biological function of NKX6.1 in the tumorigenesis of CRC. Methods: NKX6.1 suppresses tumorigenic and metastatic ability both in vitro and in vivo.

Results: NKX6.1 represses cell invasion partly through modulation of EMT. Overexpression of NKX6.1 enhances chemosensitivity in CRC cells.

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COLONOSCOPIC PERFORATIONS: A SINGLE CENTER EXPERIENCE WITH 10 YEARS IN TAIWAN Bin-Bin Shih1, Hua-Ching Lin2, Chun Yeh1 Division of Gastroenterology, Cheng Hsin Geneal Hospital, Taipei, Taiwan1 Division of Colorectal Surgey, Cheng Hsin Geneal Hospital, Taipei, Taiwan2

大腸鏡檢造成結腸穿孔：單一醫院十 年經驗 施彬彬1 林華卿2 葉淳1 振興醫院肝膽腸胃內科1 振興醫院大腸直腸外科2 Background: With the increasing study of colonoscopy including sedoanalgesic colonoscopy, the cases of iatrogenic colonic perforation may increase. In this study, we reported the detail description of perforation in our center (0.035%) that presented (a) perforations mostly occurred commonly in the rectosigmoid region, (b) sedoanalgesia is a significant risk factor of perforation, (c) therapeutic colonoscopy has higher incidence of perforation than diagnostic colonoscopy, (d) early diagnosis is critical for management.

Aims: The aim of this study was to document our experience with colonoscopic derived perforation and to figure out the conditions associated with iatrogenic colonic perforations.

Methods: Patients studied by colonoscopy were enrolled and documented from 2008 to 2017 in a single center (Chen-Hsin General Hospital, Taipei, Taiwan). The colonic perforations occurred in the colonoscopy were consequently documented and analyzed.

Results: There were 63068 patients who received colonoscopy in 10 years of period. The 22 of the procedures were associating with perforations.

The rate of perforation was 0.035%. The incidence of perforation in therapeutic colonoscopy is significantly higher than diagnostic colonoscopy (0.073% vs. 0.023%, p = 0.004). Perforation rate of colonoscopy under sedoanalgesia is significantly higher than nonsedoanalgesia (0.055% vs.

0.007%, p = 0.001). The most frequent locations of perforations were the rectosigmoid colon (n = 9) and the sigmoid colon (n = 8). Occurrence of

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perforation over the regions happened significantly in diagnostic colonoscopy than therapeutic study (p = 0.004). Most of the cases were proved to have colon perforation within 24 hours (n = 18). Managements included operation in 20 patients, endoscopic clipping in one patient, and conservative treatment in one patient. There was no mortality.

Conclusions: Our experience in colonoscopic perforations indicated that the perforation is strongly associated with the sedoanalgesia, diagnostic procedure and location of colon.

Depending on clinical situation, the alertness and knowledge of diagnosis for perforation is required to treat the complication.

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THE PREDICTIVE ROLE OF STOOLBASED TESTS FOR MUCOSAL HEALING AMONG TAIWANESE PATIENTS WITH ULCERATIVE COLITIS Hsu-Heng Yen, Yang-Yuan Chen, Chia-Wei Yang, Pei-Yuan Su, Tsui-Chun Hsu

both complete mucosal healing (0.813 vs. 0.769, respectively, p = 0.5581) and endoscopic mucosal healing (0.906 vs. 0.812, respectively, p = 0.1207).

Conclusions: In daily clinical practice, FC and iFOBT had similar predictive roles for colonic mucosal healing among Taiwanese patients with UC.

Division of Gastroenterology, Changhua Christian Hospital, Changhua, Taiwan

利用糞便檢驗來預測潰瘍性結腸炎黏 膜情形之研究 顏旭亨 陳洋源 楊佳偉 蘇培元 許翠純 彰化基督教醫院胃腸肝膽科 Background: Ulcerative colitis (UC) has emerged in the Asia Pacific area over the past two decades, and its treatment goal has shifted from symptom relief to endoscopic remission. Endoscopy is the gold standard for the assessment of mucosal healing, but it is invasive. Fecal calprotectin (FC) is a noninvasive stool-based inflammatory marker that has been utilized to monitor mucosal healing status, but its cost is high; by contrast, the immune fecal occult blood test (iFOBT) is a widely utilized stool-based screening tool for colorectal cancer.

Aims: In this study, we aimed to compare the predictive roles of iFOBT and FC for mucosal healing.

Methods: A total of 50 patients with UC were retrospectively enrolled from the electronic clinical database of Changhua Christian Hospital, Taiwan, from January 2018 to July 2019. Stool samples for iFOBT and FC, blood samples, and Mayo disease activity scores were reviewed and analyzed.

Colonic mucosa was assessed using a Mayo endoscopic subscore.

Results: The mean age of the patients was 46 years, and 62% of the patients were men. The disease distribution was as follows: E1 (26%), E2 (40%), and E3 (34%). Complete mucosal healing with a Mayo score of 0 occurred in 30% of patients.

Endoscopic mucosal healing with a Mayo score of 0 or 1 occurred in 62% of the patients. The levels of FC and iFOBT were compared among patients with and without mucosal healing. Predictive cutoff values were analyzed using a receiver operating characteristics (ROC) curve. iFOBT and FC had similar values for the area under the curve for

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ENDOSCOPIC TREATMENT STRATEGY FOR LST INVOLVING APPENDICEAL ORIFICE Chao-Wen Hsu, Min-Chi Chang, Chih-Chien Wu, Min-Hung Lee Division of Colorectal Surgery, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan

位於闌尾開口側方發育型腫瘤（LST） 的內視鏡治療戰略 許詔文 張敏棋 吳志謙 李明泓 高雄榮民總醫院大腸直腸外科 Background: The endoscopic treatment for LST involving appendiceal orifice is difficult, due to poor endoscopic maneuverability and the possibility of deep invasion into the orifice.

Aims: We shared the experience for treatment of LST involving appendiceal orifice and presented the effective treatment strategy.

Methods: This study retrospectively analyzed 10 patients with LST involving appendiceal orifice.

The clinical data included treatment modality, operative time, complication rate and disease free interval.

Results: Of 10 patients with LST involving appendiceal orifice, 9 received endoscopic treatment completely and 1 received endoscopic combined laparoscopic due to deep invasion into the orifice. Of 9 patients receiving endoscopic treatment, 7 received ESD, 1 received hybrid ESD and 1 received EMR. There were no tumor recurrence in the first time colonoscopy surveillance.

Conclusions: Although the endoscopic treatment for LST involving appendiceal orifice was difficult, we can still perform safe and effective endoscopic treatment through careful endoscopic observation and skill. For patients with deep invasion into the orifice, endoscopic combined laparoscopic treatment is a good choice for en-bloc resection.

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MODERATE TO SEVERE IBD CASES RECEIVING BIOLOGICS THERAPY ‒ AN EXPERIENCE IN A SINGLE MEDICAL CENTER OF SOUTHERN TAIWAN Huai-Yi Huang, Chi-Shu Sun, Hsing-Tao Kuo, Ming-Jen Sheu, I-Che Feng Division of Hepato-Gastroenterology, Department of Internal Medicine, Chi Mei Hospital, Tainan, Taiwan

中重度發炎性腸道疾病在台灣南部一 家醫學中心使用生物製劑之經驗 黃懷毅 孫啟書 郭行道 許銘仁 馮意哲 奇美醫院內科部胃腸肝膽科 Background: Inflammatory bowel disease, including ulcerative colitis and crohn’s disease, which mechanism and pathophysiology were not clear. Although much of the inflammatory bowel disease have a mild-moderate course, about 10%-15% patients experience severe course with frequent flares and increased morbidity. Some of these patients with poor response of immunosuppressive therapies and corticosteroids need biological therapy for disease control. Cytomegalovirus (CMV) is common and asymptomatic in most of people.

The role of cytomegalovirus in inflammatory bowel disease is important due to easily reactivation by immunosuppression and may cause therapeutic activity under estimate (CMV colitis may related with diarrhea, bloody stool and fever, which influence CDAI and Mayo score calculation).

