2021消化系聯合學術演講年會摘要手冊 by GEST 電子書上傳區

2021 消化系聯合學術演講年會會長演講 ............................................................................................... 1 特別演講 ............................................................................................... 4 外賓演講 ( 一 ) Cutting-edge of Digestive Endoscopy in Japan ...................................... 5 ( 二 ) Chronic Hepatitis B: Antiviral Therapies and Hepatocellular Carcinoma .............................................................................................. 6 ( 三 ) Recent Advances in Diagnosis and Therapy of IBD .............................. 7 ( 四 ) Antiviral Therapy and Fibrosis Regression in Chronic Hepatitis C ......... 8 ( 五 ) State of the Art Update on the Microbiome in 2021 ............................... 9 ( 六 ) Treatment Options in GERD: Medical, Endoscopic and Surgical ........ 10

專題討論 ( 一 ) The Eﬀectiveness of Digestive Cancer Screening in Taiwan ................11 ( 二 ) Metabolic Syndrome and Digestive Disease........................................ 16 ( 三 ) Recent Advances in Neurogastroenterology and Motility..................... 20 ( 四 ) The Application of Contrast Enhanced Harmonic EUS in the Hepatobilio-pancreatic Disease ............................................................ 24 ( 五 ) Functional Cure of Hepatitis B ............................................................. 30 ( 六 ) Current Status of Management of CHC in Taiwan ............................... 35 ( 七 ) Microbiota Update 2021 ....................................................................... 40 ( 八 ) Update of Systemic Therapy for HCC .................................................. 44 ( 九 ) Precision Medicine in GI Endoscopy Practice...................................... 48 ( 十 ) Diagnosis and Treatment of Small Bowel Disease .............................. 53

一般演講 C 型肝炎（一） ............................................................................................. 56 B 型肝炎（一） ............................................................................................. 61 B 型肝炎（二） ............................................................................................. 65 肝腫瘤（一） ................................................................................................ 70 肝硬化及其他肝病 ......................................................................................... 75 脂肪肝相關疾病 ............................................................................................. 78 上消化道疾病（一）...................................................................................... 82 其他消化道疾病 ............................................................................................. 87 下消化道疾病（一）...................................................................................... 91 膽胰疾病........................................................................................................ 95 C 型肝炎（二） ............................................................................................. 99 肝腫瘤（二） .............................................................................................. 104 上消化道疾病（二）.................................................................................... 108 下消化道疾病（二）.....................................................................................114

壁報展示肝 .................................................................................................................119 消化道及膽胰疾病 ....................................................................................... 194

2021 消化系聯合學術演講年會

論文摘要

台灣消化系醫學會 ( 第五十一屆 ) 學術演講年會台灣消化系內視鏡醫學會 ( 第三十次 ) 學術演講年會

2021 消化系聯合學術演講年會

會長演講（台灣消化系醫學會） NON-INVASIVE DIAGNOSIS OF LIVER FIBROSIS AND ITS CLINICAL APPLICATION Cheng-Yuan Peng（彭成元） Center for Digestive Medicine, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan

Chronic injury of the liver leads to its fibrosis. The extent of liver fibrosis is associated with the risk of long-term liver-related morbidities, such as cirrhosis and its related complications, including hepatocellular carcinoma (HCC). Thus, accurate assessment of liver fibrosis is pivotal to the prognostication and therapeutic decision-making of patients in clinical practice. Although liver biopsy is the gold standard for fibrosis staging, it is invasive and carries some risk of complications. Non-invasive assessment of liver fibrosis has thus gained popularity and become the widely accepted alternative to liver biopsy. Non-invasive diagnostic methods of liver fibrosis include serum biochemical markers that directly or indirectly reflect the severity of liver fibrosis and imaging modalities that provide a physical measure of liver stiffness. Among the serum biochemical markers, APRI, FIB-4 and FibroTest are most wellknown. Imaging modalities include ultrasound-based (vibration-controlled transient elastography, point shear wave acoustic radiation force impulse (ARFI) elastography, 2-D shear wave elastography) and magnetic resonance image (MRI)-based elastography. Various non-invasive tests have good-to-excellent diagnostic performance for predicting fibrosis stage in viral hepatitis. Identification of patients with ≥F2 and F4 METAVIR stages has traditionally been advocated for the initiation of antiviral therapy to prevent disease progression, and for the surveillance of HCC and esophageal varices, respectively.

Etiology-specific cutoffs for dichotomizing fibrosis stages have been proposed for CHB and CHC. Furthermore, these methods, including FibroScan and FIB-4 have been implemented to stratify the risk of HCC among treatment-naïve patients with chronic hepatitis B (CHB) or C (CHC). For the prediction of portal hypertension-related complications, it has been demonstrated that spleen stiffness had higher diagnostic performance than liver stiffness and combination of both may provide better diagnostic accuracy. With the advent of direct-acting antivirals (DAAs) in patients with CHC and the clinical practice of long-term nucleos(t)ide analogue (NUC) therapy in patients with CHB, the current unmet need is the risk stratification of liver-related outcomes among CHC patients achieving SVR as well as CHB patients undergoing long-term NUC therapy. Several studies have delineated longitudinal changes in serum biochemical markers or liver stiffness in parallel with fibrosis regression during NUC therapy or after DAA therapy in patients with CHB or CHC. However, the optimal cutoffs for prediction of fibrosis stage in these viral suppressed or eradicated, necroinflammationresolved patients remain to be defined and validated. Nonetheless, characterization of the longitudinal changes in these parameters may help stratify the future risk of liver-related outcomes in patients with CHB or CHC, which is relevant to the implementation of surveillance program.

2021 消化系聯合學術演講年會

會長演講（台灣消化系內視鏡醫學會） SERRATED POLYPS: A PARADIGM SHIFT IN COLORECTAL CANCER PREVENTION Chun-Che Lin（林俊哲） Center for Digestive Medicine, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan

Colorectal cancer (CRC) is a heterogeneous disease thought to result from the accumulation of various aberrant mutations in the epithelial cells lining the colorectal mucosa. Adenomas with intestinal-type dysplasia are not the only precursor lesions to CRC. Serrated polyps are believed to give rise to nearly 1525% of CRCs, via the serrated neoplasia pathway. A large proportion of interval CRCs (those that develop within recommended surveillance periods, typically 3–5 years) are believed to arise via the serrated pathway. Approximately half of the cancers in the serrated pathway have microsatellite instability. In serrated lesions, microsatellite instability is caused by epigenetic inactivation of the MLH1 gene. This inactivation is the result of methylation of the promoter region of MLH1. Before 2010, neoplastic serrated lesions were not well detected by endoscopists and were generally interpreted as harmless hyperplastic polyps (HPs) by pathologists. There is large interobserver variation among endoscopists or pathologists in this area. This creates uncertainty among endoscopists in clinical practice or clinical trials about whether they should accept pathologists’ interpretations of lesions in the serrated class. In the past decade, it has gained increasing recognition due to its close association with colorectal cancer (CRC). Advances in endoscopic technology also have improved detection of serrated polyps with a varied spectrum of histopathologic correlates. Serrated polyps includes hyperplastic polyps (HPs), sessile serrated lesions (SSLs), and traditional serrated adenomas (TSAs). HPs are the

most common, comprising approximately 75% all serrated polyps. SSLs (previously called sessile serrated adenomas or sessile serrated polyps) account for approximately 25% of serrated polyps. In general, SSLs are characterized by a larger size, location in the proximal colon, and a indistinct endoscopic appearance compared with HPs. TSAs are the leastcommon type of serrated polyp, and are typically polypoid lesions found in the distal colorectum. SSLs and TSAs are each considered precursor lesions for CRC. It is difficult to reliably differentiate sessile serrated polyps from hyperplastic polyps during endoscopy. There are, however, several clues that can help an endoscopist estimate whether a polyp is a sessile serrated polyp as opposed to a hyperplastic polyp. Sessile serrated polyps are larger on average and more often located in the proximal colon. Sessile serrated polyps have a more irregular surface, a pattern to the surface that has been called “cloudlike,” and indistinct edges compared with hyperplastic polyps. Sessile serrated polyps also have large open pits on the surface when viewed with magnification. These pits appear as large dark spots with high-definition, standard-magnification colonoscopes. Although endoscopic differentiation of sessile serrated polyps from hyperplastic polyps is challenging, endoscopic differentiation of serrated lesions as a class from conventional adenomas as a class is straightforward. There are several things that endoscopists can do to improve the detection of serrated polyps: to prescribe effective bowel preparations and improve polyp

2021 消化系聯合學術演講年會

detection, to transition to high-definition and imageenhanced colonoscopes. To aware and understand the distinct endoscopic features, and to confer and collaborate with pathologist colleagues. Besides detection and characterization, relevant serrated polyps should also be completely removed. Incomplete resection of premalignant polyps is one

of the major reasons of colonoscopy interval cancer and should be prevented. Another aspect of clinical management that will result in a decline in the prevalence of post-colonoscopy CRCs is pursuing proper post-polypectomy surveillance for individuals with serrated polyps.

2021 消化系聯合學術演講年會

特別演講 CURRENT CONTROVERSIAL ISSUES IN THE MANAGEMENT OF CHRONIC HBV INFECTION Yun-Fan Liaw（廖運範） Liver Research Unit, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taipei, Taiwan

Clinical and basic research in the past 5-6 decades have achieved general consensus in the understanding of chronic hepatitis B virus (HBV) infection and the management of chronic hepatitis B and HBV-cirrhosis. However, debatable challenges to the existing consensus in the concept and/or definitions are emerging. These include (1). ALT upper limit of normal: traditional laboratory-defined vs fixed; (2). Nomenclature for phases of chronic HBV infection: classical vs EASL proposal; (3). Indication of antiviral therapy: to treat patients vs to treat HBV;

(4). Finite vs indefinite long-term antiviral therapy for HBV-cirrhosis; (5). Issues surrounding finite antiviral therapy, including duration of consolidation therapy (APASL vs EASL) and the retreatment decision (biochemical markers vs HBsAg/ALT kinetics); (6). On-treatment risk of hepatocellular carcinoma: tenofovir vs entecavir therapy. The pros and cons of these controversial issues were reviewed, assessed and discussed in depth based on relevant lines of scientific evidence.

2021 消化系聯合學術演講年會

外賓演講（一） CUTTING-EDGE OF DIGESTIVE ENDOSCOPY IN JAPAN Hisao Tajiri Senior Adviser, Japan Gastroenterological Endoscopy Society (JGES) President, Japan Endoscopy Database (JED) Institute

Japan Gastroenterological Endoscopy Society (JGES) was established as Japan Gastrocamera Society in 1959. In 1973, the title of the society was changed to Japan Gastroenterological Endoscopy Society to focus on the gastroenterological endoscopy. The society had a membership of only 280 at the time of establishment, but it has grown to over 34,623 members in 2020. JGES is dedicated to advancing patient care and welfare, by promoting digestive disease research through endoscopy, developing and advancing endoscopic practice. Our recent activities are as follows; promoting endoscopic researches, educational seminars and lectures, two congresses every year (individual annual congress in spring and JDDW in autumn), regional meetings (meetings held by 10 regional chapters). JGES started Japan Endoscopy Database (JED) Project in 2015. The aim of this project is to construct a “dream” database to benefit both doctors and patients. This will realize an ambitious strategy to create the world’s leading database with approximately 17 million additional data every year when it is fully operational. By JED, we seek to take an initiative in the construction of infrastructure to conduct international joint researches, and we indeed have been promoting several researches of AI-assisted endoscopy with JED. Development of AI by National Institute of Informatics (NII) leads to the applications of endoscopic screening. The project aims to develop “AI” which is highly versatile and has been already utilized by many medical and screening institutes. Current AI technology is realized to decrease the rate of missed lesions during endoscopy and to decide

the accurate endoscopic treatment strategy. In the near future, we hope the following points; reduction of time and misdiagnosis, technical support in therapeutic endoscopy, and homogenization of diagnosis. The challenges we are working on are as follows; 1) While Image-Enhanced Endoscopy (IEE) developed in Japan has spread and contributed to the standardization of diagnosis at the global level, we aim to further improve the quality. For that purpose, we are further enhancing our educational programs not only in Asian countries but also all over the world and further promote internationalization projects. 2) By advancing the spread of endoscopic screening, we construct an efficient screening system to detect and diagnose many early cancers and provide minimally invasive therapy to more patients, and as a result, contribute to medical cost reduction. 3) With respect to endoscopic therapy for GI malignancies, innovation has been issued from Japan to the world nearly every 15 years, with polypectomy, EMR, and ESD. Soon there will be an emergence of new technologies that will transform future endoscopic treatment. The development and spread of safer and more reliable endoscopic treatment is the most important mission. In the future, in order to stay innovation and to lead further, what we have to do is to promote cooperation of GI endoscopists and surgeons, as well as the promotion of research and development in a midto long-term perspective with the cooperation between industry and academia. In addition to the fusion of expert human skills and machinery (robot technology), it is important to evolve the next generation technology combining AI and information systems.

2021 消化系聯合學術演講年會

外賓演講（二） CHRONIC HEPATITIS B: ANTIVIRAL THERAPIES AND HEPATOCELLULAR CARCINOMA Mindie H. Nguyen Division of Gastroenterology and Hepatology and Liver Transplant at Stanford University Medical Center, Palo Alto, CA, USA

Despite the availability of effective and safe hepatitis B vaccine for a few decades, chronic hepatitis B still affects approximately 290 million people worldwide according to a 2016 estimate. Several effective and safe oral medications have also become available in the past two decades, but a large number of patients with chronic hepatitis B continue to die prematurely due to end-stage liver failure related to cirrhosis and hepatocellular carcinoma (HCC). Strong observational as well as clinical trial data have shown that antiviral treatment with oral nucleos(t)ides are effective in lowering the risk of HCC development. More recent data have also shown that oral nucleos(t)ide therapies are also effective in increasing the 5-year survival of chronic hepatitis B who already have HCC, including patients with severe liver dysfunction, advanced tumor stage, or those receiving only palliative or supportive care for HCC. However, antiviral therapy is severely underutilized even among patients with advanced liver

disease. Only one in three U.S. patients with hepatitis B-related cirrhosis and only one in two patients with hepatitis B-related HCC received antiviral therapy at any time. In this same nationwide study of 153 million people with private health insurance from the U.S., only 15% of the chronic hepatitis B patient population in the U.S. have been diagnosed and only 5% have received antiviral therapy. Globally, only 10% of the world burden of chronic hepatitis B have been diagnosis and only about 1.6% are estimated to have received antiviral therapy. Therefore, to reduce morbidity and mortality for patients affected by hepatitis B, we need to develop better public health and clinical strategies for improved screening and diagnosis than the current risk-based strategies; we need to propose more practical treatment algorithm and initiate antiviral therapy in appropriate patients more timely; and we need to develop novel therapies with finite treatment duration and potential for cure.

2021 消化系聯合學術演講年會

外賓演講（三） RECENT ADVANCES IN DIAGNOSIS AND THERAPY OF INFLAMMATORY BOWEL DISEASE Byong Duk Ye Department of Gastroenterology and Inﬂammatory Bowel Disease Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea

With worldwide increase of its incidence and prevalence, inflammatory bowel disease (IBD) has evolved into a global burden. An improved understanding of pathophysiology and natural course of IBD has led to a significant development in the management of IBD. Advances in recent medical treatments of IBD have enabled a paradigm shift from symptomatic relief to control of inflammation for achieving disease modifications and better prognoses for patients with IBD. For optimal management of patients with IBD, the following approaches and strategies are needed to be implemented: 1) Understanding the progressive nature of IBD, especially Crohn’s disease, 2) Early diagnosis of IBD

before progression of digestive damage, 3) Proper staging of disease, 4) Prediction of disease course and individualized approach, 5) Setting appropriate therapeutic targets, 6) Earlier and timely treatment to reduce and prevent progressive digestive damage, complications and disability, 7) Proper positioning of various biologics and small molecules, 8) Tight disease monitoring using objective tools, 9) Collaboration and multidisciplinary team approach, 10) Education and engagement of patients. Consideration and application of these approaches and strategies could improve the quality of IBD care, ultimately leading to better longterm outcomes of patients with IBD.

2021 消化系聯合學術演講年會

外賓演講（四） ANTIVIRAL THERAPY AND FIBROSIS REGRESSION IN CHRONIC HEPATITIS C Massimo Pinzani University College London, Institute for Liver and Digestive Health, Royal Free Hospital, London, UK

The established success of anti-HCV treatment with DAA has consolidated the possibility of their efficacy in blocking or reversing the fibrogenic progression of HCV-induced chronic liver disease (CLD) and, more in general, has unearthed vital information about the natural history of fibrosis regression. Although more and more data on post-SVR are becoming available, there are, however, two main limitations: 1. the large majority of the current knowledge is based on the treatment of patients with cirrhosis and 2. post-SVR liver biopsy are rare since this is not the standard of care. Therefore, any definitive conclusion about the regression/stabilization of liver fibrosis following DAA-induced SVR will need to wait for further confirmations. Regardless, while it is evident that in patients with HCV-related CLD, SVR reduces the risk of liverrelated complications such as hepatic decompensation, hepatocellular carcinoma (HCC) as well as all-cause mortality, it is also increasingly apparent that in patients with clinically significant and severe portal hypertension (PH), HCV clearance does not induce a significant reduction of PH and that cirrhosis, once advanced may progress to decompensation even in absence on HCV replication. In biological terms, this can be explained by the relative autonomy acquired by the fibrogenic process

beyond a certain level of development over decades characterised by chronic fibro-inflammation and neoangiogenesis. In particular, it is conceivable that, at this stage of the disease, two major determinants may condition further clinical progression independently of the reduction of hepatocellular necrosis and inflammation induced by SVR. The first is represented by the remarkable hyperplasia of different types of activated fibrogenic myofibroblasts which is associated by a strong activation of anti-apoptotic pathways in these cells. The second is due to the extensive changes in hepatic angio-architecture consequent to neo-angiogenesis and to the contraction of scar tissue leading to elevated tissue tension which are only minimally affected by the reduction of necroinflammation following SVR. Currently, there is much debate on the possible use of non-invasive tests, such as serum markers and liver elastography, for monitoring post-SVR fibrosis regression. However, this contention occurs in the absence of clear-cut criteria for the histopathological assessment of fibrosis regression. Therefore, serum markers and elastography are not accurate in detecting fibrosis regression after SVR in HCV patients with CLD and their routine use is presently not recommended. However, yearly determinations by liver elastography could be helpful to refine the stratification of residual liver-related risk.

2021 消化系聯合學術演講年會

外賓演講（五） STATE OF THE ART UPDATE ON THE MICROBIOME IN 2021 Emad El-Omar Microbiome Research Centre, St George & Sutherland Clinical School, University of New South Wales, Sydney, Australia

The gut microbiota play a crucial role in human health and disease, having profound influence on our metabolism and multiple effects on the innate and adaptive immune systems. Almost every organ in the body is affected by the quality, diversity and metabolic output of this microbiota. Diversity of the microbiota is a surrogate for health and loss of diversity is characteristic of many human diseases. This “dysbiosis” represents an abnormal state that predisposes to a variety of diseases by maximising the harmful effect of pathobionts and the loss of beneficial effects of symbionts. The consequences of this dysbiosis include disruption of mucosal barrier function (hyperpermeability), translocation of microorganisms and their products and initiation of a state of low-grade chronic inflammation. The past

decade has seen rapid advances in understanding the role of the gut microbiome in health and disease. This is clearly most evident in the gastrointestinal tract and particularly in the context of inflammatory bowel disease, colorectal, gastric and hepatocellular cancer, and more recently, pancreatic cancer. With its direct impact on the host’s immune repertoire, metabolic networks and neuroendocrine pathways, the microbiome also exerts profound modulatory effects on almost every system within the human body. During this lecture, we will discuss the latest advances in understanding of these effects, their relationships to GI and non-GI diseases and their full impact on human health. We will also discuss future directions of research in this exciting and fast evolving medical and scientific revolution.

2021 消化系聯合學術演講年會

外賓演講（六） TREATMENT OPTIONS IN GERD: MEDICAL, ENDOSCOPIC AND SURGICAL Michael Vaezi Division of Gastroenterology, Hepatology and Nutrition, Vanderbilt University Medical Center, Nashville, TN, USA

Treatment options for patients with gastroesophageal reflux disease (GERD) include medical therapy with acid suppressive medications, surgical fundoplication or minimally invasive endoscopic therapies. Acid suppressive therapy and surgical fundoplication are highly effective therapies with track record of success for patients with GERD. However, recent concerns about the chronic complications

associated with PPI use has bolstered the impetus on exploring alternative therapies for treating GERD. Minimally invasive surgical or endoscopic therapy for GERD are now gaining some traction in GERD therapy. In this lecture I will discuss the role of each of these therapies and how to ensure patient safety for each of the options.

2021 消化系聯合學術演講年會

專題討論（一） The Effectiveness of Digestive Cancer Screening in Taiwan EFFECTIVENESS OF A MULTIDISCIPLINARY APPROACH FOR SCREENING OF ESOPHAGEAL CANCER Wen-Lun Wang（王文

）

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

Esophageal cancer (EC) is the seventh most common cancer and sixth most common cause of cancer death in the world, with estimates of 572,000 new cases and 509,000 new deaths in 2018. The incidence of EC in Taiwan is still increasing in recent decades, but the prognosis is very poor (5-year survival< 20%) because most patients were diagnosed at late stage. Because of this poor prognosis, there is a great need for effective and cost-effective ways to detect and treat curable precursor dysplasias and early-stage ESCC, but this requires screening of highrisk asymptomatic people. Two separate studies in the highest-risk areas of China (with EC incidence 100/100,000 population per year) have shown that 1-time screening with Lugol’s chromoendoscopy can reduce ESCC mortality by >30% in the following 10 years. In China, they now have a national program that endoscopically screens >200,000 asymptomatic adults each year, and the long-term effectiveness is pending. However, most high-risk areas in China, and all high-risk populations in other countries (ex. Taiwan), have EC incidence rates of about 10 to 40 cases per 100,000 population/ year, which makes such general population endoscopic screening cost prohibitive. In Taiwan, the populations with alcohol drinking,

betel nut chewing, cigarette smoking and deficiency of ALDH2 enzyme (ABCD) or with history of head and neck cancer (HNSCC) have been identified as the high-risk subjects for ESCC. Since 2008, we initiated a multidisciplinary ESCC screening program in EDA Hospital, using a questionnaire-based tool to triage the most high-risk individuals to receive advanced endoscopic screening and treatment. Based on this program, 15% of patients with history of HNSCC and 2% of asymptomatic subjects with “ABCD” risk factors were detected to have ESCC. Reciprocally, 10% of ESCC patients were found to have HNSCC. Most of the second primary cancers were detected at early stage, and thus could be treated with endoscopy or minimally invasive surgery. In the following 5 years, this policy can reduce the ESCC mortality by 10% and HNSCC mortality by 40%. Furthermore, a risk-scoring system for ESCC was developed and currently prospectively validated in two medical centers. A new non-invasive high-throughput genetic test for alcohol-metabolizing enzyme has also been developed. In future, such risk-stratification models combined with a non-invasive genetic test may potentially be incorporated into the pre-existing oral cancer prevention program, to triage screening and finally reduce mortality from ESCC.

2021 消化系聯合學術演講年會

專題討論（一） The Effectiveness of Digestive Cancer Screening in Taiwan MASS SCREENING AND ERADICATION OF HELICOBACTER PYLORI FOR GASTRIC CANCER PREVENTION IN TAIWAN Yi-Chia Lee（李宜家） Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan

台灣人口結構老化，若不針對致癌因子進行預防介入，癌症發生率將預期大幅攀升，醫療資源將大量消耗在治療晚期病患，因此，預防醫學的重要性不斷提升，以期在源頭阻斷後續癌症發生。感染、慢性發炎與癌症三者息息相關，幽門桿菌（Helicobacter pylori）與胃癌的緊密關係為典型例子，幽門桿菌會造成胃炎，長期發炎導致胃腺體破壞、胃酸下降及胃內菌相變化，進而產生癌化現象；相較於無帶菌者，帶菌者有十倍以上的胃癌風險，根據世界衛生組織分析，幽門桿菌已證實為第一級致癌物，若能將此菌清除，可以減少將近九成的胃癌發生。然而在醫院端，醫師主要面對已有症狀的病患，如何跨出醫院、在大社區針對無症狀的民眾進行早期介入，世界仍缺乏實證的指引，因為除了個人治療之外，以社區為單位有許多未解之處，包括如何擬定篩檢模式、目標族群、邀約方法、工具驗證、陽性轉介、最後到效益、成本效益與副作用評估等等，這些環節需要產官學、基層醫療、乃至社會人文等跨領域的緊密合作 [1]。在臺灣，根據幽門桿菌的重要性，業已發展出一系列客製化的胃癌防治方法，以符合各種不同社區的需求：（1）全面根除法（the mass eradication method）：馬祖過去為全台胃癌發生率最高之地方，曾高出本島三到五倍，在政府支持下，當地衛生局與學界合作於 2004 年開始介入 [2]，幽門桿菌的盛行率已由介入前將近七成降低至今約一成，馬祖胃癌發生率隨之下降 53%，死亡率也下降 25%，預期 2025 年可進一步下降胃癌發生率達 68%，死亡率降低 39%，胃癌預期將成為罕見癌症 [3]；（2）家戶篩檢法（the family unit method）：本國

原鄉胃癌發生率高出兩到三倍，在政府的規劃下，胃癌防治已列入原鄉健康不平等改善策略十大行動之一，於 2018 年開始進行試辦介入 [4]，在 60% 的幽門桿菌高度盛行之廣大社區中，發展出以家戶為單位的篩檢模式，不僅提升效率，也避免交互感染，也期降低消化道癌的其他生活危險因子；（3）二合一法（the two-in-one method）：在胃癌中等風險社區進行防治，需要考量其他高盛行疾病將競爭有限的篩檢資源。臺灣大腸癌高度盛行，我國已推行糞便潛血檢查來進行篩檢，然而民眾的篩檢參與率與陽性轉介率仍有加強之空間，2014 年在彰化縣提出結合糞便潛血與幽門桿菌糞便抗原檢查的二合一法 [5]，除了促進產業發展外，此法可降低間接成本，提升篩檢效率，除了除菌治療的好處之外，大幅提高民眾篩檢參與率達 14%，也因為初次篩檢者與具不良生活習慣者的參與提升，可增加大腸腫瘤偵出率達 30%，對兩癌防治都有正向的效果。

References: 1. Lee YC, et al. Mass eradication of Helicobacter pylori to prevent gastric cancer: Theoretical and Practical Considerations. Gut and Liver. 2016 Jan;10(1):12-26. 2. Lee YC, et al. The benefit of mass eradication of Helicobacter pylori infection: a community-based study of gastric cancer prevention. Gut. 2013 May;62(5):676-82. 3. Chiang TH, et al. Mass eradication of Helicobacter pylori to reduce gastric cancer incidence and

2021 消化系聯合學術演講年會

mortality: a long-term cohort study on Matsu Islands. Gut. 2021 Feb;70(2):243-50. 4. Bair MJ, et al. Planning mass eradication of Helicobacter pylori infection for indigenous Taiwanese peoples to reduce gastric cancer. Journal of Gastroenterology and Hepatology. 2020 Apr;35(4):609-616.

5. Lee YC, et al; Collaborators of Taiwan Communitybased Integrated Screening Group. Communitybased gastric cancer screening coupled with a national colorectal cancer screening program: Baseline results. Gastroenterology. 2021 Jan 11:S0016-5085(21)00067-6. doi: 10.1053/ j.gastro.2021.01.008. Online ahead of print.

2021 消化系聯合學術演講年會

專題討論（一） The Effectiveness of Digestive Cancer Screening in Taiwan POPULATION COLORECTAL CANCER SCREENING IN TAIWAN: WHERE ARE WE NOW AND WHERE ARE WE GOING? Han-Mo Chiu（邱瀚模） Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan

Colorectal cancer (CRC) screening is one of the most effective way of reducing CRC related death. Several previous studies have demonstrated that either colonoscopy-based screening, which is adopted in the U.S and some EU countries, or fecal immunochemical test (FIT)-based screening could effectively reduce CRC death and even CRC incidence. The FITscreening strategy is more popular as it can select high-risk subjects from large population thereby limiting the demand for colonoscopy. A most recent study from Taiwan has demonstrated that FITscreening was found to result in a 34% reduction in advanced-stage colorectal cancer (CRC) and a 40% reduction in death from CRC after 10 years of followup. Given the effectiveness being demonstrated in population studies, CRC screening is encountering challenges. First, since its outbreak in China in December 2019, COVID-19 has spread across the world and became a global pandemic. During the pandemic, cancer screening services were forced to curtail or even “off-stage” in many countries, especially in the North America and Europe, and transient pause in Asian countries. Many screening organizers were forced to rethink about further riskstratification of the screening participants and more efficient use of constrained endoscopy resources. This

is not only for addressing the screening backlogs, but also to stimulate the screening community to seriously consider the reform of current style of CRC screening toward a tailored and precision way of screening. Second, if we look at the results of Taiwan CRC Screening Program, the effectiveness of FIT screening was consistently lower in the proximal colon than in the distal colon. This arouse the attention of interval cancers, with may be secondary to insufficient performance of FIT for proximal colon and inadequate colonoscopy quality. Third, youngonset CRC is rapidly increasing not only in the West but also in Asian countries, including Taiwan. Revision of age to start screening may be needed and more relevant researches is highly demanded. Fourth, screening uptake in Taiwan is still unsatisfactory. How to increase the awareness of the public, especially the hard-to-reach population, and to minimize inequality in screening is an urgent task. Fifth, several modifiable risk factors were identified for CRC and primary prevention is expected to play additive effect together with screening. Finally, whether novel technologies such as artificial intelligence would be able to contribute to improve the effectiveness of screening is intriguing. Screening community should not hesitate to embrace them.

2021 消化系聯合學術演講年會

專題討論（一） The Effectiveness of Digestive Cancer Screening in Taiwan HCC SCREENING IN TAIWAN Sheng-Nan Lu（盧勝男） Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan

Hepatocellular Carcinoma (HCC) was not included in the national cancer program due to high fatality rate. However, early detection or screening or surveillance for HCC has been a routine for carriers/patients of chronic hepatitis B and/or C virus infection in Taiwan. Patients with non-viral origin liver cirrhosis are also candidates for HCC screening. In most of practice guidelines as well as our daily practice, combination of ultrasonography (US) and alpha-fetoprotein (AFP) are the most common screening tools. Some other tumor markers, as PIVKA II, AFP-L3, and their scoring systems, or image modalities, as EOB-MRI, are also used for HCC screening. Screening interval is also an important component of screening program. It is supposed to be 6 months, ranged from 3 to 12 months. The screening interval might be or not be related to HCC risk. Although HCC screening has been the routine practice in Taiwan for decades, there still some unmet needs and some equivocal issues to be addressed. This talk will discuss the following clinical issues: 1. Should AFP useful in HCC screening? 2. Can US can be replaced by combination scoring system of tumor

markers? 3. Should cured hepatitis C patients with mild fibrosis be candidates for HCC screening? 4. Should we adjust the normal upper limit of AFP after viral hepatitis well-controlled? 5. Should patients with metabolic associated fatty liver disease (MAFLD) be screening for HCC? 5. How many proportion of HCC patients can be detected in their early stage? Besides of above clinical issues, there is an unmet public health need. According to National Cancer Registration in Taiwan, proportion of BCLC stage 0 is slightly increasing and that of BCLC stage C is decreasing in this decade. However, the proportions of BCLC stage 0+A+B as well as stage C+D were stationary. Some patients never access screening resources. How to decrease the proportion of late stage HCC should be an important public health issue. A comprehensive control program of HCC should include all primary, secondary, and tertiary prevention projects. HCC screening plays its important role in the secondary prevention. Early detection and proper treatment increase chance of cure and prolong survival of HCC.

2021 消化系聯合學術演講年會

專題討論（二） Metabolic Syndrome and Digestive Disease METABOLIC DERANGEMENT AND RISK OF COLORECTAL NEOPLASM Han-Mo Chiu（邱瀚模） Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan

Colorectal cancer is currently one of the most prevalent cancer worldwide and nowadays more than half of the CRC happed in the Asia-Pacific area. Meanwhile, the prevalence of obesity and metabolic syndrome are also increasing in this area along with the westernization of diet and lifestyle. Whilst screening is proven effective in reducing CRC mortality, controlling its risk factors, especially the metabolic derangement via lifestyle modification, can play an additive effect in further reducing CRC related mortality, and can even contribute to reducing its incidence. Increasing body of evidences have

demonstrated that metabolic syndrome, for which insulin resistance serves as the central mechanism, play a pivotal role in colorectal tumorigenesis. Moreover, recent studies have demonstrated that gut microbiome dysbiosis was closely associated with such a derangement. In this presentation, the epidemiological clues correlating metabolic derangement to the risk of colorectal neoplasm will be introduced followed by evidences linking gut dysbiosis to it, and finally propose some potential actions that we may take.

2021 消化系聯合學術演講年會

專題討論（二） Metabolic Syndrome and Digestive Disease MAFLD: NEW CONCEPT AND CLINICAL IMPLICATIONS Jee-Fu Huang（黃志富） Hepatitis Centre and Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan Department of Internal Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung, Taiwan

Non-alcoholic fatty liver disease (NAFLD) has been recognized as the most prevalent liver disorder globally, which affects about quarter of the global population. Metabolic dysfunction, mainly insulin resistance (IR), plays a major role in the pathogenic mechanisms underlying fatty liver disease and its disease progression. Many criticisms have been voiced about the inappropriate nomenclature of NAFLD due to its somewhat confused definition. It was mainly diagnosis by exclusion and no precise safe alcohol threshold has currently been defined in an evidencebased setting. The definition may lead to mistrust between patients and physicians, patient stigma and undertreatment of diseases, limited acceptance of treatment options and sub-optimal allocation of resources. Recently, a consensus by an international panel of experts recommended a change in name for NAFLD to metabolic (dysfunction) associated fatty liver disease (MAFLD). In this regard, the step met the recent suggestion by WHO that the healthcare profession should take more care when naming a

disease. This consortium created a simplified and easily applicable comprehensive proposal for redefining of fatty liver disease. The proposed redefinition of the disease carries a high chance to increase patient awareness and understanding. It also helpful in garnering funding more effectively for research efforts to mitigate the impacts of the global disease. The measurement is particularly of importance in Asia-Pacific in parallel to the rapid Westernization in the region. The relative lower BMI in Asians is not protective from metabolic insults. Moreover, Asian people are more prone to metabolic syndrome (MetS), type 2 DM (T2DM) and NAFLD than other races. The elucidation of disease progression in terms of disease course, phenotypes and outcomes is mandatory for clinical management in the aspect of new definition. Further characterize and stratify MAFLD phenotypes and its drivers will be informative for clinical trials and management.

2021 消化系聯合學術演講年會

專題討論（二） Metabolic Syndrome and Digestive Disease CROSS TALK AMONG GUT MICROBIOTA, ANTIBIOTICS AND DIGESTIVE DISEASES Jyh-Ming Liou（劉志銘） 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. H. pylori has also been associated with obesity, metabolic syndrome, and insulin resistance in earlier observational studies. Case-control studies showed an inverse association of H. pylori and body weight. Some cohort studies showed an increase of body weight after H. pylori eradication. A randomized controlled trial also showed a trivial increase in BMI one year after H. pylori eradication. The mean BMI increased from 27.5 to 27.8 kg/m2 and 27.0 to 27.2 kg/m2 in the eradication group and placebo groups, respectively. The increase

in body weight is probably attributed to the restoration of ghrelin secretion or the relief dyspeptic symptoms. Yet, the clinical significance of this trivial increase in body weight remains questionable. Some studies showed that insulin resistance, fasting glucose, total cholesterol, and triglyceride levels were reduced after H. pylori eradication. The changes in these metabolic parameters might be attributed to the alterations in gut microbiota. However, these findings remain controversial and further well-designed randomized trials are warranted to clarify the impact of H. pylori eradication on metabolic parameters.

2021 消化系聯合學術演講年會

專題討論（二） Metabolic Syndrome and Digestive Disease ADIPOKINES, METABOLIC DERANGEMENT AND DIGESTIVE DISEASES Ming-Ling Chang（張明鈴） Division of Hepatology, Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Taoyuan, Taiwan

Adipose tissue is recognized as a highly dynamic endocrine tissue exhibiting extensive physiological functions and is composed of mature adipocytes and a stromal vascular fraction. Adipose tissue constitutes a central node in the interorgan crosstalk network and mediates the regulation of multiple organs and tissues through adipokines (also called adipocytokines), biologically active molecules causing pleiotropic effects, including modulation of angiogenesis, metabolism, and inflammation. The emerging functional characterization of adipokines suggests a close link between the endocrine and immune systems of adipose tissue. Obesity, the excessive accumulation of adipose tissue due to hyperplasia and hypertrophy, is currently considered a global epidemicand is related to low-grade systemic inflammation. This state of inflammation is characterized by alterations in adipokine regulation. Interestingly, digestive cancers such as colon cancer grow anatomically near adipose tissue. During their interaction with cancer cells, adipocytes dedifferentiate into preadipocytes or are reprogrammed into cancer-associated adipocytes, which secrete adipokines to stimulate the adhesion, migration, and invasion of tumor cells. In particular, the liver is the central metabolic hub for carbohydrate,

lipid, and protein metabolism. Both adipose tissue and the liver play important roles in the regulation of whole-body energy homeostasis, and prolonged metabolic stress leads to adipose tissue dysfunction, inflammation, and adipokine release, causing increased lipid flux to the liver, resulting in fatty liver. Moreover, adipokines are involved in modulating insulin resistance, which is at the heart of obesityrelated digestive diseases, including gastroesophageal reflux disease, Barrett’s esophagus, esophageal cancer, colon polyps and cancer, non-alcoholic fatty liver disease, cholelithiasis, gallbladder cancer, cholangiocarcinoma, pancreatic cancer, and diabetes. The specific alteration patterns of adipokine expression and the associated basis in the development of various digestive diseases might contribute to the identification of prognostic biomarkers as well as therapeutic and preventative approaches for the associated diseases. The important findings about altered adipokine profiles in the context of diseases of the digestive tract, with a perspective on the clinical implications, metabolic derangement and associated mechanistic approaches will be systematically highlighted.

2021 消化系聯合學術演講年會

專題討論（三） Recent Advances in Neurogastroenterology and Motility MUCOSAL INTEGRITY Michael Vaezi Division of Gastroenterology, Hepatology and Nutrition, Vanderbilt University Medical Center, Nashville, TN, USA

Diagnostic testing for GERD rely on short term and unreliable tests. We will describe the development and utility of a novel diagnostic testing that detects GERD based on epithelial changes due to reflux. This novel technique can differentiate GERD from nonGERD and has a unique pattern in differentiating EoE. MI technology has the advantage of being used during

endoscopy and avoiding uncomfortable catheter pH or impedance testing. It is now FDA approved for use and many investigators are exploring the opportunities make available by this unique testing modality. In this talk I will describe the technique and discuss how it can be used for differentiating esophageal disorders.

2021 消化系聯合學術演講年會

專題討論（三） Recent Advances in Neurogastroenterology and Motility ESOPHAGEAL MOTILITY TESTING IN CLINICAL PRACTICE: WHAT IS NEW ON 2021? Wei-Yi Lei（雷尉毅） Division of Gastroenterology & Hepatology, Department of Medicine, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan

Esophageal motility disorders are disorders of the esophagus that may cause symptoms such as regurgitation of food, dysphagia and chest pain. Evaluation of these disorders depends on patients presenting symptoms and may include endoscopy, barium swallow, esophageal manometry or reflux related tests. Correct use of diagnostic testing can help define mechanisms of esophageal symptoms and direct management. Over the past 5 years, high-resolution manometry (HRM) in combination with the Chicago Classification v3.0 has become the gold standard for the clinical assessment of esophageal motility disorders. It not only provides detailed pressure topography of the esophagus but also permits greater understanding of the function of the esophagogastric junction (EGJ) and the risks associated with hiatal hernia. Currently, both clinical applications and research investigations involving HRM have expanded, with introduction of novel HRM metrics. Therefore, an International HRM Working Group worked for two years to develop the Chicago Classification v4.0 (CCv4.0) and was published at the end of 2020. The changes in CCv4.0 attempt to minimize ambiguity in prior iterations of Chicago Classification and provide more standardized and rigorous criteria for patterns of disorders of

peristalsis and obstruction at the EGJ. Functional Lumen Imaging Probe (FLIP) system is a new technique to screen for motility disorders in combination with endoscopy. It can provide a threedimensional image of the esophageal lumen through use of high-resolution impedance planimetry to measure pressure changes, diameter, and volume. Initially, this technology was used to determine the degree of distensibility of EGJ. A second-generation FLIP 2.0 which combines the EGJ distensibility index with contraction patterns allows for the classification of esophageal motility. The FLIP has demonstrated its clinical utility as a diagnostic tool and as a device which is used to guide and measure response to therapy. With published normative data from healthy control patients and real-time interpretation of FLIP panometry during the endoscopy now available, FLIP is poised to become the initial test for the evaluation of esophageal motility disorders. Additionally, provocative maneuvers such as multiple rapid swallows and rapid drink challenges should be included in manometric protocol. Other supportive testing with barium esophagogram as well as novel straight leg raise test can also be considered for particular conditions.

2021 消化系聯合學術演講年會

專題討論（三） Recent Advances in Neurogastroenterology and Motility ADVANCES IN THE MANAGEMENT OF EXTRAESOPHAGEAL REFLUX DISEASE Han-Chung Lien（連漢仲） Division of Gastroenterology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan

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

to distinguish reflux from non-reflux etiologies in this heterogenous patient group who suffer from various chronic reflux-related respiratory symptoms. Using 3-pH-sensor or pharyngeal impedance-pH monitoring, we recently found that patients with suspected LPR and pathological reflux are more likely to response to proton pump inhibitor therapy. Our findings support the importance of reflux monitoring and the therapeutic role of proton pump inhibitors in the management of this challenging patient population.

2021 消化系聯合學術演講年會

專題討論（三） Recent Advances in Neurogastroenterology and Motility GASTROPAREIS AND FUNCTIONAL DYSPEPSIA: ONE OR TWO DISEASES? Yu-Chung Su（蘇育正） Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan

In addition to gastroesophageal reflux disease, functional dyspepsia and gastroparesis are among the most frequent upper gastrointestinal disorder in clinical practice. The recent Rome IV consensus revise the definition of functional dypepsia and it has been categorized into postprandial distress syndrome (PDS) and epigastric pain syndrome (EPS). Symptoms of functional dyspepsia (FD) are relatively non-specific and include epigastric pain or burning, postprandial fullness, early satiety. In contrast, gastroparesis is defined using a combination of subjective symptoms thought to represent a delay in gastric emptying and objective measures of a delay gastric emptying. In functional dyspepsia, most of the pathophysiological research evaluate the gastric sensorimotor dysfunctions, but low-grade inflammatory changes and loss of mucosal integrity in the duodenum and and potentially changes in microflora are emerging areas of interest. Pharmcological treatment of functional dyspepsia include new prokinetics and the ghrelin receptor agonist. The efficacy of tricyclic antidepressants was recently reviewed and mirtazapine is a new agent

used in the treatment of functional dyspepsia and gastroparesis. Gastroparesis occurs in several clinical settings, such as a complication of diabetes mellitus or upper gastrointestinal surgery, neurological disease, collagen vascular disorders, viral infections, drugs or, most commonly, idiopatheic, In gastroparesis, research has focused on the role of macrophages in loss of interstitial cells of Cajal, and on the role of pyloric resistance as a target for therapy, using botulinum toxin injection and gastric per-endoscopic pyloric myotomy. Functional dyspepsia and gastroparesis have been thought of as completely separate disorders with regard to etiology, pathophysiology and diagnosis. However, the common symptom presentation, together with the fact that the severity of symptoms has not been shown to correlate with the degree of gastric emptying delay in most patients with gastroparesis, may supports the notion that other pathways, such as visceral hypersensitivity and altered CNS processing, may also contribute to symptoms in both FD and gastroparesis.