Aims: CMV enteritis traditionally thought to be self-limited and supportive care was much suggested. However, the CMV enteritis may relate with biological therapy poor response due to CDAI and Mayo score calculation. We would like to now the role of CMV enteritis in IBD patients under biological therapy, and the improvement of response rate after anti-viral treatment.

Methods: The study selected the inflammatory bowel disease patients with biological therapy in Chi-mei hospital from June 2018 to June 2020.

The poor response was identified by CDAI score decrease less than 100 in CD patient or Mayo score > 6 or Mayo endoscopic sub score > 2 in UC patient. The patients were all sure CMV IgM

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antibody negative before biological therapy. We test CMV in these patients with poor response to biological therapy from endoscopic biopsy. We will start anti-virus therapy for CMV positive patients, and re-evaluation the response of biological treatment (CDAI score in CD patient and Mayo/ Mayo endoscopic sub score in UC patient).

Results: The prospective observational study showed 28 patients in Chi-mei hospital under biological therapy. 7 patients in CD group (2 receive Vedolizumab, 3 receive Adalimumab and 1 receive Infliximab). 21 patients in UC group (17 receive Vedolizumab and 4 receive Adalimumab).

In CD group, 1 people with poor response for biological therapy, the biopsy was done for check CMV and showed positive. After anti-virus therapy, the condition was improving gradually. 2 people recurrence after finish Vedolizumab course, currently applied second course health insurance biological therapy. In UC group, 4 patients receive Adalimumab and 2 patients change to Vedolizumab due to poor response after 3 times Adalimumab used by endoscopic findings. The other 2 patients receive Adalimumab showed good response initially but deteriorate later, the endoscopic biopsy showed CMV positive, and response improved after anti-virus therapy. 17 patients receive Vedolizumab and 1 patient stop treatment due to afraid of Covid-19 and refused to hospital. 1 patient showed good response initially but acute exacerbation with the stool antigen and endoscopic showed Clostridium infection, and improved after Metronidazole treatment. The other 17 patients finish the Vedolizumab course but 3 patients with second course treatment due to disease recurrence.

Conclusions: The reactivation of CMV may play an important role in IBD patients who may have good response to biologics initially but having compromised response in following treatment courses. After adequate anti-viral treatment of CMV, the patients may have adequate response to the same biologics again even approaching treatment goal of mucosa healing. In the case with compromised response to biologics, we suggested to exclude possibility of CMV reactivation and been treated if necessary before switching biologics of different mechanism.

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COPY NUMBER ALTERATIONS OF DEPRESSED COLORECTAL NEOPLASM PREDICT THE SURVIVAL AND RESPONSE TO OXALIPLATIN IN PROXIMAL COLON CANCER Jui-Hsiang Chung1, Li-Chun Chang1,2,3, Sung-Liang Yu3,4,5,6,7,8, Jin-Tung Liang9, Ming-Shiang Wu1, Han-Mo Chiu1,2 Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan1 Health Management Center, National Taiwan University Hospital, Taipei, Taiwan.2 Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan3 Centers of Genomic and Precision Medicine, National Taiwan University, Taipei, Taiwan4 Department of Clinical Laboratory Sciences and Medical Biotechnology, College of Medicine, National Taiwan University, Taipei, Taiwan5 Department of Laboratory Medicine, National Taiwan University Hospital, Taipei, Taiwan6 Institute of Medical Device and Imaging, College of Medicine, National Taiwan University, Taipei, Taiwan7 Graduate Institute of Pathology, College of Medicine, National Taiwan University, Taipei, Taiwan8 Department of Surgery, National Taiwan University Hospital, Taipei, Taiwan9

凹陷型大腸直腸腫瘤的基因變異對於 預測大腸直腸癌預後與化療反應之應 用 鍾睿翔1 張立群1,2,3 俞松良3,4,5,6,7,8 梁金銅9 吳明賢1 邱瀚模1,2 台大醫院內科部消化內科1 台大醫院健康管理中心2 國立台灣大學臨床醫學研究所3 國立台灣大學基因體暨精準醫學研究中心4 國立台灣大學醫學檢驗暨生物技術學系5 台大醫院檢驗醫學部6 國立台灣大學醫療器材與醫學影像研究所7

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P.090 8

國立台灣大學醫學院病理科 台大醫院外科部9

Background: Depressed colorectal neoplasm exhibits high malignant potential and shows rapid invasiveness.

Aims: We investigated the genomic profile of depressed neoplasms and clarified the survival outcome and treatment response of the cancers arising from them.

Methods: We examined 20 depressed and 13 polypoid neoplasms by the genome-wide copy number analysis. Subsequently, we validated the identified copy number alterations (CNAs) in an independent cohort of 37 depressed and 42 polypoid neoplasms. Finally, the CNAs were tested as biomarkers in 530 CRCs to clarify the clinical outcome of depressed neoplasms.

Results: CNAs in MYC, CCNA1, and BIRC7 were significantly enriched in depressed neoplasms and designated as the D-marker panel. CRCs with D-marker panel have a significantly shorter progression-free survival compared with those without (p = .012), especially in stage I (p =.049), T1+2 (p = .027), and proximal cancers (p = .002). The positivity of D-marker panel was an independent risk factor of cancer progression [hazard ratio (95% confidence interval) = 1.52 (1.09-2.11)]. Furthermore, the proximal CRCs with D-marker panel had a worse overall and progression-free survival when taking oxaliplatin as chemotherapy than those without.

Conclusions: The D-marker panel may help to optimize the treatment and surveillance in proximal CRC and develop a molecular test. However, the current result remains preliminary, and further validation in prospective trials is warranted in the future.

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RECURRENCE RATE OF NEOPLASMS AFTER UNDERWATER ENDOSCOPIC MUCOSAL RESECTION (UEMR) Chi-Hsing Chen, Yu-Min Lin, Ping-Hsin Hsieh Division of Hepatobiliary, Department of Internal Medicine, Chiemei Medical Center, Tainan, Taiwan

大腸鏡水下內視鏡黏膜切除術後之腫 瘤復發狀況 陳季杏 林育民 謝秉欣 奇美醫療財團法人奇美醫院胃腸肝膽科 Background: Recent studies show that underwater endoscopic mucosal resection (UEMR) is as effective and safe as conventional endoscopic mucosal resection (EMR) in treating sessile colorectal neoplasms. However, the recurrence rate of neoplasms is not reported in most of the studies.

Aims: We report the recurrence rate among patients underwent UEMR for their sessile colorectal neoplasms ≥ 10 mm.

Methods: This is a single center prospective cohort study enrolling patients who underwent UEMR between August 2015 and December 2017.

The patients received follow-up colonoscopy in a determined interval according to their index UEMR findings. The cohort was followed until December 2019.

Results: 180 lesions in 161 patients were resected

by UEMR. The mean size of neoplasm is 17.8mm.

The pathologies are low grade adenomas (n=82), high grade dysplasia or carcinoma in situ (n=63), T1 cancers (n=12), sessile serrated adenomas (n=21), and others (n=2). 146 lesions (81%) were resected in one piece while 34 lesions (19%) were resected in piecemeal. For lesions resected in one piece, 64 patients (44%) lost follow and 82 patients (56%) underwent their first follow-up colonoscopy at 12-24 months after index colonoscopy. The mean follow-up length is 23.3 months. None of the 82 patients developed local recurrence by the end of follow up. For lesions resected in piecemeal, 27 of them (79%) underwent their first follow-up colonoscopy at 3-12 months after index colonoscopy. The mean follow-up length is 26.9 months. Three of them (11%) developed

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local recurrence during the follow-up period. One of them (4%) was cured by repeated endoscopic resection while two of them (7%) eventually underwent surgery due to cancerous recurrence.

None of the patients in our cohort has diseaserelated mortality.

Conclusions: The recurrence rate after en-bloc UEMR is almost zero. Recurrence after piecemeal UEMR is 11% and may require surgical treatment.

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COLONIC PSEUDO-POLYPS, EXPERIENCE FROM A CENTRAL TAIWAN REGIONAL HOSPITAL Hung-Yao Chen-Cheng, Jeng-Shiann Shin, Jen-Chieh Huang, Chi-Hung Chen, Cheng-Chi Lee, Chun-Chin Chen, Yichih Wen Department of Gastroenterology, ChengChing General Hospital, Taichung, Taiwan

大腸假性息肉 ─ 台灣中部一家區域醫 院的經驗分享 陳鄭弘堯 辛政憲 黃仁杰 陳季宏 李政祺 陳俊欽 溫奕志 澄清醫院中港院區胃腸肝膽科 Background: Pseudo-polyps are morphological mimics of true polyps arising from the mucus membrane. As such, they represent a heterogeneous, uncommon-to-rare, and largely benign class of colorectal lesions, pseudolesions, and artifacts. In endoscopic practice their removal may increase patient morbidity and potentially mortality. Timely recognition depends upon an understanding of their typical endoscopic morphology, frequency of occurrence, location, and behavior.

Aims: Our study aims to investigate the pseudopolyps encountered in our clinical practice over the past 11 years in terms of their morphology, frequency, location, etc.

Methods: We reviewed colorectal endoscopy findings as performed and documented by a highly experienced endoscopist at a central Taiwan regional general hospital over a period of 11 years (2009 to 2020). These were correlated with pathology reports where appropriate to collect a series of lesions, pseudo-lesions, and artifacts which mimic true polyps.

Results: Only 15 lesions may be classified as pseudo-polyps, of which the single most common type were inverted diverticula (26.6%, 4/15), followed by fibroepithelial polyps (13.3%, 2/15), inverted appendix (13.3%, 2/15), and mucosal prolapse polyps (6.6%, 1/15). Various non-neoplastic inflammatory lesions or changes account for the remaining findings (26.6%, 4/15).

Conclusions: In our experience pseudo-polyps

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occur rarely. Whereas inverted diverticula, the most common form, are identifiable by morphology with or without probing, other less prevalent lesions may require histology for definitive diagnosis.

Potentially precancerous lesions should be biopsied or removed with care.

P.092

ENDOSCOPIC PAPILLARY BALLOON DILATATION LESS THAN THREE MINUTES FOR BILIARY STONE REMOVAL INCREASES THE RISK OF POST-ERCP PANCREATITIS Pei-Shan Wu1, Kuei-Chuan Lee1,2, Jiing-Chyuan Luo1,2, Tseng-Shing Chen1,2, Yi-Hsiang Huang1,2, Ming-Chih Hou1,2 Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan1 Department of Medicine, National Yang-Ming University School of Medicine, Taipei, Taiwan2

內視鏡乳突氣球擴張術小於三分鐘增 加膽道結石移除術後之胰臟炎風險 吳佩珊1 李癸汌1,2 羅景全1,2 陳增興1,2 黃怡翔1,2 侯明志1,2 臺北榮民總醫院胃腸肝膽科1 國立陽明大學內科學科2 Background: The adequate duration for endoscopic papillary balloon dilatation (EPBD) was unclear.

Aims: We aimed to investigate the effect of balloon dilatation duration of EPBD on the occurrence of post-ERCP pancreatitis (PEP).

Methods: One hundred and ninety-eight patients with common bile duct (CBD) stone treated

by EPBD were retrospectively recruited. The dilatation duration was determined according to adequate opening of the biliary orifice without bleeding. The clinical outcomes and complications of EPBD were recorded.

Results: We stratified the patients according to dilatation duration (Group A, <3 minutes; Group B, 3–5 minutes; Group C, ≥5 minutes). The group C patients had a higher proportion of large CBD stones (stones ≥10 mm) (33.3% vs. 26.8% vs. 53.5%, p = 0.01). Patients in group A had a significantly higher PEP rate than patients in group B (13.3 vs. 3.1, p = 0.032). There were no significant differences in perforation and bleeding rate among the three groups. Univariate and multivariate analyses showed that a dilatation duration of <3 minutes, CBD diameter < 10 mm

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and age ≤ 75 years were independent risk factors of PEP in post-EPBD patients.

Conclusions: In patients receiving EPBD, dilatation duration <3 minutes, lower CBD diameter, and younger age were independent risk factors of PEP.

P.093

CHOLECYSTECTOMY REDUCES SUBSEQUENT CHOLANGIOCARCINOMA RISK IN CHOLEDOCHOLITHIASIS PATIENTS WHO UNDERWENT ENDOSCOPIC INTERVENTION Chi-Chih Wang1,2,4, Ming-Hseng Tseng3, Tzu-Wei Yang2,4, Hsuan-Yi Chen2,4, Chang-Cheng Su4, Chun-Che Lin5,6, Ming-Chang Tsai1,2,4 Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan1 School of Medicine, Chung Shan Medical University, Taichung, Taiwan2 Department of Medical Informatics, Chung Shan Medical University, Taichung, Taiwan3 Division of Gastroenterology and Hepatology, Chung Shan Medical University Hospital, Taichung, Taiwan4 Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan5 School of Medicine, China Medical University, Taichung, Taiwan6

膽囊切除術可以降低總膽管結石接受 內視鏡處理患者後續的膽管癌風險 汪奇志1,2,4 曾明性3 楊子緯2,4 陳宣怡2,4 蘇章政4 林俊哲5,6 蔡明璋1,2,4 中山醫學大學醫學研究所1 中山醫學大學醫學系2 中山醫學大學醫學資訊學系3 中山醫學大學附設醫院肝膽腸胃科4 中國醫藥大學附設醫院內科部5 中國醫藥大學醫學系6 Background: Our previous study revealed that cholelithiasis patients who undergo endoscopic sphincterotomy/endoscopic papillary balloon dilatation are at a higher risk for subsequent cholangiocarcinoma than cholelithiasis patients who undergo cholecystectomy.

Aims: To clarify the relationship between recurrent biliary events and subsequent cholangiocarcinoma risk in choledocholithiasis patients.

Methods: From one million random cases in the Taiwan National Health Insurance Research Database 2004–2011, we selected symptomatic choledocholithiasis patients older than 18

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years who were admitted from January 2005 to December 2009. Cases for the control group were defined as individuals who had never been diagnosed with cholelithiasis, matching by sex and age in a 1:3 ratio. The study group was further divided into endoscopic sphincterotomy/ endoscopic papillary balloon dilatation, both endoscopic sphincterotomy/endoscopic papillary balloon dilatation & cholecystectomy and no intervention groups. Relationship between subsequent cholangiocarcinoma and recurrent biliary events was analyzed.

Results: We included 2096 choledocholithiasis patients without previous intervention or cholangiocarcinoma. A total of 12 (2.35%), 11 (0.74%) and 1 (1.00%) subsequent cholangiocarcinoma cases were diagnosed among 511 endoscopic sphincterotomy/ endoscopic papillary balloon dilatation patients, 1485 patients with no intervention and 100 endoscopic sphincterotomy/endoscopic papillary balloon dilatation & cholecystectomy patients, respectively. The incidence rates of recurrent biliary event were 527.79/1000 person-years and 286.69/1000 person-years in the subsequent cholangiocarcinoma and no cholangiocarcinoma group, showing a high correlation between subsequent cholangiocarcinoma risk and recurrent biliary events.

Conclusions: Choledocholithiasis patients, who undergo further cholecystectomy after endoscopic sphincterotomy/endoscopic papillary balloon dilatation, have decreased subsequent cholangiocarcinoma risk by reducing recurrent biliary events.

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P.094

CLINICAL VALUE OF SERUM CA199 AND CEA AS A DIAGNOSTIC AND PROGNOSTIC FACTOR FOR AMPULLA OF VATER CARCINOMA: EXPERIENCE FROM A SINGLE MEDICAL CENTER IN TAIWAN Su-Hung Wang, Ming-Jen Sheu, Hsing-Tao Kuo, Chi-She Sun, I-Che Feng, Yu-Min Lin, Poh-Poo Lim, Wen-Chieh Huang Division of Hepato-Gastroenterology, Department of Internal Medicine, Chi Mei Medical Center, Tainan, Taiwan

CA19-9 和 CEA 在壺腹癌之診斷與預 後價值：單一醫學中心經驗 王宿鴻 許銘仁 郭行道 孫啟書 馮意哲 林育民 林寶寶 黃文杰 奇美醫療財團法人永康奇美醫院胃腸肝膽科 Background: The study retrospective evaluates the serum level of CA19-9 and CEA, and other clinicopathological data in ampulla vater cancer patients.

Aims: To explore the relationship between preoperative serum CA9-9 and CEA levels and prognosis of ampulla vater cancer.