2021 消化系聯合學術演講年會

專題討論（四） The Application of Contrast Enhanced Harmonic EUS in the Hepatobiliopancreatic Disease CH-EUS FOR GASTRIC SUBMUCOSAL LESION Chih-Hsiang Chen（陳至翔） Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taipei, Taiwan

CE-EUS in GI tract ● Epithelial lesion • Invasion depth: gastric cancer and esophageal cancer • Lymph node metastases: filling defect favor malignant; sensitivity:100%, specificity: 84% ● Subepithelial lesion/tumor (SET) • Subepithelial tumor but not submucosal tumor • GIST from non-GIST • High-grade malignant GIST from low-grade malignant GIST EUS for subepithelial tumor ● EUS could be used to distinguish subepithelial tumors with endoscopic appearance, EUS layer location and EUS appearance. However, there’s much overlapping area, especially GIST and leimyoma, which are the most common SETs in UGI tract. CE-EUS for subepithelial tumor ● GIST vs. leiomyoma • GIST had higher vascularity • GIST had higher a-phase vascularity, v-phase diffuse enhancement and lower LSR • Diagnostic ability of CEH-EUS in distinguishing GIST from benign SET: sensitivity: 78-100%, specificity: 60-100% ● High-grade malignant GIST vs. low-grade malignant GIST • HGM GIST had higher rate of irregular vessel and necrotic center

References: 1. Naoto Nomura, Hidemi Goto, et al. Usefulness of contrast-enhanced EUS in the diagnosis of upper GI tract diseases. Gastrointest Endosc. 1999 Oct;50(4):555-60. 2. Sung Ill Jang and Dong Ki Lee, Contrast-enhanced endoscopic ultrasonography: advance and current status. Ultrasonography. 2014 Jul; 33(3): 161–169. 3. Kanamori A, Hirooka Y, et al. Usefulness of contrast-enhanced endoscopic ultrasonography in the differentiation between malignant and benign lymphadenopathy. Am J Gastroenterol 2006;101:45-51. 4. Humphris JL, Jones DB. Subepithelial mass lesions in the upper gastrointestinal tract. J Gastroenterol Hepatol. 2008 Apr;23(4):556-66. Epub 2007 Dec 14. 5. Humphris JL, Jones DB. J Subepithelial mass lesions in the upper gastrointestinal tract. Gastroenterol Hepatol. 2008 Apr;23(4):556-66. Epub 2007 Dec 14. 6. Lee M, Min BH, et al. Feasibility and Diagnostic Yield of Endoscopic Ultrasonography-Guided Fine Needle Biopsy With a New Core Biopsy Needle Device in Patients With Gastric Subepithelial Tumors. Medicine (Baltimore). 2015 Oct;94(40): e1622. 7. Baysal B, Masri OA, et al. The role of EUS and EUS-guided FNA in the management of subepithelial lesions of the esophagus: A large,

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singlecenter experience. Endosc Ultrasound. 2017 Sep-Oct;6(5):308-316. 8. Kannengiesser et al, Scand J. Contrast-enhanced harmonic endoscopic ultrasound is able to discriminate benign submucosal lesions from gastrointestinal stromal tumors. Gastroenterol. 2012 Dec;47(12):1515-20 9. Cho IR, Park JC, et al. Noninvasive prediction model for diagnosing gastrointestinal stromal tumors using contrast-enhanced harmonic

endoscopic ultrasound. Dig Liver Dis. 2019 Jul;51(7):985-992. 10. Takashi Tamura and Masayuki Kitano. Contrast Enhanced Endoscopic Ultrasound Imaging for Gastrointestinal Subepithelial Tumors. Clin Endosc. 2019 Jul; 52(4): 306–313. 11. S akamoto H, Kitano M, et al. Estimation of malignant potential of GI stromal tumors by contrast-enhanced harmonic EUS. Gastrointest Endosc. 2011 Feb;73(2):227-37.

2021 消化系聯合學術演講年會

專題討論（四） The Application of Contrast Enhanced Harmonic EUS in the Hepatobiliopancreatic Disease CONTRAST ENHANCEMENT ENDOSCOPIC ULTRASOUND FOR GALLBLADDER LESIONS Ming-Lun Han（韓明倫） Division of Endoscopy, Department of Integrated Diagnostics & Therapeutics, National Taiwan University Hospital, Taipei, Taiwan

Differentiating benign from malignant gallbladder lesion is challenging. The accuracy of endoscopic ultrasound is better that that of trans-abdominal ultrasound in diagnosing gallbladder polypoid lesions. Recently, more and more clinical studies show the benefit of contrast harmonic enhancement endoscopic ultrasound (CEU-EUS) for gall bladder lesion. Though gallbladder adenomas and cholesterol

polyps are both round-shaped masses; adenomas are homogeneously enhanced, while cholesterol polyps are generally heterogeneously enhanced on CEHEUS. The absence of enhancement in gallbladder sludge allows its differentiation from a tumor. A heterogeneous enhancement pattern, the presence of perfusion defects, and an irregular tumor vessel are features highly suggestive of gallbladder malignancy.

2021 消化系聯合學術演講年會

專題討論（四） The Application of Contrast Enhanced Harmonic EUS in the Hepatobiliopancreatic Disease CH-EUS FOR PANCREATIC TUMORS Hsiang-Yao Shih（施翔耀） Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan

In the past computed tomography (CT) or magnetic resonance imaging (MRI) was the preferred image modality for pancreatic tumors. If the tumor size is less than 2cm there is possible limitation for them and endoscopic ultrasonography (EUS) might overcome it. EUS could provide the information about tumor size and echogeneity and it could demonstrate the distribution of microvessels and parenchymal perfusion after we injected the contrast so called contrast enhanced harmonic EUS (CH-EUS). Combined the above we could make a more accurate evaluation about the tumor. According to the enhancement patterns they could be divided into four types: hyper-, iso, hypo-enhancement and no enhancement. Among

pancreatic solid tumors pancreatic adenocarcinoma is usually hypoenhanced, neuroendocrine tumor (NET) and gastrointestinal stromal tumor (GIST) are hyperenhanced and chronic pancreatitis is usually isoenhanced. Among pancreatic cystic lesion/neoplasm the tumor part often demonstrates hyperenhancement. Not only providing further information of pancreatic neoplasm but also CH-EUS could guide us the targeted site while endoscopic ultrasonography guided tissue acquisition (EUS-TA). There is practical value for CH-EUS to help us make the more accurate diagnosis and obtain the more precise specimen.

2021 消化系聯合學術演講年會

專題討論（四） The Application of Contrast Enhanced Harmonic EUS in the Hepatobiliopancreatic Disease EUS FOR HEPATOBILIARY DISEASE Yu-Ting Kuo（郭雨庭） Division of Endoscopy, Department of Integrated Diagnostics & Therapeutics, National Taiwan University College of Medicine, Taipei, Taiwan

Endoscopic ultrasound (EUS) has become a widely used method for the diagnosis of pancreatobiliary diseases, and EUS-guided fineneedle aspiration (FNA), in particular is commonly used for obtaining a histologic diagnosis. With improving resolution and widespread use of EUS, small liver metastases and other focal lesions in the liver and biliary tract are being increasingly discovered. Although CT, transabdominal US, and magnetic resonance imaging have been the principal tools for evaluating hepatobiliary lesions for a long time, some of these small liver or bile duct lesions are unsuspected by previous imaging tests and often have

a connotation of metastatic disease. Contrast-enhanced harmonic endoscopic ultrasound (CEH-EUS) has the potential to provide complementary information for the differential diagnosis of malignant hepatobiliary lesions. It could enhance the distinction between the target lesion and the surrounding tissue. CEH-EUS has been proposed as an adjunctive method to enable a better differential diagnosis of hepatobiliary diseases. Therefore, CEH-EUS–guided FNA is a technically feasible approach to sampling hepatobiliary lesions for diagnosis, particularly in cases where conventional EUS had failed to localize the tumor.

2021 消化系聯合學術演講年會

專題討論（四） The Application of Contrast Enhanced Harmonic EUS in the Hepatobiliopancreatic Disease CH & INTERVENTIONAL EUS FOR LIVER LESIONS Jiann-Hwa Chen（陳建華） Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taipei, Taiwan

Lesions such as hepatocellular carcinoma (HCC) or other entities at the left lobe or the caudate lobe located at the deep site of liver were not visualized well by transabdominal ultrasound and there were intervening veins that would have made it not only difficult but also hazardous to attempt percutaneous ablative treatment due to the long trajectory. Endoscopic ultrasonography (EUS) has emerged as a highly sophisticated interventional modality. EUS guided therapy provide the best solution to treat the caudate lobe lesion, i.e., in close proximity to the

stomach, which made it easily accessible by EUS. Besides, contrast enhanced harmonic EUS has been introduced for decades to investigate the characters of lesions to afford the best management for them. EUS have been developed for the interventional purpose in addition to the pancreatic disease. EUS-guided liver biopsy, ethanol injection, or abscess aspiration drainage, owing to its less invasiveness, appears to be a new innovative option for lesions that is difficult to treat by local percutaneous treatment.

2021 消化系聯合學術演講年會

專題討論（五） Functional Cure of Hepatitis B WHAT DOES NATURAL HISTORY OF HBV INFECTION HAVE TAUGHT US ABOUT THE FUNCTIONAL CURE? Rong-Nan Chien（簡榮南） Liver Research Unit, Linkou Chang Gung Memorial Hospital and University, Taoyuan, Taiwan

Spontaneous hepatitis B surface antigen (HBsAg) seroclearace in chronic hepatitis B virus (HBV) infection has long been suggested as a rare event in high endemic areas. The prevalence of HBsAg in the general population of Taiwan, however, decreased remarkably from 15-20% before age 40 to 5-10% after age 60 or 70. The cumulative probabilities of HBsAg seroclearance were 8.1% after 10 years, but increased disproportionally to 24.9% and 44.7%, respectively, after 20-25 years. The determinants for HBsAg clearance include 1) host factors: old age, persistent normal ALT, inactive HBsAg carrier and liver cirrhosis; 2) virus factors: prominent qHBsAg decline > 1 log10 IU/mL or < 200 IU/mL, HBeAgnegative, lower HBV DNA, HBV genotype B or A and HCV superinfection. Non-cirrhotic patients

without concurrent HCV and/or HDV superinfection have an excellent prognosis after spontaneous HBsAg seroclearance in terms of HBV clearance and liver disease progression compared with a persistently HBsAg-positive patients who experienced more significant ALT elevation and cirrhosis/HCC development. Cirrhotic patients, whether they had concurrent infection or not, was similar to the natural history of HBV-related cirrhosis in that HCC or decompensation may occur. Obviously, patients with cirrhosis or concurrent infection should be closely monitored for predictable complications. Considering cost-effectiveness, it seems reasonable to increase the interval of follow-up after HBsAg seroclearance for those with chronic HBV infection alone.

2021 消化系聯合學術演講年會

專題討論（五） Functional Cure of Hepatitis B NEW ENDPOINTS AND BIOMARKERS FOR HBV FUNCTIONAL CURE Chih-Lin Lin（林志陵） Department of Gastroenterology, Renai branch, Taipei City Hospital, Taipei, Taiwan

The goal of HBV cccDNA clearance, a complete or absolute cure of HBV, could be difficult to achieve. Lowering of cccDNA level or inactivation of cccDNA to prevent viral replication and induce a remission of liver disease, a functional cure, is the alternative feasible goal of HBV treatment. Currently, hepatitis B surface antigen (HBsAg) loss has been the classic endpoint of HBV functional cure. Hepatitis B viral load and quantitative HBsAg level are considered as standard virologic markers in clinical practice. The combination of low serum HBsAg level and serum HBV DNA level can predict inactive HBV carrier status and HBsAg loss. Serum HBsAg level <10 IU/mL was the strongest predictor of HBsAg loss in patients with a low viral load. On the basis of innovations in molecular medicine and genomics, several novel hepatitis B viral and host biomarkers associated with assessment of HBV functional cure have been elucidated. HBcrAg concentration was positively correlated with serum HBV DNA as well as intrahepatic cccDNA level. For treatment naïve patients, HBcrAg was used to identify inactive carriers. For patients receiving anti-HBV therapy, the lower levels of HBcrAg was strongly correlated with higher likelihood of HBsAg loss during therapy. HBV RNA was positive correlated with

intrahepatic cccDNA. HBV RNA was superior than to HBV DNA and HBsAg levels in distinguishing inactive and active hepatitis in HBeAg-negative CHB patients. The serum HBV RNA levels at baseline and at week 12 of treatment were correlated with maintained virologic response and HBsAg clearance after pegylated interferon treatment. Undetectable HBV RNA at the time of NA discontinuation had significantly lower incidence of clinical relapse than patients with detectable HBV RNA. Regarding the host biomarker, Quantification of HBV core antibodies (total anti-HBc) reflects the immune responses in different phases of HBV infection. Low baseline levels of anti-HBc predict HBsAg seroclearance in HBeAgnegative patients. In HBeAg-positive patients with pegylated-interferon or NA therapy, the baseline total anti-HBc level was significantly associated with the possibility of HBeAg seroconversion. In patients with resolved HBV infection receiving immunosuppressive therapy, high total anti-HBc and low anti-HBs at baseline were associated with HBV reactivation. In conclusions, the integration of these novel biomarkers with existing markers will help clinicians to select the patients for effective antiviral therapy and identify individuals with a higher possibility of achieving HBsAg loss.

2021 消化系聯合學術演講年會

專題討論（五） Functional Cure of Hepatitis B HOW TO MAKE HOST IMMUNITY CURE HBV? Tai-Chung Tseng（曾岱宗） Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan

Chronic hepatitis B virus (HBV) infection is a global public health issue. Although the disease cannot be cured effectively, disease management has been improved over the past decade. The introduction of potent nucleos(t)ide analogues (NAs) to suppress viral replication represented a giant leap in the control of this disease. The next challenge is how to clear HBsAg, which is defined as functional cure. Among all the proposed strategies, killing of HBV-infected hepatocytes via cytotoxic T cell (CTL)-induced immunotherapy is the most promising one. An ideal immune-therapeutic strategy should combine profound suppression of viral replication to prevent uninfected hepatocytes from HBV infection and restoration of HBV-specific CTL response to clear the infected hepatocytes. The former goal can be achieved by existing NA treatment and the later could be partially enhanced by therapeutic vaccines. Several clinical trials have been performed using different therapeutic vaccines, yet the results have been disappointing. There are two issues that must be considered. Firstly, HBV-specific CTL response may fail to be triggered by therapeutic vaccinations. Second, the immune

tolerant effects of the liver microenvironment must be considered. HBV-specific CTL response can be induced in peripheral blood, but is rapidly exhausted after the initiation of cytotoxic effects against HBVinfected hepatocytes. Either of the above issues may have led to the failure of the clinical trials. Several toll-like receptor agonists, which stimulate innate immune response, have been tested to change the liver microenvironment but failed to achieve the goal. However, if the failure was caused by the engagement of PD-1 on T cells and PD-L1 on hepatocytes, which leads to the inhibition of T cell receptor-mediated lymphocyte proliferation and cytokine secretion, PD-1 and PD-L1 inhibitor could be considered to amplify the T cell response. Such treatment is expected to be useful in patients with preserved endogenous HBVspecific CTL response. Finally, although the current results of immunotherapy in CHB treatment are unsatisfactory, it remains the most attractive method to clear the virus as long as the appropriate patient population can be selected and optimal study designs can be implemented.

2021 消化系聯合學術演講年會

專題討論（五） Functional Cure of Hepatitis B IS STOPPING NA A POSSIBLE PATH FOR HBV FUNCTIONAL CURE Wen-Juei Jeng（鄭文睿） Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan, Taiwan

HBsAg seroclearance has been regarded as an ultimate endpoint for antiviral therapy across major liver association guidelines since its correlation with the transcriptionally inactive status of intrahepatic cccDNA. However, the HBsAg decline was extremely slow during antiviral treatment with annual incidence of < 0.33% HBsAg loss rate, which more than 4-5 decades of treatment required to reach this endpoint. In 2012, Hadizyannis SJ et al reported that HBsAg loss rate be as high as 33% by 5 years follow-up after stopping 5-6 year of ADV treatment. Serial finite studies from different study groups across different

HBV genotype, patients’ ethnicity, types of Nucs all suggest that increased probability of HBsAg loss rate after stopping Nuc treatment in comparison to that during long-term viral suppression therapy. However, some concerns raised regarding finite treatment including the risk of hepatitis flare, hepatic decompensation and whether the HCC incidence will increase. In this topic, we’ll critically review the current evidence for the possibility toward functional cure by finite treatment and studies comparing the adverse event risks between finite and infinite therapy.

2021 消化系聯合學術演講年會

專題討論（五） Functional Cure of Hepatitis B UPDATE ON NEW DRUG COMBINATIONS AND STUDY DESIGN Hung-Chih Yang（楊宏志） Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan

Current antiviral therapy, including nucleos(t) ide analogues (NAs) and interferon, has significantly improved the clinical outcomes of chronic hepatitis B (CHB) patients, but it often fails to cure HBV infection. Although NAs can suppress serum viral load to the level below detection limit, the off-therapy response remains far from satisfactory, and rebound viremia frequently occurs unless loss of surface antigen (HBsAg) is achieved. The major barrier to eradication of chronic HBV infection by current antiviral therapy is the persistence of covalently closed circular (ccc)DNA, which is the intranuclear transcriptional template of HBV. Functional cure of HBV infection, defined as HBsAg seroclearance or even seroconversion, is a practical but challenging goal that is pursued by most of the current novel antiviral agents. Currently, an array of novel direct antiviral agents against HBV are being developed, including silencing RNA (siRNA), entry inhibitor, capsid inhibitor, anti-sense oligonucleotide, and geneediting strategy, targeting different steps of viral life

cycle. Along with the antiviral drugs, some agents are designed to enhance the host antiviral immunity, including therapeutic vaccines, activators of innate immunity, like toll-like receptor agonists, immune checkpoint inhibitors and T cell-based therapy. While some of these novel antiviral agents are still in the preclinical stage, quite a fewer of them move fast and are being examined in clinical trial settings. Actually, some antivirals indeed hold the promising results. In addition, several new viral biomarkers, in combination of HBsAg, have been demonstrated the utility to serve the surrogate markers of HBV cure by antiviral therapy. Emerging therapeutic strategies tend to combine more than one antiviral agents targeting different antiviral mechanisms. Therefore, this talk will introduce the recent progress and combination use of novel antiviral drugs, and discuss their potential for curing CHB, particularly paying attention to their effects on the new viral biomarkers regarding HBV cure.

2021 消化系聯合學術演講年會

專題討論（六） Current Status of Management of CHC in Taiwan C 型肝炎消除：國家政策 HCV ELIMINATION: NATIONAL POLICY Raoh-Fang Pwu（蒲若芳） Taiwan National Hepatitis C Program Oﬃce, Ministry of Health and Welfare, Taipei, Taiwan

The development of the new oral Direct-acting antiviral agent (DAA) has brought a new light of hope for the world to control chronic hepatitis C. Following a great success of beating hepatitis B, Taiwan has determined to become one of the world leaders in hepatitis C elimination. As of today, over 110,000 patients have been treated with DAAs and the observed sustained viral response at 12 weeks post treatment (SVR12) is over 98% (per protocol analysis). Learned from the ample research discoveries and experiences shared by many researchers and practitioners, the Taiwan National Hepatitis C Program (TWNHCP) Office, Ministry of Health and Welfare published the Policy Guideline highlighting the importance of the 3 policy directions and 3 strategies for Taiwan’s Hepatitis C Elimination policy. After 4 years of DAA reimbursement policy implemented, we can now claim the first phase (“Treatment spearheads prevention”) has had a good

start. Now it is the time to enter the second phase (“Screening supports treatment”). Health Promotion Administration had announced the “Adult preventive services - hepatitis B and C screening” program expanded to adults 45-79 years of age (40-79) for indigenous citizens) since September 28th, 2020. TWNHCP office also consider the importance on prioritizing the resource and attention on certain high risk groups and started the relevant preparation work. In summary, Taiwan has a good start, and on the right track to the “Hepatitis C Elimination by 2025” goal. Although different challenges need to be tackled when we enter the new phase (now we need to design effective, efficient systems to find the patients who need to be treated), we have strong belief we can accomplish these tasks for we possess all the success factors such as good public-private partnership, excellent physicians and professional teams, and strong political wills from central to local governments.

2021 消化系聯合學術演講年會

專題討論（六） Current Status of Management of CHC in Taiwan C 型肝炎防治：地方政府策略 HCV ELIMINATION: LOCAL GOVERNMENT STRATEGY Tsung-Hui Hu（胡琮輝） Department of Internal Medicine, Chang Gung Memorial Hospital, Kaohsiung, Taiwan

Viral hepatitis is a major global health burden and is one of the leading causes of death worldwide. With the introduction of DAAs for treating chronic HCV infection, national governments across the world are devising strategies to achieve the WHO goal of HCV elimination by 2030. In line with the global targets for HCV elimination, the Taiwan government has also set an ambitious target of achieving 80% of treatment coverage for the patients with chronic HCV by the year 2025. Achieving HCV elimination is complicated because there is wide variability in the distribution pattern of cases and subpopulations, within and among nations, with a large regional variation in disease subpopulations. In order to achieve the global elimination targets for HCV, innovative operational strategies are warranted to ensure early diagnosis, accessibility to treatment, and continuity of care. HCV micro-elimination approach, which focuses treatment on smaller, targeted high-risk subpopulations, has been proposed as an effective method for achieving

global elimination of HCV. This approach targets the high-risk subpopulations and is expected to provide better results in HCV elimination. Subpopulations with an increased risk or with a higher prevalence of chronic HCV infection include people who inject drugs (PWID), individuals infected with HIV/HBV; individuals diagnosed with tuberculosis or hemophilia; and individuals with chronic kidney disease and diabetes. Nowadays, several novel oral anti-HCV medications have been approved by NHI and all of the restrictions on reimbursement have been lifted completely in Taiwan since 2019. Patients with positive HCV RNA are allowed for treatment at any time. It is expected that the patients’ willingness to receive anti-HCV treatments will increase significantly because of the introduction of the novel oral medications. Therefore, development of a novel HCV treatment methodology is mandatory for HCV elimination by local government and health bureau in counties Taiwan.

2021 消化系聯合學術演講年會

專題討論（六） Current Status of Management of CHC in Taiwan C 型肝炎防治：非政府組織行動 HCV ELIMINATION: ACTIONS FROM NON-GOVERNMENT ORGANIZATIONS Chia-Yen Dai（戴嘉言） Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan

The goal of treatment of hepatitis C virus (HCV) infection which results in long-term liver outcomes including cirrhosis or hepatocellular carcinoma is to reduce all-cause mortality and liver related health adverse consequences, including endstage liver disease and hepatocellular carcinoma, by the achievement of virologic cure as evidenced by a sustained virologic response (SVR). The clinical progress against HCV infection has to meet the goal to eradicate HCV infection. Elimination of hepatitis C virus (HCV) infection is the major task supported by WHO in 2030. The goal for elimination of HCV and HBV by 2025 is set by the Ministry of Welfare and Health of Taiwan and all the non-government organizations (NGOs) have to make efforts on achieving this goal. The management of HCV infection is based on the cooperation of the works on the screening, definite diagnosis of active infection (viremia), accessibility of the health care system for treatment and the follow-up for the patients with or without SVR. To identify all chronic hepatitis C (HCV) patients, epidemiological studies are important for estimating the disease

burden, exploring the endemic communities where the prevalence of anti-HCV is high, and increasing the awareness of patients by the effective screening project to identify the patients who have exposed to HCV infection before are mandatory. With developed regimens for CHC, a high SVR rate was achieved by the major progress and advance in treating CHC by the all oral DAA therapy achieving very high SVR rates with fewer adverse effects than IFN. To overcome the cost of the tests and the medication, expend the treaters, and increase the accessibility of medication and follow-up systems such as the outreaching OPD or the specificity OPD provided by the hepatologists are very important to achieve completed cascade of care. After treatment, the follow up of patients to identified the development of HCC, even the risk of HCC occurrence decreased significant after cure of HCV infection, and to discovery the predictors for HCC development which is one of the major unmet needs, is also important. The NGOs are always the major contributors and play the important roles on achieving the goal of elimination of hepatitis.

2021 消化系聯合學術演講年會

專題討論（六） Current Status of Management of CHC in Taiwan C 型肝炎口服抗病毒藥物治療：台灣未解決之需求 DAA FOR HCV: UNMET NEED IN TAIWAN Chen-Hua Liu（劉振驊） Department of Internal Medicine and Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan

Hepatitis C virus (HCV) infection remains a leading cause of chronic liver disease which resulting in hepatocellular carcinoma (HCC), hepatic decompensation and death in Taiwan. While the interferon (IFN)-based therapy has suboptimal response and frequent treatment-related adverse events (AEs), the advent of IFN-free direct acting antivirals (DAAs) has made a paradigm shift in the care of HCV. In Taiwan, the DAAs have been reimbursed since 2017, and the scaling-up program has now been undergone of early moving forward HCV elimination as proposed by WHO. While the government has provided the unrestricted reimbursement in Taiwan, there still exist some unmet medical needs in the path of care for HCV. The following points are proposed as we have to move the barriers as possible to eradicate HCV as early as possible.

1. Reimbursement restriction: Tile 2020, all HCV-infected patients are allowed to receive government-supported free treatment. However, the payment restriction may limit the HCV elimination because patients with DAA-treatment failures or those with reinfection remain viremic and may have potential for viral transmission. 2. Limited rescue regimens for virologic failures: Till now, the rescue therapies for patients who fail to prior DAAs are limited in Taiwan. While glecaprevir/pibrentasvir (GLE/PIB) can be applied to HCV GT1 patients who fail to prior course of NS3 or NS5A containing agent. It is now not indicated

for patients with non-HCV GT1 infection or those who fail to regimens containing both NS3 and NS5A agents. Sofosbuvir/velpatasvir/voxilaprevir has been approved for retreating patients who fail to prior DAAs, however, the trials only recruited participants who failed to 2nd wave DAAs, making the actual efficacy to patients who fail to 3rd wave DAAs elusive.

3. Patients with HCV GT3 infection or other rare GT/sub-GTs: While the overall response rate of GLE/PIB and sofosbuvir/velpatasvir (SOF/VEL) for HCV GT-3 are generally excellent. However, recent studies indicated that the HCV GT-3b, particularly in those with baseline NS5A at L31, Y93 or 32del may have resistance to these patients, which increases the risk of viral failures. Additionally, some patients with rarely encountered HCV-1 subtypes have been reported to respond poorly to currently approved regimens. 4. Patients with decompensated cirrhosis: Till now, the treatment options are limited for patients with decompensated cirrhosis because protease inhibitor (PI)-based regimen are contraindicated for use for these patients. Currently, the pan-genotypic, panfibrotic, and PI-free SOF/ VEL in combination with RBV is the best choice for HCV in these patients. However, a substantial proportion of patients have medical comorbidities that may prevent the optimized treatment, such as severe anemia, concomitant use of indispensable but absolute

2021 消化系聯合學術演講年會

contraindicated medications, the presence of advanced HCC etc…. For patients who have confirmed virologic failures, no rescue therapy can be safely applied as the retreatment choice.

5. Patients with active HCC: Some studies have indicated that the SVR rates are compromised in patients with active HCC receiving SOF-based DAAs, while the SVR rates are not affected by PI-based DAAs. This would be more difficult if patients also present as decompensated

cirrhosis. Furthermore, whether the use of DAAs might promote the tumor growth remains largely unknown.

6. Patients without suitable enteral route: Although the overall clinical performance of DAAs are excellent, all these agents should be taken by enteral route, where the treatment may not be possible in patients with only parenteral route for feeding.

2021 消化系聯合學術演講年會

專題討論（七） Microbiota Update 2021 FMT ‒ PAST, CURRENT AND FUTURE Deng-Chyang Wu（吳登強） Division of Gastroenterology, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan

Fecal microbiota transplantation (FMT) is a method to directly change the recipient’s gut microbiota to normalize the composition and gain a therapeutic benefit. The history of FMT has been traced back to the 4th century and has been highly regarded since 2013, when the United States Food and Drug Administration approved FMT for treating recurrent and refractory Clostridium difficile infection. Since then, the range of FMT applications extended rapidly and broadly not only in gastrointestinal disorders, but also in extra-gastrointestinal diseases. Several studies have evaluated the prospect of altering the gut microbiome as a potential therapy for obesity and the metabolic syndrome. Moreover, the probable therapeutic effects of FMT might be seen in multiple sclerosis, autism, multidrug-resistant organisms

(MDRO) infections, multiple organ dysfunction in critical patients, and even targeting cancer treatment. Although current evidence deems FMT as a generally safe therapeutic method with few adverse effects, the long-term outcomes of FMT have not been completely elucidated. Therefore, establishing periodicity and length of regular follow-up after FMT to monitor the clinical efficacy and long-term adverse events are other essential issues. Future research should focus on identifying the gut microbiota, defining their function, and further manipulating the gut microbiota more precisely. In the years to come, we will look forward to personalized FMT for different patients and conditions according to varied host and disease genotypes/phenotypes.

2021 消化系聯合學術演講年會

專題討論（七） Microbiota Update 2021 PROBIOTIC AND MICROBIOME-BASED DRUGS Ming-Shiang Wu（吳明賢） Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan

Advances in high-throughput microbial genomic sequencing and systems biology have provided novel insights into the role of gut microbiota in health and diseases. Although whether alterations in gut microbiota are cause, consequence, or incidental to disease remains largely unknow, recent and ongoing developments in microbiome science are enabling new frontiers of research for probiotics and microbiome-

based drugs. Beyond gastrointestinal tract, novel types, mechanisms, and applications currently under study have the potential to change scientific understanding as well as nutritional applications of these interventions in various diseases and system health. In this lecture, I will review recent, emerging, and anticipated fields in probiotic and microbiomebased drugs.

2021 消化系聯合學術演講年會

專題討論（七） Microbiota Update 2021 GUT MICROBIOTA AND METABOLIC SYNDROME Chun-Ying Wu（吳俊穎） President, Taiwan Microbiota Consortium Institute of Biomedical Informatics, National Yang-Ming University, Taipei, Taiwan Division of Translational Research, Taipei Veterans General Hospital, Taipei, Taiwan

Metabolic syndrome is defined with at least 3 of the following issues: visceral obesity, low LDLcholesterol, high triglyceride, hypertension and insulin resistance. Metabolic syndrome affects 40% of people over 60 years old. Microbiota plays important roles in metabolic syndrome via increasing LPS and bacterial lipopeptides, inducing metabolic endotoxemia to activate MyD88, TLR4, NF-kB, and enhancing inflammatory cytokines, etc. Increased energy harvest by gut microbiota is also an alternative explanation. Several factors have been reported to induce dysbiosis and increase risk of metabolic syndrome, such as exposure to antibiotics, proton pump inhibitor, or H2 receptor antagonist in early life. Taking high fat diet reduces microbiota diversity, which cannot be recovered after shifting back to taking normal diet. The dysbiosis status can be transmitted into the next

generations. Exercise can increase gut microbiota, especially in colon. Our animal experiments demonstrated that fecal microbiota transplantation (FMT) can transfer the beneficial effects of diet control and exercise. In human studies, oligofructose-enriched inulin was found to improve appetite control and to reduce total body fat and trunk body fat. Allogenic FMT can improve peripheral insulin sensitivity, but not hepatic insulin sensitivity. However, FMT in obese patients with BMI > 35 did not improve microbiota diversity and did not change BMI. In conclusion, metabolic syndrome is closely related with gut microbiota. FMT is a potential to improve metabolic syndrome. Prebiotics are another promising methods. Specific bacteria or their metabolites are the targets for future studies.

2021 消化系聯合學術演講年會

專題討論（七） Microbiota Update 2021 GUT MICROBIOTA AND PEDIATRIC DISEASE Yen-Hsuan Ni（倪衍玄） Department of Pediatrics, College of Medicine and Children’s Hospital, National Taiwan University, Taipei, Taiwan

Gut microbiota acquired in infancy may predict or incline to the future development of diseases. The gut microbiota are now expanding their roles in the health and disease status: such as metabolic diseases (diabetes, obesity), cancer (colon cancer and other gastrointestional malignancies), liver diseases (fatty liver, cirrhosis), immunologic diseases (atopic diseases), brain-gut disorders (irritable bowel syndrome, autism), and so on. There are many factors influencing the constitutions of the gut microbiota, including maternal nutrition, delivery routes, diet, geography, genetic factors, age, and drugs, and antibiotics. Generally speaking, the diversity of the gut microbiota composition are the measures to implicate “dysbiosis” or not. The origin of the bacteria colonizing the neonatal gastrointestinal tract is supposed to be affected by mode of delivery, breastmilk feeding and maternal conditions. Proteobacteria, Actinobacteria, Bacteroidetes, and

Firmicutes were the major bacterial phyla patterns in infancy. The infants’ gut microbiota pattern gradually transit into the adult pattern at about the age of three, when the food intake of the children is similar to that of the adults. A long-term prospective monitoring on the development of diseases and the evolution of gut microbiota will be very helpful to unravel their critical role in the pathogenesis of many diseases and the gut microbiota may become the therapeutic target. The current focus of microbiota studies is on the metabolits which are produced by the host-microbiota interaction and these metabolites are the main reason why gut microbiota can affect many organs and diseases in our bodies. We have already proven an early colonization with R. gnavus in the gut promoted allergic disease in infants. This will help initiate our investigations about the roles of gut microbiota in children health and diseases.

2021 消化系聯合學術演講年會

專題討論（八） Update of Systemic Therapy for HCC FIRST LINE SYSTEMIC THERAPIES FOR HCC: FROM CLINICAL TRIALS TO REAL-WORLD DATA I-Cheng Lee（李懿宬） Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan

Several options of systemic therapies for hepatocellular carcinoma (HCC) have been developed in recent years. Current FDA approved first line systemic therapies for HCC include sorafenib, lenvatenib and atezolizumab plus bevacizumab. A phase I study also demonstrated promising results of pembrolizumab plus lenvatinib in the first line setting.

Clinical trials of novel combinations of immune check point inhibitors and tyrosine kinase inhibitors are ongoing. Real-world reports of current first line systemic therapies are also increasing. In this topic, we will review the updated results of clinical trials and real-world data of current first line systemic therapies for HCC.

2021 消化系聯合學術演講年會

專題討論（八） Update of Systemic Therapy for HCC SECOND LINE SYSTEMIC THERAPIES FOR HCC: CURRENT SEQUENCING OPTIONS Teng-Yu Lee（李騰裕） Division of Gastroenterology & Hepatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan

Systemic therapies for advanced hepatocellular carcinoma (HCC) have made a big progress in recent years, including tyrosin kinase inhibitor (TKI), immune checkpoint inhibitor (ICI), and ICIbased combination. Second-line systemic therapies are defined as a rescue therapy for patients who experience a tumor progression to the first-line systemic therapy, such as sorafenib, lenvatinib, or atezolirumab plus bevacizumab. Regarding the second-line systemic therapies for sorafenib users, multiple choices can be used. Several TKIs, including regorafenib, cabozantinib, ramucirumab, have been proven to be effective by the phase-III randomized controlled trials. Moreover, Several ICIs, including nivolumab, pembrolizumab, and nivolumab plus Ipilimumab, have obtained a rapid approval from the US FDA due to the durable tumor responses in the phase I/II clinical trials. However, regarding the second-line systemic therapies for lenvatinib users, evidence from clinical trials is sparce, and no confident choice can be recommended. According to the data from the ICI clinical trials, the differences in response rates seemed to be not significantly different

between patients who ever exposed to sorafenib or not, and the mechanisms in HCC treatment are also different from TKIs. Therefore, ICI may be a reasonable choice after lenvatinib therapy failure. However, the efficacy of using TKIs other than lenvatinib, such as sorafenib, remains uncertain, but some benefits from other TKI therapy after lenvatinib therapy have been reported. In 2020, with better tumor responses and survival benefits compared to those of sorafenib in the phase-III trial, atezolirumab plus bevacizumab has been approved to be the firstline systemic therapy for advanced HCC, but what can be the second-line systemic therapy after this combination therapy becomes a big challenge. Only limited evidences suggest using another ICI may be effective to some patients, but we really do not know who and how it works. Therefore, using TKI therapy, which is belonged to different mechanisms for HCC treatment, plus another ICI or not, may be a suggestion. However, evidence from clinical trials or real-world data is lacking and should be an urgent task to investigate in the future.

2021 消化系聯合學術演講年會

專題討論（八） Update of Systemic Therapy for HCC BIOMARKERS OF SYSTEMIC THERAPY FOR HCC: TOWARD PRECISION MEDICINE Ying-Chun Shen（沈盈君） Department of Medical Oncology, National Taiwan University Cancer Center, Taipei, Taiwan

From 2007 until now, there are 9 regimens approved worldwide for the treatment of advanced hepatocellular carcinoma (HCC). The mechanisms of action of these effective treatments include antiangiogenesis and immune checkpoint inhibition. Extensive research has been done to explore predictive biomarkers which can guide optimal systemic treatment for HCC patients. However, all regimens

were approved for all comers but one (ramucirumab; anti-VEGFR2 antibody) that was approved for HCC patients with alpha-fetoprotein >400 ng/ml. In the era of immunotherapy, no robust decisive biomarkers have been identified to predict the efficacy of immune checkpoint blockade-based therapy. In this talk, the histories of biomarker identification and potential barriers in HCC will be briefly reviewed.

2021 消化系聯合學術演講年會

專題討論（八） Update of Systemic Therapy for HCC SYSTEMIC THERAPY FOR HCC: NOVEL PERSPECTIVES AND FUTURE DIRECTIONS Stephen L. Chan Department of Clinical Oncology, Chinese University of Hong Kong, Hong Kong

Enhancement of systemic treatment regimens for HCC has led to remarkable changes in the treatment strategy for the cancer. First, sequential administration of systemic agents has gradually been standard practice for patients with advanced HCC. To maximize the benefits of systemic agents, optimal hepatic function is one of the crucial factors. Strategies to preserve hepatic reserves include adequate antiviral control, a rational use of TACE, less stringent criteria of switching TACE to systemic therapy. Second, TACE has been established as a standard for intermediate-stage HCC when there were no effective systemic treatment. Since large-

burdened HCC derive less benefits from TACE, clinical equipoise exists between use of systemic treatment to replace TACE in selected intermediatestage HCC. Randomized controlled trial is currently under planning to compare TACE to systemic therapy in intermediate-stage HCC. Third, systemic therapy may be adopted as neo-adjuvant treatment in selected patients with locally advanced or borderline resectable HCC. Preliminary experiences from phase I/II studies suggest pathological complete response is feasible. Future direction should not only focus on developing more novel drugs/regiments but also establish novel concepts on treatment strategies for HCC.

2021 消化系聯合學術演講年會

專題討論（九） Precision Medicine in GI Endoscopy Practice 精準醫療時代的上消化道出血處置 REVISIT UPPER GASTROINTESTINAL BLEEDING IN THE ERA OF PRECISION MEDICINE: MEDICATION MANAGEMENT, RISK SCORE AND OUTCOMES Hsiu-Chi Cheng（鄭修琦） Department of Internal Medicine, National Cheng Kung University Hospital, Tainan, Taiwan

Upper gastrointestinal bleeding is a common and deadly disease. Recurrent bleeding is an independent risk factor leading to mortality. Endoscopic treatment plus 3-day intravenous proton pump inhibitor (PPI) infusion is the current standard protocol for peptic ulcer bleeding; however, there were patients who were still at risk of recurrent bleeding even though receiving such protocol. In the era of precision medicine, physicians need to classify patients into subpopulations who differ in susceptibility to recurrent bleeding and in response to the endoscopic and acid suppression therapy. Therefore, diagnostic testing is employed for predicting the early (the first 24 hours), short-term (28 days), and long-term (>1 year) recurrent bleeding and identifying the indication for second-look endoscopy and the optimal duration and dose of PPI to reduce the risk. Within the first 24 hours, epinephrine monotherapy only at index endoscopy and hypoalbuminemia <3.0 g/dL are two factors predicting recurrent bleeding. Both Forrest class Ia/Ib lesions at index endoscopy and hypoalbuminemia <3.5 g/dL predict persistent major stigmata of recent hemorrhage on ulcer base even though patients have received 2- or 3-day PPI infusion. Such patients may need second-look endoscopy. At the short-term (28 days) follow-up, comorbidities and hypoalbuminemia are factors correlating to recurrent

bleeding. A simple scoring system, Rockall scores, represents age, comorbidity, disease severity, and endoscopic findings to predict risk of recurrent bleeding at both short-term and long-term (>1 year) follow-up and the cutoff value is 6. Accordingly, comorbidities or Rockall scores ≥6 is an indicator to select patients receiving a prolonged intravenous standard-dose PPI infusion to 7 days or a double dose of oral PPI, twice a day, to 14 days after first 3-day high-dose PPI infusion. Moreover, Rockall scores ≥6 is also an indicator to select patients receiving a prolonged course of oral PPI to one year. In addition to the risk scoring system, molecular diagnostics is also a tool employed in precision medicine. Cytochrome P-450 2C19 (CYP2C19) poor metabolizers have increased potency of gastric acid suppression with oral PPI; however, CYP2C19 genotypes might not affect the acid‐inhibitory effects of PPI at either standard- or high-dose in a continuous infusion manner in East Asia. In conclusion, through the use of hypoalbuminemia, endoscopic imaging, and the Rockall score, physicians could order a tailored treatment for each patient who has peptic ulcer bleeding to maximize treatment response and minimize cost and adverse effects, which are the aim of the precision medicine.

2021 消化系聯合學術演講年會

專題討論（九） Precision Medicine in GI Endoscopy Practice T2T 時代的發炎性腸道疾病的診治策略 CLINICAL MANAGEMENT FOR IBD IN THE TREAT-TO-TARGET ERA – IT’S TIME TO OPTIMIZE TREATMENT BASED ON MUCOSAL STATUS Chia-Hung Tu（凃佳宏） Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan

Management of inflammatory bowel disease is complex and tremendously flexible, which often entangles pharmaceutical and non-pharmaceutical options, phenotype and severity-based approaches, multi-mechanism combination medications, shifting therapies between induction and maintenance, individual risk and complication management. Treatment success depends on thorough consideration of all elements of therapeutic scheme. In the buildup of a specific strategy toward best possible outcome for an individual patient, the primary care physician has to keep in mind a new concept of treat-to-target, or in other words ‘tight-control approach’ throughout the entire course of medical care. Thanks to the continued advances and expansion of therapeutic

options since the era of biologic treatment, deep remission beyond simple loss of symptoms are being made possible to many patients. Hence the tradition of symptom-based treatment targets is not more considered appropriate for modernized medical care, while multiple parameters that reflect deeper healing are emerging and incorporated into treatment algorithms. In the presentation, multi-level treatment targets will be summarized, along with their rationales and those evidence that formed the basis for the now widely accepted ‘treat-to-target’ principle. Treat-totarget approaches will be compared to conventional strategies, with lately published studies and also real cases as examples.

2021 消化系聯合學術演講年會

專題討論（九） Precision Medicine in GI Endoscopy Practice 風險分層在監測大腸鏡檢查的應用 RISK STRATIFIED POST-COLONOSCOPY SURVEILLANCE Wei-Yuan Chang（張為淵） Department of Internal Medicine, National Taiwan University Hospital Hsin‐Chu Branch, Hsinchu, Taiwan

Colorectal cancer (CRC) is the third most common cancer in males and second most common cancer in females worldwide. 1,2 The pathogenesis of CRC is a stepwise accumulation of genetic and molecular alternations that lead to development of precancerous adenoma and progression to CRC.3-5 Hence, resecting these pre-cancerous colorectal adenomas at each colonoscopy was shown to effectively reduce CRC mortality.6,7 For average-risk population, the 5-y incidence of metachronous advanced neoplasm (AN) after polypectomy could be as high as 26% 8 thus a surveillance colonoscopy is mandatory to ensure the protection of colonoscopy. To best ultilization the limited resources of colonoscopy, the intensity of surveillance should be tailored among individuals according to their risk of metachronous AN due to their clinical proxy to CRC. Body of evidence had shown that this risk could be stratified according to their baseline colonoscopic finding,9,10 therefore current clinical guideline suggest clinicians to give surveillance recommendation based on the subject’s baseline colonoscopic finding.11 However, not only endoscopic findings, several personal factors can also help us to stratify each subject’s risk of metachronous AN after polypectomy. For example, subjects who were obesity or with metabolic syndrome had been proved to associated with higher risk of metachronous AN.12, 13 Our recent research also showed that a more active exercise habit after polypectomy can reduce the incidence of

subsequent metachronous AN. Unlike endoscopic finding, obesity, metabolic syndrome or exercise habit are modifiable factors thus they can not only help us to stratify the subjects’ risk but also serve as a primary prevention parameters for lowering subsequent AN incidence. In addition, for those with positive FIT but a negative confirmatory colonoscopy, the strategy of surveillance has also been discussed recently. In area using colonoscopy-based CRC screening program, a 10 years surveillance interval after a negative baseline colonoscopy is recommended. However, recent research from Taiwan CRC Screening Program has showed that subjects receiving subsequent FIT surveillance after negative colonoscopy would have a lower incidence of CRC in the follow-up years.14 Additionally, our recent research also showed the level of initial FIT could also predict the risk of subsequent AN after a negative confirmatory colonoscopy. These results will let clinicians re-consider the surveillance strategy for this population especially in area using FIT-based CRC screening area, like Taiwan.