Methods: The clinicopathological data of 39 patients with ampulla vater adenocarcinoma who received radical tumor resection in our center between January 2015 and December 2019 were retrospectively analyzed. The relationships between serum CA19-9 and CEA levels and survival were analyzed using Kaplan-Meier method, logrank test, and Cox regression analysis. The cutoff values for serum CA19-9 and CEA levels were 39 U/mL and 4.7 ng/mL, respectively. The main outcome measures were survival rates of patients with and without high levels of CA19-9 and CEA. Results: There were 39 patients with ampulla vater cancer who received radial tumor resection.

CA19-9 demonstrated significantly higher sensitivity in detecting these cancers. However, none of these cases had CEA > 5.0. Using KaplanMeier method, CA19-9 > 39 U/mL did not predict the survival time (p = 0.745). Multivariate analysis revealed that independent prognostic factors included age, cancer stage, and peripancreatic

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invasion.

Conclusions: CA19-9 provided more important diagnostic values than CEA in periampullary cancers. However, both CA19-9 and CEA could not predict prognosis.

P.095

FAILED BILIARY ACCESS AFTER NEEDLE KNIFE PRECUT SPHINCTEROTOMY: OUTCOMES BETWEEN REPEAT INTERVAL ERCP AND NON-ENDOSCOPIC TREATMENT Min-Hao Lo1, Nai-Jen Liu2, Cheng-Hui Lin2, Kai-Feng Sung2, Yung-Kuan Tsou2, Mu-Hsien Lee2 School of Medicine, Chang Gung University, Taoyuan, Taiwan1 Department of Gastroenterology and Hepatology, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan2

須進行針刀預切括約肌切開術之困難 內視鏡逆行性膽管攝影術失敗後：內 視鏡再治療與非內視鏡治療的比較 羅敏豪1 劉乃仁2 林政輝2 宋皚峰2 鄒永寬2 李沐憲2 長庚大學醫學系1 林口長庚紀念醫院胃腸肝膽科2 Background: Deep bile duct cannulation is the key step for endoscopic retrograde cholangiopancreatography (ERCP) but it is not always successful. Needle knife precut sphincterotomy (NKPS) is frequently performed as a salvage technique when deep bile duct cannulation using conventional methods fails.

However, NKPS has high technical requirements, so there are certain risks that deep bile duct cannulation cannot be achieved. How to adequately manage these patients with initial NKPS failure has not been well studied.

Aims: This study aims to report the outcomes of patients treated with endoscopic and nonendoscopic methods after the initial NKPS failure.

Methods: In the 15 years from 2004 to 2018, 87 patients with initial failure of NKPS who received interval endoscopic treatment (ET group, n = 43), percutaneous transhepatic treatment (PTT group, n = 25), or surgical treatment (ST group, n = 19) were retrospectively collected from computer database of the Therapeutic Endoscopy Center at Chang Gung Memorial Hospital, Linkou medical center. Demographic data (age, gender), liver biochemistry tests (serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), alkaline phosphatase (Alk-P), and total

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bilirubin), morphology of the major papilla (periampullary diverticulum or tumor, surgically altered anatomy), possible factors influencing choice of treatment type for the secondary procedure (indications and complications of the first ERCP procedure, endoscopists’ experience, and inpatient department), and outcomes of the secondary procedures (time interval between the first and second procedures, technical success rate, early adverse events, length of hospital stay after the second procedure, and 30-day mortality) were compared between the three groups.

Results: Regarding general characteristics, compared with the PTT group, the patients in the ET group had significantly lower serum levels of alkaline-phosphatase and total bilirubin. Compared to the ST group, the patients in the ET group were only significantly older. With regards to the factors influencing the choices of a secondary treatment procedure, compared with PTT group, there were significantly more patients with choledocholithiasis (69.8% vs 16.0%, p < 0.001) but fewer patients with malignant biliary stricture (20.9% vs 76.0%, p < 0.001) in the ET group. Compared to the ST group, the only difference was the inpatient department. Notably, most of the indications for initial ERCP were malignant biliary stricture (76.0%) in the PTT group and almost choledocholithiasis (84.2%) in the ST group. As to the treatment outcomes, compared with PTT group, ET group had significantly longer time interval between the first and second procedures (4 days vs 2 days, p = 0.001), lower technique success rate (79.1% vs 100%, p = 0.021), and shorter length of hospital stay after the second procedure (7 days vs 18 days, p < 0.001). Compared with the ST group, there was no significant difference. Although not statistically significant, the rate of complication was lowest in the ET group (7.0%) and highest in the ST group (15.8%). Furthermore, complications in the ET group were mild.

Conclusions: In the case of initial NKPS failure, interval ERCP may be the main treatment for patients with choledocholithiasis. Percutaneous transhepatic drainage may be the treatment of choice but interval ERCP can be the alternative for malignant biliary obstruction.

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P.096

APPLICATION OF BEDSIDE BILIARY DRAINAGE WITHOUT FLUOROSCOPY FOR ICU PATIENTS WITH BILIARY SEPSIS AND ORGAN FAILURE Chun-Chin Chen, Yi-Chih Wen, Jeng-Shiann Shin, Jen-Chieh Huang Division of Gastroenterology, Department of Internal Medicine, Cheng Ching General Hospital, Chung Kang Branch, Taichung, Taiwan

對膽道阻塞引起敗血症及器官衰竭的 加護病房病人於床邊執行內視鏡膽道 引流術之應用成效 陳俊欽 溫奕志 辛政憲 黃仁杰 澄清綜合醫院中港分院胃腸肝膽科 Background: Endoscopic retrograde cholangiopancreaticogram (ERCP) is the treatment of choice for patients with biliary obstruction due to CBD stone. However, in ICU patients with unstable vital signs and organ failure had high risk to transport these patients to endoscopy/ radiology units. Bedside ERCP with temporary biliary drainage (ERBD) may be applicable and gained success. In literature few cases reports were published.

Aims: The aim of the retrospective study was to evaluate the efficacy and safety of bedside ERBD without fluoroscopy for high-risky patients in ICU with severe cholangitis and organ failure.

Methods: Patients with CBD stones impaction with unstable vital signs and organ failure especially respiratory failure was admitted to ICU care immediately after first aid at ER. Bedside ERBD was performed as soon as possible after explaination to families about procedure indication, risk and alternative modality. Bedside transabdominal ultrasound was performed to confirm catheter/guide wire position In CBD if no bile withdraw by syrinage. Post-bedside ERBD, clinical conditions and laboratory data were followed up closely. 2nd ERCP was tried about 1-3 m later and results were analyzed.

Results: From October 2016 to January 2020, we encountered 10 patients with acute cholangitis with biliary sepsis and organ failure who were admitted into ICU for further care. In those, all

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received endotracheal tube insertion and ventilator suppport in 12 hrs after admission. 10 patients was analyzed for basic characteristics with mean age: 72.5 (63-85 years old); sex: 6 male, 4 female; hypotension and respiratory failure: 10; initial CXR: pneumonia: 3 (1 with lobar, 1 with left empyema); comorbidity: 3 DM, 4 CKD, 3 CAD; s/p cholecystectomy: 9; receive PTGBD at ER: 1 (dislodged 5 hrs after procedure and complicated with hemorrhagic shock); mean CBD stone size: 18 mm (10-22 mm); mean CBD stone number: 1.7 (1.0-3.0); Time to bedside ERBD was 12.5 hrs (6-52 hrs); success rate: 10/10 (100%); procedure time: 25 mins (15-48 mins); procedure related complications: nil; difficult cannulation: 3/10 and received needle knife fistulotomy; 1 received standard EST and stone retrieval. Transabdominal ultrasound was applicated in 2/10 patients when bile can’t be withdrawn from catheter to confirm catheter or guidewire in CBD. All 10 patients gained resolution of cholangitis; 2/10 died of profound pneumonia and respiratory failure, 8/10 with uneventful discharge In averaged 13 days (7-18 days). 8 patients received 2nd ERCP in 1-3 months and 7 patients gained successful removal of CBD stones but 1 patient needed 3rd ERCP in future due to stones impaction below fistulotomy.