References: 1. Torre LA, Bray F, Siegel RL, Ferlay J, LortetTieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin. 2015;65(2):87–108. 2. Ferlay J, Soerjomataram I, Dikshit R, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015;136(5):E359–E386.

2021 消化系聯合學術演講年會

3. N g u y e n H T, D u o n g H Q . T h e m o l e c u l a r characteristics of colorectal cancer: Implications for diagnosis and therapy. Oncol Lett. 2018;16(1):9-18. 4. Nambiar PR, Gupta RR, Misra V. An “Omics” based survey of human colon cancer. Mut Res. 2010;693(1-2):3-18. 5. Fearon ER, Vogelstein B. A genetic model for colorectal tumorigenesis. Cell. 1990; 61(5):759767. 6. 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(8):687-696. 7. 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(2):291298. 8. Lieberman DA, Rex DK, Winawer SJ, Giardiello FM, Johnson DA, Levin TR. Guidelines for colonoscopy surveillance after screening and polypectomy: a consensus update by the US Multi-Society Task Force on Colorectal Cancer. Gastroenterology. 2012 Sep; 143(3):844-857. 9. Chung SJ, Kim YS, Yang SY, Song JH, Kim D, Park MJ, Kim SG, Song IS, Kim JS. Fiveyear risk for advanced colorectal neoplasia after initial colonoscopy according to the baseline risk stratification: a prospective study in 2452 asymptomatic Koreans. Gut. 2011 Nov;60(11):1537-43.

10. Lee SM, Kim JH, Sung IK, Hong SN. The Risk of Metachronous Advanced Colorectal Neoplasia Rises in Parallel with an Increasing Number of High-Risk Findings at Baseline. Gut Liver. 2015 Nov 23;9(6):741-9. 11. G u p t a S , L i e b e r m a n D , A n d e r s o n J C , e t al. Recommendations for Follow-Up after Colonoscopy and Polypectomy: A Consensus Update by the US Multi-Society Task Force o n C o l o r e c t a l C a n c e r. G a s t r o e n t e r o l o g y. 2020;158(4):1131-1153.e5. 12. Laiyemo AO, Doubeni C, Badurdeen DS, Murphy G, Marcus PM, Schoen RE, Lanza E, Smoot DT, Cross AJ. Obesity, weight change, and risk of adenoma recurrence: a prospective trial. Endoscopy. 2012 Sep;44(9):813-8. 13. Chiu HM, Lee YC, Tu CH, Chang LC, Hsu WF, Chou CK, Tsai KF, Liang JT, Shun CT, Wu MS. Effects of metabolic syndrome and findings from baseline colonoscopies on occurrence of colorectal neoplasms. Clin Gastroenterol Hepatol. 2015 Jun;13(6):1134-42.e8. 14. P eng SM, Hsu WF, Wang YW, Lin LJ, Yen AM, Chen LS, Lee YC, Wu MS, Chen TH, Chiu HM. Faecal immunochemical test after negative colonoscopy may reduce the risk of incident colorectal cancer in a populationbased screening programme. Gut. 2020 Sep 28:gutjnl-2020-320761.

2021 消化系聯合學術演講年會

專題討論（九） Precision Medicine in GI Endoscopy Practice 精準大腸直腸癌手術 WELCOME TO THE ERA OF PRECISION AND PRESERVATION FOR COLORECTAL SURGERY Chien-Chih Chen（陳建志） Department of Colorectal Surgery, Koo Foundation Sun Yat-Sen Cancer Center, Taipei, Taiwan

Main goals of colorectal cancer treatment have been and will always be oncological safety and organ function preservation. Over the past two decades, neoadjuvant chemoradiation therapeutics have played key roles in the advancement of retal cancer treatment – particularly in achieving decreased local recurrentes rates and increased spincter preservation rates. Effective primary tumor surgical resection remains an essential component in treatment of both early and advanced colorectal cancer. Advancements in surgical instruments and approaches have synergistically

driven the evolution of surgical intervention in general. Minimal invasiveness, increased functional preservation, and decreased treatment-related complications have thus emerged as areas of emphatic focus. In this presentation, we will present the advancement of surgical modality for colorectal cancer, and how these advantages beneficial to oncological result improvement and organ function preservation.

2021 消化系聯合學術演講年會

專題討論（十） Diagnosis and Treatment of Small Bowel Disease DIAGNOSIS, NATURAL HISTORY AND TREATMENT OF EOSINOPHILIC ENTERITIS: A REVIEW Puo-Hsien Le（李柏賢） Department of Gastroenterology and Hepatology, Linkou Chang Gung Memorial Hospital, Taoyuan, Taiwan

Eosinophilic enteritis is generally considered as a benign disease, but some patients may present a more complex natural history characterized by unpredictable relapses and a chronic course. The epidemiology and pathophysiology of eosinophilic

enetritis are still unclear. For diagnosing eosinophilic enteritis, it is necessary for clinicians to have a high degree of clinical suspicion. The diagnosis, natural history and updated treatments will be reviewed here.

2021 消化系聯合學術演講年會

專題討論（十） Diagnosis and Treatment of Small Bowel Disease MANAGEMENT OF PJ SYNDROME IN THE ERA OF DEEP ENTEROSCOPY Chen-Wang Chang（章振旺） Department of Intern Medicine, Mackay Memorial Hospital, Taipei, Taiwan

Peutz-Jeghers syndrome (PJS) is a familial polyposis syndrome characterized by multiple hamartomatous polyps throughout the gastrointestinal tract. Most of the polyps are predominant in the jejunum, followed by the stomach and colon. PJS is associated with increased risk of malignancies and the most common site being colorectal cancer and followed by breast, stomach, small bowel and pancreas. Intussusception is the most frequent complication of PJS which occurred during the first decade of life, and needs multiple surgeries. In the past, surgical intervention was the only methods for management intussusception and bleeding in PJS, and was associated with short bowel syndrome or adhesion ileus. Since 2001, Yamamoto H. complete the first case of total enteroscopy by doubleballoon enteroscopy (DBE), endoscopic prophylactic polypectomy for patients with PJS can be achieved. In Taiwan, Prof. Ming-Yao Su and Dr. Tsung-Hsing Chen had also published the first experiences of 6 PJS cases with successful polypectomy by double-balloon enteroscopy (Dig Dis Sci 2011; 56:1472–1475). Deep enteroscocopy includes single-balloon, double-balloon, and spiral enteroscopy. It has been widely used in the treatment of Peutz-Jeghers syndrome. However, there may be some differences

between single-balloon in double-balloon enteroscopy in the treatment of PJS. There is also no comprehensive study or consensus on endoscopic treatment of PJS polyps. In one study of Small bowel polyp resection using device-assisted enteroscopy in Peutz-Jeghers Syndrome from France. Complete treatment was achieved in 76%. Intraoperative enteroscopy and surgical resection were performed in four (16%) and two (8%) patients. Intraoperative enteroscopy improved by 16% the complete treatment rate and the overall rate was 92%. The complication rate was 6%. The largest resectable one of polyp via endoscopy was 6cm. In one study of double-balloon enteroscopy in patients with PJS of 12-year experience showed the maximum size of resected polyps in first time are 3.63 ± 0.92 cm via oral route and 2.95 ± 1.95 via anal route. However, the experience of single balloon enteroscopy for PJS polyps were rare. In one study from Italy, the effective of prophylactic polypectomy of small bowel large polyps (> 15 mm) could be the first line treatment for conservative approach in management of PJS patients. In conclusion, current studies confirmed the efficacy and safety of endoscopic resection of small bowel polyps via deep endoscopy in PJS patients.

2021 消化系聯合學術演講年會

專題討論（十） Diagnosis and Treatment of Small Bowel Disease SHORT BOWEL SYNDROME: THE ROLE OF GASTROENTEROLOGIST Chen-Shuan Chung（鍾承軒） Division of Gastroenterology and Hepatology, Department of Internal Medicine, Far Eastern Memorial Hospital, New Taipei City, Taiwan

Short bowel syndrome (SBS) is an increasing malabsorptive disorder as a result of the loss of bowel mass and nutritional autonomy secondary to multiple surgical resection of the intestine, mesenteric infarction, neoplasms, radiation enteritis, inflammatory bowel disease, congenital diseases, etc. Several complications are associated with SBS related intestinal failure (IF), such as fluid, electrolytes and nutritional deficiencies, IF associated liver disease, cholelithiasis/nephrolithiasis, infection, metabolic bone disease and mortality. Treatment options for SBS-

IF include dietary modification, pharmacotherapy and surgical intervention. Among pharmacotherapies for control of SBS-IF related complications, glucagonlike peptide analogues are promising intestinotrophic agents for improving intestinal adaptation in SBS-IF patients. Additionally, endoscopic surveillance after intestinal transplantation is important to monitor graft rejection and improve post-transplantation outcome. Herein, I will review the role of gastroenterologists in the prevention and management programs for SBS-IF patients.

2021 消化系聯合學術演講年會

一般演講

主題：C 型肝炎（一）

①

以外展團體治療模式建立血液透析患者 C 型肝炎微清除（ERASE-C） ESTABLISHMENT OF AN OUTREACH, GROUPING HEALTH CARE SYSTEM TO ACHIEVE MICRO-ELIMINATION OF HCV FOR UREMIC PATIENTS IN HEMODIALYSIS CENTERS (ERASE-C) 1,2

1,2

余明隆黃釧峰葉明倫黃駿逸梁博程林宜竑 1 1 1,2 1,2 1 1 魏鈺儒劉大維黃志富戴嘉言謝明彥林文一 1,2 莊萬龍 1 高雄醫學大學附設醫院肝膽胰內科 2 高雄醫學大學醫學院

Background: Hepatitis C virus (HCV) prevails in uremic hemodialysis patients. Nevertheless, the treatment of chronic hepatitis C in the uremic population remains underutilization even in the era of direct-acting antivirals (DAAs). Aims: The current study aimed to achieve HCV microelimination in hemodialysis centers by a comprehensive outreach program. Methods: The ERASE-C Campaign is an outreach program for the screening, diagnosis and group treatment of HCV encompassing 2,323 uremic patients and 353 medical staff members from 18 hemodialysis centers. HCVviremic subjects were linked to care for directly acting antiviral therapy or received on-site sofosbuvir/velpatasvir therapy. The objectives were HCV microelimination (> 80% reduction of the HCV-viremic rate 24 weeks after the end of the campaign in centers with ≥ 90% of the HCVviremic patients treated) and “No-C HD” (no HCV-viremic subjects at the end of follow-up). Results: At the preinterventional screening, 178 (7.7%) uremic patients and 2 (0.6%) staff members were HCV viremic. Among them, 146 (83.9%) uremic patients received anti-HCV therapy (41 link-to-care; 105 on-site sofosbuvir/velpatasvir). The rates of sustained virological response (SVR12, undetectable HCV RNA 12 weeks after the end of treatment) in the full analysis set and per-protocol population were 89.5% (94/105) and 100% (86/86), respectively, in the on-site treatment group, which were comparable to the rates of 92.7% (38/41) and 100% (38/38), respectively, in the link-to-care group. Eventually, the HCV-viremic rate decreased to 0.9% (18/1,953), yielding an 88.3% reduction from baseline. HCV microelimination and “No-C HD” were achieved in 92.3% (12/13) and 38.9% (7/18) of the hemodialysis centers, respectively. Conclusions: Outreach strategies with mass screenings and on-site group treatment greatly facilitated HCV microelimination in the hemodialysis population.

②

醫院藥物成癮 C 肝病人接受直接抗病毒藥物轉診策略的比較 COMPARISON OF REFERRAL STRATEGIES FOR HOSPITAL-BASED HEPATITIS C PATIENTS WITH DRUG ABUSE FOR DIRECT ACTING ANTIVIRALS 郭垣宏黃寳源王潔婷蘇輝明顏毅豪陳建宏長庚醫療財團法人高雄長庚紀念醫院胃腸肝膽科系暨長庚大學醫學系 Background: Increased uptake of hepatitis C virus (HCV) treatment among people who inject drugs (PWID) will be critical to achieve HCV elimination goals. Aims: The study was to elucidate different referral strategies related to treatment uptake among hospital-based PWID after direct acting antivirals (DAA). Methods: In 2019, approximately 180 PWID regularly received opioid agonist therapy (OAT) in the drug addition clinic of our institute-Kaohsiung Chang Gung Memorial Hospital. After excluding 30 patients co-infected with Human Immunodeficiency Infection (HIV), 121 patients (67.2%) were feasible for the referral to our hepatology clinic underwent screens for DAA treatment. Based on different referral strategies, the duration of referral was divided into three parts as I. Self-intension referral for treatment (SRT) period (From Jan to Jun 2019): Patients asked for referral and treatment due to information from social media. II. Intensive referral for treatment (IRT) period (From Jul 2019 to Jun 2020): Patients were asked for referral and treatment by clinicians. III. Fast Intensive referral for treatment (FIRT) period (From Jul to Oct 2020): Patients received fast referral and quick screening for DAA in the hepatology clinic. Effect of different referral models was described and analyzed. Results: A total of 68 patients (56.1%) received referrals for the screen of DAA, the median age was 48.2 years and most (94.1%) were male. There were16 referred patients (23.5%) in SRT period, 34 (50%) in IRT period, and 18 (26.5%) in FSRT period. Monthly average referred patient number was 2.7 people in SRT period, 4.25 people in IRT period, and 4.8 people in FIRT period, respectively. Among these referred patients, 59 patients (86.8%) still had HCV viremia and suitable for DAA. Distributions of the genotype were 22 patients (37.3%) with genotype 1a (G1a), 9 (15.3%) with G1b, 5 (8.5%) with G2, 5 (8.5%) with G3, and 18 (30.4%) with G6. Two patients refused treatment,

2021 消化系聯合學術演講年會

whereas the other 57 patients underwent DAA therapies including 31 patients with Maviret, 15 with Epclusa, 9 with Harvoni and 2 with Zepatier. No patient interrupted DAA treatment and 48 patients have finished their DAA treatment. Thiry-two patients completed the following viremia test and all of them achieved sustained virologic response (SVR). Conclusions: Although HCV treatment uptake among PWID in this hospital-based setting in the DAA era remains suboptimal, it is encouraging that treatment uptake has increased after developing an intensive referral with quickto-screen and easy-to-treat programs. Innovative strategies are required to reach all hospital-based PWID infected with HCV.

③

通過電子病歷便利貼模式以促進醫院內 C 肝病人轉介給肝臟專科醫師：一項探索性研究 PUTTING “STICKY NOTES” BY THE ELECTRONIC MEDICAL RECORD TO PROMOTE INTRA-HOSPITAL REFERRAL OF ANTI-HCV(+) PATIENTS TO HEPATOLOGY SPECIALISTS: AN EXPLORATORY STUDY 朝建銘黃仁杰辛政憲李政祺陳季宏陳鄭弘堯溫奕志澄清綜合醫院中港分院胃腸肝膽科 Background: Direct-acting antiviral (DAA) regimens have achieved an excellent response for the treatment of chronic hepatitis C (CHC). However, the challenge of HCV elimination still exists on how to effectively identify those untreated patients and link them to care. Currently, OPD patients with anti-HCV(+) are often not referred for further care by non-hepatologist clinicians. The main objective of this study was, therefore, to explore a simple alert program to promote the referral of such patients to hepatologists through an intra-hospital collaboration system. Aims: Identify OPD patients with anti-HCV(+) scattered in various departments, encourage referral to hepatologists for further evaluation and treatment, and analyze the reasons behind some patients not following up. Methods: From the hospital registry of CHC patients since 2010, we excluded those patients who had undergone interferon or DAA treatments, and identified a total of 3,347 anti-HCV(+) patients who had not tested for HCV-RNA. Using the list of these patients’ OPD appointments, the case manager placed one or more sticky notes at each OPD room to remind the doctor to refer such patients to the case manager for education session upon patients’ arrival and to order the HCV-RNA test either directly or else refer to a hepatologist for further care. Results: (1) The whole-hospital screening program for CHC patients was implemented from 2019/12/05 to 2020/12/18. A total of 345 anti-HCV(+) patients in the OPD were notified and 135 patients underwent HCV RNA testing; the other 210 patients did not. The main reasons for not undergoing testing were (a) the patients had already been treated at another medical facilities (24.3%, 51/210); (b) patients had no symptoms or did not feel a need to be tested (21.4%, 45/210); (c) patients failed to show up for their OPD appointment (16.2%, 34/210); and (d) they were already terminally ill (13.8%, 29/210). (2) A total of 74 (54.8%, 74/135) patients tested positive for HCV

2021 消化系聯合學術演講年會

RNA. Of these, 54 patients underwent DAA treatment. Three main reasons for no treatment were identified: (a) old age (20%, 4/20), (b) comorbidity rendering treatment unsuitable (15%, 3/20), and (c) request transfer to another nearby hospital (20%, 4/20). (3) Of the 345 ant-HCV(+) outpatients, GI department accounted for 25.5% (88/345), non-GI department 74.4% (257/345), of which the top 3 departments were orthopedics (10.7%), neurology (9.5%), and cardiology (8.9%). Conclusions: Our study found that putting “sticky notes” by the electronic medical record, coupled with the assistance and guidance of a case manager, effectively promoted intra-hospital referral of anti-HCV(+) OPD patients to hepatology specialists for HCV RNA testing and therefore was helpful for subsequent treatment.

④

Entecavir 在 B 肝病毒／ C 肝病毒共同感染患者接受 C 肝口服抗病毒藥物治療預防 B 肝病毒或臨床再活化的作用 ROLE OF ENTECAVIR IN PREVENTING VIROLOGICAL/CLINICAL REACTIVATION OF HBV IN HCV/HBV CO-INFECTED PATIENTS RECEIVING DAA THERAPY FOR CHRONIC HEPATITIS C 1

2,3

鄭斌男劉俊人陳啟益曾國枝羅清池林志陵 1 國立成功大學醫學院附設醫院內科部 2 國立臺灣大學醫學院附設醫院內科部 3 國立臺灣大學醫學院臨床醫學研究所 4 嘉義基督教醫院胃腸肝膽科 5 大林慈濟醫院內科部肝膽胃腸科 6 嘉義聖馬爾定醫院內科部 7 臺北市立聯合醫院仁愛醫院消化內科

Background: There were lines of evidence revealed that hepatitis B virus (HBV) reactivated during interferon-free direct acting antiviral (DAA) treatment for chronic hepatitis C. Clinical reactivation developed and then nucleoside analogue (NA) was required in about 5% of patients. HBV treatment may be needed to control HBV activity during DAA treatment. The role of NA prophylaxis is still not clear and needs to define. Aims: To investigate the role of prophylactic NA could prevent virology/clinical reactivation of HBV in HCV/ HBV co-infection patients during DAA treatment for CHC. Methods: This is a multi-Centre, open-label, randomized, active controlled study. HBV/HCV co-infected treatmentnaïve or treatment-experienced patients without decompensated liver cirrhosis will be included. DAA treatment included TFDA approved 12-week regimens for any genotype CHC. Patients were randomized to three groups including 12-wk DAA treatment (group 1), 12-week DAA treatment plus 12-week ETV 0.5 mg per day (group 2), and 12-week DAA treatment of plus 24-week ETV 0.5 mg per day (group 3). All patients were followed till 72 weeks after starting DAA treatment. HBV virological reactivation (VR) is defined as an increase of HBV DNA level more than ten folds of baseline HBV DNA during study period with prior quantifiable HBV DNA at baseline or presence of HBV DNA with prior unquantifiable HBV DNA during study period. Clinical reactivation is defined as the presence of abnormal ALT level (>2X ULN) and virological reactivation.

2021 消化系聯合學術演講年會

Results: A total of 57patients with mean age of 61 years, including 26 males and 31 females, were enrolled and 19 patients were randomized to the three groups. The baseline demography of patients was comparable among 3 groups. Currently, all of the enrolled patients have complete 12week DAA treatment and 12-week after stopping drug treatment. The sustained virological response (SVR) was achieved in all 57 patients (100%). At baseline, seven patients exhibited undetectable HBV DNA and the median HBV DNA of remaining patients was 259 IU/ ml (20~269280 IU/mL). During all observation period, HBV VR occurred in 12 patients (63.2%) of group 1, two patients of group 2, and no patient of group 3 (p <0.001). During 12-week DAA treatment period, HBV VR occurred in 10 patients (53.6%) of group 1 and no patients of ETV treated (group 2 and group 3) (p < 0.001). From stopping drug treatment to 12-week of follow-up period, HBV VR were still seen in six patients in group 1. Notably, five patients of group 2 had HBV VR after stopping ETV. Patients still received ETV in group 3 did not exhibit HBV VR. No clinical reactivation occurred in patients of each group. Conclusions: DAA treatment exhibited excellent effectiveness to clear HCV in HBV/HCV co-infected patients. HBV VR was common during DAA treatment in HBV/HCV co-infected patients. ETV prophylaxis could reduce the incidence of HBV VR and prevent clinical reactivation.

⑤

無法手術切除的肝癌患者在直接作用抗病毒藥物時代下的慢性 C 型肝炎治療 ANTIVIRAL THERAPY FOR CHRONIC HEPATITIS C PATIENTS WITH UNRESECTABLE HEPATOCELLULAR CARCINOMA IN THE ERA OF DIRECTACTING ANTIVIRALS 陳立書楊勝舜李少武黃耀光蔡炘儒李騰裕臺中榮民總醫院胃腸肝膽科 Background: Antiviral therapy for chronic hepatitis C (CHC) becomes fast and easy in the era of direct-acting antivirals (DAAs); however, the benefits of DAA therapy in patients with unresectable hepatocellular carcinoma (HCC) should be further discussed. Aims: We aimed to investigate the benefits of DAA therapy in patients with unresectable HCC when compared to interferon (IFN) therapy. Methods: In this hospital-based cohort study, all patients with HCCs in Barcelona Clinic Liver Cancer (BCLC) stage B or C, who received IFN or DAA for CHC, were retrospectively recruited during the period from 2009 to 2020 (IFN: from Jan, 2009 to Jan, 2015; DAA: from Jan, 2015 to May, 2020). Patients with HCCs diagnosed after antiviral therapy were excluded. The patient characteristics and virological responses were compared between the DAA and the IFN users. Odds ratio (OR) for sustained virological response (SVR) was analyzed. Cumulative incidences of overall survival were compared between patient subgroups. Results: In total, 91 patients (83 in BCLC stage B & 8 in BCLC stage C) were analyzed; 72 and 19 patients received DAA and IFN, respectively. Amongst DAA users, the median age was significantly older (DAA vs. IFN: 70, IQR: 63.25-77.75 vs. 64, IQR: 61-68; p=0.008). The SVR rates tended to be higher in DAA users when compared to IFN users (DAA vs. IFN: 87.5% vs. 68.42%; p=0.077), particularly in those who completed the antiviral therapy (per protocol) (DAA vs. IFN: 94.03% vs. 76.47%; p=0.049) and those in BCLC stage B (DAA vs. IFN: 94.92% vs. 76.47%; p=0.041). All patients in BCLC stage C received DAA therapy, and the SVR rate was 87.5%. In multivariable regression analysis, 4-week virological response (OR 5.77, 95% confidence interval [CI]: 1.7219.42) and within up-to-7 criteria (OR 2.99, 95% CI: 0.969.29) were independent factors associated with SVR. The 2-year cumulative incidences of overall survival amongst

2021 消化系聯合學術演講年會

patients in BCLC stage B were not significantly different between the two study groups (DAA vs. IFN: 78.33%, 95% CI: 65.7%-90.96% vs. 83.59%, 95% CI: 66.59%-100%; p=0.676), respectively. Conclusions: Compared to IFN therapy, more patients with unresectable HCCs could receive DAA therapy for CHC, particularly in the elderly, with a high SVR rate. Rapid virological response and limited tumor burden are subjective to achieve SVR.

⑥

台灣 C 型肝炎感染之受刑人接受 DAA 治療之成效以及安全性分析 REAL-WORLD EFFICACY AND SAFETY OF DIRECT-ACTING ANTIVIRAL THERAPY IN PRISONERS WITH HEPATITIS C INFECTION IN TAIWAN 1

李政澤蔡宗佑蕭望德陳浤燿朱家聲林伯昌 1 1,3 許偉帆彭成元 1 中國醫藥大學附設醫院消化醫學中心 2 中國醫藥大學附設醫院感染科 3 中國醫藥大學醫學系

Background: Hepatitis C virus (HCV) infection is a global health issue and is one of the leading causes of liver cirrhosis and hepatocellular carcinoma. Directacting antiviral agents (DAAs) are the current mainstream treatment for HCV infection. We already knew that the prevalence of HCV infection in prisoners is much higher than the general population. However, real-world data about treatment efficacy in prisoners with HCV infection in Taiwan is insufficient. Aims: We aimed to collect prisoners with HCV infection in Taiwan, to investigate the frequency of injection drug use, and compare the characteristics including treatment efficacy between PWID (persons who inject drugs) and non-PWID patients with HCV infection. Methods: We retrospectively enrolled HCV-infected patients who had received DAA therapy at Taichung Prison Pei-de Hospital, Clinic of Taichung Women’s Prison, and Clinic of Taichung Detention Center from January 2017 to September 2020. We recorded the patient characteristics, treatment efficacy (sustained virological response at 12 weeks after the end of DAA therapy (SVR12)), and adverse effects. Results: We enrolled 416 patients with HCV infection under DAA treatment, 287 of them (69%) had prior drug injection history. The most prevalence genotype is genotype 6, followed by 1a, 3, 1b, 2 and mixed genotypes, 35.8%, 24.5%, 14.7%, 12.3%, 10.6% and 2.2% respectively. Comparing baseline characteristics between PWID and non-PWID patients with HCV infection, we found that PWID patients with HCV infection are younger than nonPWID (43 y/o vs 45 y/o, p=0.021). PWID patients with HCV infection had higher proportion of HIV/HCV coinfection rate compared to non-PWID (18.1% vs 8.5%, p = 0.012). There was no difference of factors between hypertension, diabetes mellitus, prevalence of hepatitis B

2021 消化系聯合學術演講年會

主題：B 型肝炎（一） virus (HBV) in PWID and non-PWID. The most frequently prescribed DAA regimen was GLE/PIB (38.2%), followed by SOF/VEL (31.0%), SOF/LDV ± RBV (21.9%), and others (8.9%). There was no SVR12 rate difference between PWID and -non-PWID group (95.8% vs 96.1%, p = 0.794). Conclusions: We found genotype 6 was the major genotype in both PWID and non-PWID patients. We found significantly higher HIV prevalence in PWID patients, which might correlate to sharing a common transmission route with HCV by blood transmission. According to our study, HCV screening seems to be important in prisoners with drug injection history, and a high possibility of HIV coinfection needs to be considered in this group of patients.

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Tenofovir 與 Entecavir 在降低慢性 B 型肝炎患者肝癌風險的比較 ─ 系統性統合分析 HEPATOCELLULAR CARCINOMA INCIDENCE WITH TENOFOVIR VS ENTECAVIR IN CHRONIC HEPATITIS B: A SYSTEMATIC REVIEW AND METAANALYSIS 1

曾政豪許耀峻陳子皓 Fanpu Ji 陳溢松蔡英楠 4 4 5 Hoang Hai , Le Thi Thanh Thuy , Tetsuya Hosaka , 5 6 7 Hitomi Sezaki , John A. Borghi , Ramsey Cheung , 4 7 Masaru Enomot , Mindie H. Nguyen 1 義大癌治療醫院肝膽胃腸科 2 義大醫院肝膽胃腸科 Department of Infectious Diseases, the Second Affiliated 3 Hospital of Xi’an Jiaotong University, Xi’an, China Department of Hepatology, Osaka City University 4 Graduate School of Medicine, Osaka, Japan Department of Hepatology, Toranomon Hospital, Tokyo, 5 Japan Lane Medical Library & Knowledge Management Center, 6 Stanford University, Palo Alto, CA, USA Division of Gastroenterology and Hepatology, Stanford 7 University Medical Center, Palo Alto, CA, USA Background: Whether tenofovir disoproxil fumarate and entecavir differ in their association with hepatocellular carcinoma (HCC) risk in chronic hepatitis B (CHB) patients remains controversial, and prior meta-analyses have different conclusions with substantial heterogeneity. Aims: We aimed to enroll updated data and elucidate the source of heterogeneity. Methods: We searched PubMed, Embase, Web of Science, and the Cochrane library for relevant studies with time-toevent data for incident HCC in CHB patients receiving at least one year of tenofovir disoproxil fumarate or entecavir monotherapy published between January 1, 2006 and April 17, 2020 and also abstracts from major international conferences in 2018 and 2019. (PROSPERO submission ID: 176513) We pooled covariate-adjusted HRs for HCC using a random-effects model, assessed for the presence of heterogeneity among the included studies by I2 statistic and Cochran’s Q test, and determined the source of heterogeneity via pre-specified subgroup analyses. Results: A total of 31 studies involving 119,053 patients were analyzed: The five-year cumulative HCC incidence with entecavir and tenofovir disoproxil fumarate in studies with unmatched populations were respectively 5.97%

2021 消化系聯合學術演講年會

(95% CI, 5.81-6.13%, 28 studies) versus 3.06% (95% CI, 2.86-3.26%, 13 studies), and 3.44% (95% CI, 3.083.80%) versus 3.39% (95% CI, 2.94-3.83%) from eight studies with matched populations (either by pre-specified individual variable or by propensity scores). Analysis of 14 comparative studies with covariate adjustment found tenofovir disoproxil fumarate and entecavir were not associated with different HCC risks (adjusted HR, 0.88; 95% CI, 0.73-1.07; P=0.20), though heterogeneity was significant (I 2=56.4%, P=0.004). In subgroup analysis for hospital-based clinical cohort studies, there was no difference in HCC incidence between the two regimens (adjusted HR, 1.03, 95% CI, 0.88-1.21; I2=0%). However, tenofovir disoproxil fumarate was found more effective than entecavir in administrative database research (adjusted HR, 0.67, 95% CI, 0.59-0.76; I2=0%). Conclusions: Since our study finds no significant difference between tenofovir disoproxil fumarate and entecavir in their association with incident HCC, we suggest treatment should be guided by patient tolerability and affordability rather than one drug being more effective than the other.

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Entecavir 以及 Tenofovir 對 B 型肝炎病毒相關肝細胞癌切除後復發和死亡的比較 COMPARISON OF ENTECAVIR AND TENOFOVIR ON RECURRENCE AND MORTALITY OF HEPATITIS B VIRUS-RELATED HEPATOCELLULAR CARCINOMA AFTER CURATIVE RESECTION 1,2

蔡明釗王植熙劉約維楊志權胡琮輝 1 高雄長庚紀念醫院胃腸肝膽科系 2 長庚大學臨床醫學研究所 3 高雄長庚紀念醫院一般外科

Background: It is unclear whether entecavir (ETV) and tenofovir disoproxil fumarate (TDF) have different effects on hepatocellular carcinoma (HCC) recurrence and death in patients receiving curative hepatectomy for HBV-related HCC. Aims: To compare the long-term efficacy of ETV and TDF in HCC recurrence and overall survival of patients after curative hepatectomy for HBV-related HCC. Methods: A total of 20,572 patients with HCC who received hepatectomy between January 2010 and December 2019 from the Chang Gung Research Database (CGRD) of Taiwan were screened for study eligibility and 431 consecutive patients treated with ETV (n = 347) or TDF (n = 84) after curative hepatectomy for HBV-related HCC of BCLC stage 0 or A were finally analyzed. HCC recurrence and overall survival of patients were compared between ETV and TDF groups. We also applied propensity score matching (PSM) to 1:2 balance the 2 treatment cohorts. Results: After a median follow-up of 49.7 months, 146 patients (33.9%) had HCC recurrence, 57 (13.2%) died, and 7 (6.1%) received liver transplantation. No difference was observed between ETV and TDF in the HCC recurrence (HR, 1.089; 95% CI, 0.721-1.645, p = 0.684) and death or liver transplantation (HR, 1.25; 95% CI, 0.636-2.457, p = 0.517). However, the PSM analysis (n = 219) found that ETV therapy was an independent risk factor for late postoperative HCC recurrence (HR, 2.684; 95% CI, 1.1636.190, p = 0.021). Conclusions: TDF therapy was associated with a significant lower risk of HCC late recurrence compared with ETV therapy among patients who underwent curative hepatectomy.

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⑩

張國欽林明宗陳建宏蔡明釗顏毅豪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

陳俞宏施宇隆謝財源黃文彥樊修龍黃瑋琛 1 三軍總醫院胃腸肝膽科 2 三軍總醫院放射腫瘤部 3 三軍總醫院一般外科 4 國防醫學院臨床免疫學實驗室

HBcrAg 是在慢性 B 型肝炎並代償性肝硬化病人經抗病毒治療後發生肝癌預測因子 HBCRAG PREDICTS HEPATOCELLULAR CARCINOMA DEVELOPMENT IN CHRONIC B RELATED LIVER CIRRHOSIS PATIENT LONG-TERN EFFECT OF ANTIVIRAL TREATMENT

Background: Although the viral marker hepatitis B corerelated antigen (HbcrAg) could predict the development of hepatocellular carcinoma (HCC) in patients with chronic hepatitis B (CHB).However, the relationship between HBcrAg and HCC in CHB related LC patients with longtern nucleos(t)ide analog (NA) therapy is unclear. Aims: We investigated whether HBcrAg levels are associated with development of HCC, especially in CHB with LC patients who under long-tern antiviral treatment. Methods: This retrospective study enrolled 1108 naïve patients diagnosed with HBV-related LC. They received NA therapy from April 1999 to February 2015 and all patients were the virus was complete suppressed. The values for the laboratory tests, and disease history were collected. Results: Among the 1108 patients, 219 of 1108 developed HCC within a median follow-up of 6.8 years. The overall 1-, 3- and 5-year cumulative incidence of HCC was 3.2%, 10.4%, and 15.2%, respectively. In multivariate analysis in patients with old age (hazard ratios (HR): 1.21, 95% CI: 1.06-1.39, p = 0.005), high AFP level (HR: 1.38, 95% CI: 1.02-187, p = 0.035), high FIB-4 level (HR: 2.26, 95% CI: 1.65-3.11, p < 0.001), DM (HR: 1.58, 95% CI: 1.18-2.10, p = 0.002) and high HBcrAg levels (HR: 1.68, 95% CI: 1.192.37, p = 0.003) were independent risk factors for HCC. At the end of the study, the higher FIB-4 and PIVKA-II level were predicted the liver related mortality for the HBV related LC patients. Conclusions: Patients with CHB related LC had the potential for progression to HCC even under long-term NA therapy. Old age, high AFP level, high FIB-4, DM, and high HBcrAg level were independent risk factors for HCC development after effective antiviral therapy in the CHB patients with LC.

台灣 B 型肝炎患者中俱免疫活性及病毒性專一性 CD8 T 細胞呈現衰竭及耗弱的細胞表型 EXHAUSTION (PD-1+) AND DEPLETION (FAS+) PHENOTYPE OF IMMUNE ACTIVATED AND HBV-SPECIFIC CD8 T CELLS IN TAIWANESE CHRONIC HEPATITIS B PATIENTS 1,4

1,4

Background: Nowadays, even with vaccine prevention and effective drug treatment, chronic hepatitis B virus (HBV) infection still endangers the health of millions. Research report also indicates that chronic hepatitis B (CHB) is closely related to liver cirrhosis and hepatocellular carcinoma. Current evidence suggests that HBV-specific T cells play an important role in virus elimination. In this study, we used personalized immune analysis to recognize pathogenic factors on T cells in chronic HBV infection. Aims: To determine main pathogenic factors and improve treatment effectiveness of HBV infection. Methods: Peripheral blood mononuclear cells (PBMC) were isolated from whole blood by standard gradient centrifugation on Ficoll-paque Plus (GE Healthcare). Flow-cytometry analysis: Cells were initially harvested and washed twice with PBS. Cells were then suspended in Live/Dead binding solution for 30 minutes. Virus-specific T cells evaluation: For viral peptide-MHC (pMHC) complex staining, peptide-exchange was used in the UV-crosslinker (CL-1000 Ultraviolet crosslinker UVP). Tetramerization of pMHC was used with biotinylated MHC monomer and fluorophore-tag streptavidin. For cytokine intracellular staining, PBMC were cultured for 10 days and restimulated with virus overlapping peptides (15mer peptides overlapping by 10 residues spanning genotype B HBV core protein, JPT). The cells were fixed and permeabilized to allow intracellular labelling with the IFN-γ antibody. The cells were analyzed with a FACS Canto II (BD Biosciences, Heidelberg, Germany). Results: Flow cytometry results of ex vivo staining reveal that activation (CD38+) levels of T cells are similar in CHB patients and healthy controls. However, activated CD8 T cells in CHB patients are significantly exhausted (PD-1+) and depleted (Fas+) compared to those in healthy

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donors. Virus pMHC-tetramer complex staining results also showed that expression of PD-1 was distinctly elevated in HBV-specific CD8 T cells. Additionally, HBV-specific CD8 T cells are more exhausted (PD-1+) than non-virusspecific cell groups in our statistical study. Identically, PD-1 expression on IFN-γ-producing CD8 T cells in CHB patients are greatly increased in our preliminary data. Conclusions: Our findings demonstrate activation (CD38+) levels of T cells are similar in CHB patients and healthy controls. However, the results show a higher expression of PD-1 and Fas not only on CD8 T cells of CHB patients, but also on the activated (CD38+) CD8 T cell portion. Moreover, pMHC-tetramer complex staining reveals exhausted (PD-1+) phenotype of HBV-specific CD8 T cells. Identically, PD-1 expression on IFN-γ-producing CD8 T cells in CHB patients is greatly increased in our preliminary data. Therefore, making use of personalized immunological mapping is an ideal method to determine main pathogenic factors and improve treatment effectiveness of HBV infection.

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以 B 型肝炎核心免疫球蛋白 M 抗體效價區分類似急性 B 型肝炎之慢性 B 型肝炎急性發作 IGM ANTI-HBC TITER HELPS TO IDENTIFY ACUTE HEPATITIS B LIKE CHRONIC HEPATITIS B WITH ACUTE EXACERBATION 1

1,2

魏銘漢蘇東弘洪俊銘曾岱宗王嘉齊林志陵 6 1,2,7 1,2 1 1,2,7 黃奕文劉俊人劉振驊楊宏志陳培哲 1,2,7 高嘉宏 1 國立臺灣大學醫學院附設醫院內科部肝膽胃腸科 2 國立臺灣大學醫學院附設醫院肝炎研究中心 3 國立臺灣大學醫學院附設醫院內科部整合醫學科 4 佛教慈濟醫療財團法人台北慈濟醫院內科部肝膽腸胃科 5 臺北市立聯合醫院仁愛院區肝膽腸胃科 6 國泰綜合醫院肝臟中心 7 國立臺灣大學醫學院臨床醫學研究所 Background: The management of acute hepatitis B (AHB) was different from those with chronic hepatitis B with acute exacerbation (CHB-AE). However, it may be difficult to differentiate these two conditions in clinical practice. Aims: This study aims to revisit the role of IgM anti-HBc to guide the correct diagnosis. Methods: Patients with a positive IgM anti-HBc test reported to the Taiwan Center for Disease Control as AHB during 2005-2015 from 4 tertiary medical centers were retrospectively collected. Their medical records and prior history of CHB were reviewed to confirm the diagnosis of AHB, or CHB-AE. The best cut-off level of IgM antiHBc titer to differentiated between AHB and CHB-AE was investigated. The transmission route of AHB, and outcomes of both AHB and CHB-AE were analyzed. Results: A total of 276 patients with positive IgM antiHBc were collected. After review of medical records, 134 patients were AHB and 142 patients were actually CHBAE. Among 152 patients with analyzable IgM anti-HBc, 86 and 66 patients were in AHB and CHB-AE group respectively. We found that the threshold of 15 S/CO for IgM anti-HBc help to differentiate AHB from CHBAE with a sensitivity of 71%, a specificity of 94%. In patients of AHB, 99% of them cleared HBsAg at 6 months later. In contrast, in patients of CHB-AE, 22% of them achieved HBsAg seroclearance 6 months after this acute exacerbation episode. The most common causes for AHB are sexual contact (62%), puncture/piercing injury (24%), occupational exposure (7%) or man who have sex with men

2021 消化系聯合學術演講年會

主題：B 型肝炎（二） (MSM, 7%). There is no difference in transmission route between male and female. Conclusions: Patients of CHB-AE with positive IgM antiHBc has a distinct phenotype of acute exacerbation, with high rate of HBsAg seroclearance. A threshold of 15 S/CO of IgM anti-HBc titer may help differentiate AHB from CHB-AE.

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以 Tenofovir Disoproxil Fumarate 或 Entecavir 治療慢性 B 型肝炎停藥後的病毒復發 ─ 台灣中區肝病研究聯盟前瞻性世代研究的期中分析 HEPATITIS B VIRUS RELAPSE AFTER CESSATION OF TENOFOVIR DISOPROXIL FUMARATE OR ENTECAVIR THERAPY FOR CHRONIC HEPATITIS B ‒ A MIDTERM ANALYSIS OF A PROSPECTIVE COHORT STUDY OF THE CENTRAL TAIWAN RESEARCH ALLIANCE FOR LIVER DISEASES (CENTRAL) GROUP 1

蘇維文吳志昇李騰裕彭成元陳詩典顏聖烈 7 4 9 10 1 2 黃仁杰林俊哲陳宗勉廖光福徐友春楊基滐 3 4 8 楊勝舜賴學洲蔡明璋 1 彰化基督教醫院胃腸肝膽科 2 秀傳紀念醫院胃腸肝膽科 3 臺中榮民總醫院胃腸肝膽科 4 中國醫藥大學附設醫院消化系內科 5 衛生福立部彰化醫院肝膽腸胃科 6 彰濱秀傳紀念醫院胃腸肝膽科 7 澄清綜合醫院中港分院胃腸肝膽科 8 中山醫學大學附設醫院肝膽腸胃科 9 童綜合醫院胃腸肝膽科 10 台中慈濟醫院肝膽腸胃科 Background: The relapse of hepatitis B virus (HBV) remains an important issue after cessation of nucleos(t)ide analogue (NA) therapy in patients with chronic hepatitis B (CHB). Aims: The aim of this study was to investigate the risk factors of HBV relapse after stopping tenofovir disoproxil fumarate (TDF) or entecavir (ETV) therapy. Methods: In total, 10 hospitals in central Taiwan joined this prospective cohort study. CHB patients, who discontinued TDF or ETV therapy according to the NA stopping rules of the modified Asian Pacific Association for the Study of the Liver (APASL) guidelines, were prospectively recruited since 29 January 2015. Patients with liver cirrhosis, active malignancies, hepatitis C virus, hepatitis D virus or human immunodeficiency virus coinfection, liver transplantation history, immune disorders, a history of NA therapy other than TDF or ETV, or a follow-up period of less than 24 weeks were excluded. During the follow-up period, serum alanine aminotransferase (ALT), HBV DNA, and quantitative hepatitis B surface antigen (qHBsAg) levels

2021 消化系聯合學術演講年會

were measured every 3 months, and the above-mentioned tests were checked more frequently if clinically indicated. Virologic relapse (VR) was defined as a serum HBV DNA level of > 2000 IU/mL and clinical relapse (CR) was defined as a serum HBV DNA level of > 2000 IU/ mL with an ALT level of > 2X upper limit of normal. Both cumulative incidences of and hazard ratios (HRs) for the predictors of HBV relapse were analyzed. Results: As of 30 June 2020, 255 patients (85 HBeAgpositive and 170 HBeAg-negative prior to NA therapy) had been enrolled for this analysis (152 TDF and 103 ETV users), with the median duration of prior NA therapy of 3.0 years (25–75% interquartile ranges [IRQs]: 3.0-3.2). The median follow-up period was 1.2 years (25–75% IRQs: 0.6-2.1). The 3-year cumulative incidence of VR was 86.8% (95% confidence interval [CI]: 81.6-92.0), and the 3-year cumulative incidence of CR was 62.4% (95% CI: 55.3-69.5). In addition, 29 (11.4%) patients experienced ALT elevations > 500 IU/L, and NA therapy was restarted in 103 (40.4%) patients. Eight (3.1%) patients experienced liver decompensation. However, the 3-year cumulative incidence of HBsAg loss was 5.9% (95% CI: 1.8-10.0). In multivariable analysis, qHBsAg < 100 IU/mL at the end of therapy was independently associated with a reduced risk in VR (HR: 0.48, 95% CI: 0.32-0.72; P < 0.001) and CR (HR: 0.55, 95% CI: 0.32-0.92; P < 0.05). Moreover, amongst patients with qHBsAg < 100 IU/mL at the end of therapy, the 3-year cumulative incidence of HBsAg loss was 24.7% (95% CI: 9.2-40.2). Conclusions: HBV relapse is common after cessation of NA therapy, and qHBsAg < 100 IU/mL may be a alternative endpoint to discontinue NA therapy.

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治療中 e 抗原消失（無 e 抗體）和 B 型肝炎核心相關抗體是預測 e 抗原陽性慢性 B 型肝炎病人停止貝樂克或惠立妥後 B 型肝炎病毒復發的重要因子 HBEAG LOSS (NO ANTI-HBE ANTIBODY) DURING TREATMENT AND HBCRAG WERE IMPORTANT PREDICTORS FOR HBV RELAPSE IN HBEAG-POSITIVE CHRONIC HEPATITIS B PATIENTS WHO DISCONTINUED ENTECAVIR OR TENOFOVIR 1

陳建宏彭成元胡琮輝王景弘洪肇宏盧勝男長庚醫療財團法人高雄長庚紀念醫院胃腸肝膽科系暨 1 長庚大學醫學系 2 中國醫藥大學附設醫院胃腸肝膽科 Background: The predictors of HBV relapse in HBeAgpositive patients who discontinued entecavir or tenofovir disoproxil fumarate (TDF) remain unclear. Aims: To investigate HBV relapse rates and predictors in HBeAg-positive patients without cirrhosis who discontinued entecavir or TDF. Methods: A total of 195 and 105 HBeAg-positive patients without cirrhosis who had stopped entecavir and TDF treatment, respectively, for at least 6 months were recruited. All patients fulfilled the stopping criteria of antiviral-agent stopping criteria of Taiwan’s National Health Plan. Results: Patients who discontinued TDF therapy had significantly higher rates and earlier time of virological and clinical relapse than those who discontinued entecavir therapy in all and propensity score-matched patients. Multivariate analysis showed that TDF group, old age, HBeAg loss (no anti-HBe antibody (Ab)) during treatment, higher HBsAg levels at baseline and higher hepatitis B core related antigen (HBcrAg) levels at end-of-treatment (EOT) were independent factors of virological and clinical relapse in all and PS-matched patients. Patients with HBeAg loss during treatment had significantly higher rates of offtherapy HBV relapse and HBeAg seroreversion than those with HBeAg seroconversion during treatment. The HBcrAg level at EOT was also an independent factor of HBeAg seroreversion in all patients and patients with HBeAg seroconverion during treatment. Combination of age <40 years at baseline and HBcAg level <4.5 log U/mL at EOT had the lowest clinical relapse rate (17.5%) at 60 months in the entecavir group.

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Conclusions: Patients with HBeAg loss (no anti-HBe Ab) during treatment and lower HBcrAg at EOT were significant predictors for off-therapy HBV relapse and HBeAg seroreversion after cessation of entecavir or TDF therapy in HBeAg-positive patients.

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e 抗原陰性 B 型肝炎使用 Tenofovir 停藥後的早期肝炎復發較晚期復發嚴重 EARLY OFF-TDF HEPATITIS FLARE IS MORE SEVERE THAN LATE FLARE IN HEPATITIS B E ANTIGEN-NEGATIVE PATIENTS 1,2

1,2

1,2,3

劉彥君鄭文睿彭建維簡榮南 1 長庚大學醫學院 2 林口長庚紀念醫院胃腸肝膽科系 3 林口長庚紀念醫院肝病研究中心

廖運範

1,3

Background: Hepatitis B flare occurred much earlier and more severe in patients stopping tenofovir (TDF) than entecavir (ETV). More than half of the off-TDF flare occurs within 6 months after end-of-treatment (EOT). Aims: Considering the magnitude of HBV DNA upsurge from undetectable at end of treatment (EOT) may be greater than that from an already gradually increased level, this study aims to investigate whether earlier off-TDF flares are also more severe due to greater stimulation of HBV. Methods: HBeAg-negative chronic hepatitis B (CHB) patients who had stopped TDF by APASL stopping rule and encountered hepatitis flare, defined as alanine aminotransferase >5 upper limit of normal, within two years after end-of-treatment (EOT) were included in the study. Early flare and late flare were defined by the time from EOT to hepatitis flare within 6 months and 6-24 months, respectively. The peak level of ALT, total bilirubin, INR during off-therapy flare, the incidence of hepatic decompensation, which defined as total bilirubin >2 mg/dL and INR ≥ 1.5, as well as changes of HBV DNA before and during hepatitis flare, were compared between these two groups. Results: Among 126 enrolled patients, hepatitis flare developed within 6 months from EOT in 89 (71%) patients and 37 (29%) between 6-24 months. Patients with early flare showed higher peak ALT level (600 vs. 322 U/L, p<0.001; in cirrhosis: 596 vs. 282 U/L, p=0.025; in noncirrhosis: 610 vs. 334 U/L, p=0.009], and higher bilirubin level (1.2 vs. 0.9 mg/dL, p=0.014) than those with late flare. Hepatic decompensation was observed only in patients with early flare (4/89 vs. 0/37, P=0.45). The median HBV DNA surge (peak minus preceding level) was significantly higher in early flares than late flares (7.10 vs. 2.52, log10, p<0.001). Conclusions: Early hepatitis flare seems to be more severe than late flare in patients stopping TDF. This phenomenon may result from the abrupt surge in HBV DNA level from viral suppressed status. More stringent off-therapy monitoring is necessary within 6 months off-TDF.

2021 消化系聯合學術演講年會

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慢性 B 型肝炎 e 抗原陰性病人停止貝樂克或惠立妥治療後有發生病毒復發但無臨床復發其表面抗原的變化 HBSAG CHANGES AFTER CESSATION OF ENTECAVIR OR TENOFOVIR IN HBEAG-NEGATIVE PATIENTS WHO EXPERIENCED VIROLOGICAL RELAPSE WITHOUT CLINICAL RELAPSE 曾子寧陳建宏胡琮輝王景弘洪肇宏盧勝男長庚醫療財團法人高雄長庚紀念醫院胃腸肝膽科系暨長庚大學醫學系 Background: The HBsAg changes after cessation of entecavir or tenofovir disoproxil fumarate (TDF) in chronic hepatitis B (CHB) patients who achieved virological suppression after transient virological relapse without clinical relapse remains unclear. Aims: We investigated the HBsAg changes after virological relapse without clinical relapse in HBeAg-negative CHB patients who discontinued entecavir or TDF. Methods: This study included 472 HBeAg-negative CHB patients without cirrhosis who received entecavir or TDF treatment. All patients enrolled had post-treatment follow-up for at least 24 months. Of the 472 patients, 72 experienced virological relapse but no clinical relapse and 124 had a persistent virological suppression (Group I) during follow-up after cessation of entecavir or TDF therapy. Results: Of the 72 patients who experienced virological relapse without clinical relapse, 25 had a virological suppression (HBV DNA < 2000 IU/mL at least 1.5 years until last visit after transient virological relapse) (Group II) and 47 had a persistent or intermittent HBV DNA > 2000 IU/mL (Group III) after virological relapse. Only HBsAg decline from the first virological relapse to end of treatment was an independent factor for virological suppression after virological relapse (OR: 25.47, 95% CI: 2.10-309.3, P=0.011). Patients in Groups I (P<0.001) and II (P=0.011) experienced a larger drop in post-treatment HBsAg levels than patients in Group III. Patients in Group I experienced a larger drop in HBsAg levels than patients in Group II (P<0.001). Patients in Groups I and II exhibited a greater post-treatment HBsAg decline than patients in Group III (both, P<0.001). However, the HBsAg decline was compatible between patients in Groups I and II (P=0.846). Of the 124 patients in Group I and 25 patients in Group

II, 43 and 9 experienced post-treatment HBsAg loss, respectively. The 6-year cumulative rates of HBsAg loss in the Groups I and II was 43.5% and 31.7%, respectively (P=0.285). Conclusions: Patients who had a virological suppression after transient virological relapse (Group II) exhibited a similar HBsAg decline and HBsAg loss rate compared with patients who had a persistent virological suppression (Group I) after cessation of entecavir or TDF therapy.

2021 消化系聯合學術演講年會

⑯

介白素 10 預測慢性 B 型肝炎病人接受貝樂克治療發生早期血清表面抗原濃度下降 INTERLEUKIN-10 PREDICTS EARLY HBSAG DECLINE IN PATIENTS WITH CHRONIC HEPATITIS B RECEIVING ENTECAVIR THERAPY 蔡宗佑賴學洲蘇文邦莊伯恒許偉帆彭成元中國醫藥大學附設醫院消化醫學中心 Background: Early HBsAg decline, defined as a decline of ≥75% from baseline at Months 3 and 12 of entecavir (ETV) treatment in HBeAg-positive and -negative patients, respectively, independently predicts a virological response and HBeAg seroconversion in HBeAg-positive patients, an HBsAg level of <100 IU/mL in HBeAg-negative patients, and HBsAg loss in all patients. Aims: We aimed to identify serum cytokines or chemokines predictive of early HBsAg decline during ETV therapy in patients with chronic hepatitis B (CHB). Methods: We used the magnetic bead-based multiplex immunoassays (LEGENDplex; Biolegend, CA, USA) to measure 13 serum cytokine or chemokine (IL-4, IL-6, IL10, IL-12p70, IL-13, IL-17, IL-21, IL-27, IL-28B, IL35, IFN-γ, IP-10, and CXCL13) levels at baseline and treatment week 4 and performed genotyping in 10 SNPs in 8 cytokine or chemokine genes and interferon-response genes (IL-1β, IL-4, IL-10β, IL-12β, IL-13, IL-17A, IL-27, and IP-10). Results: A pilot study in 40 HBeAg-positive and 40 HBeAg-negative CHB patients, of which 20 each exhibited an early HBsAg decline during ETV therapy versus 20 who did not (matched for potentially confounding factors in a 1:1 ratio) identified IP-10, IL-10, IL-17A, IL-27, IL-4 levels at baseline, at 4 weeks of treatment, or changes between these two time points as factors related to early HBsAg decline. We further measured these cytokines levels and performed SNP analysis in additional 110 HBeAg-positive and 207 HBeAg-negative CHB patients receiving ETV therapy (final: 150 HBeAg-positive and 247 HBeAg-negative patients with 46 and 69 patients exhibiting an early HBsAg decline, respectively). A multivariate analysis revealed that ALT (OR: 1.001, 95% CI: 1.001-1.002, P = 0.0071), HBsAg (OR: 3.931, 95% CI: 1.876-8.238, P = 0.0003), and IL-10 ≥3.1 pg/mL at baseline (OR: 3.209, 95% CI: 1.168-8.812, P = 0.0237) were independent predictors of early HBsAg decline in HBeAg-positive patients. A multivariate analysis revealed that ALT (OR: 1.002, 95%

CI: 1.001-1.003, P = 0.0002), HBV DNA (OR: 1.622, 95% CI: 1.185-2.219, P = 0.0025), HBsAg (OR: 5.428, 95% CI: 2.526-11.664, P < 0.0001), IL-17A rs2275913 [G/G allele] (OR: 3.029, 95% CI: 1.348-6.759, P = 0.0072), and IL-10 ≥ 2.0 pg/mL at baseline (OR: 2.372, 95% CI: 1.0655.281, P = 0.0345) were independent predictors of early HBsAg decline in HBeAg-negative patients . Early HBsAg decline was an independent predictor of achieving <100 IU/mL HBsAg during ETV therapy in HBeAg-positive patients (HR: 3.846, 95% CI: 1.075-13.759, P = 0.0383) and HBeAg-negative patients (HR: 8.274, 95% CI: 4.46214.749, P<0.0001). A multivariate analysis identified HBsAg (HR: 0.359, 95% CI: 0.214-0.603, P = 0.0001), IP10 ≥110 pg/mL at baseline (HR: 3.766, 95% CI: 1.22611.563, P = 0.0004), and early HBsAg decline (HR: 11.592, 95% CI: 3.405-39.461, P < 0.0001) as independent predictors of HBsAg seroclearance (n = 14) during ETV therapy in all patients. Conclusions: Baseline serum IL-10 level predicted early HBsAg decline both in HBeAg-positive and HBeAgnegative CHB patients, whereas baseline serum HBsAg and IP-10 levels and early HBsAg decline predicted HBsAg seroclearance in CHB patients receiving ETV therapy.

2021 消化系聯合學術演講年會

主題：肝腫瘤（一）

⑰

對雷莎瓦有客觀反應的晚期肝癌患者的反應持續時間、臨床效益以及後續治療的角色 DURATION OF RESPONSE AND OUTCOMES IN ADVANCED HEPATOCELLULAR CARCINOMA PATIENTS WITH OBJECTIVE RESPONSE TO SORAFENIB: ROLE OF SUBSEQUENT TREATMENT 1,2

黃國維李沛璋陳怡岑趙毅蘇建維侯明志 1 黃怡翔 1 臺北榮民總醫院內科部胃腸肝膽科 2 臺北市立聯合醫院陽明院區內科部 3 臺北榮民總醫院護理部 4 臺北榮民總醫院腫瘤醫學部

Background: Sorafenib is the standard of care for advanced hepatocellular carcinoma (HCC) since 2008, but the objective response rates were only 2% to 10% in previous clinical trials and real-world data. Little is known for the duration of response and long-term outcome in HCC patients with objective response to sorafenib. There are emerging second-line therapies for patients who failed for sorafenib in recent years. Aims: In this study, we aimed to delineate the duration of response and the role of subsequent treatment after responding to sorafenib. Methods: From August 2012 to December 2019, 992 patients received sorafenib treatment for advanced HCC in Taipei Veterans General Hospital were retrospectively reviewed. Of them, 21 (2.1%) achieved complete responses (CR) and 55 (5.5%) had partial responses (PR) based on mRECIST criteria. The impacts of sequential therapy after sorafenib on overall outcomes were analyzed. Results: The median duration of response was 17.3 months (range 2.3-44.5 months) for patients achieving CR, and 10.0 months (range 1.9-71.3 months) in PR patients. The median overall survival (mOS) was 40.8 months (95% confidence interval [CI]: 28.6-52.9 months) for the 76 patients, including not reached for CR, and 26.6 months (95% CI: 23.0-30.2 months) in PR patients. Patients experienced treatment-related adverse events (TRAE) had better mOS than those without (47.8 vs 19.2 months, p=0.004). Afterward, 65 patients (85.5%) discontinued sorafenib due to progressive disease or adverse events. Of them, 28 patients received subsequent systemic treatment, including nivolumab (n=8), regorafenib (n=12), and chemotherapy (n=8). Patients with subsequent systemic

therapy had a significantly longer post-sorafenib survival (PSS) than those with best supportive care (BSC) only (median PSS: 26.6 vs. 8.0 months, p < 0.001). Sorafenibnivolumab sequential therapy had the longest mOS than sorafenib-regorafenib, sorafenib-chemotherapy, or sorafenib-BSC in these patients (55.8, 36.3, 25.6 and 27.4 months, respectively; p = 0.020, 0.048, and 0.044 for sorafenib-nivolumab vs. sorafenib-regorafenib, sorafenibchemotherapy, and sorafenib-BSC). Conclusions: For advanced HCC patients with response to sorafenib, the duration of response can last for one year, and subsequent immunotherapy provided the best survival.

2021 消化系聯合學術演講年會

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對於無法手術切除的肝癌患者接受 Sorafenib-Regorafenib 順序治療與接受 Sorafenib 治療失敗兩組之存活比較：單一醫學中心的經驗 COMPARISON OF OVERALL SURVIVAL BETWEEN PATIENTS WITH UNRESECTABLE HEPATOCELLULAR CARCINOMA RECEIVING SORAFENIBREGORAFENIB SEQUENTIAL THERAPY AND THOSE FAILING SORAFENIB THERAPY: SINGLE MEDICAL CENTER EXPERIENCE

treatment (mOS for ALBI grades 1 and 2, not reached and 30.1 months, respectively, P = 0.040), whereas in cohort 2 with sorafenib therapy alone, assessment of liver reserve at the end of sorafenib therapy through ALBI grade stratified the overall survival after sorafenib treatment failure (mOS for ALBI grades 1 and 2, 5.5 and 4.4 months, respectively, P = 0.037). Conclusions: Regorafenib therapy improved survival in patients with unresectable HCC who progressed after sorafenib therapy in real-world settings. On-treatment ALBI grade might be a prognostic factor for overall survival.

張哲維王鴻偉賴學洲莊伯恒蘇文邦彭成元中國醫藥大學附設醫院消化醫學中心 Background: Regorafenib improved survival in patients with advanced hepatocellular carcinoma (HCC) who progressed after sorafenib therapy in RESORCE study. Aims: We aimed to compare the overall survival between patients with unresectable hepatocellular carcinoma who received sorafenib-regorafenib sequential therapy and those who failed sorafenib therapy. Methods: A total of 88 patients (cohort 1) with unresectable HCC who received sorafenib-regorafenib sequential therapy were enrolled from September 2012 to July 2020. Another historical cohort including 90 patients (cohort 2) who did not receive further targeted therapy after sorafenib treatment failure were enrolled for comparison. Baseline and on-treatment clinical characteristics, laboratory data and imaging findings were collected. Overall survival was determined using the Kaplan–Meier curve, and comparison between groups was made using the log-rank test as univariate analysis. Results: The two HCC cohorts had liver reserve of Child-Pugh A after sorafenib treatment failure (cohort 1 [sequential therapy with sorafenib and regorafenib]: 94.4% versus cohort 2 [sorafenib therapy alone]: 94.3%). The 6-month overall survival rates after sorafenib treatment failure for cohorts 1 and 2 were 89.0% and 35.9%, respectively. The one-year survival rates after sorafenib treatment failure for cohorts 1 and 2 were 72.1% and 20%, respectively. The median overall survival (mOS) after sorafenib treatment failure was not yet reached for cohort 1 and 4.5 months for cohort 2 (P < 0.001). In cohort 1 with sequential therapy, assessment of liver reserve at the initiation of regorafenib therapy through ALBI grade stratified the overall survival after the initiation of sorafenib

2021 消化系聯合學術演講年會

⑲

治療後 Alpha-Fetoprotein 下降以及治療前的 Fibrosis 4 Score 是肝細胞癌症病人接受 Lenvatinib 後評估療效的獨立預測因子 ALPHA-FETOPROTEIN RESPONDER AND BASELINE FIBROSIS 4 SCORE WERE THE INDEPENDENT PREDICTORS FOR OBJECTIVE RESPONSE IN HEPATOCELLULAR CARCINOMA PATIENTS RECEIVING LENVATINIB- THE REAL WORLD EXPERIENCE 1,2

1,2

林伯庭林錫銘 1 林口長庚紀念醫院胃腸肝膽科系 2 長庚大學醫學院 Background: Lenvatinib was approved as a promising multi-kinase inhibitor agent for unresectable hepatocellular carcinoma (HCC). Those patients who could achieve objective response after treatment might have better clinical outcome. Aims: Therefore, we aimed to investigate the predictors of objective response in HCC patients receiving lenvatinib. Methods: From March 2018 to April 2020, a total of 78 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. Alpha-fetoprotein (AFP) responder was defined as decreased of AFP more than 10% within 4-8 weeks among patients with baseline AFP > 10 ng/ml. Predictors for objective response and clinical outcome were analyzed. Results: Among the 78 patients, the median age was 67.3 years old, and 69.2% were male. Thirty-seven patients (59.7%) fulfilled the criteria of AFP responder and eighteen patients (23.1%) achieved objective response after treatment. Patients with objective response had significantly better outcome than those patients without objective response. (1st year cumulative survival rate 100% vs 48%, log-rank P = 0.008; 1st year cumulative progression rate 53% vs 89%, log-rank P = 0.001). In multivariate logistic regression analysis, AFP responder (adjusted OR: 3.128, P = 0.0275) and fibrosis 4 (FIB-4) score less than 3.25 (adjusted OR: 4.146, P = 0.0267) were the independent predictive factors for achieving objective response. Moreover, patients with AFP response and FIB-4 score less than 3.25 had longer progression free survival (PFS) than patients without AFP response and FIB-4 score more than

3.25 (AFP: 8.7 vs 5.0 months, log-rank P = 0.012; FIB-4: 14.9 vs 7 months, log-rank P = 0.033). Conclusions: AFP responder and better FIB-4 score were independent predictors for objective response in HCC patients receiving lenvatinib. Furthermore, longer PFS was observed in those patients with AFP response and better FIB-4 score.

2021 消化系聯合學術演講年會

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現實世界中合併標靶治療以及免疫治療在無法切除之肝細胞癌的療效以及安全性 THE EFFICACY AND SAFETY OF COMBINING TARGETED THERAPIES WITH IMMUNE CHECKPOINT INHIBITORS IN UNRESECTABLE HEPATOCELLULAR CARCINOMA IN A REAL-WORLD SCENARIO 1

1,2

姜學謙郭欣瑜李楊成蔡宏名王昊宸林毅志 1 1 1 1 1 1 陳炯瑜鄭斌男陳柏潤康瑞文邱彥程邱宏智 1 1 1 1 1 簡世杰劉玠晏吳毅晉張定宗莊喬雄 1 成大醫院內科部 2 國立成功大學臨床醫學研究所 3 台南市立醫院內科部 4 成大醫院放射科 5 成大醫院外科部

with TKIs appeared to confer longer overall survival (OS) than PD-1 inhibitors alone (median OS, 16.5 vs 12.0 months; p = 0.398). The incidence of treatment-related adverse events was similar between patients receiving PD-1 inhibitors alone and those with the combination of PD-1 inhibitors and TKIs (p = 0.885). Among 56 patients with the combination of PD-1 inhibitors and TKIs, 16 patients were switched to different TKIs and 25 patients were treated continuously with previous TKIs. The ORR of patients with and without change of TKIs were 25% and 28% (p = 1.000), respectively. Conclusions: Combination therapies of PD-1 inhibitors with TKIs seem to have potential survival benefit and did not increase toxic effects compared to PD-1 inhibitor use alone. Moreover, there was similar efficiency regarding to combination of originally experienced TKIs or switch to other TKIs. Further larger scale and prospective studies are needed to verify the results of the current study.

Background: Immunotherapy using immune checkpoint inhibitors, e.g., programmed cell death protein-1 (PD-1) inhibitors combined with molecular targeted agents, have showed potential synergic effect and promising efficacy in unresectable hepatocellular carcinoma (uHCC). Aims: This study compared efficiency and safety between PD-1 inhibitors alone and combination therapies of PD-1 inhibitors with tyrosine kinase inhibitors (TKIs) in a realworld cohort of patients with uHCC. Methods: From November, 1, 2015 to November, 30, 2020, 172 patients with uHCC were treated with PD-1 inhibitors in combination with or without TKIs at the National Cheng Kung University Hospital and Tainan Municipal Hospital. The overall treatment response and its effect on survival were assessed. The tumor response was evaluated using the modified RECIST (mRECIST) based on serial contrast-enhanced CT or MRI. The follow-up cut‐ off date was set on December 30, 2020. Results: Among the 172 patients, 63 patients were excluded (9: pathology proven combined hepatocellular cholangiocarcinoma, 8: follow-up loss, 30: died before first radiologic survey, and 16: incomplete planned radiographic evaluation). Of the remaining 109 patients, 53 patients were treated with PD-1 inhibitors alone and 56 patients were administered with PD-1 inhibitors and TKIs. The baseline characteristics were balanced between the patients with and without combination with TKIs. The overall objective response rates (ORR) of patients with and without combination TKIs were 27.3% and 28.3% (p = 1.000), respectively. The combination of PD-1 inhibitors

2021 消化系聯合學術演講年會

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Pembrolizumab 合併 Lenvatinib 用於不可手術切除含括高腫瘤負擔肝癌 LENVATINIB PLUS PEMBROLIZUMAB FOR UNRESECTABLE HEPATOCELLULAR CARCINOMA ACROSS HIGH TUMOR BURDEN 1

1,2

吳啟榮李杰如洪雅文侯明志黃怡翔 1 臺北榮民總醫院內科部胃腸肝膽科 2 國立陽明大學臨床醫學研究所

Background: Combination of multi-kinase inhibitor (MKI) with immune checkpoint inhibitors (ICIs) may improve the efficacy for unresectable hepatocellular carcinoma (HCC). MKI therapy could potentially enhance T cell infiltration and activation, consequently, cooperate with ICI to produce synergistic anti-tumor effects. The phase 1b Keynote-524 study shows promising data by combining Pembrolizumab with Lenvatinib for advanced HCC. However, those with high tumor burden were excluded in the clinical trial. Aims: The study tried to evaluate the treatment response and safety of lenvatinib plus pembrolizumab for HCC in real-world setting especially in patients with high tumor burden. Methods: From Jul. 2019, patients who received pembrolizumab plus lenvatinib for unresectable HCC were prospectively enrolled in this study. The status of HCC was either in advanced HCC or failed by prior systemic therapy. The dosage of pembrolizumab was 2 mg/kg every 3 weeks. The dose of lenvatinib complied to the standard body weight recommendation. A total of 54 patients who had received at least 2 cycles of pembrolizumab were evaluated in this report. High tumor burden, defined as tumor ≧ 50% liver size or main portal vein (Vp4) invasion. The tumor responses were assessed with Response Evaluation Criteria in Solid Tumors (RECIST) v1.1 and modified RECIST (mRECIST). The treatment related adverse events (TRAEs) were graded according to Common Terminology Criteria for Adverse Events (CTCAE) v5.0. Results: Of the 54 HCC patients, 33 (61.1%) were treated as the first-line systemic therapy. The objective response rate (ORR) and disease control rate (DCR) were 59.3% and 87% by mRECIST criteria, respectively, including 4 (7.4%) achieved complete response (CR), 28 (51.9%) had partial response (PR), 15 (27.8%) with stable disease (SD), and 7 (13%) had progressive disease (PD). Surprisingly, patients with high tumor burden has significantly higher PR and SD rate than those with low-medium tumor burden. In

multivariate regression model, high tumor burden, AFP ≧ 400 (mg/ml), no prior ICIs exposure were independent predictors of response to lenvatinib-pembrolizumab combination therapy. The most common TRAEs in any grade were fatigue 33 (57.9%), palmar-plantar syndrome 30 (52.6%), hypertension 26 (45.6%), and hypothyroidism 19 (33.3%). The Grade 3/4 TRAEs were 3 (5.3%) with psoriasis-like skin reaction, 3 (5.3%) decreased appetite. Patients with high tumor burden did not have higher risk of TRAEs compared with those with low-medium tumor burden. Conclusions: Lenvatinib plus pembrolizumab can provide high response and disease control rates, with similar TRAEs rates for uHCC across high tumor burden that excluded from previous clinical trials.

2021 消化系聯合學術演講年會

主題：肝硬化及其他肝病

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以新生抗原疫苗和 PD1 免疫檢查點抑制劑合併治療小鼠肝細胞癌可達到協同作用 SYNERGISTIC EFFECT OF NEOANTIGEN VACCINATION AND PD1 BLOCKADE IN THE TREATMENT OF HEPATOCELLULAR CARCINOMA IN MICE 1

1,2,3

翁孟慈楊士鋒劉心雲李宣書 1 台大醫院內科部 2 臺灣大學生物科技研究所 3 肝病防治學術基金會

1,3

許金川

Background: Neoantigens are personalized nonsynonymous mutation-based epitopes in cancer cells. Synthetic peptides harboring the mutation epitopes have been used as personalized vaccines to treat melanoma and glioblastoma. In this study, we used this strategy to treat hepatocellular carcinoma (HCC) in mice. Aims: To evaluate the therapeutic effect of neoantigen vaccination and its combination with PD1 blockade. Methods: Whole-exome sequencing (WES) was conducted using matched genomic DNAs from normal tail tissue of a C57BL/6 mouse and from a subcutaneously implanted tumor by a syngenic HCC cell line Hep55.1. Nonsynonymous mutation in the tumor were identified and those mutations with positive expression in the tumor tissue were selected by RNA sequencing (RNA-seq) of the tumor. After prediction of binding affinity, neoantigen peptides harboring respective mutated residues were synthesized. Immune responses were analyzed at the level of single neoantigen by flow cytometry, IFN-γ enzyme-linked immunospot (ELISPOT) and correlated with tumor size. Results: 19 neoantigen peptides were synthesized and subcutaneously injected into respective normal mice. Among them, 6 peptides induced splenocyte reactivity of both ex vivo IFN-γ ELISPOT and IFN-γ intracellular cytokine staining detected by flow cytometry. Compared with control group, the tumor sizes were not significantly different after peptide vaccine or PD1 blockade monotherapy, whereas the combination of peptide vaccine with PD1 blockade induced significant control of tumor growth. Conclusions: Around 32% (6/19) of selected epitope candidates were immune reactive. The preliminary results indicate that combination of peptide vaccination and PD-1 blockade may become a promising therapy for hepatocellular carcinoma.

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比較 Rosuvastatin 和 Silymarin 對於肝硬化病患改善長期存活率之探討 COMPREHENSIVE EVALUATION OF EFFECTS OF ROSUVASTATIN AND SILYMARIN FOR IMPROVING LONGTERM SURVIVAL IN PATIENTS WITH LIVER CIRRHOSIS 1

1,2

郭昭成黃建豪 1 林口長庚紀念醫院肝膽胃腸科 2 長庚大學醫學院 Background: Statins have a major role in reducing LDL cholesterol, mainly via its potent inhibition of of 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, resulting in inhibition of cholesterol generation and serum cholesterol levels downregulation. Besides their well-known beneficial cardiovascular effects and lipidlowering property, statins also exhibit multiple pleiotropic effects such as antioxidative, antiproliferative and antiinflammatory properties, as well as the capacity to improve endothelial function and to stimulate neoangiogenesis. Silymarin (silybum marianum), the active ingredient in milk thistle, has exhibited promising antifibrotic activity in experimental liver injury and is widely used as a nonprescription agent in patients with chronic liver disease. Silymarin functions as an antioxidant and may decrease hepatic injury via cytoprotection and inhibition of Kupffer cell function. However, silymarins and rosuvastatin are still widely used as a non-prescription agent in patients with chronic liver disease. Aims: Silymarin and Rosuvastatin have a potential therapeutic benefit through simultaneous enhancement of FXR/DDAH-1/eNOS pathway for hepatic and renal function. It is hence intriguing to evaluate whether statin or silymarin has much beneficial effect in the vulnerable group of chronic liver disease that patients with liver cirrhosis. Methods: By analyzing big data from the center for big data analytics and statistics of CGMH Hospital, 49380 patients who met the inclusion diagnostic criteria of liver cirrhosis (LC) between 2006~2017 were screened. Exclusion criteria included previously diagnosed HCC before enroll, age <12 years old and no available staging information during follow-up. Silymarin group was defined as consecutive use of 3 tablets of silymarin a day for at least 3 months. Rosuvastatin group was defined as consecutive use of at least 1 tablet of rosuvastatin 5mg a day for at least 3 months. The primary outcome was 5-year

2021 消化系聯合學術演講年會

(60 months) mortality analyzed by Cox-regression model after adjusting for time-dependent covariate MELD scores. Age, sex, cirrhotic etiologies, number of admissions and Charlson Comorbidity Index (CCI) were also adjusted in the multivariate analysis. Results: Totally 12,616 patients were enrolled after exclusion criteria (Figure 1). The mean age was 54.26 ± 15.13-year-old. 8,462 (67.07%) were male. For the etiology of cirrhosis, 12.46% were HBV, 13.36% were HCV, 4.34% were HBV + HCV co-infection and 12.22% were alcoholic, while 57.62% were other etiologies including NASH. Mean follow-up time was 62.32 ± 44.22 months. 2,903 patients died during follow-up (23.01%). There were 1,141 patients in the silymarin group and 326 patients in the rosuvastatin group. Age, etiologies of cirrhosis, CCI, number of admissions and MELD score, silymarin use, rosuvastatin use correlated with primary outcome after long-term follow-up by Cox univariable analysis (Figure 2). After adjusting the above covariate and time-dependent MELD scores, rosuvastatin consecutive use for at least 3 months were associated with lower hazard ratio (0.851), p = 0.0047 (Figure 3). As shown in Figure 4 by Kaplan-Meier plot, use of rosuvastatin group has better outcome curve than control group irrespective of MELD score. Conclusions: By Cox-regression model after adjustment of time-dependent MELD and other covariates including age, etiologies of cirrhosis, CCI and number of admissions, the hazard ratio for death was lower in the rosuvastatin group. In this big data study, consecutive use of at least 1 tablet of rosuvastatin 5mg a day for 3 months in patients with liver cirrhosis correlated with better survival outcome irrespective of MELD score.

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比較內視鏡靜脈曲張結紮術與非選擇性 β 阻斷劑預防肝癌病患併發食道靜脈曲張首次出血：期中分析 ENDOSCOPIC VARICEAL LIGATION VERSUS NON-SELECTIVE β-BLOCKER FOR PRIMARY PREVENTION OF ESOPHAGEAL VARICEAL BLEEDING IN PATIENTS WITH HEPATOCELLULAR CARCINOMA: INTERIM ANALYSIS 1,2

2,3

1,2

楊宗杰陳炳憲李沛璋黃怡翔侯明志 1 臺北榮民總醫院胃腸肝膽科 2 國立陽明大學醫學系 3 臺北榮民總醫院內視鏡診斷暨治療中心

Background: It is not clear which of endoscopic variceal ligation (EVL) or non-selective β-blocker (NSBB) is the better choice for primary prevention of esophageal variceal bleeding (EVB) in patients with hepatocellular carcinoma (HCC) and concomitant esophageal varices (EVs). Aims: This study aimed at evaluating the efficacy and feasibility of EVL or NSBB to prevent first EVB in patients with HCC concomitant with large EVs. Methods: From August 2009 to July 2014, we prospectively enrolled 61 patients with HCC and concomitant large EVs (F2 and/or F3) without history of EVB. Thirty-one and 30 patients were randomly assigned into the EVL group (Group A) and the NSBB group (Group B), respectively. EVB, upper gastrointestinal bleeding (UGIB), EVB-free survival, overall survival and adverse events were compared between the groups. Results: After a median follow-up of 7.2 months in group A, 3 (9.7%) patients had EVB and 13 (41.9%) died. In group B, 11 (36.7%) patients had EVB and 15 (50.0%) died after a mean follow-up of 7.6 months. The EVB rate was significantly lower in group A than in group B (9.7% vs. 36.7%, p = 0.016). No significant difference was found between the two groups in terms of the UGIB rate (25.8% vs. 43.3%, p = 0.150), the incidence of adverse events (38.7% vs. 36.7%, p = 0.869), EVB-free survival (p = 0.224) and overall survival (p = 0.978). Conclusions: It is likely that EVL is associated with a lower incidence of EVB compared with NSBB in patients with HCC concomitant with large EVs.

2021 消化系聯合學術演講年會

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MAC-2 結合蛋白糖基化異構體血中濃度與肝靜脈壓力梯度相關且可預測肝硬化病患之細菌感染 MAC-2 BINDING PROTEIN GLYCOSYLATION ISOMER BLOOD LEVELS CORRELATE WITH HEPATIC VENOUS PRESSURE GRADIENT AND PREDICT BACTERIAL INFECTIONS IN CIRRHOTIC PATIENTS 1,2

1,2

吳佩珊謝昀蓁李癸汌黃怡翔侯明志林漢傑 1 臺北榮民總醫院胃腸肝膽科 2 國立陽明大學內科學科

Background: Mac-2-binding protein glycosylation isomer (M2BPGi) is a novel serum biomarker for liver fibrosis. Aims: We aimed to evaluate the association between M2BPGi and hepatic venous pressure gradient (HVPG) and to investigate the predictive value of M2BPGi on complications of cirrhosis. Methods: Forty-eight cirrhotic patients who underwent HVPG measurement with retrievable serum samples in Taipei Veterans General Hospital were retrospectively enrolled. Serum M2BPGi levels were measured. The Pearson correlation test was used to analyze the correlation between serum M2BPGi levels and HVPG. Cox proportional hazards regression models were used to identify predictors for mortality and complications of cirrhosis. Results: Serum M2BPGi levels correlated with HVPG (R = 0.41, p = 0.004) but not correlated with other hemodynamic parameters. M2BPGi levels were significantly higher in patients with HVPG ≥16mmHg than HVPG < 16 mmHg (p = 0.007). On multivariate Cox regression analysis, higher serum levels of M2BPGi [≥ 6 cut-off index (C.O.I.)] did not predict 5-year mortality for cirrhotic patients and the result was consistent in patients without hepatocellular carcinoma. Interestingly, serum M2BPGi ≥ 6 C.O.I. was an independent predictor of bacterial infections within 5 years [Hazar ratio (HR) = 4.59, 95% confidence interval (CI) = 1.74-12.09, p = 0.002]. However, serum M2BPGi ≥ 6 C.O.I. failed to predict the occurrence of other cirrhosisrelated complications, including variceal bleeding, ascites formation, spontaneous bacterial peritonitis, hepatorenal syndrome, and hepatic encephalopathy. Conclusions: Serum M2BPGi levels correlated with HVPG and higher serum M2BPGi levels might have a potential predictive role in the development of bacterial infection for cirrhotic patients.

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星狀細胞特異腎素原受體過度表達透過活化 ERK/TGF-β1/SMAD3 路徑惡化小鼠肝纖維化 HEPATIC STELLATE CELLSPECIFIC (PRO)RENIN RECEPTOR OVEREXPRESSION EXACERBATED LIVER FIBROSIS THROUGH ACTIVATION OF ERK/TGF-β1/SMAD3 PATHWAY 謝昀蓁李癸汌藍耿欣霍德義黃怡翔侯明志林漢傑臺北榮民總醫院胃腸科 Background: The (pro)renin receptor (PRR) activation upregulates the expression of profibrotic genes in kidney and heart. Aims: We aimed to investigate the role of PRR in hepatic fibrogenesis. Methods: Primary mouse hepatic stellate cells (HSCs) were isolated for PRR expression analysis. Experimental fibrosis was studied in thioacetamide (TAA)-treated C57BL/6 mice. A lentiviral vector expressing PRR cDNA from the α-smooth muscle actin (α-SMA) promoter was used for HSC-specific gene overexpression. Results: The PRR is upregulated in the mouse fibrotic livers, and in vitro and in vivo activated HSCs. The HSCspecific PRR overexpression exacerbated liver fibrosis in TAA-injured mice with induced HSC activation and increased profibrotic genes expression, including collagen 1α1, PAI-1, fibronectin transcript levels as well as α-SMA levels. Mice with HSC-specific PRR overexpression upregulated the hepatic ERK1/2-TGF-β1/Smad3 pathway. Conclusions: (Pro)renin receptor is upregulated in fibrotic livers and activated HSCs, and its overexpression exacerbated liver fibrosis through activation of ERK1/2TGF-β1/Smad3 pathway. Thus, PRR is a promising therapeutic target for liver fibrosis.

2021 消化系聯合學術演講年會

主題：脂肪肝相關疾病

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Propranolol 可以抑制肝硬化小鼠的 T Helper 細胞饋乏相關的免疫機能障礙 PROPRANOLOL SUPPRESSES THE T-HELPER CELL DEPLETIONRELATED IMMUNE DYSFUNCTION IN CIRRHOTIC MICE 1

4,5

蔡弘正黃加璋黎子豪楊盈盈劉志偉黃怡翔 4 4 侯明志林漢傑 1 臺北榮民總醫院內科部風濕免疫科 2 臺北榮民總醫院內科部內分泌新陳代謝科 3 新光吳火獅紀念醫院內科部風濕免疫科 4 臺北榮民總醫院內科部胃腸肝膽科 5 臺北榮民總醫院教學部臨床技術訓練科

B a c k g ro u n d : B a c t e r i a l t r a n s l o c a t i o n ( B T ) a n d splenomegaly contribute to cirrhosis-associated immune dysfunction (CAID) including T cell depletion, infection, and chronic inflammation. β-blockers have been reported to decrease BT and improve splenomegaly. Methods: This study explores the modulation of β1 and β2 adrenergic receptors (ADRB1/ADRB2) by propranolol treatment on the peripheral and splenic immune dysfunction of cirrhotic mice. In vivo experiments were performed in bile duct ligation (BDL)- and thioacetamide (TAA)-cirrhotic mice receiving two weeks of propranolol treatment. Acute effects of propranolol were evaluated in T-helper (Th) cells isolated from spleen of cirrhotic mice. Results: Over-expression of β1 and β2 adrenergic receptors (ADRB1/ADRB2) in spleen and T lymphocytes was associated with high peripheral/splenic lipopolysaccharide binding protein levels. Moreover, a decrease in Th cells percentage, increase in Treg subset, and cytokines were accompanied by increased apoptosis, proliferation, and reduced white pulp hyperplasia in cirrhotic mice, which were counteracted by propranolol treatment. The Thcell depletion, systemic inflammation, BT, and infection were improved by chronic propranolol treatment. Acute propranolol treatment inhibited apoptosis, Tregconditioned differentiation, and promoted Th2-conditioned d i ff e r e n t i a t i o n t h r o u g h A D R B - c y c l i c a d e n o s i n e monophosphate (cAMP) signals in cirrhotic mice. Conclusions: In conclusion, suppression of ADRB1 and ADRB2 expressions in spleen and splenic T lymphocytes by acute and chronic propranolol treatment ameliorate systemic and splenic immune dysfunction in cirrhosis.

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非肥胖性非酒精性脂肪肝疾病的代謝與身體組成 THE METABOLIC PROFILES AND BODY COMPOSITION OF LEAN NONALCOHOLIC FATTY LIVER DISEASE 1

1,2

鄭泓志鄭煜明王嘉齊陳建華 1 台北慈濟醫院胃腸肝膽科 2 慈濟大學醫學系

Background: Non-alcoholic fatty liver disease (NAFLD) is the commonest cause of chronic liver disease which is associated with obesity and diabetes. However, NAFLD has been reported in lean patients especially in Asian population. The pathogenesis and metabolism of lean NAFLD are puzzling and poorly understood. Little is known about the body composition in lean individuals with NAFLD. Aims: To investigate the metabolic profile and body composition in lean individuals with NAFLD compared with obese NAFLD patients and lean healthy controls. Methods: The participants of Tzu Chi NAFLD cohort (TCNC) including health controls or NAFLD patients were enrolled. NAFLD was defined as fatty liver in imaging without hepatitis B virus, hepatitis C virus infection, drug, alcohol or other known causes of chronic liver disease. Lean NAFLD was defined as NAFLD in lean subjects (BMI < 23 kg/m2). Results: A total of 880 subjects were included for final analysis. Of 394 NAFLD patients, 65 (16.5%) patients were diagnosed as lean NAFLD. Lean NAFLD patients were elder, higher percentage of female gender, lower ALT, diastolic blood pressure, triglyceride, and waist circumference but higher HDL than non-lean NAFLD patients. Using binary regression analysis, elder age and lower waist circumference were associated with leanNAFLD. Compared with lean healthy controls, lean NAFLD patients had higher BMI, waist circumference and percentage of HT. In body composition, fatty tissue index (FTI), lean tissue index (LTI) and total body water (TBW) were lower in lean-NAFLD than non-lean NAFLD patients; but they were comparable with lean healthy controls. Conclusions: In conclusion, the prevalence of lean NAFLD was 16.5% in this study population and it was higher in elder age especially of female subjects. Lean NAFLD patients had different metabolic profiles compared with lean healthy controls, but different body composition compared with non-lean NAFLD patients.

2021 消化系聯合學術演講年會

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M2BPGi 用來評估非酒精性脂肪肝病造成的肝纖維化的可用性 UTILITY OF M2BPGI FOR ASSESSING LIVER FIBROSIS OF NON-ALCOHOLIC FATTY LIVER DISEASE 1

1,2

劉家宏鄭煜明王嘉齊陳建華 1 台北慈濟醫院胃腸肝膽科 2 慈濟大學醫學系

Background: The serum level of Mac-2 binding protein glycosylation isomer (M2BPGi) has been found to increase with the severity of liver fibrosis in patients with chronic hepatitis B virus (HBV) or hepatitis C virus (HCV) infection. However, the diagnostic performance of liver fibrosis in NAFLD patients remains unclear. Aims: To realize the picture of serum M2BPGi levels in healthy controls and the difference between healthy controls and NAFLD patients. Methods: The participants of Tzu Chi NAFLD cohort (TCNC) including health controls or NAFLD patients were enrolled in Taipei Tzu Chi Hospital. NAFLD was defined as fatty liver in imaging or histology without HBV, HCV, drug, alcohol or other known causes of chronic liver disease. Acoustic radiation force impulse (ARFI) was used as standard reference for the severity of liver fibrosis. Results: A total of 777 subjects were included for final analysis. The serum M2BPG1 levels correlated with APRI and FIB-4 score, respectively (p=0.000). Of them, 376 (48.4%) were NAFLD patients and 401 were healthy controls. In the group of health controls or NAFLD patients, the M2BPGi levels were significantly higher in female subjects than those of male subjects (p=0.027). Categorized by age, the levels of M2BPGi were significantly higher in elder age groups either in healthy controls or NAFLD patients. Compared with healthy controls, NAFLD patients had significantly higher levels of BMI, waist circumference, metabolic components and liver fibrosis markers such as APRI, and M2BPGi, but no difference in FIB-4 score. According to FIB-4 score, intermediate risk group had higher APRI and M2BPGi than low risk group. Conclusions: The serum M2BPGi levels correlated with two non-invasive biomarkers of liver fibrosis including APRI and FIB-4 score. They were significantly higher in female or elder population. Furthermore, M2BPGi levels were different either between NAFLD patients and healthy controls or between low risk and intermediate risk of NAFLD patients, suggesting a good marker for assessing liver fibrosis of NAFLD patients.