Conclusions: Our experiences indicate that urgent bedside ERBD is an effective and feasible treatment for ICU patients with severe cholangitis and organ failure. Good ERCP skills is mandatory for success results. Initial pneumonia seems to be an important factor of mortality despite successful urgent biliary stenting.

P.097

PERCUTANEOUS CHOLECYSTOSTOMY AS AN ALTERNATIVE IN PATIENTS WITH ACUTE CHOLANGITIS AND BILIARY OBSTRUCTION Man Si Wong1, Hung Yu Chung1, Yu Liang Hung1, Shang Yu Wang1, Chun Nan Yeh1, Yi Yin jan1, Huan Wu Chen2 Division of General Surgery, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan1 Department of Medical Imaging and Intervention, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan2

以經皮膽囊引流術進行急性膽管炎及 膽管阻塞之暫時性替代治療 黃文詩1 鐘宏佑1 洪宇亮1 王尚煜1 葉俊男1 詹益銀1 陳煥武2 林口長庚紀念醫院一般外科1 林口長庚紀念醫院影像診療部2 Background: Percutaneous cholecystostomy (PC) is a bridging procedure for treatment of acute cholecystitis. PC has also been applied under other clinical circumstance, such as biliary obstruction with cholangitis.

Aims: In present study, we tried to investigate efficacy of PC when it is alternatively used in acute cholangitis and biliary obstruction.

Methods: From 2012 to 2018, specific procedure code was used to identify patients who underwent PC at Chang Gung Memorial Hospital Linkou. After excluding patients undergoing PC due to acute cholecystitis, other gallbladder related conditions, and malignant biliary obstruction, there were 23 patients fulfilling inclusion criteria. Laboratory tests were done at 2 time points: pre-PC and post-PC. Results: The mean duration between 2 time points was 4.06 days. Significant improvement on laboratory data, including white-blood-cell count, C-reactive protein, and hepatic function, was noted.

Total bilirubin (p<0.001) was also decreased. The indications and associated conditions were all investigated.

Conclusions: PC can be an alternative treatment for selected patients with acute cholangitis and biliary obstruction. PC can temporize definitive treatments. Definitive treatments, such as repeated ERCP by experienced hands and biliary surgery, are still necessary later.

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P.098

THE RISK OF ESOPHAGEAL VARICEAL BLEEDING DURING ENDOSCOPIC RETROGRADE CHOLANGIOPANCREATOGRAPHY Hsiao-Sheng Lu1, Tsung-Chieh Yang1,2, Chung-Yu Chang1,2, Yi-Hsiang Huang1,2, Ming-Chih Hou1,2,3 Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan1 Faculty of Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan2 Endoscopy Center for Diagnosis and Treatment, Taipei Veterans General Hospital, Taipei, Taiwan3

內視鏡逆行性膽胰管攝影術之食道靜 脈曲張出血風險 呂學聖1 楊宗杰1,2 張重昱1,2 黃怡翔1,2 侯明志1,2,3 臺北榮民總醫院胃腸肝膽科1 陽明大學醫學系2 臺北榮民總醫院內視鏡診斷暨治療中心3 Background: Endoscopic retrograde cholangiopancreatography (ERCP) is a widely performed procedure nowadays. However, the risk of esophageal variceal bleeding during ERCP has rarely been assessed.

Aims: The aim of this study is to evaluate the risk of esophageal variceal bleeding in patients with esophageal varices receiving ERCP. Methods: From October 2010 to June 2016, the study retrospectively enrolled 37 patients with esophageal varices who received elective ERCP. The patient’s risk of the variceal bleeding and all-cause gastrointestinal (GI) bleeding were evaluated.

Results: In the study cohort, 24 (64.9%) patients had high risk EV. Most of the patients were male (59.5%), hepatitis B related cirrhosis (43.2%), Child-Pugh classification B (48.6%) and receiving ERCP due to CBD stone (45.9%). No esophageal variceal bleeding event was noted in this study.

Five patients (13.5%) experienced significant GI bleeding. The etiology of significant GI bleeding is duodenal ulcer bleeding (20%), Gastric Dieulafoy’s lesion bleeding (20%), Gastric variceal bleeding (20%), and undetermined (20%, negative findings in upper and lower GI endoscopies). One patient

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had post-ERCP pancreatitis. No perforation or procedure associated mortality were noted.

Conclusions: The risk of esophageal variceal bleeding during endoscopic retrograde cholangiopancreatography is low and ERCP is a safe procedure even the patient had high risk esophageal varices.

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P.099

COMPARISON OF ENDOSCOPIC AND SURGICAL TREATMENT OF PATIENTS WITH ADENOMA OF THE MAJOR DUODENAL PAPILLA: OUTCOME OF A SINGLE MEDICAL CENTER Hsing-Hung Cheng, Wen-Hsin Huang, Chi-Ying Yang, Chun-Fu Ting, Cheng-Yuan Peng, Jaw-Town Lin Center for Digestive Medicine, Department of Internal Medicine, China Medical University Hospital, China Medical University, Taichung, Taiwan

手術切除與內視鏡切除主壺腹乳頭腺 瘤之比較：一個醫學中心之經驗

suffering from pancreatitis. Major complication rate was 18%. In Group II, 7 patients (47%) had wound leakage, intra-abdominal abscess, and sepsis requiring drainage and antibiotics treatment. Two of 7 patients had septic shock and acute respiratory failure requiring endotracheal intubation. The duration time of hospitalization was 7.2 ± 5.3 days in Group I and 33.53 ± 20.03 days in Group II (P < 0.0001).

Conclusions: Compared with surgery, ESP group had significantly shorter hospital stay and fewer complications. Endoscopic treatment of major duodenal papilla adenoma appears to be feasible. The majority can undergo complete resection. However, due to one mortality and higher complication in uremic patients, careful preresection evaluation for uremic patients should be emphasized.

鄭幸弘 黃文信 楊其穎 丁俊夫 彭成元 林肇堂 中國醫藥大學附設醫院消化醫學中心 Background: Adenomas of major duodenal papilla are rare and has a potential for malignant transformation. Standard treatment has been surgical approach. However, endoscopic snare papillectomy (ESP) provides an alternative option.

Aims: The aims of this study was to assess the technical feasibility, clinical outcome, and adverse events of ESP in comparison to surgical treatment of patients with adenomas of the major duodenal papilla.

Methods: Between November 2004 and June 2020, sixty-three patients (32 women, 31 men, age range 38-92) with adenomas of the major duodenal papilla at ERCP were retrospectively reviewed.

Thirty-three patients undergoing ESP (Group I) and fifteen patients undergoing surgical resection (13 Whipple resection and 2 transduodenal local resection) (Group II) were enrolled in the study.

Results: Except for tumor size (18.1±8.4 mm in Group I and 32.47 ± 8.97 mm in Group II), there were no significant difference between two groups in clinical characteristics. ESP was technically feasible in 32 (97%) patients. Twenty-five of 33 (78%) patients were successfully treated with one tumor removal procedure. In Group I, Six uremic patients (18%) suffering from GI bleeding and bacteremia after tumor resection required blood transfusion and intravenous antibiotics therapy.

One of 6 patients expired because of severe bacterial sepsis. Besides, two patients were

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P.100

POST-LAPAROSCOPIC CHOLECYSTECTOMY MIRIZZI SYNDROME: 15 YEARS EXPERIENCE FROM A SINGLE INSTITUTE AND LITERATURE REVIEW Wai-Shan Chung, Shang-Yu Wang, Chun-Nan Yeh, Yi-Yin Jan Division of General Surgery, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan

腹腔鏡膽囊切除術後 Mirizzi 症候群： 單一中心十五年經驗及文獻回顧 鍾煒珊 王尚煜 葉俊男 詹益銀 林口長庚紀念醫院一般外科 Background: Laparoscopic cholecystectomy (LC) is the definitive treatment for symptomatic cholecystolithiasis.

Post-cholecystectomy syndromes (PCS) occurrence is about 10% regarding LC and only 0.4 to 4 % are noted as major complications. One of the PCS, Postlaparoscopic cholecystectomy Mirizzi syndromes (PLCMS), dose not frequently occur. There have been few cases reported.