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台灣非酒精性脂肪肝病的臨床及病理表現：多中心研究 CLINICOPATHOLOGICAL FEATURES OF NONALCOHOLIC FATTY LIVER DISEASE IN TAIWAN: A LARGE MULTICENTER COHORT STUDY 1

林志陵戴啟明鄭斌男陳啟益彭成元王嘉齊 7,8 7,8 劉俊人高嘉宏 1 臺北市立聯合醫院仁愛院區消化內科 2 義大醫院內科部胃腸肝膽科 3 國立成功大學醫學院附設醫院內科部 4 嘉義基督教醫院內科部胃腸肝膽科 5 中國醫藥大學附設醫院內科部消化系中心 6 台北慈濟醫院內科部 7 國立臺灣大學醫學院附設醫院肝炎研究中心 8 國立臺灣大學醫學院設醫院內科部

Background: Non-alcoholic fatty liver disease (NAFLD) is gradually becoming one of the most prevalent chronic liver diseases in Taiwan. Currently, liver biopsy remains the gold standard for the diagnosis and assessment of NAFLD severity. Histological scoring systems are widely used for the management of NAFLD. Aims: The aim of this study was to evaluate the correlation between histological features and clinical manifestations of NAFLD in Taiwan. Methods: Patients with clinically diagnosed NAFLD who received liver biopsy were retrospectively enrolled. Histopathological evaluation was based on the Nonalcoholic Steatohepatitis Clinical Research Network (NAS-CRN) scoring system and the correlation with clinical manifestations were assessed. The clinical features included anthropometric parameters, clinical and biochemical characteristics as well as non-invasive fibrosis assessment. Statistical analyses were performed by chisquare test, Fisher’s exact test, ANOVA test, Student’s t test. Results: A total of 456 patients with clinical diagnosis of NAFLD were recruited. NAFLD was excluded in 53 (11.6%) patients, because their hepatic steatosis on liver histology was less than 5%. NAS-CRN scoring system was evaluated in 403 patients with NAFLD. According to the scoring category, NAS < 3 (non-NASH) were found in 88 (21.8%), NAS 3–4 (borderline NASH) in 179 (44.4%), and NAS ≥ 5 (definite NASH) in 136 (33.7%). Compared with the patients with non-NASH and borderline NASH, the definite NASH patients had significantly higher serum

2021 消化系聯合學術演講年會

levels of glucose (p = 0.016), AST (p < 0.0001), ALT (p < 0.0001), rGT (p = 0.026), prothrombin time (p < 0.0001). Patients with definite HASH had a higher proportion of significant fibrosis (F2-F4) than borderline and nonNASH patients [75/136 (55.1%) vs. 70/179 (39.1%) vs. 16/88 (18.2%), p < 0.0001). Regarding the non-invasive assessment for liver fibrosis, patients with definite NASH had significantly higher NAFLD fibrosis score (-1.04 ± 1.95 vs. -1.62 ± 1.64, p = 0.049), FIB-4 (1.86 ± 2.32 vs. 1.09 ± 0.99, p = 0.003) and APRI (0.94 ± 1.08 vs. 0.39 ± 0.37, p < 0.0001), than those with non-NASH. Conclusions: In this large multi-center cohort study, the prevalence of NASH among patients with NAFLD in Taiwan was 33.7%. The severity of liver fibrosis was significantly associated with the presence of NASH. In addition, NASH patients had significantly higher scores of non-invasive fibrosis assessment than non-NASH patients, including NAFLD fibrosis score, FIB-4, and APRI. Therefore, non-invasive fibrosis assessment can be clinically useful for liver fibrosis progression in NAFLD patients.

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腸道菌叢和 PNPLA3 基因多型性對瘦型和肥胖型非酒精性脂肪肝的影響 EFFECT OF GUT MICROBIOTA AND PNPLA3 POLYMORPHISMS ON LEAN AND OBESE NONALCOHOLIC FATTY LIVER DISEASE 1

1,2

蔡雨潔黃寳源陳建宏姚志謙蔡成枝蔡明釗 1 高雄長庚紀念醫院肝膽腸胃科 2 長庚大學醫學院臨床醫學研究所

Background: Nonalcoholic fatty liver disease (NAFLD) is commonly associated with obesity but also found in nonobese individuals. The PNPLA3 variant (rs738409) is by far the most important genetic determinant of NAFLD. To date, there is no study exploring the differences and associations between the gut microbiota and PNPLA3 on the lean and obese NAFLD patients. Aims: To evaluate the association between gut microbiota and lean and obese NAFLD, while considering the role of PNPLA3 variants. Methods: This is a prospective study at Kaohsiung Chung Gung memorial hospital, Taiwan, from December 2019 and November 2020. We recruited 35 lean NAFLD patients, 70 obese NAFLD patients, and 35 healthy individuals. Fecal samples were collected to analyze the V4 region of the 16S rRNA gene for intestinal bacteria composition. Results: The indices of alpha-diversity were not significant different among three groups. The partial least squares discriminant analysis (PLS-DA) showed that there was a significant separation between obese NAFLD and lean NAFLD or health individuals. Subjects with obese NAFLD showed a lower Firmicutes to Bacteroidetes (F/ B) ratio compared with lean NAFLD (p = 0.038). One phylum, 26 genera and 11 bacterial species resulted differentially abundant among health group and NAFLD groups. Although the frequencies of PNPLA3 GG + GC were significant different in health individuals, lean and obese NAFLD, respectively (54.3%, 82.9%, and 72.9%, p = 0.027), no significant alterations in diversity between groups stratified by PNPLA3 G and C alleles. Conclusions: Lean and obese NAFLD patients have a different gut microbiota composition compared with health individuals, which was not associated with PNPLA3 polymorphisms.

2021 消化系聯合學術演講年會

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酒精代謝基因 ALDH2 突變加劇高脂肪飲食誘導的代謝症候群，並影響腸道菌群的組成和多樣性 ALCOHOL METABOLIC GENE ALDH2 MUTATION EXACERBATED HFDINDUCED METABOLIC SYNDROME AND AFFECTED GUT MICROBIOTA COMPOSITION AND DIVERSITY 1

胡瑞庭莊曉莉陳信宜楊賢馨 1 國泰綜合醫院肝臟中心 2 國家動物中心

to WT-M. There were no significant differences between WT-F and WT-M. Conclusions: The ALDH2 mutation exacerbated HFDinduced metabolic syndrome and affected gut microbiota composition and diversity in the male WT and ALDH2 mice. Mutation of alcohol metabolic gene ALDH2 may induce NAFLD and metabolic syndrome without alcohol consumption. The clinical role of ALDH2*2 mutation is important on the pathogenesis of nonalcoholic fatty liver disease and needs further studies.

Background: Our earlier study proved that ALDH2*2 mutation may exacerbate HFD-induced NAFLD and metabolic syndrome in male WT and ALDH2 mice. Mutation of the alcohol metabolic gene ALDH2 may induce NAFLD and metabolic syndrome in the absence of alcohol consumption. The clinical role of ALDH2*2 mutation on gut microbial communities needs further studies. Aims: Ｗe studied the role of ALDH2*2 mutation on gut microbial communities and the pathogenesis of NAFLD. Methods: We evaluated the roles of ALDH2 on the high fat diet-induced non-alcoholic fatty liver disease by animal model. The 4-5weeks male and female wild-type C57BL/6J and ALDH2 knock-in mice (WT-M, ALDH2-M, WT-F, and ALDH2-F) were fed a high-fat diet for 16 weeks (n=6-8, respectively). Results: Hepatic gene expression of IRS2, GLUT4, PGC1alfa were significantly decreased in the ALDH2-M group compared with the WT-M group. PICRUSt was applied to predictive functional and taxonomic profiling of gut microbial communities that showed insulin signal pathway in the ALDH2-M group was higher than WT-M group. The Heatmap showed altered abundance and bacterial classification of 100 OTUs after high-fat diets in WT and ALDH2 mice based on redundancy analysis. ALDH2-M exhibited higher abundances of Deferribacteres phylum and decreased Actinobacteria phylum compared to WTM. ALDH2-M had markedly increased insulin signal pathway and decreased butanoate metabolism, cysteine and methionine metabolism, seleno-compound metabolism, RIG-I-like receptor signaling pathway, RNA polymerase, Staphylococcus aureus infection, and bacterial invasion of epithelial cells compared to WT-M. Moreover, ALDH2-F markedly increased the RIG-I-like receptor signaling pathway, inorganic ion transport, and metabolism compared

2021 消化系聯合學術演講年會

主題：上消化道疾病（一）

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從 2015 到 2020 年第一次做胃鏡病人合併幽門螺旋桿菌感染的陽性率及接三合療法成功根除率的變化 WHAT IS NEW IN PATIENTS WITH POSITIVE NAÏVE HP INFECTION AND FIRST EGD FROM 2015 TO 2020? 陳啟益陳柏岳周莒光蔡崇榮許銘澤陳盛煊嘉義基督教醫院胃腸肝膽科 Background: It had been known to find and treat HP infection for decades. The incidence and prevalence rate decreased due to the high successful eradication rate. The rate of peptic ulcers and complications of ulcer disease were also decreased significantly. In 2020, we can only find the true real-world HP status in patients with first endoscopy. The true eradication rate of H. pylori infection can be evaluated in first HP-positive patients. Aims: To collect the positive HP infection rate in naive EGD patients and to evaluate the successful eradication rate of standard triple therapy. Methods: We collected the patients who first came to our endoscopy unit with first endoscopic examination. Those who had positive HP infection according to both positive CLO test and histologic examination were treated with standard triple therapy for 14 days. After triple therapy, there were 8 weeks of PPI for peptic ulcer disease and 8 weeks of H2 blocker for non-ulcer disease. UBT was done 4 weeks later. The eradication rate of HP was depended on UBT data. Results: There were 11427 patients who received EGD from Jan-Sep 2015 and 1327 patients from Sep to Dec 2020. There were only 9% (1046 patients) in 2015 and 18% (242 patients) received naive endoscopy in 2020. The positive HP infection was revealed in 287 patients (27%) in 2015 and 27/242 (11.1%) in 2020. There was no DU found in these 27 HP positive patients. Standard triple therapy for HP infection was done in HP-positive patients. In 2015, the HP positive rate was 41% (33/80).The eradication rate was 85% in 2015 and 88% in 2020 with negative UBT. The HP infection rate was declined from 27% in 2015 to 11.1% in 2020. However, the HP eradication rate increased from 85% in 2015 to 88% in 2020. Conclusions: In 2020, the naïve EGD rate was 18% in all daily EGD. The HP positive rate was 11% in naïve endoscopy. The succeful eradication rate of standard triple therapy was as high as 88% in these naïve endoscopy with positive HP infection. The association between DU and HP was unexpected low in 2020.

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比較第一線不含 Bismuth 的 7 天期幽門桿菌四合一療法，由 Esomeprazole 或 Lansoprazole 當基底對於幽門桿菌清除率的影響 COMPARISON OF ERADICATION RATES FOR ESOMEPRAZOLE AND LANSOPRAZOLE- BASED SEVENDAY NON-BISMUTH CONCOMITANT QUADRUPLE THERAPY FOR FIRSTLINE ANTI-HELICOBACTER PYLORI TREATMENT 洪國棟梁志明蔡成枝戴維震吳耿良高雄長庚紀念醫院胃腸肝膽科系 Background: Seven-day non-bismuth concomitant quadruple therapy is commomly administrated for physicans, thus which is sufficient in achieving a grade A report card for first-line anti-Helicobacter pylori. There were rare studies to comparing eradication rates between different proton pump inhibitos in concomitant quadruple therapy. The current study focused on the comparison of eradication rates and adverse effects for esomeprazole and lansoprazole- based seven-day non-bismuth concomitant quadruple therapy for first-line anti-Helicobacter pylori treatment Aims: To comparing eradication rates between different proton pump inhibitos (Esomeprazole and Lansoprazole) in concomitant quadruple therapy. Methods: We retrospectively enrolled a total of 206 H. pylori-infected naïve patients. They were prescribed with either a 7-day non-bismuth containing quadruple therapy group (EACM group, esomeprazole 40 mg twice daily, amoxicillin 1 g twice daily, metronidazole 500 mg twice daily, and clarythromycin 500 mg twice daily for 7 days; LACM group, lansoprazole 40 mg twice daily, amoxicillin 1 g twice daily, metronidazole 500 mg twice daily, and clarythromycin 500 mg twice daily) from 2016-07 to 201902. 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. Follow-up studies to assess treatment responses were carried out 8 weeks later. Results: There were 6 cases and 3 cases lost follow-up in group EACM and group LACM, respectively. The baseline

2021 消化系聯合學術演講年會

characteristics were similar between two groups in age, sex, socal habits, and endoscopic findings. The eradication rates for EACM group (n = 105) and LACM group (n = 101) were 86.7% (95% confidence interval [CI] = 78.7% to 92.5%) and 90.1% (95% CI = 82.6% to 95.2%) (p = 0.443) in intention-to-treat (ITT) analysis; 91.9% group (n = 99) (95% CI = 84.7% to 96.4%) and 92.9% group (n = 98) (95% CI = 85.9% to 97.1%) (p = 0.804) in per protocol (PP) analysis. Importantly, univariate analysis showed that 7-day concomitant therapy, metronidazole resistance (p = 0.044) were the clinical factors influencing the failure of H. pylori eradication. The adverse events were also similar between two groups (11.1% versus 10.2%, p = 0.837). However, more diarrhea symptome was observred in LACM group thans EACM group (7.1% versus 1.0%, p = 0.029) Conclusions: The eradication rates and adverse effects between esomeprazole and lansoprazole- based nonbismuth containing quadruple therapy as first-line H. pylori treatment were similar in this study.

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北台灣與南台灣幽門螺旋桿菌抗藥性之比較與影響抗藥性產生之臨床因子的探討 ANTIBIOTIC RESISTANCES OF H. PYLORI IN THE NORTHERN AND SOUTHERN REGIONS OF TAIWAN AND THE CLINICAL FACTORS PREDICTING ANTIBIOTIC RESISTANCE OF H. PYLORI 1,10

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4,10

5,10

蔡峯偉吳登強楊智欽蔡成枝陳冠仰 6,10 7,10 8,10 2,10 5,10 劉玉華李嘉龍葉宏仁郭昭宏李熹昌 9,10 9,10 施長碧許秉毅 1 高雄榮民總醫院內科部胃腸肝膽科 2 高雄醫學大學附設醫院內科部胃腸內科 3 台大醫院內科部胃腸肝膽科 4 高雄長庚紀念醫院內科部胃腸肝膽科 5 臺北市立聯合醫院仁愛院區內科部消化內科 6 新光吳火獅紀念醫院內科部胃腸肝膽科 7 國泰綜合醫院內科部腸胃內科 8 臺中榮民總醫院內科部胃腸肝膽科 9 臺南市立安南醫院內科部消化內科 10 台灣胃酸相關疾病與腸道微菌叢研究聯盟 Background: While the global prevalence of antibioticresistant Helicobacter pylori (H. pylori) is increasing, there is much regional variation, and local data are required to guide eradication therapy. Aims: (1) to compare the patterns of the primary antibiotic resistance of H. pylori in the northern and southern regions of Taiwan, and (2) to investigate the clinical factors predicting resistant strains of H. pylori. Methods: From August 2018 to October 2020, a total of 585 H. pylori strains isolates from H. pylori-infected patients living in the northern and southern regions of Taiwan, who didn’t receive eradication therapy before. The H. pylori strains were tested for the susceptibility to amoxicillin, clarithromycin, metronidazole, tetracycline and levofloxacin using the Epsilometer test method. We compared the frequencies of antibiotic resistance between the strains isolated from the northern and southern regions of Taiwan. Additionally, the clinical factors related to the frequency of antibiotic resistance of H. pylori were analyzed by multivariate analysis. Results: The frequencies of resistance to amoxicillin, clarithromycin, metronidazole, tetracycline and levofloxacin of H. pylori stains isolated from patients in the northern Taiwan (n = 200) were 1.0%, 19.0%, 33.0%, 0% and 28.5%, respectively. The corresponding frequencies

2021 消化系聯合學術演講年會

of antibiotic resistance of H. pylori stains isolated from patients in the southern Taiwan (n = 384) were 0.8%, 17.4%, 33.3%, 0.8% and 30.5%, respectively. There were no differences in the frequencies of antibiotic resistance between groups. Multivariate analysis revealed that female gender and presence of underlying disease were the two independent factors predicting clarithromycin resistance with an odds ratio of 1.86 (95% confidence interval [CI]: 1.19 – 2.91) and 1.82 (95% CI: 1.18 – 2.82), respectively. The only independent risk factor predicting metronidazole resistance was female gender (odds ratio of 3.02; 95% CI: 2.1 – 4.4). Conclusions: The H. pylori-infected patients living in the northern and southern regions of Taiwan have similar antibiotic resistance rates of H. pylori. Both clinical isolates from the patients in the two regions have high frequencies of antibiotic resistance to clarithromycin, metronidazole and levofloxacin. Female gender is an independent risk factor predicting both clarithromycin and metronidazole resistances of H. pylori.

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高劑量雙重藥物在幽門桿菌感染的第一線治療 RABEPRAZOLE-BASED HIGH-DOSE DUAL THERAPY AS THE FIRST-LINE TREATMENT OF PATIENTS WITH HELICOBACTER PYLORI INFECTION 陳世源李嘉龍洪志聖吳啟華賴永智江技坤黃鼎鈞陳信佑國泰綜合醫院消化內科 Background: Two weeks high dose dual therapy (HDDT) has recently proved to be as effective as triple therapy in the treatment of Helicobacter pylori (HP) infection. Only two such studies in Taiwan are published in the literature. Aims: From December 2018 to December 2020, 246 consecutive patients with treatment-naïve HP infection were treated with rabeprazole 20 mg and amoxicillin 750 mg qid for 2 weeks. Either urea breath test or rapid urease test was used for the confirmation of eradication 4 weeks after completion of the regimen. Methods: From December 2018 to December 2020, 246 consecutive patients with treatment-naïve HP infection were treated with rabeprazole 20 mg and amoxicillin 750 mg qid for 2 weeks. Either urea breath test or rapid urease test was used for the confirmation of eradication 4 weeks after completion of the regimen. Results: There were 136 men and 110 women with a mean age of 53.7 ± 13.5. All the patients had completed the 14days regimen but 18 patients did not come back for follow up HP status. Among those with follow up, 25 patients still had positive results. The per protocol eradication rate was 89.0% (203/228), whereas the intention to treat was 82.5% (203/246). The patients were divided into 3 groups. Those with active or inactive gastric or duodenal ulcers are stratified to group 1, those with any gastritis or duodenitis as group 2 and others as group 3. Subgroup analysis did not reveal any statistically difference in the eradication rate. Only minor adverse events are noted in this study. Conclusions: Our study did not prove the eradication rate as high as that of other published studies in Taiwan. Further multicenter study is warranted.

2021 消化系聯合學術演講年會

㊲

14 天混合療法與 14 天高劑量二合療法在第一線幽門螺旋桿菌除菌治療的單一醫院：初步報告 14 DAYS HYBRID THERAPY VS 14 DAYS HIGH-DOSE DUAL THERAPY FOR FIRST-LINE ERADICATION OF HELICOBACTER PYLORI IN A SINGLE REGIONAL HOSPITAL: A PRELIMINARY REPORT 黃昌弘李熹昌黃庭章林聰蓉林志陵林光洋陳冠仰臺北市立聯合醫院仁愛院區消化內科 Background: H. pylori infection causes chronic gastritis which significantly increasing the peptic ulcers, gastric adenocarcinoma and mucosa-assocoated lymphoid tissue (MALT) lymphoma. Eradication of H. pylori prevents ulcer recurrence and leads to a significant reduction of gastric malignancy. Unfortunately the failure rate of conventional triple therapy is increasing. Both 14 days hybrid therapy and 14 days high dose dual therapy reported from Taiwan can achieve > 95% eradication rate respectively. Fewer studies compared 14 days hybrid therapy with high dose dual therapy. Aims: The purpose of this study was to evaluate the efficacy of 14 days hybrid vs 14 days high-dose dual therapy for first line H. pylori eradication. Methods: From March 2019 to December 2020, we conducted the prospective randomized controlled trial for patients who had not been treated for H. pylori before. Totally 102 patients was enrolled and randomized to receive either 14 days hybrid group (rabeprazole 20 mg and amoxicillin 1 g twice daily for first 7 days, followed by rabeprazole 20 mg, amoxicillin 1 g, clarithromycin 500 mg, metronidazole 500 mg twice daily for another 7 days) and 14 days high-dose dual group (rabeprazole 20 mg and amoxicillin 750 mg four times per day for 14 days) H. pylori infection status was confirmed by any two positive result of these three tests (rapid urease test, pathology and urea breathing test [UBT]) or positive culture result. Eradication efficacy was accessed with UBT at least 4 weeks after completion of treatment. Eradication rates were examined by ITT and PP analysis. Results: Ninety-seven patients (48 patients in 14 days hybrid group and 49 patients in 14 days high dose dual group) completed the study. The compliance rates were 94% and 96% respectively. The eradication rate was 91.7% in hybrid group and 87.8% in high-dose dual group

(P=0.531) by ITT analysis. The eradication rate was 91.7% in hybrid group and 89.6% in high-dose dual group (P=0.730) by PP analysis. Univarite analysis for the clinical and bacterial factors identify that amoxicillin resistance decreased the eradication rate in high-dose dual group (P=0.006). Adverse events were high in hybrid group than high-dose dual group (37.5% vs 18.4%, P=0.03). Hybrid group showed significant higher in “bad taste” than highdose dual group (17 patients vs 1 patient, P<0.0001). Conclusions: In this study, the eradication rates of 14 days hybrid therapy and 14 days high-dose dual therapy were approaching 90%, we thought both therapies could be used as first-line H. pylori eradication regimen. But amoxicillin resistance significantly decreased the eradication rate when using high-dose dual therapy. Adverse events were high when using hybrid therapy but did not interfere compliance rate.

2021 消化系聯合學術演講年會

㊳

以高劑量二合療法作第一線幽門螺旋桿菌治療時預測除菌失敗之宿主與細菌因子 THE HOST AND BACTERIAL FACTORS PREDICTING ERADICATION FAILURE OF HIGH-DOSE DUAL THERAPY IN THE FIRST-LINE TREATMENT OF H. PYLORI INFECTION 1,10

2,10

3,10

4,10

5,10

許秉毅楊智欽蔡成枝陳冠仰劉玉華 6,10 7,10 8,10 9,10 4,10 蔡峯偉李嘉龍葉宏仁郭昭宏李熹昌 8,10 1,10 9,10 許斯淵施長碧吳登強 1 臺南市立安南醫院消化內科 2 國立臺灣大學醫學院附設醫院內科部胃腸科 3 高雄長庚紀念醫院內科部胃腸肝膽科 4 臺北市立聯合醫院仁愛院區內科部胃腸肝膽科 5 新光吳火獅紀念醫院內科部胃腸科 6 高雄榮民總醫院內科部胃腸肝膽科 7 國泰綜合醫院內科部胃腸肝膽科 8 臺中榮民總醫院內科部胃腸肝膽科 9 高雄醫學大學附設醫院內科部胃腸科 10 台灣胃酸相關疾病暨微菌叢聯盟 Background: High-dose dual therapy has recently become one of the hot issues in the treatment of H. pylori infection because the novel therapy is able to achieve a high eradication rate and also can avoid the use of unnecessary antibiotics. However, what are the risk factors affecting eradication outcome of the new eradication therapy remains unclear. Aims: To investigate the host and bacterial factors predicting eradication failure in the first-line treatment of H. pylori infection by of high-dose dual therapy. Methods: From August 2018 to October 2020, 236 H. pylori-infected patients receiving first-line eradication therapy with 14-day high-dose dual therapy (rabeprazole 20 mg and amoxicillin 750 mg q.i.d for 14 days) in a clinical trial were prospectively assessed for drug adherence and adverse effects at the end of week 2. Post-eradication H. pylori status was examined by urea breath test 6 weeks after the end of treatment. To determine the independent factors affecting the treatment response, 16 host and bacterial parameters (including age, gender, smoking, alcohol consumption, type of gastrointestinal disease, CYP2C19 genotype, IL-1B -511 genotype, drug adherence, and antibiotic resistances) were assessed by univariate and multivariate analyses. Results: Intention-to-treat analysis showed that thirty-one out of 236 infected participants failed to eradicate H. pylori

by 14-day high-dose dual therapy. Univariate analysis demonstrated that amoxicillin resistance of H. pylori (P = 0.019) and poor drug adherence (P = 0.017) were the risk factor related to eradication failure. The patients harboring amoxicillin-resistant strains had a lower eradication rate than those harboring sensitive strains (40.0% vs 87.6%). Additionally, patients with poor drug adherence had a lower eradication rate than those with good adherence (40.0% vs 87.9%). Multivariate analysis revealed that only amoxicillin resistance was the independent risk factors predicting eradication failure with an odds ratio of 12.0 (P = 0.008; 95% confidence interval: 1.9 – 76.2). Conclusions: Amoxicillin resistance is an independent risk factor predicating eradication failure in the first-line treatment of H. pylori infection by high-dose dual therapy.

2021 消化系聯合學術演講年會

主題：其他消化道疾病

㊴

內視鏡超音波導引細針抽吸和內視鏡超音波導引細針切片的差異：一個南臺灣內視鏡超音波單位的經驗 DIFFERENCES FROM ENDOSCOPIC ULTRASONOGRAPHY-FINE NEEDLE ASPIRATION (EUS-FNA) TO ENDOSCOPIC ULTRASONOGRAPHYFINE NEEDLE BIOPSY (EUS-FNB): EXPERIENCE IN A SOUTHERN TAIWAN EUS UNIT 施翔耀陳以勳高雄醫學大學附設中和紀念醫院胃腸內科 Background: Endoscopic ultrasonography-guided tissue acquisition (EUS-TA) has been the preferred choice of modality for obtaining the cells/tissue from lesions of pancreas or biliary tract and the sub-epithelial lesions In the gastrointestinal tract. Initially we acquired the specimen by means of fine needle aspiration (FNA). Towards the trend of not only getting cells but also tissue fine needle biopsy (FNB) is on the rise. We compared the differences between the period of FNA and FNB at our unit. Aims: Delineate the differences between EUS-FNA and EUS-FNB and provide some references for the choice of FNA or FNB while considering EUS-guided tissue acquisition. Methods: From June 2011 to December 2020 we performed one hundred and eighty-eight EUS-TA in the Kaohsiung Medical University Hospital. Except for the demographic data we recorded the characters of the lesions, factors about the procedure, result of the acquired specimen and the occurrence of adverse event or not. Before December 2019 most of our EUS-TA was FNA and we shifted to EUS-FNB since then. We divided the patients into two groups: FNA and FNB groups. Results: Among the 188 patients one hundred twenty-seven patients belongs to FNA group and 61 patients FNB group. Average age is 60.2 (60.2 ± 12.1) vs 61.3 (61.3 ± 12.8) years old (FNA vs FNB). About gender male predominance is in FNA group but no in FNB group. Pancreas is the most common location of lesion in both groups, following by stomach. As for the character of the lesions the most common is the solid neoplasm in both groups. We all used the Franseen type needle. About the size of the needles, in the FNA group more 22g-sized needles were used than 19g-sized ones (22g vs 19g 106 vs 21) and in the FNB group all the needles were 22g-sized. As for the application

of negative pressure we used to provide the negative pressure by means of syringe (FNA group) and then we shifted to slow pull mainly (FNB group). About the number of puncture and procedure time 4.4 vs 5.4 times/session and 65 vs 58 minutes (FNA vs FNB group) demonstrated respectively. The cytological results were divided into five subgroups (positive, suspicious, atypia, negative, no specimen) and the histologic results were divided into two subgroups (positive and negative). Our positive rate in cytological specimen was 52% in FNA group and 76% in FNB group and 53% in FNA group and 80% in FNB group regarding histologic specimen. We tried to compare the equality between macroscopic on site evaluation (MOSE) and final microscopic result and the rate of equality was both 85% in two groups. When talking about the adverse events pancreatitis and hemorrhage were the leading postprocedure complications. The incidence was 0.8% vs 6.6% in pancreatitis and 0.8% vs 6.6% in hemorrhage (FNA vs FNB group). Conclusions: In the era of EUS-FNB the 22g-sized needle is sufficient for obtaining adequate tissue. By means of FNB higher positive cytological and histologic results were observed. No less number of puncture and significantly shorter procedure time was demonstrated in our unit. Due to limited sample size more data should be collected for comparison with the literature.

2021 消化系聯合學術演講年會

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神經內分泌腫瘤在一個區域醫院的研究 ─ 特別關注病理分析 A STUDY OF NEUROENDOCRINE TUMOR IN A REGIONAL HOSPITAL ‒ SPECIAL EMPHASIZE ON PATHOLOGICAL ANALYSIS 1

王璞張廷安李熹昌林聰蓉林志陵陳冠仰 1 臺北市立聯合醫院仁愛院區消化內科 2 臺北市立聯合醫院仁愛院區病理科

Background: Neuroendocrine neoplasms (NENs) are neoplasms that arise from cells of the endocrine (hormonal) and nervous systems. They most commonly occur in the digestive tract, but they are also found in the pancreas, lungs, liver and the rest of the body. They usually grow slowly over many years, but some are fast-growing forms. Well differentiated neuroendocrine tumors (NETs) were traditionally referred to as carcinoid tumors in the gastrointestinal tract. Poorly differentiated neuroendocrine carcinomas (NECs) are all high-grade carcinomas that resemble small cell carcinoma or large cell NEC of the lung. Aims: To evaluate the pathological report of neuroendocrine tumors using our pathological database system in recent nine years and compare them with the involved organ and prognosis. Methods: Collecting all the pathological report of biopsy and resection specimens (including polypectomy, EMR, ESD and surgical resection) of neuroendocrine tumors from January. 1, 2011 to April 30, 2020 and analyze the histology, diagnosis, classification and staging based on the 2010 and 2019 World Health Organization (WHO) classification. Results: There were 116 patients, 64 were male and 52 were female. The mean age of all patients was 66.2 ± 14.4 years old (mean ± SD). The mean age of male patients was 64.6 ± 15.3 years old (mean ± SD). The mean age of female patients was 68.0 ± 13.2 years old (mean ± SD). Totally, there were 142 tumors. Among them, eighty eight tumors were in GI tract (61.9%), which included fifty eight at rectum (65.9%), eleven at stomach (12.5%), nine at colon (10.2%), four at duodenum (4.5%), three at terminal ileum (3.4%), two at appendix (2.2%), one at esophagus (1.1%). Among digestive systems (88 GI tract, 18 liver and 6 pancreas), there were one hundred and twelve tumors (78.9%). The tumor size was from 0.2 cm to 12.5 cm, mean size was 1.68cm. According to the pathological report,

seventy eight tumors were well differentiated (60.5%), nine tumors were moderately differentiated (6.9%), fourty two tumors were poorly differentiated (32.6%). In the well differentiated tumors, fifty five were G1 grade (94.8%), two were G2 (3.4%) and one was G3 (1.7%). Most of the well differentiated tumors had pT1aNxMb stage and only one was pT3NxMb, according to the American Joint Committee on Cancer (AJCC) staging classification. Conclusions: Most of neuroendocrine tumors arose from digestive system. Among digestive system, the majority tumors were from GI tract. Among GI tract, most of the tumors were from rectum. According to the pathological histology, the majority of rectal tumors showed well differentiated (carcinoid), G1 grade (low grade), Ki67 immunohistochemical stain <3% and pT1aNxMb staging, with relatively good prognosis. Beyond the rectum, the possibility of moderate to poor differentiation were increased, with G2 to G3 grade (moderate to high grade), which revealed relatively poor prognosis. Therefore, carefully searching for any polyp or nodule when doing endoscopy and sending for pathological classification is mandatory to verify the accurate prognosis.

2021 消化系聯合學術演講年會

㊶

牽引輔助內視鏡黏膜下剝離術的療效與安全性 ─ 隨機臨床試驗統合分析 EFFICACY AND SAFETY OF TRACTIONASSISTED ENDOSCOPIC SUBMUCOSAL DISSECTION: A META-REGRESSION OF RANDOMIZED CLINICAL TRIALS 1

蘇怡佳鄭勝偉康以諾張君照 1 臺北醫學大學附設醫院消化內科 2 臺北市立萬芳醫院消化內科 3 臺北醫學大學附設醫院教學部 Background: Endoscopic submucosal dissection (ESD) is widely used to treat gastrointestinal lesions. A tractionassisted (TA) strategy has been recently developed for ESD. Some randomized clinical trials (RCTs) and a metaanalysis on this topic have previously been published, but consensus is yet to be established. Therefore, we wished to update this topic and reveal the source of heterogeneity by subgroup analysis of lesion location and meta-regression using lesion size. Aims: To evaluate the safety and efficacy between tractionassisted ESD and conventional ESD. Methods: We searched PubMed, Embase, Web of Science, and the China National Knowledge Infrastructure to identify randomized clinical trials that compared TA-ESD and C-ESD. No filters for language or date of publication were used. Outcomes included complete resection rate, resected specimen size, procedure time, hemostasis usage (frequency), overall complication rate, perforation rate, and delayed bleeding rate. We used the mean difference (MD) for continuous outcomes in a random-effects model and Peto odds ratio (POR) for binary outcomes where any zero cell existed. Effect sizes and their 95% confidence intervals (CIs) were determined. Results: 12 out of 929 identified articles, including 1499 patients, were analyzed. According to pooled results, TAESD produced similar R0 resections to C-ESD, but its procedure time (minutes) was shorter than that of C-ESD (MD–16.02, 95% CI – 22.71 to – 9.33). Moreover, TA-ESD had a lower complication rate (POR 0.47, 95%CI 0.29 to 0.76) and perforation rate (POR 0.24, 95% CI 0.10 to 0.56) than CESD. A nonsignificant difference in delayed bleeding rate was observed, although there was a trend toward this being lower in TA-ESD than C-ESD (POR 0.90, 95% CI 0.46 to 1.75, I2=12%). Conclusions: The traction-assisted strategy improves safety and efficacy in the treatment of patients with ESD. However, we observed different effect sizes in the esophagus, stomach, and colorectum.

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腸道微菌叢移植在菌叢失衡腸道疾病的效果：統合分析與系統性回顧 EFFICACY OF FECAL MICROBIOTA TRANSPLANTATION IN DYSBIOSIS RELATED GASTROINTESTINAL DISORDERS A SYSTEMATIC REVIEW AND META-ANALYSIS 1

1,2

方冠傑葉欣榮蘇建維唐瑞祥張君照 1 臺北醫學大學附設醫院消化內科 2 枋寮醫院肝膽腸胃內科 3 臺北榮民總醫院胃腸科

Background: Fecal microbiota transplantation (FMT) is the transferal of feces from a healthy donor to a patient with disease associated with disturbances in the gut microbiota. Manipulating gut microbiota is a potential treatment for intestinal dysbiosis related disorder. Aims: This study aimed to elucidate whether fecal microbiota transplantation (FMT) would be alternative treatment in treating associated disease. Methods: We performed a systematic literature search of PubMed, EMBASE, Cochrane Library. Selection criteria included RCTs of FMT in gut dysbiosis related disorders, involving clostridium difficile infection, inflammatory bowel disease, irritable bowel syndrome and constipation. We used Cochrane Collaboration’s Risk of Bias tool to assess bias in the RCTs. We estimated the summary relative risk (RR) with 95% confidence interval (CI) for each outcome using a random effects model. P values of less than 0.05 were considered significant. Results: We included eleven RCTs comprising a total of 709 patients with recurrent CDI. Four studies revealed FMT with a significant trend toward resolution of rCDI compared with FMT and medical treatment (RR = 2.67, 95% CI = 1.13–6.17, p = 0.0003, I2 = 37%). Three of five RCTs comprising a total of 217 patients with IBD. There was a nonsignificant trend toward resolution of UC compared with FMT and conventional therapy (RR = 1.90, 95% CI = 0.94–3.83, p = 0.05, I2 = 66%). Two RCTs comprising a total of 100 patients with IBS. There was a no trend toward resolution of IBS compared with FMT and conventional therapy (RR = 0.80, 95% CI = 0.23–2.80, p = 0.03, I2 = 89%). One RCT comprising 30 patients revealed nonsignificant trend toward resolution of constipation (RR = 2.75, 95% CI = 0.99–7.68, p = 0.05) Most adverse events caused by FMT were mild and self-limited; no severe adverse events happened because of FMT.

2021 消化系聯合學術演講年會

Conclusions: Despite variation in processes, FMT appears to be effective and relatively safe treatment in treating gut dysbiosis related disorders besides recurrent CDI. Furthermore, some studies revealed that FMT is more effective method than traditional medical treatment and should be considered referring to as first-line therapy in the future.However, large scale randomized control trial might be launched to support this point.

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微生物叢對下泌尿道症狀的影響 THE IMPACT OF URINE MICROBIOTA IN PATIENTS WITH LOWER URINARY TRACT SYMPTOMS 1

2,3,4

3,4

沈群勝李香瑩阮雍順李經家吳文正 4,5 吳登強 1 高雄巿立小港醫院內科 2 高雄市立大同醫院泌尿科 3 高雄醫學大學附設中和紀念醫院泌尿部 4 高雄醫學大學醫學系 5 高雄醫學大學附設中和紀念醫院胃腸內科

3,4

Background: Inflammation and infection are causative factors of benign prostatic hyperplasia (BPH). Urine is not sterile, and urine microbiota identified by DNA sequencing can play an important role in the development of BPH and can influence the severity of lower urinary tract symptoms (LUTS). Aims: The impact of urine microbiota in patients with lower urinary tract symptoms. Methods: We collected mid-stream voided urine samples from BPH patients and control participants and stored them in a freezer at -80°C. All enrolled participants were requested to provide information about their clinical characteristics and complete the International Prostate Symptom Score (IPSS) questionnaire. Each step of the procedure, including the extraction of the genomic DNA from the urine samples; the amplification by polymerase chain reaction (PCR); PCR product quantification, mixing, and purification; DNA library preparation; and sequencing was performed with quality control (QC) measures. Alpha diversity was indicative of the species complexity within individual urine samples, and beta diversity analysis was used to evaluate the differences among the samples in terms of species complexity. Pearson’s correlation analysis was performed to calculate the relationship between the clinical characteristics of the participants and the microbiota species in the urine samples. Results: We enrolled 77 BPH patients and 30 control participants who reported no recent antibiotic usage. Old age, high IPSS and poor quality of life were observed in the participants of the BPH group. No significant differences were observed in the alpha diversity of the samples. In the beta diversity analysis, there was a significant difference between the microbiota in the samples of the BPH and control groups according to ANOSIM statistical analysis. On comparing the groups, the ten bacterial genera

2021 消化系聯合學術演講年會

主題：下消化道疾病（一） present in the samples of the BPH group in descending order of abundance were: Sphingomonas, Bacteroides, Lactobacillus, Streptococcus, Alcaligenes, Prevotella, Ruminococcaceae UCG-014, Escherichia_Shigella, Akkermansia, and Parabacteroides. Spearman’s correlation analysis revealed that urine samples showing the presence of the bacterial genera Haemophilus, Staphylococcus, Dolosigranulum, Listeria, Phascolarctobacterium, Enhydrobacter, Bacillus, [Ruminococcus]torques, Faecalibacterium, and Finegoldia correlated with a high IPSS, and severe storage and voiding symptoms (P<0.05). Conclusions: Our current study shows that dysbiosis of urine microbiota may be related to the development of BPH and the severity of LUTS. Further research targeting specific microbes to identify their role in the development of diseases is necessary and might provide novel diagnostic biomarkers and therapeutic options.

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脂肪肝與代謝症候群為糞便潛血陽性年輕族群的大腸腺瘤強力預測因子 POSITIVE FECAL IMMUNOCHEMICAL TEST STRONGLY PREDICTS ADENOMAS IN YOUNGER ADULTS WITH FATTY LIVER AND METABOLIC SYNDROME 1

葉人豪王文倫林志文陳仁傑許家彰李青泰 3 王照元 1 義大醫院胃腸肝膽科 2 義大醫院健診部 3 高雄醫學大學附設中和紀念醫院大腸直腸外科

Background: The incidence of early-onset colorectal cancer is increasing. Aims: This study explored the feasibility of fecal immunochemical test (FIT) and risk factors for predicting colorectal neoplasm in younger adults. Methods: This single-center study included 6457 participants underwent health examination from 2013 to 2016 including index colonoscopy (3307 individuals aged 30–49 years as the younger adult group and 3150 aged ≥50 years as the average-risk group). Primary outcomes were adenoma detection rate (ADR) and advanced ADR (AADR). Findings of younger participants were stratified by the results of FIT and clinical risk factors and were compared with those of the average-risk group. Results: Among participants aged 30–49 years, a positive FIT was associated with significantly higher ADR (28.5% vs. 15.5, P < 0.001) and AADR (14.5% vs. 3.7%, P < 0.001) than a negative FIT. Moreover, a positive FIT was associated with higher AADR in younger participants than in average-risk counterparts (14.5% vs. 9.8%, P = 0.028). Although no single risk factor predicted FIT positivity in younger participants, nonalcoholic fatty liver disease (NAFLD) was independently associated with higher ADR (odds ratio = 2.60, 95% CI = 1.27–5.34, P = 0.001) and metabolic syndrome was independently predictive of higher AADR in younger participants than in average-risk participants (odds ratio = 3.46, 95% CI = 1.66–7.21, P = 0.001). Conclusions: A positive FIT in people aged 30–49 years implies a higher risk of colorectal neoplasm, particularly among patients with NAFLD and metabolic syndrome.

2021 消化系聯合學術演講年會

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臺灣年輕及中老年成人之大直腸癌發生率及期別趨勢之差別分析 DIFFERENCES OF COLORECTAL CANCER INCIDENCE TREND AND STAGE DISTRIBUTION BETWEEN YOUNGER AND OLDER-AGED ADULTS IN TAIWAN 1,2

1,2

林裕民張鴻俊張麗文劉玉華孫灼基楊國卿 1 新光吳火獅紀念醫院胃腸肝膽科 2 輔仁大學醫學系

Background: Recent studies reported rising incidence of colorectal cancer (CRC) among young adults in the western countries. Aims: We aim to understand the trend of CRC incidence and stage distribution among young adults in Taiwan. Methods: We acquire the data from cancer registration system in Taiwan from year 2010 to 2018. We analyze the CRC incidence and stage from two age groups. Younger and older-aged groups are defined as 30-49 and 50-74 years of age respectively. The CRC clinical stage is determined according to AJCC 7th edition. The difference of incidence trend and stage distribution are evaluated by linear regression analysis and chi-square analysis. A p<0.05 is considered as significant. Results: A total of 16,921 and 89,825 are identified as younger and older-aged CRCs respectively in the study period from cancer registry database. CRC crude incidence rises from 20.9 to 25.7 per 100,000 among the youngeraged group (p for trend: p=0.001). CRC crude incidence declines from 149.3 to 129.8 per 100,000 among the olderaged groups (p for trend: p=0.003). Stage 0+I+II, stage III+IV and unclear stage of younger-aged CRCs are 33.6%, 48.8% and 17.6% respectively. Stage 0+I+II, stage III+IV and unclear stage of older-aged CRCs are 42.5%, 39.9% and 17.6% respectively. The stage distributions of younger and older-aged CRCs reveal significant difference, p<0.001. Conclusions: Our results indicate that younger adults with CRC present with increasing Incidence trend and more advanced stage. These findings suggest that novel strategies may begin at an earlier age for the prevention of CRC.

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臨床利用人工智慧於大腸鏡檢時區分腫瘤性或非腫瘤性息肉 CLINICAL APPLICATION OF ARTIFICIAL INTELLIGENCE TO DIFFERENTIATE NEOPLASTIC OR NON-NEOPLASTIC POLYP DURING COLONOSOCPY EXAMINATION 陳信佑洪志聖李嘉龍國泰綜合醫院消化內科 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 adenomatous polyps from hyperplastic polyps during colonoscopic examination. Methods: We collected 15445 frames of colon images (5524 subjects from pathology comfirned hyperplastic polyps and 15445 subjects from pathology comfirmed adenomatous polyps) in Cathay General HospitalTaipei from January 1st -2016 to April 30th -2020. All these images were sent to AI training model (YOLOv4, CSPDarknet53, set up by Hong-Yuan Mark Liao and Chien-Yao Wang). We trained computer how to differentiate adenomatous polyps from hyperplastic polyps. After trained computer AI, real time image of colon polyps was used for accuracy testing. Results: Total 1151 real time image of colon polyps was used for accuracy testing. The AI recognized 107 lesions correctly from 219 pathology comfirmed hyperplastic polyps (48.9%). Besides, the AI recognized 829 lesions correctly from 932 pathology comfirmed adenomatous polyps (88.9%). Significant low accuracy rate was noticed during recognizing hyperplastic polyps. Conclusions: Deep neurological network training is a potential new technology to help endoscopists to mark and find colon polyps during colonoscopic examination. It can also be used to assist doctors to differentiate neoplastic polyps from non-neoplastic polyps. This can help doctor to decide the way of treatment during colonoscopy examination. The low accuracy rate during recognizing hyperplastic polyps may due to relative fewer training

2021 消化系聯合學術演講年會

data in hyperplastic polyps group. However, the accuracy rate was relative well in adenomatous group. Under the well-trained model and deep neurological learning, AI can well help physicians to identify tubular adenoma from hyperplastic colon polyps in the future.

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冷套環息肉切除術在微小或是小型大腸息肉的根除率 RATE OF COMPLETE RESECTION OF DIMINUTIVE AND SMALL COLORECTAL POLYPS USING COLD SNARE POLYPECTOMY 1

朱淯銘李嘉龍洪志聖黃世鴻江技坤黃鼎鈞 1 1 1 陳信佑賴永智涂天健 1 國泰綜合醫院消化內科 2 國泰綜合醫院病理科

Background: Cold snare polypectomy (CSP) is currently the mainstay for removal of diminutive or small colorectal polyps because of its less events of delay post-polypectomy bleeding from thermal injury. However, the complete resection is still the clinical encountered issues. Aims: To access the complete resection rate of diminutive and small colorectal polyps using cold snare polypectomy. Methods: From the beginning to the end of 2020, those with diminutive or small colorectal polyps during colonoscopy removed by CSP were enrolled into this study. Device used specifically for CSP was used (Boston Scientific, CAPTIVATORTM II). All resected specimen were retrieved and margins were evaluated for completeness of removal pathologically. Each confounding factor was explored to evaluate its influence on the resection rate. Results: There were 431 patients with a mean age of 62.8 and 160 female. A total of 571 polyps were resected with 238 diminutive and 333 small polyps. Complete resection rate for all, diminutive and small polyps was 76.7%, 75.2% and 77.8% respectively. Incomplete resection did not have statistically difference in polyp size (p=0.817), age (p=0.086) or sex (p=0.716), except location (p=0.03). Besides, individual difference also existed among colonoscopists (p=0.004), especially for those with physicians’ experiences (p=0.013). No major bleeding event was noted in these series. Conclusions: CSP is easy and effective in removal of diminutive to small colorectal polyps no matter the size of the polyp and patient’s age or gender. However, the polyp eradication rate is related to operator’s experience and the location of the polyps. Awareness of the tips of CSP and salvage procedures during colonoscopy should remain in operators’ mind.

2021 消化系聯合學術演講年會

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傳統大腸鏡黏膜切除術與水下黏膜切除術於大型大腸息肉之比較 ─ 一個區域醫院的經驗 CONVENTIONAL ENDOSCOPIC MUCOSAL RESECTION (CEMR) VS UNDERWATER ENDOSCOPIC MUCOSAL RESECTION (UEMR) IN TREATMENT OF LARGE COLORECTAL POLYPS ‒ A REGIONAL HOSPITAL EXPERIENCE 區士方楊昇勳林廷嘉台南市立醫院肝膽腸胃內科 Background: Underwater endoscopic mucosal resection was first reported in 2012 and then became a popular procedure for management of colorectal polyps. Some studies have shown better outcomes compared to conventional endoscopic mucosal resection. Aims: In our hospital, we started to use underwater endoscopic mucosectomy since 2016/09. We would like to compare the outcomes of UEMR vs CEMR for large colorectal polyps. Methods: We identified all patients with large colorectal polyps (> 2 cm) treated using the UEMR technique at Tainan Municipal Hospital between October 1, 2016 and September 30, 2020 with follow-up through December of 2020. We compared the size of resection, en-bloc resection rate, location and morphology of colorectal polyps. Results: 52 patients (mean age: 65.2 ± 10.8 years; 61.5% males) with polyps removed using the UEMR technique (Group 1) were matched with 36 patients (mean age: 62.5 ± 13 years; 55.5% males) who had polyps removed using CEMR (Group 2). We resected larger polyps at UEMR group (2.76 cm vs 2.45 cm, P value < 0.05). En-bloc resection rate was slightly better in UEMR group (40% vs 33%), especially in larger size 3 cm-4 cm (39% vs 20%) with similar rate of application of hemoclip (80% vs 75%). Two had recurrence at UEMR group. Conclusions: UEMR is a good alternative procedure for CEMR and en-bloc resection rate seems better in larger size (> 3cm) of colorectal polyps

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體外震波對糖尿病鼠肛門括約肌的作用 THE EFFECT OF EXTRACORPOREAL SHOCK WAVE THERAPY ON ANAL SPHINCTER IN A DIABETIC RAT MODEL 1,2

吳耿良楊世正黃寳源梁志明蘇輝明蔡成枝 1 高雄長庚紀念醫院胃腸肝膽科系 2 長庚大學醫學系

1,2

Background: Fecal incontinence is a highly prevalent nonfatal illness associated with considerable embarrassment, anxiety and poor quality of life, occurs in up to 20% of patients with chronic diabetes. The effect of shock wave on anorectal motility is never studied. We concern whether shock wave could treat fecal incontinence in diabetic patients by regenerate peripheral myenteric plexus or induce muscular hypertrophy. Aims: We investigate the mechanisms of shock wave on anorectal motility in a diabetic rat model to demonstrate whether shock wave activates peripheral myenteric plexus or muscular regeneration. Methods: twenty-four male Wistar rats were studied and separated three groups in randomized order. First group (eight rats) was controls. Secondary and third were diabetic rats, the secondary group (eight rats) received shock wave and third received sham procedure. Anorectal pressure was recorded by anorectal manometry. Blood was taken for measurement of intestinal motility peptides and inflammation markers. Subjects was sacrificed for immunhistochemical stains (nerve density, muscle mass) of anorectum. Results: Diabetic rats have less anorectal pressure than controls (P < 0.001). After 6 weeks of shock wave, we noted an increasing anorectal pressure in diabetic rats than those received sham procedure (P < 0.05). There was less ghrelin level in diabetic rats after 6 weeks shock wave than sham procedure. Comparing with the diabetic groups after sham procedure, the PGP9.5 immuno-positive area increased in shock wave group (22 ± 4 : 5 ± 1, P = 0.01). There was not significant difference in mass trichrome stain area between shock wave and sham procedure. Conclusions: Low-energy shock wave could increase anorectal pressure and increase myenteric plexus but be not related with muscular hypertrophy in diabetic rats with fecal incontinence.

2021 消化系聯合學術演講年會

主題：膽胰疾病

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預防內視鏡逆行性膽胰管攝影後胰臟炎：隨機對照試驗統合分析之系統性文獻回顧 EFFICACY OF GABEXATE MESILATE IN PREVENTING POST ENDOSCOPIC RETROGRADE CHOLANGIOPANCREATOGRAPHY PANCREATITIS: A META-ANALYSIS OF RANDOMIZED CLINICAL TRIALS 1

張雋威康以諾張君照 1 臺北醫學大學附設醫院消化內科 2 臺北醫學大學教學部 Background: Endoscopic retrograde cholangiopancreatography (ERCP) is an endoscopic intervention technique used for both diagnoses and treatment of biliary and pancreatic disorders. The most common adverse event is post ERCP pancreatitis (PEP), despite improvements in the skills and experience of medical practitioners. The evidence provided by syntheses of the preventative effects of gabexate mesilate against pancreatitis among patients undergoing ERCP is limited and highly heterogeneous. In response to the controversial results, and limited evidence, it is necessary to update this topic by gathering all relevant RCTs that compared the preventative effects of gabexate mesilate and placebo in patients undergoing ERCP. Aims: This study aimed to provide overview of gabexate mesilate on preventing PEP by synthesizing all relevant randomized controlled trials (RCTs). Methods: We searched three databases for relevant RCTs. Two authors independently extracted data of pancreatitis incidence after ERCP, abdominal pain within 48 hours, and hyperamylasemia for quality assessment and meta-analysis. Results: Thirteen RCTs with 3718 patients undergoing ERCP met the eligibility criteria and were included. The results revealed that the use of gabexate mesilate led to lower PEP (Peto odds ratio: 0.66, 95% confidence interval [CI]: 0.49 to 0.89), especially in the subgroup of gabexate mesilate infusion starting more than 30 min (Risk ratio: 0.45, 95% CI: 0.29 to 0.72). Conclusions: The present synthesis found that gabexate mesilate could be an option of prophylactic treatment of pancreatitis for patients undergoing ERCP, and reveals that it is favorable to administer it starting 30 min before the ERCP. This evidence may improve the clinical prevention of PEP.

內視鏡逆行性膽胰管鏡術後輕度及中重度胰臟炎之比較：台灣南部一家醫學中心之經驗 COMPARISON OF MILD AND MODERATE TO SEVERE POST-ERCP PANCREATITIS: EXPERIENCE OF A MEDICAL CENTER IN SOUTHERN TAIWAN 1

余冠璋李沅融李昀達孫煒智 1,2 1,2 蔡騌圳陳文誌 1 高雄榮民總醫院內科部胃腸肝膽科 2 國立陽明大學醫學系 Background: Post-ERCP pancreatitis (PEP) is the most common complication following ERCP. A variety of patient-related and procedure-related risk factors have been identified. Some protective factors have also been advocated, such as rectal NSAIDs, pancreatic stenting, and lactate ringer hydration. There are no reports regarding the difference of these well-known risk and protective factors or other clinical results between mild and moderate to severe PEP. Aims: To compare mild and moderate to severe PEP and investigate the possible factors associated with the severity of PEP. Methods: From January 2010 to December 2020, excluding patients with chronic pancreatitis or altered anatomy, there were 2327 patients who underwent the first therapeutic ERCP at our hospital. A total of 146 (6.3%) patients who developed PEP were included in the final analysis of the study, including 105 (4.5%) mild degree, 28 (1.2%) moderate degree, and 13 (0.6%) severe degree. The comparison was made between mild (group A) and moderate to severe PEP (group B) regarding baseline characteristics, endoscopic findings, details of intervention, risk factors for PEP, and protective factors for PEP. Results: Two groups were similar with regard to baseline characteristics, endoscopic findings, details of intervention, patient-related risk factors for PEP, and protective factors for PEP. Except that there were more patients with total cannulation time > 10 minutes in group B than group A (63.4% versus 36.2%, p = 0.005), no significant differences were observed for the other procedure-related factors. There were more concomitant minor post-ERCP complications in group B than group A (26.8% versus 4.8%, p = 0.003). In multivariate logistic regression analysis, total cannulation time > 10 minutes (OR: 4.05; 95% CI, 1.56-10.49; p = 0.004) and concomitant minor post-ERCP complications

2021 消化系聯合學術演講年會

52 (OR: 9.47; 95% CI, 2.44-36.73; p = 0.001) were associated with moderate to severe PEP. Conclusions: Patients with moderate to severe PEP were more encountered with total cannulation time > 10 minutes and concomitant minor post-ERCP complications, which might be the possible predictive factors.

探討 ─ 在使用經內視鏡膽道金屬支架置放於惡性膽管狹窄之前，先置放經內視鏡過十二指腸乳突膽囊支架能否降低急性膽囊炎的發生率？ DOES “ENDOSCOPIC TRANSPAPILLARY GALLBLADDER STENTING (ETGBS)” BEFORE ENDOSCOPIC BILIARY STENTING (EBS) WITH METAL STENT IN MALIGNANT BILIARY STRICTURE DECREASE INCIDENCE OF ACUTE CHOLECYSTITIS? 1,2

李奇郡王堯生吳忠翰黃千睿 1 1 吳瓔蓉陳炯瑜 1 國立成功大學醫學院附設醫院胃腸肝膽科 2 台南新樓醫院內科 Background: Endoscopic biliary stenting with metal stent for malignant biliary stricture is now the first recommended endoscopic intervention for treatment of malignant biliary stricture, like pancreatic cancer or cholangiocarcinoma. However, Acute cholecystitis is one of complicated after endoscopic biliary metal placement due to cystic duct blockage. According to our knowledge and literature review, there was no study about the clinical impact of“endoscopic transpapillary gallbladder stenting (ETGBS)” before metal stent placement in malignant biliary stricture decrease on incidence of acute cholecystitis. Aims: To evaluate if “endoscopic transpapillary gallbladder stenting (ETGBS)” before metal stent placement in malignant biliary stricture decrease incidence of acute cholecystitis. Methods: 106 patients from Feb 2018 to Oct 2020 underwent first time endoscopic biliary metal stenting with or without prior ETGBS in our hospital were retrospectively analyzed. Patient after cholecystectomy, benign biliary stricture, intolerant to procedure were excluded. ETGBS was performed first with 7fr – 12 to 15 cm double pigtail plastic stents after successful endoscopic retrograde cystic duct cholangiogram and deep wire cannulation. After ETGBS, self-expandable metal stent with or without covered membrane was placed alongside the previous gallbladder plastic stent. Both stents were placed across the stricture and papilla. ETGBS was not performed if there was no cystic duct opacified. Patient backgrounds, indications, type of metal stents, technique

2021 消化系聯合學術演講年會

53 success rate, procedure complications were recorded. Results: The mean age of patients were 64.3 ± 13.2 y/ o [38-94 y/o] with 61 men and 45 women (57.5%, 42.5%). Etiology of malignant biliary stricture were cholangiocarcinoma (n=6, 5.7%); pancreatic duct cancer (n=86, 81.1%); bile duct metastatic cancer (n=9, 8.5%); ampulla of Vater cancer (n=4, 3.8%); duodenal cancer (0.9%, n=1). ETGBS was performed for 48 patients, technically successful rate was 39.5% (n=19), otherwise, ETGBD was not performed in 58 patients due to failed to identify cystic duct cholangiogram. Overall complication were acute cholecystitis (10.4%, n=11), cholangitis (9.4%, n=9); metal stent migration (4.7%, n=5); pancreatitis (0.9%, n=1); other sepsis (0.9%, n=1). One patient was within 30 days mortality due to disease. Neither bleeding nor bowel perforation happened. Acute cholecystitis in successful ETGBS, failed ETGBS, and no ETGBS were 5.3% (1/19), 20.7% (6/29), and 6.9% (4/58), p=0.22. Comparing cystic duct contrast opacified without drainage and no cystic duct contrast opacified, incidence of acute cholecystitis is higher (20.7% vs. 6.9%, p=0.07). Conclusions: ETGBS before EBS with metal stent is techinically feasible. Although it is techinically difficult in patient with malignant biliary stricture, possible cystic duct malignant invasion, and difficult accessaries manipulation in narrowing bile duct. While doing metal stent placement, cystic dyct contrast opacified, ETGBS maybe lower the risk of acute cholecystitis after metal stenting. More cases still need to be enrolled in this series in the future.

術前使用抗生素能有效降低活體肝臟移植病患接受內視鏡逆行性膽胰管攝影術後發生膽管炎的風險：一醫學中心之經驗 ANTIBIOTIC ADMINISTRATION BEFORE ENDOSCOPIC RETROGRADE CHOLANGIOPANCREATOGRAPHY IN PATIENTS WITH LIVING DONOR LIVER TRANSPLANTATION CAN EFFECTIVELY REDUCE THE RISK OF ACUTE CHOLANGITIS: A SINGLE MEDICAL CENTER EXPERIENCE 林群凱黃文信彭成元林俊哲林肇堂中國醫藥大學附設醫院消化醫學中心 Background: Current clinical guidelines recommend routine antibiotic prophylaxis before endoscopic retrograde cholangiopancreatography (ERCP) in liver transplant recipients (LTRs). However, a recent study reported the risk of infectious complications after ERCP in LTRs was not affected by administration of prophylactic antibiotics. Aims: Our study aimed to compare the risk of post-ERCP cholangitis between living donor LTRs with and without antibiotic treatment before ERCP, and to investigate the risk factors of post-ERCP cholangitis. Methods: In this retrospective study, all patients with living donor liver transplantation undergoing ERCP were evaluated from January 2007 to October 2020. All living donor liver transplantation and ERCPs were performed at a single medical center. Only the first ERCPs were enrolled in this study, and patients with acute cholangitis before ERCP were excluded. The effect of prevention of post-ERCP cholangitis and bacteremia by antibiotics administration before ERCP was analyzed. Multivariate analyses were performed to identify the risk factors of postERCP cholangitis in living donor LTRs. Results: One hundred and sixty-four living donor LTRs underwent 646 ERCPs between January 2007 and October 2020. Only the first ERCP in 154 patients were enrolled for study. Among them, 8 patients who were diagnosed with acute cholangitis before ERCP were excluded. Antibiotics were administered before ERCP in 54 patients, and not administered in 92 patients. Post-ERCP cholangitis occurred in 5 patients (5/54, 9.3%) and 27 patients (27/92, 29.3%) with and without antibiotics administration, respectively. Post-ERCP bacteremia occurred in 10 patients (10/92, 10.9%) without antibiotics administration. No bacteremia was detected in patients with antibiotic

2021 消化系聯合學術演講年會

54 administration before ERCP. Multivariate analyses revealed old age, without antibiotic use before ERCP, and need for biliary stenting were independent risk factors of post-ERCP cholangitis. Conclusions: Antibiotic administration before ERCP in patients with living donor liver transplantation can effectively reduce the risk of post-ERCP cholangitis and bacteremia. Old age, without antibiotic use before ERCP, and need for biliary stenting are independent risk factors of post-ERCP cholangitis.

重症膽道感染致敗血症患者經皮膽道引流和床邊內視鏡膽道引流之比較 COMPARISON OF PERCUTANEOUS AND BESIDE ENDOSCOPIC BILIARY DRAINAGE IN CRITICALLY ILL PATIENTS WITH BILIARY SEPSIS 廖苡君蔡炘儒陳家昌童春芳楊勝舜彭彥鈞臺中榮民總醫院胃腸肝膽科 Background: Early biliary drainage is necessary in critical ill patients with clinical evidence of biliary obstruction. Endoscopic biliary drainage (EBD) or percutaneous transhepatic biliary drainage (PTBD) is usually used for biliary decompression in critical ill patients. Is EBD superior to PTBD is still unknown. Aims: To compare clinical outcomes between bedside, radiation-free endoscopy biliary drainage and fluoroscopic guided percutaneous drainage in critical patients. Methods: A retrospective study was conducted for critical ill patients admitted to intensive care unit (ICU) with biliary obstruction and cholangitis in Taichung Veteran General Hospital. Biliary drainage with bedside EBD or transport to radiology unit for PTBD were decided by physicians according to clinical conditions. The technical success, complications and 30-day mortality rate were evaluated. Results: From January 2011 to April 2020, a total of 47 patients at ICU received biliary drainage. Sixteen patients received EBD and 31 patients received PTBD were included. The baseline characteristics were not significantly different between both groups, including APECHE II score and total bilirubin level. Biliary drainage of EBD group was successfully conducted in 15 (93.8%) patients. Mean procedure time of EBD group was 28.1 ± 15.6 minutes. Only two patients (12.5%) in EBD group encountered post-procedure pancreatitis. The 30-day mortality rate was not significant different (32.72% vs. 31.25%, P = 0.96) in both groups. In multivariate analysis, medical history of malignancy other than pancreatobiliary origin (OR: 5.70, 95% confidence interval [CI]: 1.79-18.14), pre-drainage prothrombin time (OR: 1.20, 95% CI: 1.04-1.38) and creatinine (OR: 1.49, 95% CI: 1.14-1.94) were independent prognostic factors of 30-day mortality. Conclusions: Bedside EBD is safe and effective as PTBD in critical ill patients. Bedside procedure may carry less risk of transport in critical ill patients.

2021 消化系聯合學術演講年會

主題：C 型肝炎（二） 55

C 型肝炎根除減少肝硬化發生率與肝硬化併發症風險：台灣全國性 C 型肝炎世代研究（T-COACH） HEPATITIS C VIRUS ERADICATION DECREASES THE RISKS OF LIVER CIRRHOSIS AND CIRRHOSIS-RELATED COMPLICATIONS: A REAL-WORLD NATIONWIDE STUDY OF A TAIWANESE CHRONIC HEPATITIS C COHORT (T-COACH) 1,2,3

4,5

1,8

許偉帆蔡佩倩陳啟益曾國枝賴學洲郭行道 10 10 11 12 12 13 洪肇宏董水義王景弘陳志州李佩倫簡榮南 13 14 15 15 15 16,17 林俊彥楊基滐羅錦河戴啟明林志文高嘉宏 16,17 16,17 18 19 20 劉俊人劉振驊顏聖烈白明忠蘇維文 21 21 22 23 23 24 朱正心陳志仁羅清池鄭斌男邱彥程王嘉齊 25 25 26 26 4,5 4,5 鄭錦翔蔡維倫林漢傑黃怡翔黃志富戴嘉言 4,5 4,5 1,3 莊萬龍余明隆彭成元 1 中國醫藥大學附設醫院內科部消化醫學中心 2 中國醫藥大學生物醫學研究所 3 中國醫藥大學醫學系高雄醫學大學附設中和紀念醫院肝膽胰內科暨肝炎防 4 治中心高雄醫院大學醫學系、肝炎研究中心、液態生物檢體 5 暨世代研究中心 6 嘉義基督教醫院內科部 7 大林慈濟醫院內科部 8 中國醫藥大學中醫系 9 奇美醫學中心內科部胃腸肝膽科 10 嘉義長庚紀念醫院內科部胃腸肝膽科系高雄長庚紀念醫院內科部胃腸肝膽科系暨長庚大學醫 11 學系 12 柳營奇美醫院胃腸肝膽科 13 林口長庚紀念醫院胃腸肝膽科系 14 秀傳紀念醫院內科部胃腸肝膽科 15 義大醫院內科部胃腸肝膽科暨義守大學醫學系 16 國立台灣大學臨床醫學研究所 17 國立台灣大學附設醫院內科部胃腸肝膽科 18 彰濱秀傳紀念醫院內科部胃腸肝膽科 19 台東馬偕紀念醫院內科部胃腸肝膽科 20 彰化基督教醫院內科部胃腸肝膽科 21 馬偕紀念醫院內科部胃腸肝膽科 22 天主教聖馬爾定醫院內科部國立成功大學附設醫院內科部胃腸肝膽科暨國立成功 23 大學醫學系 24 台北慈濟醫院內科部胃腸肝膽科 25 高雄榮民總醫院內科部胃腸肝膽科 26 臺北榮民總醫院內科部胃腸肝膽科

Background: It is currently unknown how hepatitis C virus (HCV) eradication with pegylated interferon and ribavirin (PR) therapy affects the incidence of new-onset liver cirrhosis (LC) in patients without cirrhosis and the incidence of decompensated liver disease (DLD) or hepatocellular carcinoma (HCC) in patients with cirrhosis. Aims: To evaluate the effect of HCV eradication by PR therapy and factors predictive of new-onset LC and liverrelated complications (DLD or HCC) in patients with CHC. Methods: Taiwanese chronic hepatitis C cohort (T-COACH) is a nationwide HCV registry cohort from 23 hospitals in Taiwan recruited between 2003 and 2015. This study enrolled 10,693 patients with chronic hepatitis C (CHC), linked to the Taiwan National Health Insurance Research Database, receiving PR therapy for at least 4 weeks for new-onset LC and liver-related complications. Results: Of the 10,693 patients, 1372 (12.8%) patients had LC, and the mean age was 54.0 ± 11.4 years. The mean follow-up duration was 4.38 ± 2.79 years, with overall 46,798 person-years. The 10-year cumulative incidence rates of new-onset LC were 5.0% (95% confidence interval [CI]: 3.2–7.7) in patients without cirrhosis with a sustained virologic response (SVR) and 21.9% (95% CI: 13.4–32.4) in those without SVR (hazard ratio [HR]: 0.22, P < 0 .001). The 10-year cumulative incidence rates of liver-related complications were 21.4% (95% CI: 11.1–37.2) in patients with cirrhosis with SVR and 47.0% (95% CI: 11.1–86.0) in those without SVR after adjustment for age, sex, and competing mortality (HR: 0.52, P < 0 .001). Conclusions: HCV eradication with PR therapy decreased the incidence of new-onset LC in noncirrhotic patients and the incidence of liver-related complications in cirrhotic patients with CHC.

2021 消化系聯合學術演講年會

肝硬度和 Fibrosis-4 對於慢性 C 肝病人直接抗病毒藥物治療後肝臟相關併發症發生的風險評估 LIVER STIFFNESS AND FIBROSIS-4 INDEX IN RISK ASSESSMENT OF LIVER-RELATED COMPLICATIONS OCCURRENCE FOR CHRONIC HEPATITIS C PATIENTS AFTER DIRECT-ACTING ANTIVIRALS

肝纖維掃描比 FIB-4 指數有較好預測全口服抗病毒藥治癒慢性 C 型肝炎後肝腫瘤發生與肝失去代償的能力 FIBROSCAN IS SUPERIOR TO FIB4 IN PREDICTING DE-NOVO HCC OCCURRENCE AND HEPATIC DECOMPENSATION IN CHRONIC HEPATITIS C PATIENTS TREATED WITH DIRECT-ACTING ANTIVIRALS THERAPY

郭垣宏紀廣明洪肇宏盧勝男胡琮輝陳建宏王景弘長庚醫療財團法人高雄長庚紀念醫院胃腸肝膽科系暨長庚大學醫學系 Background: Chronic hepatitis C (CHC) patients after elimination of virus remained at risk of liver-related complications (LRC). Aims: This study was to determine whether liver stiffness (LS) and fibrosis-4 index (Fib-4) were useful in assessing LRC occurrence for CHC patients after direct-acting antivirals (DAA). Methods: This retrospective study enrolled CHC patients achieving sustained virological response (SVR) after DAA. Patients with LS measured by transient elastography and complete lab data at SVR were followed and analyzed. The demographics, clinical characteristics and LRC development were obtained from medical chart reviews. Results: A total of 697 patients were enrolled. In a median follow-up of 21.4 months after SVR, thirty-nine ptients developed LRC including 28 hepatocellular carcinoma (HCC). The 30-month cumulative incidence of LRC and HCC was 7.7% and 5.1%, respectively. While the performance in predicting the occurrence of LRC and HCC were 0.820 and 0.774 for LS, they were 0.775 and 0.737 for Fib-4. The optimal cutoffs of LS and Fib-4 were 14.5 kilopascal and 2.9 for LRC prediction. While diabetes was associated with LRC, LS and Fib-4 were with LRC and HCC in multivariate analysis. A risk-score system combining LS, Fib-4 and diabetes was developed for LRC risk assessment. Patients were stratified into low- (score 0-1), intermediate- (score 2-3) and high-risk (score 4) groups with LRC cumulative incidence of 1.7%, 14.9% and 36.4%, respectively (p<0.001). Conclusions: For patients with CHC after DAA, LS and Fib-4 at SVR were independently associated with LRC and HCC occurrence. A risk scoring system based on LS, Fib-4 and diabetes was useful to assess the risk of LRC developments.

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劉彥君徐正二鄭文睿林俊彥簡榮南戴達英 1,2 沈一嫻 1 長庚大學醫學院 2 林口長庚紀念醫院胃腸肝膽科系

Background: It has been recognized that pre- and postdirect acting antivirals (DAAs) liver stiffness measurements (LSM) as well as fibrosis-4 (FIB-4) index can predict occurrence of hepatocellular carcinoma (HCC). However, there’s limited information for prediction of hepatic decompensation. Aims: This study aims to compare the predictive performances of pre- and post-DAA LSM and FIB-4 for hepatic adverse outcomes. Methods: Chronic hepatitis C patients who received DAA treatment during March 2015 to December 2019 in Chang Gung Memorial Hospital, Linkou branch and had available baseline and follow-up LSM, FIB-4 index were recruited. LSM assessed by transient elastography (TE, Fibroscan) and FIB-4 index were prospectively recorded at baseline and after sustained virological response (SVR). Predictions for early hepatic adverse outcomes including de novo HCC occurrence, HCC recurrence and hepatic decompensation within two years after completing DAA therapy were compared between LSM and FIB-4 at pre-therapy and 12, 24 weeks after end-of-therapy achieving SVR using area under receiver operating characteristic curve (AUROC). Results: Among 949 patients enrolled, 568 (60%) were male, 288 (30%) had pretherapy cirrhosis, 127 (13%) had pretherapy eradicated HCC and 64% were genotype 1. The incidences of de-novo HCC and hepatic decompensation within two years after end-of-treatment showed 2.7% and 2.8%, respectively. Pretherapy LSM demonstrated better predictive values for de-novo HCC than pretherapy FIB4 index (AUROC: LSM vs. FIB-4 = 0.821 vs. 0.728, p = 0.032); however, post-SVR LSM had the better prediction for hepatic decompensation than post SVR FIB-4 (AUROC:

2021 消化系聯合學術演講年會

58 LSM vs. FIB-4 = 0.939 vs. 0.889, p = 0.043). Among the 127 patients post HCC curative treatment, 29.1% HCC recurrences was observed during 2-year follow-up. Both fibroscan and FIB-4 had poor predictability for HCC recurrence before and after DAA treatment. Conclusions: Liver stiffness measurement by Fibroscan is superior to FIB-4 index in predictions for de-novo HCC and hepatic decompensation.

慢性 C 型肝炎合併血小板低下患者接受非干擾素全口服新藥治療前之血小板生成素可預測治療後血小板是否明顯改善 BASELINE THROMBOPOIETIN LEVEL IS ASSOCIATED WITH PLATELET COUNT IMPROVEMENT IN THROMBOCYTOPENIC CHRONIC HEPATITIS C PATIENTS AFTER SUCCESSFUL DIRECT-ACTING ANTIVIRAL AGENT THERAPY 1

1,2

陳彥均曾志偉曾國枝 1 佛教慈濟醫療財團法人大林慈濟醫院 2 慈濟大學醫學系 Background: Thrombocytopenia can rapidly improve in chronic hepatitis C (CHC) patients receiving directacting antiviral agents (DAA). The role of baseline (BL) thrombopoietin (TPO) in this phenomenon is unclear. Aims: To evaluate the association between BL TPO and the platelet count improvement at SVR12. Methods: From 2016 to 2019, a total of 104 CHC patients receiving DAA, with a sustained virologic response and BL thrombocytopenia, at Dalin Tzu Chi Hospital, were enrolled in this retrospective study. Significant platelet count improvement (defined as a >10% platelet count improvement ratio at SVR12) and platelet count improvement ratio, [platelet count (EOT or SVR12)– platelet count (BL)]/platelet count (BL), were analyzed for correlation with BL TPO. Results: This cohort included 40 men (38.5%). Seventytwo (69.2%) patients had advanced fibrosis. The platelet count [median (range)] increased from 110.5 (32–149) × 103/µL at BL to 116.5 (40–196) and 118.0 (35–275) × 103/ µL at end of treatment (EOT) and 12 weeks after EOT (P12), respectively, (EOT vs. BL, P<0.001; P12 vs. BL, P<0.001).BL TPO was positively correlated with significant platelet count improvement (P<0.001), platelet count improvement ratio at EOT (P=0.004), and P12 (P<0.001). Conclusions: Baseline TPO level might be a useful marker for predicting significant platelet count improvement in thrombocytopenic CHC patients after successful DAA therapy.

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2021 消化系聯合學術演講年會

使用全口服抗病毒藥物治療成功之代償失調 C 肝患者其肝臟功能、FIB-4 Index 及肝病預後積分之序列變化 SEQUENTIAL CHANGES OF SERUM BIOCHEMISTRIES PROFILES, FIB-4 INDEX, CTP SCORE AND MELD SCORE IN DECOMPENSATED HCV-INFECTED PATIENTS AFTER SUCCESSFUL SOFOSBUVIR-BASED DAAS THERAPY 1

1,2

2,3

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蘇品碩吳思賢朱啟仁蘇建維林崇祺李發耀 1,2 1,2 黃怡翔侯明志 1 臺北榮民總醫院胃腸肝膽科 2 國立陽明大學醫學系 3 臺北榮民總醫院健康管理中心

Background: For patients diagnosed to have chronic hepatitis C (CHC) related liver cirrhosis with decompensation, poor prognosis was documented mainly attributed to higher likelihood to develop hepatocellular carcinoma and portal hypertension related complications such as jaundice, refractory ascites, variceal bleeding, and hepatic encephalopathy. In this condition, successful hepatitis C virus (HCV) eradication can reduce the risk of cirrhotic complications, decrease the necessity of liver transplantation, and improve patient survival. Sofosbuvir is an HCV NS5B nucleotide polymerase inhibitor which rapidly revolutionized the treatment landscape of CHC. More importantly, it is the cornerstone direct-acting antiviral (DAAs) agent frequently used in HCV-infected patients with hepatic decompensation. Aims: To date, real-world data on the dynamic change of biochemistries profiles, Fibrosis-4 (FIB-4) Index, Child Turcotte Pugh (CTP) score and Model for End-Stage Liver Disease (MELD) score in patients with HCV related hepatic decompensation after successful DAA treatment are limited in Taiwan. Therefore, we conducted this study to investigate the above important topics. Methods: From December 2015 to November 2020, a total of 50 consecutive HCV related liver decompensation patients who successfully treated with sofosbuvir-based all oral DAAs regimens (sofosbuvir/daclatasvir: 7, sofosbuvir/ ledipasvir: 31, sofosbuvir/velpatasvir: 11, sofosbuvir/ ledipasvir then sofosbuvir/velpatasvir: 1) were enrolled for analyses. Sequential changes of biochemistries profiles, FIB-4 index, CTP score and MELD score were assessed before DAAs treatment and 12 weeks after the completion of therapy.

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Results: Mean age of enrolled patients was 67 ± 12.5 years and eight (16%) patients belonged to CTP class C. Genotype distribution was as follows: 1a: 2; 1b: 35; 2: 9; 6: 3; and one patient with unclassified HCV genotype. HCV RNA level before treatment was 5.49 ± 1.3 log10 IU/mL and 32% of them with a baseline HCV RNA > 2,000,000 IU/mL. After achieving HCV clearance by DAAs, statistically significant hepatic function improvement (albumin, ALT/AST, total bilirubin, PT INR) were noted at 12 weeks after completion of therapy. Besides, markedly decrease of FIB-4 index (10.8 ± 7.0 vs. 7.8 ± 4.1, p<0.05), CTP score (8.0 ± 1.2 vs. 6.7 ± 1.4, p<0.05) and MELD score (12.8 ± 3.6 vs. 11.5 ± 3.1, p<0.05) were found after successful DAAs therapy. However, phenomenon of hepatic decompensation still remained in a proportion of subjects. Conclusions: After viral clearance by successful DAAs therapy, hepatic function, FIB-4 index, CTP and MELD scores were significantly improved in most HCV-infected patients presented with hepatic decompensation. Longterm follow-up studies are warranted to investigate the consequential hepatic beneficial effects after HCV cure and risk factors for disease progression.

2021 消化系聯合學術演講年會

直接作用 C 肝抗病毒藥物直接改善健康生活品質：花東多中心 C 型肝炎世代研究 BETTER LIFE QUALITY IS ASSOCIATED WITH SUCCESSFUL DIRECT-ACTING ANTIVIRAL THERAPY: A TWO-CENTER COHORT OF PATIENTS WITH HEPATIC C VIRUS INFECTION IN EASTERN TAIWAN 1

易志勳王仁宏翁銘彣劉作財雷尉毅梁書瑋 1 1 1 林霖洪睿勝陳健麟 1 佛教慈濟醫療財團法人花蓮慈濟醫院內科部肝膽腸胃科 2 佛教慈濟醫療財團法人花蓮慈濟醫院醫學研究部

after treatment (P = NS) except for improvement in sleep quality (P = 0.033). Multivariate analysis didn’t find any clinical or demographic characteristics was associated with improvements in HRQoL (P = NS) except for baseline anxiety positively correlated with improvements in SF36 items of physical role functioning and emotional role functioning (both P < 0.05). Conclusions: Our study has demonstrated that HCV patients with SVR after DAA therapy appear to have improvements in HRQoL, liver fibrosis, depression, and GI symptoms. This work indicates that alteration toward better HRQoL can be complex and beyond successful DAA therapy.

Background: Improvement in health-related quality of life (HRQoL), psychological distress, and liver fibrosis have been reported in patients with chronic hepatitis C virus (HCV) infection after successful direct-acting antiviral (DAA) therapy. However, the mechanism about their interrelationships has not been well investigated. Aims: The aim of this study was to investigate the impact of DAA therapy on HRQoL, psychological distress, and liver fibrosis, and was also to evaluate potential factors that are associated with those outcomes after DAA therapy. Methods: Patients with chronic HCV infection receiving DAA therapy were prospectively recruited in two tertiary referral medical centers in eastern Taiwan (Hualian and Taitung). All patients were required to complete assessments including Short-Form-36 (SF-36), Pittsburgh Sleep Quality Index (PSQI) score, Taiwanese Depression Questionnaire score, State Trait Anxiety Inventory (STAI) score, GI symptoms, and Fibrosis-4 (FIB-4) index before and after DAA therapy. Data were compared between at the baseline (before initiating therapy) and at the end of the therapy. Factors associated with outcome improvement were evaluated by multivariate analysis. Results: We enrolled 175 patients, aged 60 ± 11.8 years, 54.3% female, of whom 169 (96.6%) patients had sustained virologic response (SVR). Improvement of liver fibrosis (FIB-4 index) depression, GI symptoms, and SF-36 items of vitality, bodily pain, physical role functioning, emotional role functioning, social role functioning, and mental health were demonstrated among patients had SVR after DAA therapy (all P < 0.05). However, anxiety, sleep quality, or SF-36 items of physical functioning as well as general health perceptions were note significantly changed after the treatment (P = NS). Regarding patients without SVR, most outcome variables remained similar at baseline and

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主題：肝腫瘤（二） 61

肝腫瘤電燒後氣泡滯留的臨床意義 THE CLINICAL IMPLICATION OF AIR BUBBLES RETENTION AFTER RFA OF LIVER TUMOR 鄒騰信嚴卓立錢政弘基隆長庚紀念醫院肝膽腸胃科 Background: Radiofrequency ablation (RFA) of liver tumors is widely used to treat unresectable early stage HCC. Air bubbles formation is constantly seen during radiofrequency ablation (RFA) therapy. The increased echogenicity, due to microbubbles of gas, is known to remain for 15–180 mins after radiofrequency ablation. Air bubbles retention more than 12 hours after treatment is not infrequent in clinial practice and we noticed some patient with prolonged air bubble retention developed liver abscess afterward. RFA induce air bubbles in ablation zones (necrosis zone or thermal lesion) because ablation heating raises the tissue temperature to near the boiling point. The risk of developing a post-RFA liver abscess is low, i.e. 0.3~6.7%. High risk (up to 44%) of abscess after RFA if patient has history of biliary tract drainage procedure, such as enterobiliary anastomosis, biliary stenting or sphincterotomy, even receiving prophylactic antibiotics(most patient pancreatic malignancy or colonadenocarcinoma). Most liver abscess occurs between 3 to more than 60 days after RFA. Symptoms of liver abscess were similar to post-ablation syndrome. Postablation syndrome occurs from 24 to 48 hours following ablation and lasts no longer than 10 days. Most liver abscess (79%) after RFA appear as air within the abscess and early diagnosis might not be easy. Aims: We therefore retrospectively reviewed the clinical data to investigate the correlation of air bubbles retention after RFA and it’s correlation to abscess. Methods: Patients with hepatocellular carcinoma, metastatic liver tumors or others underwent radiofrequency ablation therapy between July 2015 and July 2020 in CGMH keelung branch were included. Definition of air bubble retention were air bubble detected on follow-up abdominal echo within 3 days after RFA. Diagnosis of liver abscess were patients has fever which was higher than 38℃ for more than 1 days or/and the leukocyte count was greater than 11 × 10 9/L without other causes and culture were positive or had a purulent appearance from the aspirate from the ablation zone with/ without air bubble retention in the ablation zone. RFA procedure were performed by one

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experience operator. Internally Cooled Electrodes system was adopted (BIG-TIP, RF Medical Co., Ltd). This system includes an electrode, the tip of which is internally cooled by chilled water. The device is equipped with a 200-W generator and uses 17-gauge straight electrode with 3 cm or 4 cm active part. Results: There were 582 patients with total 665 liver tumor between July 2015 and July 2020 in CGMH keelung branch (non of which receive prophylactic antibiotic before procedure). Totally 552 numbers of RFA procedure have follow-up sonography report withing 72 hrs after RFA. Air bubbles formation whithing 72 hours in 25 numbers of RFA and there is no airbubble formation in 527 numbers RFA. Liver absess formation in two different patiens among the group with air bubble retention withing 72 hours. Liver abscess retention in 4 different patients among the group without airbubble retention withing 72 hours. Mean age were not different among patients with liver abscess or without liver abscess formation. However, mean AST, ALT and WBC after RFA were higher in abscess group (Table 1). Most of the tumors which has airbubble retention were HCC and most patients has single tumor and were in ChildPugh classfication A. Most patients with airbubble retention after RFA have fever (Table 2). Airbubble retention within 72 hours after RFA were significantly related to abscess formation afterwards. The incidence of liver abscess after RFA were 2.4% in our series. Conclusions: Air bubbles retention is not infrequent after RFA. Air bubbles might be an important sign of abscess after RFA. Aseptic procedure and closer monitoring of the patients during and after radiofrequency ablation procedures are more important to prevent an abscess formation and early detect a complication.

2021 消化系聯合學術演講年會

根據復發後生存率，以 6 個月來定義肝癌肝切除術後的早期復發 6 MONTHS AS A CUTOFF TIME POINT TO DEFINE EARLY RECURRENCE AFTER LIVER RESECTION OF HEPATOCELLULAR CARCINOMA BASED ON POST-RECURRENCE SURVIVAL

演化式學習建立預測肝癌手術後早期復發之人工智慧預測模型 EVOLUTIONARY LEARNING DERIVED CLINICAL-RADIOMIC MODELS FOR PREDICTING EARLY RECURRENCE OF HEPATOCELLULAR CARCINOMA AFTER SURGICAL RESECTION 1

卓韋儒王植熙陳肇隆鄭汝汾王景弘顏毅豪 1 長庚醫療財團法人高雄長庚紀念醫院胃腸肝膽科系長庚醫療財團法人高雄長庚紀念醫院肝臟移植中心及 2 外科部長庚醫療財團法人高雄長庚紀念醫院肝臟移植中心及 3 放射診斷科

李懿宬黃若瑜陳亭君周家揚李潤川何信瑩 1,5 黃怡翔 1 臺北榮民總醫院胃腸肝膽科 2 國立交通大學生物資訊及系統生物研究所 3 臺北榮民總醫院一般外科 4 臺北榮民總醫院放射線部 5 國立陽明大學臨床醫學研究所

Background: Hepatocellular carcinoma (HCC) is among the leading causes of cancer-related death worldwide. The majority of patients with HCC develop tumor recurrence after liver resection (LR). Tumor recurrence is generally classified into early or late recurrence by using 24 months as the cut-off time point based on the assumed mechanisms. However, this paradigm of recurrence has been shown to be unreliable based on a recent genomic study. Postrecurrence survival (PRS) has been adopted to differentiate early versus late recurrence among patients with pancreatic ductal adenocarcinoma who have undergone surgical resection. Aims: To determine the optimal cut-off time point of early versus late recurrence relative to post-recurrence survival (PRS) among patients who underwent liver resection (LR) for hepatocellular carcinoma (HCC) in a high-volume liver surgery center in East Asia. Methods: This was a retrospective study. Patients who underwent LR for HCC between 2011 and 2018 at Kaohsiung Chang Gung Memorial Hospital were enrolled. The optimal cut-off time point to differentiate early versus late recurrence was evaluated relative to PRS. Results: Among 826 patients, 282 (34.1%) of the patients experienced recurrence, with a median time to recurrence of 12.2 months. Six months was defined as the optimal cutoff time point based on sensitivity analyses relative to PRS. Ninety (31.9%) of the patients developed early recurrence within 6 months, and 192 patients (68.1%) developed late recurrence beyond 6 months. Early recurrence was associated with worse PRS (median PRS, 13.2 versus 48.9 months, p < 0.001), as well as overall survival (OS) (median OS, 16.2 versus 65.4 months, p < 0.001), than late recurrence. Conclusions: Six months was identified as the cut-off time point to differentiate early versus late recurrence among patients undergoing LR for HCC.