Aims: Present study reported a series of 6 patients identified in our institute and reviewed literatures about PLCMS. Methods: From 2003 to 2017, there were 6 patients who suffering from PLCMS in our institute identified based on results of endoscopic retrograde cholangiopancreatography (ERCP).

Clinical data, diagnostic image, and treatment condition were all reviewed. A retrospective review of previously published literature about PLCMS was also conducted.

Results: All the 6 patients of our series underwent elective LC without previous acute cholecystitis attack, obstructive jaundice nor biliary track infection episode. There were 2 operations converted to conventional cholecystectomy which also proceeded additional choledochotomy with T-tube insertion. One patient underwent LC with additional choledochotomy and T-tube insertion.

The shortest time of PLCMS onset is 15 days after cholecystectomy while the longest is 76 days.

The median time of PLCMS diagnosed is 36.8 days after cholecystectomy. Almost all patients (n=5) suffered from abdominal pain while only 1

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patient developed jaundice. All patients underwent ERCP and PLCMS was diagnosed thereafter.

Low insertion of cystic duct was revealed by ERCP among those 2 out of the 3 patients who had T-tube insertion. Juxta-papillary diverticulum near to or at the margin of papilla was noted by ERCP in 2 patients. All patients received plastic stent insertion and stone retrieval was conducted for 5 patients. Compared with previous literatures, clips related PLCMS was predominantly reported while our series were mainly about recurrent choledocholithiasis. Besides, we noted a longer onset time of PLCMS than cases reported in previous literatures.

Conclusions: PLCMS may occur to patients with asymptomatic cholecystolithiasis, especially to those who had low insertion of cystic duct or Juxtapapillary diverticulum. ERCP plays an important role as a diagnostic tool and effective treatment.

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P.101

ESTABLISHING THE BLOOD REFERENCE INTERVALS OF ELASTASE-1 IN TAIWAN: A PROSPECTIVE STUDY Su-Fen Chi1, Wei-Ting Dong1, Jiunn-Min Wang1, Ya-Yu Wang2, Sheng-Shun Yang3, Teng-Yu Lee3 Department of Pathology & Laboratory Medicine, Taichung Veterans General Hospital, Taichung, Taiwan1 Division of Family Medicine, Taichung Veterans General Hospital, Taichung, Taiwan2 Division of Gastroenterology and Hepatology, Taichung Veterans General Hospital, Taichung, Taiwan3

建立臺灣人的 Elastase-1 血液檢驗值 標準：一個前瞻性研究 姬素芬1 董韋廷1 王俊民1 王雅瑜2 楊勝舜3 李騰裕3 臺中榮民總醫院病理檢驗部1 臺中榮民總醫院家庭醫學科2 臺中榮民總醫院胃腸肝膽科3 Background: Elastase 1 (IRE-1) is a serine protease synthesized by pancreatic acinar cells, and it has been used as a clinical indicator of pancreatitis or pancreatic cancer in Japan.

However, Taiwanese data regarding the blood level of IRE-1 remain lacking.

Aims: This study aimed to establish the blood reference intervals of IRE-1 in Taiwan.

Methods: We prospectively recruited 400 subjects who received a full-day course of physical checkup, which was composed of comprehensive blood tests, digestive endoscopy, and abdominal sonography, in Taichung Veterans General Hospital during the period from 1 May, 2019 to 20 November, 2019. The concentrations of IRE-1 in fresh serum or plasma samples were measured (IATRO IRE1Ⅱ, LSI Medicine Corporation, Japan).

In addition, the IRE-1 levels were measured again after storage in a freezer (both 2-8°C and -20°C for 7 days). Other pancreas-related blood parameters, such as amylase, lipase, Ca-199, lipid profiles, and HBA1C, were also collected.

We analyzed the associations of IRE-1 with other the blood parameters by using multivariable regression analysis (Spearman’s correlation).

The 99% reference intervals of blood IRE-1 were

calculated by using MedCalc Statistical software (CLSI C28-A3).

Results: The IRE-1 levels in the serum samples were consistent and highly correlated in various different temperature conditions (correlation coefficients [r] = 0.971 in -20°C); however, the IRE-1 levels in the plasma samples were not consistent in -20°C (r = 0.430). Furthermore, the 95% reference interval of IRE-1 was established between 30.0 and 221.0 ng/dL. Moreover, the 99% reference interval of IRE-1 was established between 22.0 and 359.0 ng/dL. In multivariable analysis, triglyceride (r = 0.11), lipase (r = 0.51), and CA-199 (r = 0.18) were significantly associated with IRE-1 (all P < 0.05). Interestingly, HBA1C (r = 0.09) was significantly related to IRE-1 among patients with HBA1C < 6.5% (P < 0.05), but was not related among patients with HBA1C ≥ 6.5% (P = 0.71).

Conclusions: The stability of IRE-1 in serum is better than that in plasma; therefore, serum is a suggestive form for sample storage. The blood reference intervals of IRE-1 in Taiwan were first established in this study, and a higher IRE-1 level should be kept alert for screening a pancreasrelated disorder.

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P.102

GI SPECIALIST CAN DO FAIR OR BETTER CARE FOR ALL GI CANCER PATIENTS ─ FROM SOUP TO NUTS Chun-Chin Chen, Yi-Chih Wen, Jeng-Shiann Shin, Jen-Chieh Huang Division of Gastroenterology, Department of Internal Medicine, Cheng Ching General Hospital, Chung Kang Branch, Taichung, Taiwan

胃腸科專科醫師可以做好所有胃腸科 癌症病人的照護 ─ 從開始到結束 陳俊欽 溫奕志 辛政憲 黃仁杰 澄清綜合醫院中港分院胃腸肝膽科 Background: Cancer is the leading cause of death in Taiwan and elsewhere in world. Five of ten leading cancer-related mortality are GI cancers, including Hepatocelluar carcinoma (HCC), Colon cancer, Gastric cancer, Pancreatic cancer and Esophageal cancer. So, GI specialist play an important role for GI cancer diagnosis, staging, treatment planning, response evaluation, complication management, follow up strategy and even hospice care. Benifits of GI specialists for GI cancer care include EMR/ESD, GI/biliary stenting, GI bleeding management, ERCP for obstruction jaundice, liver tumor biopsy and RFA, ascites diagnosis and management, nutrition, liver function evaluation, bedside ultrasound examination, etc.

Aims: In Taiwan, there is no emphasis on GI specialist training including GI oncology except part of HCC. In HCC, GI specialist can do comprehensive care in any stage with fair or better care compared to surgeon, medical oncologist or radio-oncologist. So, basis on it, whether GI specialist can do same or better care in other GI cancer patients? We try to establish other GI cancer care experience and collect patient’s data from diagnosis, treatment planning, adjuvant or palliative therapy to death. Compare all the data to other documented cancer survial in different stage. To define whether GI specialist can do fair or better care and encourage more GI specialists to learn how to handle all GI cancer patients.

Methods: In all GI cancer patients, diagnosis is made by tissue proof, or image and/or tumor markers basis on diagnosis guildline. Staging was

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made according to AJCC. Treatment guideline was adapted with guideline of NCCN or our hospital and oncology textbook. Cancer committee was held to discuss these patients. All the patient’s data was recorded and analyzed to compare to other documented survival rate in different stage.

Results: From Dec. 2011 to Dec. 2019, we enrolled 253 GI cancer patients. In those, 81 patients are HCC, 70 patients are Colon cancer, 29 patients are Esophageal cancer, 37 patients are Gastric cancer, 20 patients are Pancreatic cancer and 16 patients are others (Duodenal adenocarcinoma, Ampullar vater cancer, Cholangiocarcinoma, GIST, Pseudomyxoma peritoneii, PNET with liver metastases). And 153 in 253 patients are in advanced stage (stage III and IV). We compare survival benifit in different stage, especially focus on advanced stage. Fair or better survival benifit was achieved in all GI cancer patients especially in advanced stage of all GI cancer. Statistic analysis is conducted in different stage and enough follow up period (>12 m), 1 and 2-yr survival rate with p < 0.05 in BCLC B & C of HCC, Stage III of colon, gastric, esophageal, pancreatic cancer, and stage IV of gastric, pancreatic cancer.

Conclusions: Throughout the 7-year experience, it reveals that GI specialist can do fair or better care for all GI cancer patients in any stage, especially in advanced stage. Consideration of conducting all GI cancer comprehensive care in GI department may be valuable and promising for achieving better survival and patient-doctor relationship.