Background: Current prediction models for early recurrence of hepatocellular carcinoma (HCC) after surgical resection remain unsatisfactory. Aims: The aim of this study is to develop accurate prediction models with interpretability using both clinical and radiomic features to predict early recurrence of HCC after surgical resection. Methods: 517 consecutive HCC patients receiving resection with contrast-enhanced computed tomography (CECT) images before resection were retrospectively enrolled. Tumor segmentation of all CECT images including non-contrast phase, arterial phase and portal venous phase were manually performed for radiomic feature extraction. A novel evolutionary learning derived method called GARSL (Genetic Algorithm for predicting Recurrence after Surgery of Liver cancer) was proposed to design prediction models for early recurrence of HCC within 2 years after surgery. Results: A total of 143 features, including 26 pre-operative clinical features, 5 post-operative pathological features and 112 radiomic features, were finally adopted to develop GARSL pre-operative and post-operative models. GARSL pre-operative and post-operative models achieved the test performance 0.739 and 0.741 of areas under the receiver operating characteristic curves (AUCs), respectively, for early recurrence of HCC within 2 years. The accuracy of GARSL models derived from evolutionary learning method was significantly better than models derived from other well-known machine learning methods or the ERASL models using clinical features only. Conclusions: The GARSL models using both clinical and radiomic features significantly improved the accuracy to predict early recurrence of HCC after surgical resection, which were significantly better than other well-known machine learning derived models and currently available clinical models.

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2021 消化系聯合學術演講年會

LI-RADS 系統在肝癌病患的臨床相關性 CLINICAL ASSOCIATIONS OF LIRADS CATEGORY IN PATIENTS OF HEPATOCELLULAR CARCINOMA

以 ALBI 分級為基準的 BCLC 系統列線圖預測模式評估肝癌患者的預後 ALBUMIN-BILIRUBIN GRADE-BASED NOMOGRAM OF THE BCLC SYSTEM FOR PERSONALIZED PROGNOSTIC PREDICTION IN HEPATOCELLULAR CARCINOMA

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1,2

陳俊廷蔡維倫陳文誌孫煒智王威登鄭錦翔 1 高雄榮民總醫院腸胃肝膽科 2 國立陽明大學醫學院 3 高雄榮民總醫院放射線部

Background: Non-invasive diagnostic method for hepatocellular carcinoma (HCC) is a clinical challenge. The liver imaging reporting and data system (LI-RADS) is a comprehensive system as a diagnostic criteria for HCC. However the clinical associations of LI-RADS are not clear. Aims: This study aimed to investigate the diagnostic performance and clinical associations of LI-RADS in patients of HCC. Methods: This retrospective study included 439 consecutive pathologically confirmed HCC patients between January 2015 and September 2018 in VGHKS. Two blinded radiologists independently evaluated each patients and assigned a LI-RADS diagnostic category. Clinical associations of LI-RADS-5 in HCC patients were analyzed. Results: Among the 439 patients of HCC, 376 (86%) patients were classified as LI-RADS-5 and 63 (14%) of patients as non-LI-RADS-5. Uni-variate analysis found that tumor size (Hazard ratio [HR] = 1.793, 95% confidence intervals [CI] = 1.016-3.165, p = 0.044), AFP level (HR = 2.357, 95% CI = 1.084-5.127, p = 0.031), tumor differentiation (HR = 5.097. 95% CI = 1.825-14.234, p = 0.002), and main portal vein (MVP) thrombosis (HR = 11.308, 95% CI = 1.537-83.18, p = 0.017) were associated with LI-RADS 5 category and multi-variate analysis found that MPV thrombosis (HR = 8.509, 95% CI = 1.121-64.58, p = 0.038) and tumor differentiation (HR = 3.958, 95% CI = 1.402-11.17, p = 0.009) were independently associated with LI-RADS-5 category. However, cox regression analysis found that LI-RADS-5 category was not associated with mortality in HCC. Conclusions: In patients with confirmed HCC, main portal vein thrombosis and tumor differentiation were associated with LI-RADS-5 category. But LI-RADS-5 was not related to clinical outcome in HCC patients.

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2,3

4,5

何樹仁柯智傑蘇建維侯明志黃怡翔霍德義 1 敏盛綜合醫院胃腸肝膽科 2 臺北榮民總醫院內科部 3 臺北榮民總醫院胃腸肝膽科 4 臺北榮民總醫院醫學研究部 5 國立陽明大學醫學院藥理研究所

Background: The prognostic accuracy of individual hepatocellular carcinoma (HCC) patient in each Barcelona Clinic Liver Cancer (BCLC) stage is unclear. Aims: We aimed to develop and validate an albuminbilirubin (ALBI) grade-based nomogram of BCLC to estimate survival for individual HCC patient. Methods: Between 2002 and 2016, 3690 patients with newly diagnosed HCC were prospectively enrolled and retrospectively analyzed. Patients were randomly split into derivation and validation cohort by 1:1 ratio. Multivariate Cox proportional hazards model was used to generate the nomogram from tumor burden, ALBI grade and performance status (PS). The concordance index and calibration plot were determined to evaluate the performance of this nomogram. Results: Beta coefficients from the Cox model were used to assign nomogram points to different degrees of tumor burden, ALBI grade and PS. The scores of the nomogram ranged from 0 to 24, and were used to predict 3- and 5-year patient survival. The concordance index of this nomogram was 0.77 (95% confidence interval [CI]: 0.71–0.81) in the derivation cohort and 0.76 (95% CI: 0.71-0.81) in the validation cohort. The calibration plots to predict both 3and 5-year survival rate well matched the 45-degree ideal line for both cohorts, except for ALBI-based BCLC stage 0 in the validation cohort. Conclusions: The proposed ALBI-based nomogram of BCLC system is a simple and feasible strategy in the precision medicine era. Our data indicate it is a straightforward and user-friendly prognostic tool to estimate the survival of individual HCC patient except for very early stage patients.

2021 消化系聯合學術演講年會

ALBI 分級：對於無法手術切除的肝細胞癌接受 Sorafenib-Regorafenib 順序治療的患者是一項治療反應與存活的預測指標 ALBI GRADE: A PREDICTOR OF TREATMENT RESPONSE AND OUTCOME FOR PATIENTS WITH UNRESECTABLE HEPATOCELLULAR CARCINOMA RECEIVING SORAFENIBREGORAFENIB SEQUENTIAL THERAPY 王鴻偉賴學洲莊伯恒蘇文邦高榮達彭成元中國醫藥大學附設醫院消化醫學中心 Background: Regorafenib improved survival in patients with advanced hepatocellular carcinoma (HCC) who progressed after the use of sorafenib in RESORCE study. Aims: We aimed to investigate the predictors of treatment response and outcome in patients with unresectable HCC receiving sorafenib-regorafenib sequential therapy. Methods: A total of 88 patients with unresectable HCC who received sorafenib-regorafenib sequential therapy were enrolled from September 2012 to July 2020. Baseline and on-treatment clinical characteristics, laboratory data and imaging findings were collected. Tumor response was evaluated based on the modified Response Evaluation Criteria in Solid Tumor (mRECIST). Overall survival and progression free survival were determined using the Kaplan–Meier curve, and comparison between groups was made using the log-rank test as univariate analysis. For the multivariate Cox regression or logistic regression analyses, we adopted two models (Child-Pugh class-based and ALBI grade-based) for analysis due to the confounding between Child-Pugh score and ALBI grade. Results: Patient characteristics at the initiation of regorafenib therapy were 72.7% (n = 64) BCLC stage C and 94.3% (n = 83) Child-Pugh class A. A total of 19 patients (21.6%) died during a median follow-up period of 18 months. Best tumor response after regorafenib therapy showed that the objective response rate (ORR) was 19.3% and disease control rate (DCR) was 48.9%. Patients with ALBI grade 1 had significantly higher DCR than those with ALBI grade 2 (P = 0.013). According to an ALBI grade-based multivariate logistic regression analysis, male gender (OR: 0.188, 95% CI: 0.047–0.755; P = 0.018) and ALBI grade 1 (OR: 4.678, 95% CI: 1.583–13.82; P = 0.005) were independent predictors for disease control after regorafenib therapy. The progression-free survival (PFS)

after regorafenib therapy was 4.2 months (95% CI: 3.2-5.1). ALBI grade (1 versus 2) and Child-Pugh score (5 versus 6) could stratify the risk of PFS after regorafenib therapy in univariate analyses (P = 0.042 and 0.042, respectively). In a separate Child-Pugh score-based or ALBI grade-based model, either Child-Pugh score or ALBI grade and AFP (<20 versus ≥20 ng/mL) were independent predictors for PFS by multivariate analyses (P = 0.037, 0.044 and P = 0.034, 0.034, respectively). The median overall survival (OS) (either from the initiation of sorafenib or regorafenib therapy) was not yet reached in this cohort and the 1, 2, and 3-yr survival rates of the entire cohort receiving sequential therapy was 94.9, 78.9 and 63.7%, respectively. According to an ALBI grade-based multivariate Cox regression analysis, ALBI grade 1 (HR: 0.365, 95% CI: 0.135–0.985; P = 0.047) and AFP <20 ng/mL (HR: 0.339, 95% CI: 0.124–0.925; P = 0.035) were independent predictors for OS of sorafenib-regorafenib sequential therapy. However, Child-Pugh score was not a predictor for OS. Patients with ALBI grade 2 and AFP ≥20 ng/mL had the worst PFS (after regorafenib) and OS (from the initiation of sorafenib therapy) compared to those with ALBI grade 1 and AFP <20 ng/mL or those with ALBI grade 1/AFP ≥20 ng/mL and ALBI grade 2/AFP <20 ng/mL (PFS: P = 0.001, P = 0.018, and OS: P < 0.001, P = 0.048, respectively). Conclusions: ALBI grade at the initiation of regorafenib therapy is an independent predictor for disease control, PFS and OS. A combination of ALBI grade and AFP could stratify the risks of PFS and OS for patients with unresectable HCC receiving sorafenib-regorafenib sequential therapy.

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主題：上消化道疾病（二） 67

陽離子幫浦阻斷劑治療無效之逆流症狀病人的臨床特徵 CLINICAL CHARACTERISTICS OF PROTON PUMP INHIBITOR NONRESPONDERS WITH REFLUX SYMPTOMS 1,3,4

1,5

1,2

1,4,6

王彥博陳昶宇宋寬益林弘恩陳炳憲 1,2,4 1,3,4 侯明志盧俊良 1 臺北榮民總醫院內科部內視鏡診斷與治療中心 2 臺北榮民總醫院內科部胃腸肝膽科 3 國立陽明大學腦科學研究所 4 國立陽明大學醫學院醫學系 5 臺北市立聯合醫院忠孝院區消化內科 6 西園醫院腸胃肝膽科

Background: Gastroesophageal reflux disease (GERD) is a common gastrointestinal disease presented with classical symptoms such as heartburn and regurgitation, or atypical symptoms including chest pain, cough, hoarseness, globus sensation, dry mouth and, dysphagia. Proton pump inhibitors (PPI) have good response in treating GERD and therefore PPI trial remained empirical management for patients. However, about one-third of GERD patients didn’t respond to PPI treatment. The etiologies of PPI failure are heterogeneous. Pain modulators including psychotropics, gabapentenoids, prokinetics may help treating these patients. According to Rome IV criteria of functional esophageal disorders, patients with reflux symptoms are categorized into erosive esophagitis, nonerosive reflux disease, reflux hypersensitivity and functional heartburn. The management differs between these subtypes. To date, the distribution and characteristics of PPI non-responders with reflux symptoms are less known in Taiwan. Aims: To evaluate the PPI non-responders with esophagogastroduodenoscopy, 24 hours pH impedance (MII-pH) and high resolution esophageal manometry (HRM) in a tertiary medical center in Taiwan. Methods: We reviewed the data from a prospectively recorded functional esophageal disease database in Taipei Veterans General Hospital. Patients with reflux symptoms including heartburn, regurgitation, dysphagia, chest pain, belching and globus sensation were enrolled. All the patients had persistent symptoms which resolved <50% after at least 8 weeks of standard dose proton pump inhibitors. Basic demographic profiles, symptom severity (0-3), duration (months), frequency (times/week), Chinese GERDQ questionnaire, and reflux symptom index were

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obtained from the patients. The patients are asked to fast at least 8 hours before exam. Esophagogastroduodenoscopy was performed. HRM was performed with 32 circumferential pressure channels with 16 impedance channels solid-state catheter (Medical Measurement Systems, Netherlands) according to Chicago classification of esophageal motility disorders version 3.0. MII-pH was performed with impedance catheters with 7 impedance (6 channels) and 1 pH sensors and Ohmega Ambulatory Impedance and pH Recorder (Medical Measurement Systems, Netherlands). The MII-pH result was interpreted with Rome IV criteria of esophageal disorders. Parametric data are presented as mean ± SD unless otherwise stated. Statistical analysis was performed by Student’s t test, ChiSquare tests or one-way ANOVA tests as appropriate. Statistical significance was defined as P < 0.05. SPSS version 18 was used for statistical analysis. Results: From September, 2017 to December, 2018, total 58 consecutive PPI non-responders with reflux symptoms were enrolled in this study. The patients’ average age was 50.89 ± 12.79 years old and 36 (62%) were female. 47 (81%) patients had high Chinese GERQDQ score (>11) while 32 (55%) patients had high RSI score (>13). The predominant symptoms include regurgitation (72%), globus (71%), heartburn (69%) belching (60%), cough (45%), chest pain (41%), dysphagia (28%) and epigastric pain (21%). With esophagogastroduodenoscopy, 35 (60%) patients were found with reflux esophagitis, including 30 (52%) Los Angles Grade. A, 3 (5%) Grade.B, 1 (2%) Grade. C and 1 (2%) Grade. D reflux esophagitis. 28 (48%) patients had endoscopic hiatal hernia and 2 (3%) patients had esophageal cervical inlet patch. In HRM analysis, 19 (33%) patients were found with esophageal dysmotility including 11 (19%) ineffective esophageal motility, 7 (12%) EGJ outflow obstruction and 1 (2%) absent contractility. 39 patients were found with manometric hiatal hernia, significant higher than endoscopic diagnosis rate (p<0.001). Categorized by MII-pH result, 13 patients (22%) had gastroesophageal reflux disease, 14 patients (24%) had reflux hypersensitivity and 31 patients (53%) had functional esophageal disorders including functional heartburn, functional globus and functional belching. Conclusions: In PPI-nonresponders with reflux symptoms in Taiwan, other than typical reflux symptoms, globus and belching are the most common presenting. More than 90% were found with Los Angles Grade 0-A endoscopic reflux esophagitis. Over half of them had functional esophageal disorders while one fourth had reflux hypersensitivity. MII-

2021 消化系聯合學術演講年會

68 pH can help find out these patients who are less or not likely to respond to PPI, avoiding unnecessary PPI use. With HRM, one third PPI non-responders were found with esophageal dysmotility. More patients with hiatal hernia could be identified by HRM compared with endoscopy. With MII-pH and HRM, PPI non-responders can be categorized according to Rome IV criteria and further management toward these patients can be individualized according the functional exam’s results.

比較藍雷射影像系統（BLI）及窄頻影像（NBI）對頭頸部腫瘤患者篩檢食道癌的的效果：一教學醫院之經驗 SCREENING BY IMAGE ENHANCED ENDOSCOPY FOR ESOPHAGEAL CARCINOMA IN HEAD AND NECK CANCER PATIENTS, THE BENEFIT BY BLUE LASER IMAGING (BLI) COMPARED WITH NARROW BAND IMAGING(NBI): AN EXPERIENCE IN AN ACADEMIC MEDICAL CENTER 丁俊夫蕭望德張安迪林肇堂中國醫藥大學附設醫院消化醫學中心及內科部消化系 Background: Early detection of esophageal cancer at the time of diagnosing cancer of the head and neck is a new strategy for improving the long‐term outcome of cases with head and neck cancers associated with esophageal cancer. In the past, narrow band imaging (NBI) plus Lugol staining could be the standard examination for the detection of esophageal cancer in head and neck cancer patients. A novel image-enhanced endoscopy technology by BLI (blue laser imaging) and LCI (linked color imaging) provides another screening method for detecting esophageal neoplasia. Aims: To investigate clinical outcomes for screening by image enhanced endoscopy for esophageal carcinoma in head and neck cancer patients and compared the benefit of blue laser imaging (BLI) and narrow band imaging (NBI). Methods: From September, 2020 to December, 2020, we used two image enhanced endoscopy systems (Fuji film and Olympus system), Fuji film system (BLI and LCI) first, followed by Olympus system (NBI plus Lugol staining), for screening esophageal cancer in head and neck cancer patients. We analyzed the incidence of esophageal cancer in head and neck cancer patients and detection rate of Fuji film and Olympus system. Results: All 51 consecutive patients with diagnosed head and neck cancer received endoscopic esophageal screening with image-enhanced endoscopy, including 31, 10, 9 and 1 of oral cancer, oropharyngeal cancer, hypopharyngeal cancer, and laryngeal cancer respectively. Forty-eight and 3 were male and female respectively. The mean age was 57.8 years-old (range, 26-84 years). Total ten patients (10 of 51; 19.6%) had 13 esophageal neoplasm after screening, including 8 early esophageal neoplasm (high grade intraepithelial neoplasm or carcinoma in situ) and 2

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69 advanced esophageal cancer. Most patients (8 of 10; 80%) had superficial neoplasia, The incidence rate of synchronous and metachronous esophageal neoplasia was 14.7% (5 of 34) and 29.4% (5 of 17). Multiple lesions were found in 3 patients (3 of 10, 30%). The locations in the esophagus demonstrated 7, 3 and 3 in the upper, middle, and lower esophagus respectively. The upper esophagus was the most common location (7 of 13; 53.8%). The incidence was higher with hypopharyngeal cancer obviously (4 of 10; 40%) and oropharyngeal cancer (2 of 9; 22.2%), and lower in oral cancer (15 of 104; 12.9%). The detection rate was 92.3% (12 of 13 esophageal neoplasia) by Fuji film system (BLI and LCI) screening, which had the same detection rate by Olympus system (NBI plus Lugol staining). Conclusions: The risk of esophageal cancer associated with cancer of the head and neck is high. Early detection of esophageal neoplasia could improved the long-term outcomes of cases with head and neck cancers associated with esophageal cancer. The highest esophageal cancer incidence was seen for hypopharyngeal cancer. The upper esophagus was the most common location with synchronous or metachronous esophageal neoplasia. Image enhanced endoscopy by BLI and LCI systems could reach the similar detection rate compared with screening by narrow-band imaging and Lugol staining

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食道胃接合部上皮下腫瘤手術切除與內鏡切除的比較研究：一個醫學中心之經驗 COMPARISON STUDY OF SURGICAL VERSUS ENDOSCOPIC RESECTION OF ESOPHAGOGASTRIC JUNCTION SUBEPITHELIAL TUMORS: A SINGLE CENTER EXPERIENCE 1

張琮承江承翰陳冠至方惠玲林政寬李宗熙 1,2 鍾承軒 1 亞東紀念醫院肝膽腸胃科 2 輔仁大學醫學院

Background: The incidence and prevalence of upper gastrointestinal tract subepithelial tumors (SETs) are increasing. Advancements in endoscopic resection (ER) technique, such as endoscopic submucosal dissection (ESD) and submucosal tunneling endoscopic resection (STER) have been applied to the management of esophagogastric junction (EGJ) SETs while surgical resection (SR) is sometimes difficult in this area. Aims: We aimed to compare surgical versus endoscopic resection of EGJ SETs in terms of efficacy and safety. Methods: Between January 2010 and August 2020, we retrospectively collected the demographic, endoscopic and pathological data of patients with EGJ SETs, which was defined as within 1 cm proximal and 2cm distal to the EGJ, after either surgical or endoscopic resection. Technical and clinical success rates and adverse events were compared between two groups. Results: Totally 16 and 20 patients were enrolled in SR and ER (10 ESD and 10 STER) group, respectively. The mean ± SD (SR vs ER) of age (57.50 ± 13.10 vs 50.30 ± 13.10 year-old, p = 0.097), gender ratio (female/male 4/12 vs 10/10, p = 0.709), technical success rate (100% vs 100%), en bloc rate (100% vs 100%), location of tumor (esophageal/gastric site, 0/16 vs 6/14, p = 0.850) and follow-up period (1,231 ± 1,364 vs 697 ± 445 days, p = 0.108) were not different between two groups, while larger gross and pathological tumor size (4.14 ± 2.20 vs 1.02 ± 0.49 cm, p < 0.001, and 4.40 ± 1.90 vs 0.90 ± 0.40 cm, p < 0.0001), longer hospital stay (8.80 ± 7.30 vs 4.90 ± 1.30 days, p = 0.025), longer procedure time (176.10 ± 88.40 vs 46.50 ± 33.80 minutes, p < 0.0001), higher complication rate (18.75% vs 0%, p < 0.0001) were noticed in SR group. The histopathology reported 33% (56.25% and 15.00% in SR and ER group, respectively) were gastrointestinal stromal tumors (GISTs). Additionally, tumor size ≥ 12

2021 消化系聯合學術演講年會

70 mm had sensitivity and specificity of 75% and 60%, respectively, to predict GIST (area under ROC = 0.698). Conclusions: In our study, one-third of EGJ SETs were GIST and tumor size ≥ 12mm could predict the possibility of GIST. ER is an efficient and safe procedure for small EGJ SETs with both diagnostic and curative intents.

人工智慧内視鏡影像判讀系統於早期食道腫瘤診斷的應用 APPLICATION OF AI-ASSISTED IMAGE RECOGNITION SYSTEM IN DIAGNOSING EARLY ESOPHAGEAL NEOPLASMS 1,2,3

1,2

王耀廣王祥辰吳宜珍 1 高雄醫學大學附設中和紀念醫院胃腸內科 2 高雄醫學大學醫學系 3 高雄醫學大學臨床醫學研究所 4 國立中正大學機械系光機電整合工程 Background: Diagnosis of early esophageal neoplasia, including dysplasia and superficial cancer, is a great challenge for endoscopists. Recently, the application of artificial intelligence (AI) using deep learning in the endoscopic field has made significant advancements in diagnosing gastrointestinal cancers. Aims: We aimed to test the ability of an AI-assisted image analysis system in differentiating histological grades of esophageal neoplasms, including low-grade squamous dysplasia, high-grade squamous dysplasia and squamous cell carcinoma (SCC). Methods: In the present study, we constructed a single-shot multibox detector using a convolutional neural network for diagnosing different histological grades of esophageal neoplasms and evaluated the diagnostic accuracy of this computer-aided system. A total of 936 endoscopic images were used as training images and these images included 498 white-light imaging (WLI) and 438 narrow band imaging (NBI) images. The esophageal neoplasms were divided into three classifications: squamous low-grade dysplasia, squamous high-grade dysplasia, and squamous cell carcinoma, based on pathological diagnosis. Results: This AI-system analyzed 264 test images in 10 seconds, and the sensitivity, specificity and diagnostic accuracy of this system in detecting esophageal neoplasms were 96.2%, 70.4% and 90.9% respectively. The accuracy of this AI-system in differentiating the histological grade of esophageal neoplasms was 92%. Our system showed better accuracy in diagnosing NBI (95%) than WLI (89%) images. Conclusions: Our results showed the great potential of AI-system in identifying esophageal neoplasms as well as differentiating histological grades.

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2021 消化系聯合學術演講年會

探討細胞自噬在腫瘤微環境、幽門桿菌致病株及異種移植粒線體影響胃癌細胞惡化之角色 STUDY ON THE ROLES OF AUTOPHAGY IN MICROENVIRONMENT, HELICOBACTER PYLORI VIRULENT STRAIN AND MITOCHONDRIAXENOGRAFT RELATED GASTRIC CANCER TUMORIGENESIS 1

1,4

吳秉儒林姵妏朱曼菱黃斌劉校生吳登強 1 高雄醫學大學附設中和紀念醫院胃腸內科 2 高雄醫學大學熱帶醫學碩士學位學程 3 高雄醫學大學生物醫學暨環境生物學系 4 高雄醫學大學醫學系

Background: Many cancer cells undergo apoptosis through loss of the mitochondrial membranes potential. Loss of membrane potential leads to dysfunction of mitochondria, which are recruited and degraded by selective autophagy machinery, named as mitophagy. Autophagy and mitophagy are involved in normal cell physiology and cancer development. However, their relationship and the underlying mechanism remainpoorly understood. Bacteria Helicobacter pylori (H. pylori) infection causes the syndromes of gastrointestinal tract, induces cell transformation and proceeds to gastric cancer (GC). It also affects cancer cell malignancy through regulation of autophagy. H. pylori also induces the secretion of hepatocyte-derived growth factor (HDGF), and affects the differentiation of mesenchymal stem cells to cancerassociated fibroblasts as well as affects the proliferation and metastasis of GC cells. Despite H. pylori induction of autophagy has been reported, however, there is no conclusive conclusion as well as lack of the exploration of the underlying mechanism. Aims: The objective of this study is to reveal the novel role and mechanism of autophagy and related mitophagy during gastric cancer (GC) tumorigenesis under the stimulation of Helicobacter pylori (H. pylori) infection, microenvironment influence, and exogenous mitochondria transplantation. Methods: Gastric cancer cells (AGS) were co-incubated with Helicobacter pylori (ATCC 49503 strain), adipocytederived mesenchymal stem cells (ADMSC), or exogenous mitochondria which were extracted from human umbilical vein endothelial cells (HUVEC) and human gastric epithelial cells (GES-1) cells. Under the above tumor

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microenvironment, the autophagic activity was examined by immunoblotting and immunofluorescent assay (IFA). Human derived growth factor (HDGF) secretion was examined by ELISA assay in GC cells. We modulated autophagic activity using pharmacological inducers and inhibitor plus genetic silencing lentivial shRNAs. To determine the role of autophagy in GC tumorigenesis and HDGF secretion, GC tumorigenicity was determined by MTT, soft agar, and transwell assaies. Results: Our current findings are as the following: 1). GC cells co-cultured with H. pylori or exogenous mitochondria increased autophagic and mitophagic activities; 2) iPSC co-cultured with H. pylori increased autophagic activity; 3) Autophagy plays a suppressive role in the proliferation of H. pylori infected GC cell. Conclusions: Our data reveal that either H. pylori infection or exogenous mitochondria transplantation of gastric cancer cells leads to increased autophagic activity. Intriguingly, further manipulating autophagic activity by autophagy inducer and inhibitor reveals that autophagy plays a suppressive role in gastric cancer proliferation.

2021 消化系聯合學術演講年會

胃癌細胞移植粒線體後之粒線體蛋白質體學研究 THE REGULATION OF MITOCHONDRIAL PROTEOME AFTER HETEROLOGOUS MITOCHONDRIA TRANSPLANTATION IN GASTRIC CANCER 1

1,3

陳金蘭劉忠榮施翔耀黃斌吳登強盧建宇 1 高雄醫學大學附設中和紀念醫院胃腸內科 2 高雄醫學大學生物醫學暨環境生物學系 3 高雄醫學大學醫學系

1,3

Background: Mitochondria shows a multifunction in cell physiological responses. With the hypothesis of endosymbiosis, mitochondria can move to cells even across the different species. Transplanted with the autologous mitochondria, the malignance of breast cancers were reduced. In our previous study, heterologous mitochondria transplantation showed significant regulation in the malignance of AGS gastric cancer cell. Therefore, it attracts the interests of how the exogenous mitochondria affect the microenvironment of total mitochondria. In the present study, the AGS gastric cancer cell transferred with mitochondria extracted from gastric epithelial cells of normal tissue (GES-1), which showed a lower mitochondria membrane potential (MMP), exhibited a attenuated malignance, however, transferred with vascular endothelial cells (EAhy) that with higher MMP showed an increased malignance. Aims: The mitochondria purified from these treatments were subjected to quantitative proteomics analysis, for which the physiological effects of transplanted mitochondria in regulating cancer metastasis can be further investigated. Methods: The current experiment was designed as four groups: AGS cytosol, AGS mito, AGS+GES cytosol, AGS+GES mito. The GES-1 mitochondria was extracted and then incubated with AGS for 16 hours. The mitochondria were collected by the commercialized kit. The proteins from purified mitochondria and cytosol were digested with trypsin. The resulting peptides were labeled with isobaric tags for relative and absolute quantitation (iTRAQ, AGS cytosol:130n, AGS mito:126, AGS+GES cytosol:130c, AGS+GES mito:131) and then subjected to nLC-MS/MS analysis. After the algorithm against human database. The mitochondrial proteins with increasing fold >1.5 or decreasing fold <0.5 were further analyzed by

ingenuity pathway (IPA) software. Results: In the MS/MS analysis, around 4000 proteins were identified in the cytosolic fraction, while 300 proteins were identified in the mitochondrial fraction. 288 proteins with elevated expression and 127 proteins with decreased expression as compared to the AGS groups in the cytosolic fraction, and 31 proteins with increased expression and 16 protein with decreased expression were identified separately. The IPA analysis revealed that these proteins are involved in the signaling pathways including ERK/MAPK, VEGF, STAT3, JAK/Stat, and GAP junction. With this valuable data, the proteome and possibly the subsequent physiological functions of the mitochondria of AGS cells can be further investigated, particular in the aspects of metabolomics variation, cell cycle, and the progression of malignance. Conclusions: Mitochondria transplantation showed a significant regulation in the migration and malignance of AGS. Further investigate the mitochondrial proteome can provide a valuable reference for discussing the changed mitochondrial efficiency in the development of cancer cells.

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主題：下消化道疾病（二） 73

探討微菌叢植入治療應用於重度或復發性困難梭狀芽孢桿菌引起之腹瀉病患的療效及安全性 ─ 台灣北部單一醫學中心經驗 TO EVALUATE THE EFFICACY AND SAFETY OF FECAL MICROBIOTA TRANSPLANTATION FOR SEVERE AND RECURRENT CLOSTRIDIOIDES DIFFICILE ASSOCIATED DIARRHEA ‒ EXPERIENCES OF A TERTIARY CENTER IN NORTHERN TAIWAN 1

曾柏鈞鍾承軒陳冠至林政寬朱芳業廖俊星 3 3,4 陳介章吳明賢 1 亞東紀念醫院內科部 2 亞東紀念醫院臨床病理科 3 國立臺灣大學醫學院附設醫院內科部 4 國立臺灣大學醫學院

Background: Gut microbiota are associated with human health and many diseases including Clostridoides difficile associated diarrhea (CDAD) which has climbing incidence globally. Fecal microbiota transplantation (FMT) has been demonstrated as an alternative treatment for antibiotics failure CDAD. In Taiwan, FMT has been indicated for recurrent and refractory CDAD since September 2018, however, the efficacy and safety have been seldom reported. Aims: We aimed to evaluate the efficacy and safety of FMT for recurrent and refractory CDAD at a tertiary hospital in northern Taiwan. Methods: We collected clinical data from the patients who received FMT for recurrent or refractory CDAD between October 2019 and August 2020 at Far Eastern Memorial Hospital. The primary and secondary outcome was improvement of diarrhea and FMT-related adverse events (AEs), respectively, within 10 weeks after FMT. The administration of FMT was through colonoscope injection with 300 mL of stool suspension from eligible donors into the terminal ileum or cecum of recipients. The stool donors were related or unrelated to the recipients. The criteria for stool donors included both stool and serum analysis as well as clinical and social risk assessment. We also explored the microbial diversity of pre- and posttransplant stool specimens from three patients using 16S rRNA gene sequencing. Results: Totally five (1 female and 4 male) patients who received FMT under diagnosis of recurrent (n = 1) and refractory (n = 4) CDAD. The mean (± SD) age was 72.4 (±

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9.6) years old. All of them used fidaxomicin before FMT, however, four (80%) of them had fidaxomicin treatment failure, and one (20%) patient was recurrent CDAD after 2 weeks successful fidaxomicin therapy. Until the end of November 2020, none of them had relapse and AEs with average follow-up period of 302 (±95) days. One patient died after FMT 7 months due to bladder cancer without documented recurrence of CDAD. All (100%) of enrolled patients who (n = 3) completed the microbial diversity of pre- and post-transplant stool specimens achieved successful engraftment with microbiota similar to donors. The diversity and richness of microflora of patients after FMT increased by principal co-ordinates analysis, Simpson index, Shannon index, and Chao1 estimator. Conclusions: This study has demonstrated FMT as an efficient and safe treatment for refractory and recurrent CDAD. The clinical success rate was 100% without FMTrelated AE within 10 weeks. Further studies are needed to elucidate the long-term outcome.

2021 消化系聯合學術演講年會

Vancomycin 和 Fidaxomicin 治療困難梭菌相關性腹瀉的觀察 ─ 單一醫學中心經驗 SURVEILLANCE OF VANCOMYCIN AND FIDAXOMICIN FOR CLOSTRIDIUM DIFFICILE-ASSOCIATED DIARRHEA TREATMENT ‒ A SINGLE CENTER EXPERIENCE

CCI was identified as one risk factor for treatment failure. Most patients with vancomycin treatment failure received fidaxomicin treatment with acceptable successful rate (79.2%) subsequently. In the future, those patients who experienced vancomycin and fidaxomicin treatment failure may be candidates for receiving FMT for better outcome.

曾威創陳冠至鍾承軒曾柏鈞林政寬廖俊星亞東紀念醫院內科部 Background: Clostridium difficile-associated diarrhea (CDAD) has become one of the most common hospitalacquired infections. The main treatments for CDAD are antibiotics such as oral vancomycin and fidaxomicin. Aims: In this study, we aimed to evaluate the efficacy of vancomycin and fidaxomicin for CDAD and to identify the potential candidates for fecal microbiota transplant (FMT) for those with treatment failure. Methods: This retrospective study was conducted by medical chart review for the patients diagnosed of CDAD who received vancomycin (125 mg four times daily) and fidaxomicin (200 mg twice daily) orally for 10 days at Far Eastern Memorial Hospital from January 2018 to August 2020. The successful rates of CDAD treatment and identification of risk factors for treatment failure were analyzed in both vancomycin and fidaxomicin groups. Results: A total of 166 patients who diagnosed of CDAD were treated with vancomycin and fidaxomicin orally. In total group, the mean (± standard deviation (SD)) age was 72.36 (± 14.72) years old. Female was found of predominance (53%). The mean (± SD) Charlson Comorbidity Index (CCI) was 6.80 (± 2.61). Among them, 161 patients and 48 patients ever received vancomycin and fidaxomicin treatment respectively, and the successful rate was 52.8% for vancomycin group and 79.2% for fidaxomicin group. In vancomycin group, there was no significant difference between successful and failure subgroup by age (P=0.26) and sex (P=0.54), however, the failure subgroup of vancomycin had significantly higher CCI (P=0.01). In fidaxomicin group (n=48), there were 43 patients who ever experienced treatment failure of vancomycin. The successful rate of fidaxomicin group was 79.2%. There was no significant difference between successful and failure subgroup of fidaxomicin by age (P=0.29), sex (P=0.39), and CCI (P=0.22). Conclusions: High failure rate (47.2%) for CDAD treatment was found in vancomycin group, and higher

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大腸癌和腺瘤患者糞便中的核梭桿菌和脆弱類桿菌的檢測 DETECTION OF FUSOBACTERIUM NUCLEATUM AND BACTEROIDES FRAGILIS FROM STOOL OF COLONORECTAL CANCER AND ADENOMA PATIENTS

結腸無莖型鋸齒狀腺瘤與增生性息肉粘膜上微生物的差異 THE DIFFERENCE OF MUCOSAL MICROBIOTA BETWEEN COLONIC SESSILE SERRATED ADENOMA AND HYPERPLASTIC POLYP

吳孟杰王耀廣翁碧娟劉忠榮余方榮吳登強 1 高雄醫學大學附設中和紀念醫院胃腸內科 2 高雄巿立大同醫院內科 3 高雄醫學大學醫學系 1,2

1,3

Background: Colorectal cancer (CRC) is one of the most common cancer in the world and there are approximately 16 thousand cases diagnosed and 6 thousand deaths reported annually in Taiwan. Most CRC arise from adenoma-cancer pathway. The risk factors are associated with development of CRC including smoking, alcohol, red meat consumption and obesity. The relationship between different bacterial species and the development of colorectal cancer have been reported in recent years. Aims: We evaluated the stool Fusobacterium nucleatum and Bacteroides fragilis in patents who diagnosed with colorectal cancer, adenoma or non-neoplastic lesion. Methods: Fecal samples were collected from the patients diagnosed with colorectal adenocarcinoma, colorectal adenoma and health controls. DNA was extracted from stool by QIAamp DNA Stool Mini Kit (QIAGEN, Hilden, Germany). The stool was tested for the presence of F. nucleatum and B. fragilis. Results: This study included one hundred forty six patients. Fecal samples from 36 cancer patients, 47 adenoma polyp patients, and 63 control patients were analyzed. We detected the presence of F. nucleatum in 50.0% (18/36) of cancer patient, 46.8% (22/47) of polyp patients and 27.0% (17/63) of control cases. B. fragilis was detected in samples from 38.9% (14/36), 36.2% (17/47), and 23.8% (15/63) of patients in the cancer, polyp, and control groups, respectively. We detected stool F. nucleatum significantly less common in health control than that in cancer patients (p<0.05) or adenoma patients (p<0.05). B. fragilis was not significantly higher in fecal samples of cancer patients (p=0.113) and adenoma patients (p=0.158) than control cases. Conclusions: In our study, F. nucleatum was found to be associated with CRC patients and colonorectal adenoma patients, but B. fragilis was not.

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1,2

吳耿良戴維震邱逸群胡銘倫盧龍生郭仲謀 1 高雄長庚紀念醫院胃腸肝膽科系 2 長庚大學醫學系

Background: Colonic serrated polyps are divided into sessile serrated adenoma and hyperplastic polyp. Sessile serrated adenoma progresses to malignancy but hyperplastic polyp benign, the cause is not well understood. The gastrointestinal microorganisms are related with colorectal carcinogenesis. Whether the distribution of the gastrointestinal microorganisms cause the difference between sessile serrated adenoma with hyperplastic polyp is not clear. Aims: We aimed to clarify the specific microorganisms in the colon mucosa of sessile serrated adenoma and hyperplastic polyp, then assess the correlation between serrated polyps and inflammation. Methods: Fifty subjects divided as five groups: controls, hyperplastic polyp, adenoma (tubular, villous), sessile serrated adenoma and adenocarcinoma were recruited. Demographic and clinical variables (age, sex, BMI, anatomic location, polyp size, and clinical indications) were recorded and their colonic mucosa and stool were taken. We used NGS to analyze microorganisms and analyzed serum inflammatory cytokines by Luminex. Results: Fifty patients (57 ± 11 years old; 31 males; BMI: 24.5 ± 5.0 kg/m 2) were recruited and divided as these groups: 10 controls, 10 patients with hyperplastic polyp, 9 with tubular adenoma and 9 with villous adenoma, 7 with sessile serrated adenoma and 5 with adenocarcinoma. Lower abundance and diversity of fecal and mucosal microbiota were found in sessile serrated adenoma and adenocarcinoma group. More numbers of fusobacteriales in sessile serrated adenoma and more Bacteroidales in hyperplastic polyp were found. More significant pantothenate and coenzyme A biosynthesis was found in hyperplastic polyp than sessile serrated adenoma. Higher levels of serum IL-8 (p = 0.005) in colon cancer patients than controls were noted. Conclusions: More numbers of mucosal fusobacteriales are found in sessile serrated adenoma and more Bacteroidales in hyperplastic polyp, it could be related with pantothenate and coenzyme A biosynthesis.

2021 消化系聯合學術演講年會

膠囊內視鏡在小兒患者之功效與安全性 EFFICACY AND SAFETY OF CAPSULE ENDOSCOPY IN PEDIATRIC PATIENTS

以氣囊輔助式小腸鏡診斷之梅克爾憩室：一台灣多醫學中心之臨床研究 MECKEL’S DIVERTICULUM DIAGNOSED BY BALLOON-ASSISTED ENTEROSCOPY: A CLINICAL STUDY OF MULTI-MEDICAL CENTERS IN TAIWAN

廖苡君林宛姿張崇信廖思嘉柯忠旺楊勝舜 1,2 吳孟哲 1 臺中榮民總醫院肝膽胃腸科 2 臺中榮民總醫院小兒胃腸科

Background: Capsule endoscopy (CE) is a noninvasive examination which enabling excellent visualization of the small bowel mucosal lesion. FDA had approved CE for pediatric patients older than 2 years of age in 2009. Aims: To evaluate the clinical efficacy and safety of CE in pediatric patients. Methods: From April 2014 to December 2020, CE procedures performed for diagnosis of small-bowel disease in children less than 18 years of age at Taichung Veteran General Hospital were analyzed. Data of indications, endoscopic findings, diagnostic outcome, and complications associated with the procedure were collected and reviewed retrospectively. Results: Among 36 patients, the completion rate was 91.9% (n = 34), with an average age of 12.6 ± 3.0 years old. Suspicion or evaluation of inflammatory bowel diseases (44%) was the most common indication for CE (25% for patients with suspicion of Crohn’s disease (CD), 16% for patients known to have CD). Other common indications of CE were abdominal pain (33%) and obscure gastrointestinal bleeding or iron deficiency anemia (20%). One CE remained in the stomach for more than 11 hours till the end of examination. No procedure related complications occurred. A total of 20 CE procedures showed positive findings, and the overall diagnostic yield rate was 54.1%. Small bowel ulcers (65%) were the most common findings, and 24.3% of CE examinations resulted in a new diagnosis and led to change in therapy. Conclusions: CE is a safe and feasible diagnostic method to study the small intestine in children, especially for CD and abdominal pain. CE has great value to aid in diagnosis, monitor disease activity, and assist patient management in CD.

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2,14

3,14

4,14

5,14

周仁偉鍾承軒凃佳宏章振旺黃天祐 6,14 7,14 8,14 9,14 10,14 顏旭亨張崇信林敬斌王彥博許文鴻 11,14 12,14 13,14 11,14 11,14 郭家榮莊喬雄蔡騌圳蘇銘堯邱正堂 1 中國醫藥大學附設醫院消化醫學中心 2 亞東紀念醫院胃腸肝膽科 3 國立台灣大學附設醫院肝膽腸胃科 4 馬偕紀念醫院胃腸肝膽科 5 三軍總醫院胃腸肝膽科 6 彰化基督教醫院胃腸肝膽科 7 臺中榮民總醫院胃腸肝膽科 8 中山醫學大學附設醫院胃腸肝膽科 9 臺北榮民總醫院胃腸肝膽科 10 高雄醫學大學附設中和紀念醫院胃腸肝膽科 11 林口長庚紀念醫院胃腸肝膽科系 12 國立成功大學附設醫院肝膽腸胃科 13 高雄榮民總醫院胃腸肝膽科 14 台灣小腸醫學會 Background: Patients with Meckel’s diverticulum are usually asymptomatic; however, some patients present with symptoms, including gastrointestinal bleeding, abdominal pain, intestinal obstruction, and diverticulitis. In the past, Meckel’s diverticulum is difficult to diagnose preoperatively because of the endoscopic inaccessibility. The newly developed balloon-assisted enteroscopy allows endoscopic access to the entire small intestine. Aims: The aim of this current study was to investigate the clinical characteristics, endoscopic features, histopathological findings, treatment methods and outcomes of patients with Meckel’s diverticulum diagnosed by balloon-assisted enteroscopy in Taiwan. Methods: From September 2005 to November 2020, we conducted a retrospective study of patients with Meckel’s diverticulum diagnosed by balloon-assisted enteroscopy at several medical centers in Taiwan. Balloon-assisted enteroscopy, using the double-balloon endoscopy or singleballoon enteroscopy, was performed in patients with suspected small intestinal disorders. The age, sex, clinical presentations, endoscopic features, histopathological findings, treatment methods and outcomes of patients with Meckel’s diverticulum diagnosed by balloon-assisted

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enteroscopy were collected and analyzed. Results: A total of 54 patients with Meckel’s diverticulum diagnosed by balloon-assisted enteroscopy were enrolled into our current study. There were 45 males and 9 females with a male to female ratio of 5:1. The mean age of all patients was 33.90 ± 17.50 years (range, 4-85 years). Gastrointestinal bleeding (86.9% of all patients) accounted for the major indication of balloon-assisted enteroscopy, followed by abdominal pain (5/54, 9.3%), suspected small bowel tumor (1/54, 1.9%), and Crohn’s disease follow-up (1/54, 1.9%). Double-balloon enteroscopy was performed in 53.7% of all patients and single-balloon enteroscopy was performed in another 46.3% of all patients. The diagnostic approach method of Meckel’s diverticulum: the retrograde approach enteroscopy was performed in 98.1% of all patients and the antegrade approach enteroscopy was performed in 1.9% of all patients. In the distance between Meckel’s diverticulum and the ileocecal valve: the distance was ≤ 60 cm in 57.4% of all patients and the distance was > 60 cm in 42.6% of all patients. The diagnostic yield of modalities other than balloon-assisted enteroscopy was as follows: capsule endoscopy, 40.0%; Meckel’s scan, 35.7%; computed tomography, 14.6%; small bowel series, 12.5%; and angiography, 11.1%. The endoscopic features of Meckel’s diverticulum showed a large ostium in 49 out of 54 patients (90.7%), a small ostium in 4 out of 54 patients (7.4%), and a polypoid lesion in 1out of 54 patients (1.9%). Surgical treatment was performed in 40 patients (40/54, 74.1%) and conservative medical treatment was performed in three patients (14/54, 25.9%). As for the heterotopic tissue of Meckel’s diverticulum, heterotopic gastric tissue was identified in 22 of 42 patients (52.4%), heterotopic pancreatic tissue was identified in 5 of 42 patients (11.9%), and heterotopic colonic tissue was identified in 1 of 42 patients (2.4%). Conclusions: From the results in our current study, balloon-assisted enteroscopy is a very useful modality in detecting Meckel’s diverticulum than other conventional modalities. Although symptomatic Meckel’s diverticulum is rare in adults, it should be considered in adult patients presenting with obscure gastrointestinal bleeding in Taiwan.