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THE OUTCOME OF ENDOSCOPIC RESECTION OF LARGE GASTROINTESTINAL NEOPLASMS: A SINGLE HOSPITAL EXPERIENCE Kun-Feng Tsai, Li-Fu Kuo, Sheng-Yeh Tang, Yi-Ting Wu, Ping-I Hsu An Nan Hospital, China Medical University, Tainan, Taiwan

消化道大型腫瘤之治療成果 ─ 單一醫 院經驗 蔡坤峰 郭立夫 湯昇曄 吳奕霆 許秉毅 台南市立安南醫院 Background: In the era of minimal invasive treatment, endoscopic resection have been developed for decades. Endoscopic resection of large gastrointestinal neoplasms was used as an alternative treatment which could preserve the gastrointestinal tract to avoid organ dysfunction.

Aims: The aim of the study was to show the outcomes from endoscopic resection of large gastrointestinal neoplasms in our hospital.

Methods: From January 2018 to Jun 2020, patients with large (≥20 mm) gastrointestinal neoplasms for endoscopic resection were included. Resection details and the demographic data were collected for analysis.

Results: 129 neoplasms (123 colon neoplasms, 2 gastric neoplasms and 4 esophageal neoplasms) in 124 patients were found in our study. 111 neoplasms which received endoscopic mucosal resection showed mean size of the neoplasm 24 mm (range 20–45 mm), complete endoscopic resection rate (94%). Two patients were referred for additional surgery to complete the tumor resection. Post-EMR bleeding rate was 1.8%. No perforation was found. In 18 patients received endoscopic submucosal dissection, the result showed mean size of the neoplasm 41 mm (range 22–65 mm), complete endoscopic resection rate (100%) and complication rate (0%).

Conclusions: In our hospital, endoscopic resection of large gastrointestinal neoplasms is safe and effective for large neoplasms.

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7-LNCRNA PROGNOSTIC SIGNATURE OF GASTRIC CANCER FROM TCGA DATABASE Szu-Jen Wang1,2, Meng-Shun Sun2, Hsi-Jung Chen2, Ching-Yang Tsai2 Graduate Institute of Clinical Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan1 Division of Gastroenterology, Department of Internal Medicine, Yuan’s General Hospital, Kaohsiung, Taiwan2

從 TCGA 胃癌資料庫中評估七個長鏈 非編碼 RNA（lncRNA）的臨床預後 效益 王嗣仁1,2 孫盟舜2 陳錫榮2 蔡青陽2 高雄醫學大學臨床醫學研究所1 阮綜合醫院消化內科2 Background: Recent studies demonstrated that the dysregulated long non-coding RNAs (lncRNAs) expression profiles were related to the progression and survival in patients with various cancers including gastric cancer.

Aims: This study aimed to find out a long noncoding RNA (lncRNA) signature to predict the prognosis of gastric cancer from The Cancer Genome Atlas (TCGA) database.

Methods: 1. LncRNAs expression profiles and corresponding clinicopathological data for 375 patients with gastric cancer were obtained from The Cancer Genome Atlas (TCGA), including 375 tumor-part specimens and 32 non-tumor-part specimens. 2. Differentially expressed lncRNAs (DELs) between tumor-part and non-tumor-part specimens of gastric cancer were identified using the edgeR package, using an false discovery rate (FDR) < 0.05 and log2 |fold change (FC)| > 2. 3. The least absolute shrinkage and selection operator Cox (LASSO Cox) regression model was used to narrow down the candidates of lncRNA. 4. Next, the key lncRNAs in Lasso Cox regression were further analyzed with a stepwise multivariate Cox regression model. The lncRNAs fitted in the multivariate Cox regression model and independently associated with overall survival were selected to construct a prognostic risk formula. 5.

The R software version 3.6.1 and the “edgeR”, “glmnet”, “survival”, “timeROC” and “survminer”

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package were utilized to analyze. 6. The risk scores were calculated based on the formula generated through the multivariate Cox regression model. Using the median risk score as the cutoff value, patients in the dataset were divided into lowrisk or high-risk groups correspondingly. 7. The efficiency of the predictive model was estimated by the Receiver operating characteristic curve (ROC curve) and Harrell’s C-index statistic.

Results: Based on lncRNA expression profiling of 375 patients with gastric cancer from the TCGA database, a total of 1272 DELs were selected out including 221 down-regulated DELs and 1051 up-regulated DELs (Fig. 1). 20 lncRNAs were identified using LASSO Cox regression. Finally, 7 lncRNAs (AC012531.1, AC022387.1, AL121987.1, AL136418.1, GATA2-AS1, ST8SIA6-AS1 and TLX1NB) were confirmed in the multivariate Cox regression model (Fig. 2). The risk score was calculated by the formula as follows: Risk score = 0.53770* AC012531.1 - 0.53260* AC022387.1 + 1.46382* AL121987.1 - 0.40559* AL136418.1 -0.60623* GATA2-AS1 + 0.35453* ST8SIA6AS1 -0.78559* TLX1NB. According to this 7-lncRNAs signature, the corresponding AUC for the predictive model of 3-year and 5-year survival was 0.971 and 0.988, respectively (Fig. 3). It had a Harrell’s C-index statistic of 0.93 (95% CI: 0.880.97), indicating a high predictive ability for survival time of gastric cancer. Kaplan-Meier analysis also revealed that for the TCGA cohort, the high-risk group had significantly poorer survival than the low-risk group (Log-Rank test p < 0.001) (Fig. 4).

Conclusions: Our data-mining survey constructed the 7-lncRNA model can be a biomarker to predict the prognosis of gastric cancer. Further studies were needed to confirm this signature model.

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EFFECTIVENESS OF APIGETRIN ON THE TREATMENT OF HUMAN GASTRIC CANCER: MEDICINAL IMPORTANCE AND THERAPEUTIC POTENTIAL THROUGH SCIENTIFIC RESEARCH WORK ANALYSIS Dinesh Kumar Patel, Kanika Patel Department of Pharmaceutical Science, Sam Higginbottom University of Agriculture, Technology and Sciences, Payagraj, India Background: Despite the development of modern allopathic medicine, medicinal plants are still the best option for some of the Human disorders.

Widely used with considerable importance in international trade as well. Apigetrin is a flavonoid compound separated from medicinal plants such as Scutellaria baicalensis Georgi, Matricaria chamomilla, Stachys tibetica and Teucrium gnaphalodes.

Aims: Apigetrin is a flavonoidal compound found to be present in the many plant leaves and seeds which have possess antimutagenic, antioxidant, anti-cancer and anti-inflammatory activities.

Numerous scientific studies have proven the biological importance of fruits and vegetables containing diets for the effectiveness against various forms of cancerous disorders of human being. In order to know the biological importance of apigetrin in gastric disorders, here in the present investigation numerous scientific data have been collected and analyzed from different scientific research works.

Methods: Effectiveness of apigetrin on Human gastric cancer has been investigated in the present investigation through scientific data analysis of different research works. Role of Bcl-2, and enhancing Bax, Caspase-9/-3 and poly ADPribose polymerase (PARP) in the gastric cancer treatment have been also investigated through scientific data analysis of various research works.

Results: Scientific data analysis of various research works of scientific field revealed the biological importance of apigetrin in the medicine due to their pharmacological activities and therapeutic potential. Scientific data analysis revealed that apigetrin has beneficial effects on gastric cancer cells through suppression of proliferation and induction of apoptosis in gastric cancer cells. Effectiveness of apigetrin on gastric

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cancer is mainly through interaction on Bcl-2, Bax, Caspase-9/-3 and PARP however apigetrin administration significantly inhibited the gastric cancer cell xenograft tumorigenesis in some research work.

Conclusion: Scientific data analysis revealed the biological importance of apigetrin in the medicine for the effective treatment to being a better candidate against human gastric cancer.

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BIOMARKER IN CURCUMIN TREATMENT EFFICACY OF ALIMENTARY SYSTEM CANCER Hung-Hua Liang Graduate Institute of Clinical Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan

薑黃素治療消化系癌症的效果與生物 標記相關角色的探討 梁宏華 臺北醫學大學臨床醫學研究所 Background: Malignancies of alimentary system, included hepatocellular carcinoma (HCC) and colorectal cancer (CRC) are both high prevalence and death rate. Traditional treatments of HCC and CRC are surgical resection followed with adjuvant chemotherapy and/or radiotherapy.

Natural products have shown to be less toxic than synthetic compounds, and they have attracted much interest in recent research. Curcumin possesses antioxidant, anti-inflammation and is a promising anti-cancer agent.

Aims: Cancer biomarker provides possibility to predict the therapeutic responses and improve treatment efficacy. With the present study we are going to explore the biomarker as a guide of curcumin efficacy. This study explores the roles of specific biomarkers expression on the efficacy of curcumin in HCC and CRC. Methods: First, we found that HepG2 cells, which expressed higher levels of miR-200a/b, were more resistant to curcumin treatment than HepJ5 cells.

Second, we focus on the role of HSP27 in curcumin treatment of CRC. Each cell line experiments were performed for analysis applicable biomarker for curcumin treatment efficacy in alimentary system cancer.

Results: The MTT assay revealed that the cell viability after curcumin treatment was increased with overexpressing miR-200a/b in HepJ5 cells compared with the control cells. By cell cycle analysis and TUNEL assay, we found that apoptosis was increased dramatically in J5-control cells compared with overexpressing miR-200a/b in HepJ5 cells after curcumin treatment. We evaluated the levels of Bcl-2, Bax, and Bad by Western blot, and found a decrease of Bcl-2 levels

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and increase of Bad levels in the J5-control cells treated with curcumin compare to overexpression miR-200a/b cells. It was found that the silencing of HSP27 (HSP27-KD) resulted in increased cell viability to curcumin in CRC cells by SRB assay.

In addition, cell cycle analysis showed that the curcumin treatment caused cell cycle arrest at the G2/M phase in the control group, and apoptosis was reduced in the HSP27-KD group. Curcumin treatment also resulted in a decrease in antiapoptotic proteins, p-Akt, Akt, Bcl-2 and p-Bad, and increase in pro-apoptotic proteins Bad and c-PARP levels in the control cells but not in the HSP27-KD cells. Moreover, we found lower reactive oxygen species, superoxide and autophagy induction levels in the HSP27-KD cells as compared to the control cells.

Conclusions: All these results indicated that miRNA 200a/b and HSP27 can be a good predictive biomarker for curcumin resistance in HCC and CRC, respectively. With detection and modulation of the biomarkers, we can predict therapeutic efficacy and develop personalized therapy in the future.

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RE-DISCOVERING THE CLINICAL SIGNIFICANCE AND CHARACTERISTICS OF CLOSTRIDIUM INNOCUUM INFECTION IN NEW DIAGNOSTIC MICROBIOLOGY ERA: A CASECONTROL STUDY Yi-Chun Kuo1, Yi-Ching Chen2, Mi-Chi Chen3, Yung-Ta Chang4, Cheng-Hsun Chiu2,5 College of Medicine, Chang Gung University, Taoyuan, Taiwan1 Division of Pediatric Infectious Disease, Department of Pediatrics, Chang Gung Memorial Hospital, Taoyuan, Taiwan2 Division of Pediatric Gastroenterology, Department of Pediatrics, Chang Gung Memorial Hospital, Taoyuan, Taiwan3 Department of Laboratory Medicine, Chang Gung Memorial Hospital, Taoyuan, Taiwan4 Molecular Infectious Disease Research Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan5

無害梭狀桿菌所造成之臨床重要性與 疾病特色的再發現：一病例對照研究 郭奕均1 陳苡靜2 陳米琪3 張永達4 邱政洵2,5 長庚大學醫學系1 林口長庚紀念醫院兒童感染科2 林口長庚紀念醫院兒童胃腸科3 林口長庚紀念醫院檢驗醫學部4 林口長庚紀念醫院分子感染症醫學研究中心5 Background: Clostridium innocuum (CI) once was considered to be a low pathogenic microorganism before, but increasing evidence showed that it has the potential to cause Clostridium-associated diarrhea (CAD), especially extra-intestinal clostridial infection (EICI) in recent years. More importantly, CI is intrinsically resistant to vancomycin. A comprehensive clinical study on CI infection is sparse.

Aims: This study aims to evaluate the clinical characteristics, outcomes, and antimicrobial susceptibility of CI infections.

Methods: A retrospective case-control study was conducted at Chang-Gung Memorial Hospital from 2014 to 2019. A total of 152 non-repetitive CI isolates were identified using MALTI-TOF

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MS Biotyper. Cases with CD infection were selected as the controls because it is the most important organism in clostridium species.

Clinical information, laboratory testing results, and antimicrobial susceptibility (AST) were reviewed via an electronic medical record system.

Results: The study enrolled 456 patients (152 matched pairs). Baseline characteristics such as age, gender, Charlson’s comorbidity score were similar in both groups. CI group tended to present with more EICI (36.8% versus 8.2%, P<0.001) and gastrointestinal (GI) tract-related complications, including ileus, bowel perforation, clinical sepsis and shock (26.3% versus 11.2%, P<0.001) than CD group. No significant difference was noted in the mortality rates among the two groups. For CI infection, chronic kidney disease (OR 8.55), solid tumor (OR 3.46), ICU admission (OR 7.27), and shock status (OR 7.99) were four independent risk factors for both 30-days and overall mortality.

Antimicrobial susceptibility rates in CI isolates for metronidazole, ampicillin-sulbactam, penicillin, and clindamycin are 100% (20/20), 100% (21/21), 79.5% (35/44), 68.2% (30/44), respectively.

Conclusions: Compared to CD, C. innocuum is a clinically significant pathogen that may cause EICI and severe GI-tract infection with a high risk of complication. Metronidazole and ampicillinsulbactam are the potential drug of choice for treating CI-related disease.

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THE EFFECT OF THE SALIVARY, GASTRIC AND STOOL MICROBIOME ON GASTROESOPHAGEAL REFLUX DISEASE Hsin-Yeh Chen1, Keng-Liang Wu1,2, Yi-Chun Chiu1,2, Chih-Chien Yao1, Wei-Chen Tai1,2, Seng-Kee Chuah1,2 Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan1 College of Medicine, Chang Gung University, Kaohsiung, Taiwan2

胃腸道微生物對於胃食道逆流的影響 陳興曄1 吳耿良1,2 邱逸群1,2 姚志謙1 戴維震1,2 蔡成枝1,2 高雄長庚紀念醫院肝膽胃腸科系1 長庚大學醫學院2 Background: There are different microorganisms in the gastrointestinal tract, and those are related to inflammation. Whether the microorganisms in the saliva, gastric juice and stool are related to inflammation in reflux esophagitis and Barrett’s esophagus is not clear.

Aims: We aim to identify the specific microorganisms from the saliva, gastric juice and stool that are related to reflux esophagitis and Barrett’s esophagus and to study the correlation between these microbiota and inflammation.

Methods: Three groups (13 controls; 31 patients with reflux esophagitis and 10 patients with Barrett’s esophagus) were recruited. We investigated the amount and diversity of microorganisms in saliva, gastric juice and stool by using 16S rRNA gene pyrosequencing and analyzed serum inflammatory cytokines by ELISA. Results: In saliva, we found more Staphylococcaceae, Tannerellaceae, and Ammoniphilus in the Barrett’s esophagus group.

In gastric fluid, there were more Atopobiaceae and Coriobacteriia in Barrett’s esophagus but more Helicobateraceae in controls. In stool, more Bacteroidetes, Prevotellaceace, and Nanoarchaeaeta were found in Barrett’s esophagus patients. Higher serum IL-6 and IL-10 levels were found in Barrett’s esophagus patients.

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Peptostreptococcus in saliva was correlated with IL-6 (Pearson’s correlation, r=0.637 p<0.001), and Streptococcus in stool was correlated with IL-6 (r=0.551, p<0.001).

Conclusions: Saliva Peptostreptococcus may be one of the factors causing these diseases by causing the secretion of the inflammatory cytokine IL-6 and subsequent progression to Barrett’s esophagus. Further study is needed to clarify this phenomenon and to determine whether eliminating these microorganisms can improve Barrett’s esophagus.

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