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壁報展示

第一部分：肝 P.001 在慢性乙型肝炎病毒相關肝硬化的患者中，將 Tenofovir Disoproxil Fumarate 更換為 Tenofovir Alafenamide 對腎臟功能影響的回溯式世代研究 A RETROSPECTIVE COHORT STUDY OF THE INFLUENCE OF RENAL FUNCTION AFTER TENOFOVIR DISOPROXIL FUMARATE SHIFTING TO TENOFOVIR ALAFENAMIDE IN CHRONIC HEPATITIS B VIRUS RELATED CIRRHOTIC PATIENTS

12.0, p value = 0.111). There is significant improvement in the eGFR < 90 group after TAF therapy (eGFR before: 73.1 ± 11.8, eGFR after: 76.7 ± 13.2, p value = 0.008) (Figure 1). Conclusions: This study suggests that switching from TDF to TAF is associated with improvement of renal function in eGFR < 90 patients.

賴皝綸林瑞昌林裕鴻王俊雄郭明正張國寬魏克承毛元治陳一毅牟聯瑞台南市立醫院（委託秀傳醫療社團法人經營）肝膽胃腸科 Background: Tenofovir disoproxil fumarate (TDF) is known to cause the development of nephrotoxicity and bone density loss. In contrast to TDF, tenofovir alafenamide (TAF) is a prodrug with a favorable renal safety profile due to approximately 90% lower tenofovir plasma concentrations. Aims: This study aimed to compare the renal function change in patients with chronic HBV related cirrhosis who originally received tenofovir disoproxil fumarate therapy and then were shifted to tenofovir alafenamide. Methods: We performed a retrospective study of HBV related cirrhotic patients who were treated with TDF and then shifting to TAF since May 2020. All patients were followed up every 4 weeks or more frequently. This study conformed to the institutional review board of Tainan Municipal Hospital. The renal function was examined at the time points before switching from TDF to TAF and after switching to TAF in the most recent outpatient followup. The patients were divided into two groups according to their estimated glomerular filtration rate (eGFR). A paired student t-test was used to compare the renal function change in different time points of the two groups (eGFR ≥ 90 and eGFR < 90). Continuous data are expressed as mean ± standard deviation and categorical data are expressed as number (percentage). Results: A total of 73 patients (eGFR ≥ 90: 31, eGFR < 90: 42, male: 54 (%), female: 19 (%), average age: 59.9 ± 10.5 years old) were enrolled. All basic characteristics of the patients were revealed in table 1. The results showed no significant difference of renal function change in eGFR ≥ 90 group (eGFR before: 102.9 ± 13.3, eGFR after: 100.5 ±

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P.002

P.003

韋立得在慢性 B 型肝炎嚴重急性發作的治療成效：單一醫學中心經驗 SAFETY AND EFFICACY OF TENOFOVIR ALAFENAMIDE FOR PATIENTS WITH SEVERE EXACERBATION OF CHRONIC HEPATITIS B: REAL-WORLD EXPERIENCE OF ONE SINGLE MEDICAL CENTER

服用惠立妥或貝樂克治療的慢性 B 型肝炎患者改用韋立得 12 週後的體重變化 THE BODY WEIGHT CHANGES OF SWITCHING TO A 12-WEEK TENOFOVIR ALAFENAMIDE IN PRIOR TENOFOVIR DISOPROXIL FUMARATE OR ENTECAVIR TREATED CHRONIC HEPATITIS B PATIENTS

黃儀倢李少武李騰裕童春芳廖思嘉葉宏仁張繼森楊勝舜張崇信臺中榮民總醫院肝膽腸胃科 B a c k g r o u n d : Te n o f o v i r a l a f e n a m i d e ( TA F ) i s recommended as first-line therapy for chronic hepatitis B (CHB). Aims: The efficacy and safety of TAF in patients with severe acute exacerbation (SAE) of CHB is uncertain. We conduct the study to evaluate the efficacy of TAF in CHB patients with SAE. Methods: From May 2019 to June 2020, 12 CHB patients with SAE, defined as an elevation of alanine aminotransferase (ALT) > 10 upper limit of normal who received 25 mg TAF in Taichung veteran general hospital were enrolled for analysis. We evaluated the virological and biochemical responses. Results: 12 CHB patients with SAE, mean age of 47.6 ± 10.12 and 50% male, treated with a median duration of 7.47 ± 4.4 months. The median baseline HBV DNA level was 6 ± 1.37 log IU/ml and the median baseline qHBsAg was 4.06 ± 1.27 log IU/ml ; the median baseline ALT and peak ALT level were 719 ± 279 U/L and 836 ± 416 U/L, respectively (Table1). The 6-month virological response rate is 51%; the 6-month ALT normalization rate by local laboratory criteria and by AASLD criteria were 64% and 42%, respectively (Figure 1 & 2). The dynamic change in HBsAg level from baseline to month 6 is significant (p = 0.018) (Figure 3). No liver decompensation and no adverse effect were noted during treatment. Conclusions: TAF provided favorable efficacy and safety for chronic hepatitis B patients with SAE.

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鄭斌男劉俊人馮意哲陳志州曾逸豪余明隆 8 2,3 黃怡翔陳培哲 1 國立成功大學醫學院附設醫院內科部 2 國立臺灣大學醫學院附設醫院內科部 3 國立臺灣大學醫學院臨床醫學研究所 4 奇美醫學中心內科部 5 柳營奇美醫院肝膽胃腸科 6 阮綜合醫院內科部 7 高雄醫學大學附設醫院肝膽胰內科 8 臺北榮民總醫院胃腸肝膽科

Background: Hepatitis B virus (HBV) infection has been reported to have inverse association with hyperlipidemia and cardiovascular events. However, reports that showed body weight (BW) increased during tenofovir alafenamide (TAF)-containing regimens in human immune-deficient virus (HIV) raise the needs to investigate the impact of TAF treatment in chronic hepatitis B (CHB) patients. Aims: To compare the BW profiles following switching to a 12-week TAF in prior tenofovir disproxil fumarate (TDF) or entecav CHB patients. Methods: CHB patients treated with TDF or entecavir for at least 1 years and then switched to TAF were enrolled. BW, sugar and lipid profiles, liver biochemical tests were examined before switching and 12 weeks after switching to TAF. Results: A total of 117 patients, including 79 males and 38 females, were enrolled since May 2020 in seven hospitals. Among them, 74 patients received TDF and 43 patients received ETV before switching to TAF. At baseline, comparable age, ALT, albumin, prothrombin time, creatinine and eGFR and BW were observed between the two groups of patients. Prior ETV-treated patients had lower levels of cholesterol (p<0.001), triglyceride (p=0.037), LDL (p=0.009), but not HDL (p=0.020) than prior TDF-treated patients. Of them, 53 prior TDF- and 22 prior ETV-treated patients had been followed for at least 12 weeks after switching to TDF. Following 12-week TAF treatment, BW significantly increased in prior TDF-treated

2021 消化系聯合學術演講年會

P.004 group (66.7 ± 12.6 kg to 67.4 ± 12.2 kg, p=0.002), but not in prior ETV-treated group (61.3 ± 9.9 kg to 61.6 ± 9.6 kg, p=0.316). There was a trend of increased percentage of BW in prior TDF group (1.3 ‒ 2.5%) than prior ETV group (0.6 ‒ 2.5%) at 12-week TAF treatment. Conclusions: Patients treated with TDF exhibited lower lipid profiles than ETV. BW increased significantly and shortly after switching to TAF in prior TDF-treated CHB.

韋立得、貝樂克和惠立妥對於貝樂克和惠立妥停藥後病毒復發病人再治療的療效和腎功能安全性的比較 COMPARISON OF THE RETREATMENT EFFICACY AND RENAL SAFETY OF TAF, ENTECAVIR AND TDF AFTER HBV RELAPSE IN PATIENTS WHO DISCONTINUED ENTECAVIR OR TDF THERAPY 邱紹銘陳建宏胡琮輝王景弘洪肇宏盧勝男高雄長庚紀念醫院胃腸肝膽科 Background: The retreatment efficacy and renal safety of tenofovir alafenamide (TAF) after HBV relapse in patients who discontinued nucleos(t)ide analogues remain unclear. Aims: To compare the one-year retreatment efficacy and renal safety of entecavir, tenofovir disoproxil fumarate (TDF) and TAF after HBV relapse in patients who discontinued entecavir or TDF therapy. Methods: This retrospective study included 229 patients without cirrhosis who received entecavir (n=79), TDF (n=101) and TAF (n=50) retreatment for at least one year. All patients who discontinued entecavir or TDF therapy fulfilled the stopping criteria for antiviral agents according to the 2012 guidelines of APASL in the past course of treatment. All patients who received retreatment fulfilled the retreatment criteria of Taiwan’s National Health Plan. Acute kidney injury (AKI) is defined as increase in serum creatinine by ≥0.3 mg/dL as KDIGO guideline. Results: There was no significant difference in baseline characteristics among three groups. The rates of virological response (HBV DNA < 20 IU/mL) at one year of retreatment in three groups were 85.7% (entecavir group), 86% (TDF group) and 83.7% (TAF group), respectively (p=0.934). Multivariate analysis showed that only higher baseline HBV DNA level was an independent factor for virological response at one year of retreatment (OR: 0.363, 95 CI: 0.241-0.547, p<0.001). The rates of ALT normalization (ALT ≤ 40 U/L) at one year of retreatment in three groups were 82.3% (entecavir group), 78.2% (TDF group) and 86% (TAF group), respectively (p=0.246). However, TDF group (37.0 ± 33.9 U/L) had higher ALT levels at 12 months of retreatment than TAF (22.7 ± 11.3 U/L, p=0.014) and entecavir (27.1 ± 16.5 U/L, p=0.018) groups. There was no significant differences in eGFR decline at one year of retreatment from baseline among three groups (p=0.743). Two patients experienced AKI

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P.005 during TDF therapy and no patient experienced AKI during entecavir and TAF therapy (p=0.292). Conclusions: TAF, entecavir and TDF had similar effectiveness in virological and biochemical responses and renal safety at one year of retreatment.

韋立德治療成效 TAF EFFICACY IN REAL-WORLD TREATMENT NAÏVE CHB PATIENTS 張庭遠黃釧峰戴嘉言黃志富莊萬龍高雄醫學大學附設醫院肝膽胰內科 Background: Tenofovir Alafenamide (TAF) is a novel tenofovir prodrug, and it has demonstrated non-inferior 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 evidence of TAF in local real-world CHB patients are still limited. Aims: We aim to determine the efficacy 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 48. Secondary endpoints were changes in alanine aminotransferase (ALT), estimated glomerular filtration rate as per Modification of Diet in Renal Disease (MDRD) (eGFRMDRD). All laboratory data were collected as per the standard of care practice every 3-6 month. Results: In total, data of 98 naïve CHB patients treated with TAF for at least 12 months were analyzed. Median age was 51 years, 79.6% of patients were male, 4.1% of patients were cirrhotic, and 22.2% and 23.3% of patients had a history of. 84 patients have baseline and 12-month HBV DNA data. After 48-week treatment of TAF, 74/84 (88.1%) patients achieved DNA viral suppression. After 48-week treatment of TAF, ALT normalization rate was 80.5% and 68.3% according to ALT < 40 IU/L and AASLD 2018 criteria, respectively. After 48-week treatment of TAF, HBeAg loss was 41.0% and HBeAb seroconversion rate was 33.0%. For the renal safety, the median eGFRMDRD was stably maintained (from 92.7 mL/min/1.73m2 to 93.0 mL/min/1.73m2). In the baseline eGFRMDRD 60-90 mL/ min/1.73m2 group, the eGFRMDRD changed from 78.8 mL/min/1.73m2 to 85.7 mL/min/1.73m2 (P=0.02). Conclusions: TAF had high HBV undetectable rate, HBeAg loss and HBeAb seroconversion rate. It also improved renal function in patients with eGFR 60-90 mL/ min/1.73m2.

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P.006 韋立得治療慢性 B 型肝炎一年療效：一個真實世界經驗 ONE-YEAR EFFICACY OF TENOFOVIR ALAFENAMIDE IN CHRONIC HEPATITIS B PATIENTS: A REALWORLD EXPERIENCE 1,2

1,2

陳益程簡榮南許朝偉戴達英 1 林口長庚紀念醫院胃腸肝膽科 2 長庚大學醫學院

1,2

month 12 were statistically significant in creatinine and eGFR (both p<0.001). All patients were tolerable to TAF and compensated at entry and during treatment. Conclusions: One-year efficacy of TAF treatment revealed HBV DNA <20 IU/mL in ~70%, ALT normalization in ~80% and HBeAg seroclearance in ~30% in real-world clinical practice. Creatinine increased and eGFR decreased significantly at month 12. Longer term follow-up is warranted.

Background: Tenofovir alafenamide (TAF) is a novel prodrug to deliver tenofovir to hepatic cells more efficiently at a lower dose than tenofovir disoproxil fumarate (TDF). The real-world experience in the efficacy of TAF to treatment of chronic hepatitis B (CHB) is limited. Aims: To explore one-year efficacy of TAF in CHB patients in a single medical center. Methods: Two hundred and 21 CHB patients treated with TAF between 2019 May and 2019 Nov were retrospectively reviewed in electronic medical records. Those with prophylactic antiviral therapy before chemotherapy (n=64), a history of hepatocellular carcinoma (n=21), coinfection with hepatitis C virus (n=5) and treatment duration less than 12 months (n=16) were excluded. Primary endpoint was HBV DNA <20 IU/mL (or undetectable) at month 12. Secondary endpoints included the rates of ALT normalization (≤36 U/L) and HBeAg seroclearance, and changes of creatinine and estimated glomerular infiltration rate (eGFR) at month 12. Results: A total of 115 patients were included for analysis. The mean age was 52.7 ± 11.5 years and mean BMI was 25.7 ± 3.4 kg/m2. There were 80 (69.6%) males, 35 (30.4%) HBeAg-positive, 57 (49.6%) treatment-naïve, 10 (8.7%) cirrhosis, and 16 (14%) diabetes. Baseline median (IQR) AST, ALT, total bilirubin and HBV DNA were 84 (55-135) U/L, 149 (100-241) U/L, 0.8 (0.6-1.0) mg/dL and 6.74 (5.74-8.13) log IU/mL, respectively. The median treatment duration was 15.6 (13.7-17.0) months. Baseline mean creatinine and eGFR were 0.83 ± 0.23 mg/ dL and 96.6 ± 17.4 mL/min/1.73m2, respectively, with 62 (65.3%) ≥90 mL/min/1.73m2 and 30 (31.6%) 60-90 mL/ min/1.73m2. HBeAg seroclearance occurred in 11 (31.4%), ALT normalization in 90 (78.3%) and HBV DNA <20 IU/ mL in 67 (68.4%, follow-up DNA available in 98 patients) at month 12. The mean creatinine and eGFR at month 12 were 0.87 ± 0.27 mg/dL and 93.7 ± 17.0 mL/min/1.73m2, respectively. Paired comparisons between baseline and

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P.007 接受治療之慢性 B 型肝炎患者長期縱向聲輻射力脈衝（ARFI）的變化 LONGITUDINAL CHANGES IN ACOUSTIC RADIATION FORCE IMPULSE (ARFI) VALUES IN PATIENTS WITH CHRONIC HEPATITIS B RECEIVING NUCLEOS(T)IDE ANALOGUE THERAPY 王鴻偉陳昇弘賴學洲莊伯恒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醫學中心 Background: The benefits of long-term nucleos(t)ide analogue (NA) therapy for patients with chronic hepatitis B (CHB) include regression of liver fibrosis and a decrease in the incidence of liver-related events. Acoustic radiation force pulse (ARFI) elastography is one of the useful noninvasive methods to monitor the dynamic changes of liver stiffness longitudinally. Aims: We aimed to investigate the longitudinal ARFI changes in patients with CHB receiving NA therapy. Methods: A total of 175 patients with CHB who received NA therapy, including ETV and TDF and had at least two sessions of ARFI studies including at baseline and another time point during the treatment period were enrolled retrospectively. Baseline clinical characteristics, liver histopathology, liver-related events (hepatocellular carcinoma, ascites, esophageal variceal bleeding, and encephalopathy) and ARFI measurement data were collected. The association between ARFI values and other fibrosis markers, including FIB-4 and histopathology (METAVIR score), was evaluated by Spearman correlation. The trend of serial ARFI values according to the severity of fibrosis categorized by baseline liver stiffness measurement (LSM) was determined by Jonckheere-Terpstra trend test. Generalized linear mixed model (GLMM) was used to compare longitudinal repeated measurements by first-order autoregressive correlation structure and the time trend. Kaplan-Meier analysis with the log-rank test was used to compare the factors as univariate analysis. Results: For 175 patients during the follow-up period encompassing 10 time points of measurement, a total of 870 measured LSM values were recorded. Baseline characteristics were median age: 47 years, 44% (n = 77) cirrhosis, 73.7% (n = 129) male, and 46.3% (n = 81) HBeAg positive. A total of 11 patients (6.3%) had liverrelated events during a median follow-up period of 4 years

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(208 weeks). Baseline LSM was moderately correlated with METAVIR fibrosis stage and baseline FIB-4 (r = 0.488 and 0.301, respectively). The serial median LSM values decreased during antiviral therapy (from baseline 1.59, to 1 year 1.20, to 4 years 1.17 m/sec). The median percentage decline in LSM at 4 weeks, 6 months, 1 year, 2 years and 4 years were about 7, 10, 15, 20 and 30% compared with baseline LSM. The serial median LSM values declined significantly in patients with baseline LSM ≥1.59 m/sec (from baseline 2.40 to 4 years 1.34 m/sec, time trend P = 0.025) and declined numerically in patients with baseline <1.59 m/sec (from baseline 1.25 to 4 years 1.09 m/sec, time trend P = 0.276). The serial median LSM values and percent changes in LSM values in the group with baseline LSM ≥ 1.59 m/sec were significantly greater than those in the group with baseline LSM <1.59 m/sec (P < 0.001). Baseline LSM higher than a cutoff value of 1.59 m/sec was significantly associated with the cumulative incidence of liver-related events by Kaplan-Meier analysis (8.3% versus 1.6% at 60 months, P = 0.017). Patients with baseline LSM ≥ 1.59 m/sec and 1-year LSM ≥ 1.20 m/sec had a significantly higher cumulative incidence of liver-related events compared to the other subgroups by Kaplan-Meier analysis (13.4% versus 0% at 60 months, P = 0.004). Conclusions: CHB patients receiving NA therapy exhibited a LSM decline of up to 30% in median values after 4 years of treatment. Patients with a higher baseline LSM (≥1.59 m/sec) had significantly greater improvement in LSM longitudinally than did those with a lower baseline LSM (<1.59 m/sec). Further external validation is warranted.

2021 消化系聯合學術演講年會

P.008

P.009

利用健保資料庫分析慢性 B 型肝炎患者使用惠立妥及貝樂克發生肝癌在台灣的研究 HEPATOCELLULAR CARCINOMA INCIDENCE IN CHRONIC HEPATITIS B PATIENTS TREATED WITH TENOFOVIR VERSUS ENTECAVIR: AN ANALYSIS USING THE NATIONAL HEALTH INSURANCE RESEARCH DATABASE (NHIRD)

Tenofovir Alafenamide（TAF）於慢性 B 型肝炎病人在兩個第三期臨床試驗五年病毒抑制和安全性的結果 MAINTENANCE OF HIGH LEVELS OF VIRAL SUPPRESSION AND IMPROVED SAFETY PROFILE OF TENOFOVIR ALAFENAMIDE (TAF) RELATIVE TO TENOFOVIR DISOPROXIL FUMARATE (TDF) IN CHRONIC HEPATITIS B PATIENTS TREATED FOR 5 YEARS IN 2 ONGOING PHASE 3 STUDIES

1,3

方冠傑蘇建維高偉育葉欣榮唐瑞祥張君照 1 臺北醫學大學附設醫院消化內科 2 臺北榮民總醫院胃腸肝膽科 3 枋寮醫院肝膽腸胃內科

Background: Tenofovir disoproxil fumarate (TDF) and entecavir are both recommended as first-line treatments for chronic hepatitis B virus (HBV) infection. However, whether it would increase the incidence rate of de-novo hepatocellular carcinoma (HCC) is still obscure. Aims: We aimed to elucidate the difference of HCC incidence in CHB patients treated with ETV compared to TDF. Methods: Using a nationwide database of Taiwan, we identified 74,880 HBV patients who received nucleos(t) ide analogues (NA). 6,656 HBV Patients treated with Tenofovir and 26,029 HBV Patients with Entecavir during 2006 to 2016. Factors determining the incidence of de-novo HCC were analysed by Cox proportional hazards model and propensity score matching analysis. Results: During our study period, 430 patients developed HCC. 93 patients in the TDF group. The incidence of HCC was not significantly different between TDF and ETV group through in univariate analusis. Competing risk multivariate analysis also found no significant difference of HCC incidence between the two groups (HR: 0.852; 95% CI, 0.677-1.072, P = 0.1022). Old age, male gender, cirrhosis, alcoholic liver disease, use of metformin, and use of PPI were associated with significantly higher risk of HCC in multivariate analysis. Conclusions: We found there was no statistically significant difference with an increased risk of HCC between the long-term use of ETV and TDF. Randomized trials are needed to support this finding.

Henry LY Chan , Maria Buti , Kosh Agarwal , 4 5 6 Patrick Marcellin , Young Suk Lim , Maurizia Brunetto , 7 8 9 Wan-Long Chuang , Harry LA Janssen , Scott Fung , 10 11 11 Namiki Izumi , John F. Flaherty , Kris Mar , 11 11 11 Vithika Suri , Bing Gao , Gregory Camus , 11 11 12 Anuj Gaggar , Diana Brainard , Calvin Q. Pan , 13 14 15 Shalimar , Way Kai Seto , Edward Gane 1 The Chinese University of Hong Kong, Hong Kong 2 Hospital Universitari Vall d’Hebron, Barcelona, Spain Kings College Hospital Institute of Liver Studies, London, 3 UK 4 Hôpital Beaujon, Clichy, France Asan Medical Center, University of Ulsan College of 5 Medicine, Seoul, Korea 6 Università di Pisa, Italy Kaohsiung Medical University Chung-Ho Memorial 7 Hospital, Kaohsiung, Taiwan Toronto Centre for Liver Disease, Toronto Western and General Hospital, University Health Network, Toronto, 8 Ontario, Canada 9 University of Toronto, Toronto, Ontario, Canada Japanese Red Cross Musashino Hospital, Musashino, 10 Japan 11 Gilead Sciences, Inc., Foster City, CA, USA 12 NYU Langone Health, New York, NY, USA 13 All India Institute of Medical Science, New Delhi, India LKS Faculty of Medicine, The University of Hong Kong, 14 Hong Kong 15 Auckland Clinical Studies, Grafton, New Zealand Background: In 2 identically-designed double-blind (DB), randomized (2:1), Phase 3 studies (Study 108 in HBeAgnegative patients [N=425] and Study 110 in HBeAgpositive patients [N=873]), TAF demonstrated antiviral efficacy non-inferior to that of TDF with superior renal and bone safety. After completing up to 3 years of DB

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P.010 treatment, all patients were eligible to receive open-label (OL) TAF through Week 384 (Year 8). Aims: Here we present study results at Year 5. Methods: Efficacy was assessed by individual study and included serial virologic, biochemical, and serologic assessments, while safety data were pooled including changes in estimated GFR (by Cockcroft-Gault method; eGFRCG) and changes in hip and spine bone mineral density (BMD) by DXA scans. Resistance testing by population sequencing of pol/RT and phenotyping was performed annually through Year 5. Results: Of 1298 randomized and treated patients, 1157 (89%; 775 TAF; 382 TDF) entered the OL phase, including 180 and 202 TDF-treated patients who began OL TAF at Week 96 (TDF-OL TAF 3y) or Week 144 (TDF-OL TAF 2y) depending upon timing of a protocol amendment. At Week 240 (Year 5), 999 (77%; 675 TAF, 136 TDFTAF OL 3y, 188 TDF-TAF OL 2y) patients remained on treatment. High rates of virologic control were achieved and maintained in patients receiving TAF throughout and for TDF patients who rolled over to TAF at Weeks 96 or 144 (Table). Rates of ALT normalization and serologic responses were also comparable among groups. Of 44 patients who qualified for population sequencing, 8 with amino acid changes are undergoing phenotypic testing with results pending. Rates of Grade 3/4 adverse events (AEs) and AEs leading to discontinuation were low and similar among groups. After experiencing declines in eGFRCG and in hip/spine BMD over 2 or 3 years of TDF treatment, renal and bone outcomes were improved following the switch to OL TAF. Conclusions: After 5 years of treatment virologic suppression rates remained high, and TAF was safe and well-tolerated with improved renal and bone safety in patients switching from TDF.

食物共服對於 Tenofovir Alafenamide (TAF) 在從 TDF 轉換之病毒已抑制的慢性 B 型肝炎病人中 96 週有效性與安全性的影響 IMPACT OF COADMINISTRATION WITH OR WITHOUT FOOD ON THE 96WEEK EFFICACY AND SAFETY OF TAF IN VIRALLY SUPPRESSED CHRONIC HBV PATIENTS SWITCHED FROM TENOFOVIR DISOPROXIL FUMARATE TO TAF 1

Jia-Horng Kao , Wan-Long Chuang , Chi-Yi Chen , 4 5 6 Sang Hoon Ahn , Scott Fung , Magdy Elkashab , 7 8 Hie-Won Hann , Natarajan Ravendhran , 9 10 10 Tuan Trong Nguyen , Susanna K Tan , John F Flaherty , 10 10 10 10 Kris Mar , Anuj Gaggar , Bing Gao , Diana Brainard , 11 12 13 Charles Pham , Young-Suk Lim , Maria Buti , 14 Pietro Lampertico 1 National Taiwan University Hospital, Taipei, Taiwan Kaohsiung Medical University Chung-Ho Memorial 2 Hospital, Kaohsiung, Taiwan 3 Chia-Yi Christian Hospital, Chiayi, Taiwan 4 Severance Hospital, Seoul, Korea 5 University of Toronto, Toronto, Ontario, Canada 6 Toronto Liver Centre, Toronto, Ontario, Canada Thomas Jefferson University Hospital, Philadelphia, PA, 7 USA 8 Digestive Disease Associates, Catonsville, MD, USA Tuan Nguyen, M.D., Research & Education, Inc., San 9 Diego, CA, USA 10 Gilead Sciences, Inc., Foster City, CA, USA Memorial Hermann Sugar Land Hospital, Sugar Land, TX, 11 USA Asan Medical Center, University of Ulsan College of 12 Medicine, Seoul, Korea 13 Hospital Universitari Vall d’Hebron, Barcelona, Spain Fondazione IRCCS Ca’ Granda Ospedale Maggiore 14 Policlinico, Milano, Italy Background: TAF has shown noninferior efficacy to TDF with superior bone and renal safety in a virally suppressed switch population of CHB patients taking TDF long-term. In contrast to the registrational trials where all patients were required to take TAF or TDF with food, given limited information on food effect at the time, patients who participated in the switch study were permitted to take their study drug without or with food in a manner similar to how they took TDF.

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P.011 Aims: We undertook a sub-analysis to evaluate the impact of giving TAF once daily without or with food. Methods: In this Phase 3 study (Study 4018; NCT02979613), CHB patients virally suppressed on TDF were randomized (2:1) to switch to TAF or remain on TDF for 48 weeks, after which patients received open-label TAF for an additional 48 weeks (TAF-TAF and TDF-TAF groups, respectively). The efficacy and safety of TAF-TAF and TDF-TAF treatment were assessed over 96 weeks for patients taking study drug without vs with food by serial HBV DNA levels, and routine clinical and laboratory safety assessments, including change in creatinine clearance by the Cockcroft-Gault method (eGFRCG), and changes in hip and spine bone mineral density (BMD) by serial DXA scans. Results: Of 488 patients randomized and treated, 162 (33%) continued taking study drug without food with a similar distribution of patients among treatment arms (n=81 each for the TAF-TAF and TDF-TAF groups). Groups were well matched at baseline except a higher proportion of Asian patients took their study drug without vs with food (TAF-TAF group 90% vs 75% and TDF-TAF group 95% vs 78%, respectively). At Week 96, antiviral efficacy was maintained, and treatment responses were similar in those taking study drug without vs with food (Table). Grade 3 or 4 adverse events and serious adverse events were generally comparable for those taking drug without vs with food, and in patients who took TAF without food for 96 weeks (TAF-TAF) or for 48 weeks (TDF-TAF), improvements in eGFRCG and in hip and spine BMD were observed. Conclusions: In CHB patients taking TAF without food for up to 96 weeks, antiviral efficacy was maintained, renal and bone parameters improved, and safety and tolerability were comparable to those receiving TAF treatment with food. These results lend support for the administration of TAF without regard to food.

貝樂克 0.5 mg 和 1 mg 對慢性 B 型肝炎併嚴重急性惡化之療效比較 ENTECARVIR 0.5 VS. 1MG FOR CHRONIC HEPATITIS B WITH SEVERE ACUTE EXACERBATION 1,2

1,2

許景翔蔡維倫陳文誌孫煒智蔡峯偉鄭錦翔 1 高雄榮民總醫院腸胃肝膽科 2 國立陽明大學醫學院

Background: Chronic hepatitis B virus (CHB) infection is the leading cause of cirrhosis and hepatocellualr carcinoma (HCC) in Taiwan. Spontaneous severe acute exacerbation (SAE) is not uncommon in the natural history of chronic HBV. There remained controversies regarding choosing which kind of nucleos(t)ide analogue (NUCs) and their appropriate doses in CHB with SAE. Aims: The aim of the study is to compare the therapeutic outcome of entecavir 0.5 vs. 1mg in CHB with SAE. Methods: Consecutive patients with chronic hepatitis B with SAE admitted to Kaohsiung Veterans General Hospital from 2009 to 2016 who received the entecavir (ETV) 0.5 mg (N = 48) or 1 mg (N = 114) were enrolled. Severe AE was defined as an abrupt rise of alanine aminotransferase (ALT) to > 5X the upper limit of normal (ULN; the ULN is 40 U/liter), accompanied by a total bilirubin level of > 2.0 mg/dl or prolongation of the prothrombin time (PT) by > 3 s. Patients with alcohol use of more than 30 g/day, who took hepatotoxic agents, and who had HCC were excluded. Baseline characteristics and clinical outcome of ETV 0.5 vs. 1 mg were compared. Results: The baseline characteristics were comparable between the two groups except that the ETV 0.5 mg group had higher ALT and albumin level. By week 24, 17 (15%) patients in the ETV 0.5 mg group and 11 (23%) patients in the ETV 1 mg group died or received liver transplantation (P > 0.05). Uni-variate analysis found that age, cirrhosis, level of ALT, prothrombin time (INR), MELD score, albi grade, presence of ascites or hepatic encephalopathy were associated with overall mortality in 24 weeks. Multi-variate analysis found that age, cirrhosis, MELD score, albi grade and hepatic encephalopathy were independently associated with overall mortality in 24 weeks. ETV 0.5 vs. 1 mg group had similar overall mortality in uni-variate and multivariate analysis in 24 weeks. Biochemical and virological response at 48 weeks were similar in ETV 0.5 and 1 mg group.

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P.012 Conclusions: ETV 0.5 mg and 1 mg had similar outcome in CHB with SAE. Age, cirrhosis, MELD score, albi grade and hepatic encephalopathy were independently associated with overall mortality in 24 weeks in patients who received ETV treatment.

慢性 B 型及 C 型肝炎合併感染患者其 C 肝病毒對 B 肝病毒複製的影響 IMPACT OF HCV VIREMIA ON HBV REPLICATION IN PATIENTS WITH CHRONIC HBV/HCV COINFECTION 1,2

3,4

1,2

曾志偉劉紋君陳啟益張定宗曾國枝 1 大林慈濟醫院內科部 2 慈濟大學醫學系 3 國立成功大學附設醫院內科部 4 國立成功大學醫學院 5 嘉義基督教醫院內科部

Background: Hepatitis B virus (HBV) biomarkers reflect the status of HBV infection; however, their role in patients with chronic hepatitis B and C (HBV/HCV) coinfection remains unknown. Aims: This study evaluated the characteristics of HBV biomarkers in patients with chronic HBV/HCV coinfection. Methods: One hundred untreated HBV/HCV coinfected patients were enrolled. Active viral infection was defined as viral load above 1,000 U/L and 15 U/L for HBV and HCV, respectively. Blood samples were analyzed for HBV biomarkers, including hepatitis B surface antigen (HBsAg), hepatitis B core-related antigen (HBcrAg), HBV DNA, and HBV pregenomic RNA (HBV pgRNA). The impact of HCV viremia was also studied. Results: A total of 71 (71%) patients had active HCV and 25 (25%) had active HBV. HBsAg, HBcrAg, and HBV DNA correlated with each other (P < 0.001). HBV pgRNA displayed no correlations with HBV DNA, HBsAg, or HBcrAg. Patients with HCV viremia had significantly lower HBV DNA, HBsAg, and HBcrAg levels as well as higher HBV pgRNA levels and lower HBV DNA:pgRNA ratio than those without viremia (HBV DNA, P < 0.001; HBsAg, P = 0.015; HBcrAg, P = 0.006; HBV pgRNA, P = 0.073; and HBV DNA:pgRNA ratio, P < 0.001). Conclusions: The low levels of HBsAg and HBcrAg in patients with HCV viremia indicate that HCV viremia impairs the HBV mRNA translation. In addition, the relatively high HBV pgRNA level, low HBV DNA and low HBV DNA: pgRNA ratio suggest that HCV viremia may be responsible for the decrease of HBV pgRNA reverse transcription activity.

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P.013 以 ALBI 評分來預測 C 型肝炎病患接受直接作用抗病毒藥物後的肝癌發生率／復發率 BASELINE ALBUMIN-BILIRUBIN (ALBI) SCORE PREDICTS INCIDENT OR RECURRENT HEPATOCELLULAR CARCINOMA IN CHRONIC HEPATITIS C PATIENTS RECEIVING DIRECTACTING ANTIVIRAL AGENTS 1

1,2,3

1,4

1,3

謝宗霖許偉帆賴學洲莊伯恒林俊哲黃冠棠 1,3 1,3 林肇堂彭成元 1 中國醫藥大學附設醫院內科部消化醫學中心 2 中國醫藥大學生物醫學研究所 3 中國醫藥大學醫學院 4 中國醫藥大學中醫學院

Background: Hepatocellular carcinoma (HCC) is the cancer with second highest mortality rate in Taiwan between 2012 and 2019. Direct-acting antiviral agents (DAAs) have been the standard therapy for patients with chronic hepatitis C (CHC) with an excellent sustained virologic response (SVR) rate. However, factors predictive of the incident or recurrent HCC in patients with CHC after DAA therapy are still unknown. Aims: To evaluate factors predictive of incident or recurrent HCC in patients with CHC after DAA therapy. Methods: From September 2012 to April 2020, 1060 patients with CHC and available FIB-4 data at baseline and 12 or 24 weeks after DAA therapy (PW12) without active HCC at baseline or hepatitis B virus coinfection who had received a complete course of DAA therapy were enrolled in this retrospective study. Demographic data, virological features, and factors associated with HCC occurrence recorded at baseline and PW12 were collected. The predictive performance of three liver functional or fibrotic models (aspartate aminotransferase to platelet ratio index [APRI], FIB-4, and albumin-bilirubin [ALBI] sore) for occurence of HCC was examined using receiver operating characteristic (ROC) curve analysis with the DeLong test. Results: Of 1060 patients, 542 (51.1%) patients were male, and 285 (26.9%), 209 (19.7%) and 303 (28.6%) patients had liver cirrhosis, diabetes mellitus and hypertension, respectively. The median age was 57 (47–66) years (first quartile–third quartile). The ALT, total bilirubin, albumin, AFP, FIB-4, and ALBI score were 56 (34–96) U/L, 0.8 (0.6–1.1) mg/dL, 4.4 (4.0–4.6) g/dL, 4.38 (2.73–9.52) ng/mL, 2.37 (1.29–4.57), and -2.95 (-3.20 – -2.68), respectively. 630, 245, 42, and 115 patients had genotype

1, 2, 3, and 6 HCV infections, respectively, and 26 patients had mixed genotype HCV infection (2 patients lacked HCV genotype data). 1043 out of 1060 patients (98.4%) achieved sustained virologic response at 12 weeks after DAA therapy. The median follow-up period from 12 weeks after DAA therapy was 12.83 (9.78–28.49) months, and 27 (2.5%) and 40 (3.8%) patients suffered from incident and recurrent HCC, respectively. Among the three liver functional or fibrotic models, FIB-4 at baseline had the highest area under curve (AUC, 0.829, 95% confidence interval [CI]: 0.786–0.871), but the AUCs between FIB4 and ALBI score at baseline (p = 0.835), FIB-4 at PW12 (p = 0.982), and APRI at PW12 (p = 0.401) were not significantly different using ROC curve analysis with the DeLong test. Age (hazard ratio [HR]: 1.053, 95% CI: 1.025–1.081, p < 0.001), male (HR: 2.657, 95% CI: 1.512– 4.670, p = 0.001), liver cirrhosis (HR: 5.806, 95% CI: 2.753–12.244, p < 0.001), and ALBI score at baseline (HR: 2.333, 95% CI: 1.052–5.176, p = 0.037) were independent predictors of incident or recurrent HCC in multivariate Cox regression analysis. Conclusions: ALBI score and APRI at baseline, and FIB4 at baseline and PW12 had similar predictive performance for incident or recurrent HCC in patients with CHC after DAA therapy. ALBI score at baseline was a predictor of incident or recurrent HCC by multivariate Cox regression analysis.

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P.014

P.015

接受 C 肝口服抗病毒藥物治療成功者可減少肝臟硬度 REDUCTION OF SHEAR-WAVE ELASTOGRAPHY BUT NOT SHEAR-WAVE DISPERSION AFTER SUCCESSFUL HEPATITIS C TREATMENT WITH DIRECT-ACTING ANTIVIRAL AGENTS

台中某醫學中心使用宜譜莎治療 C 型肝炎受刑人的經驗 SOFOSBUVIR AND VELPATASVIR (EPCLUSA®) TO TREAT PRISONERS WITH CHRONIC HEPATITIS C ‒ AN EXPERIENCE IN A TAICHUNG MEDICAL CENTER

蘇培元蘇維文伍麗莎許柏格徐友春顏旭亨彰化基督教醫院胃腸肝膽科 Background: Successful antiviral treatment in patients with hepatitis C can lead to reduced liver stiffness. However, the data on the effectiveness of the two-dimensional (2-D) shear-wave elastography (SWE), shear-wave dispersion (SWD), and attenuation image (ATI) is limited in patients with HCV infection treated with antiviral therapy. Aims: We attempted to compare the 2-D shear-wave elastography (SWE), shear-wave dispersion (SWD), and attenuation image (ATI) with transient elastography (TE) and controlled attenuation parameter (CAP) in patients under direct-acting antiviral (DAA) therapy. Methods: Patients with chronic hepatitis C infection undergoing DAA therapy from January 2018 to June 2020 were retrospectively examined. The results of 2-D SWE, SWD, ATI, TE, and CAP were recorded before and 12 weeks after the completion of DAA therapy. Results: A total of 122 patients with median age of 61-years were investigated; among them, 121 (99.2%) achieved sustained virological response (SVR) at 12 weeks after DAA therapy. FIB-4, aspartate aminotransferase-toplatelet ratio index (APRI), 2-D SWE, and TE were reduced after the DAA therapy. CAP was increased; however, SWD and ATI showed no statistically significant changes after DAA therapy. 2-D SWE and TE was strongly correlated (r = 0.885–0.897, p < 0.001). Albumin and baseline liver stiffness measurement (LSM) were independent factors of LSM changes after DAA therapy. Conclusions: DAA therapy can significantly decrease liver stiffness (using both 2-D SWE and TE) but not SWD and ATI values in patients with hepatitis C. The increased CAP is also observed after DAA therapy.

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1,3

許偉帆朱家聲陳浤燿蕭望德蔡宗佑彭成元 1 中國醫藥大學附設醫院消化醫學中心 2 中國醫藥大學生物醫學研究所 3 中國醫藥大學醫學系

Background: The hepatitis C virus (HCV) burden is high among people who inject drugs (PWID) and prisoners. Treatment of people in prison is a crucial field of HCV micro-elimination, and therapy in this population must be prioritized to meet the World Health Organization (WHO) HCV elimination goals by 2030. The combination of sofosbuvir and velpatasvir (Epclusa®) is an effective and safe direct-acting antiviral agent (DAA) to treat patients with chronic hepatitis C (CHC). However, the experience of Epclusa to treat prisoners with CHC is limited. Aims: The study aimed to evaluate the efficacy and safety of Epclusa to treat HCV in prisoners in Taiwan. Methods: From May 2015 to April 2020, 416 patients with CHC were treated with DAAs. Among them, 129 patients who received Epclusa therapy were enrolled in this retrospective study. Demographic data, virological features, and adverse effects were collected. Results: Among 129 prisoners, 93 were PWID, and 36 were non-PWID. The majority of patients were GT6 (44.2%) and GT1a (24%); other patients were GT3 (14%), GT2 (9.3%) and GT1b (8.5%). The rate of sustained virologic response (SVR) by intent-to-treat (ITT) analysis was 92.2% (119/129) [PWID: 91.4% (85/93); nonPWID: 94.4% (34/36)] and the rate of SVR by modified ITT analysis was 100% (119/119). SVR (ITT) rates among different genotypes were 96.8% (30/31) in GT1a, 100% (11/11) in GT1b, 100% (12/12) in GT2, 88.9% (16/18) in GT3, and 87.7% (50/57) in GT6, respectively. SVR (ITT) rates were 92.7% (115/124) in patients with cirrhosis and 80% (4/5) in patients without cirrhosis. The rates of abnormal alanine aminotransferase and direct hyperbilirubinemia (defined by direct to total bilirubin more than 30% in patients with total bilirubin more than 1.3 mg/dL) were decreased 2 weeks after initial therapy. The most common adverse effect was skin rash.

2021 消化系聯合學術演講年會

P.016 Conclusions: Epclusa is effective and safe for prisoners. The efficacy was not affected by PWID or liver cirrhosis. Loss of follow-up was the reason for non-SVR (ITT). Because of the high prevalence of HCV infection in PWID, universal screening in this group of patients may be necessary to meet the WHO HCV elimination goal by 2030 (or Taiwan HCV elimination goal by 2025).

新全基因型直接抗病毒藥物治療 C 型肝炎屏東地區之真實世界經驗 CURRENT ANTI-HCV THERAPY WITH NEWLY APPROVED DIRECT ANTIVIRAL AGENT APPLIED IN THE CLINICAL PRACTICE-WORLD EXPERIENCE IN PING-TUNG COUNTY 1

文士祺郭武憲鄭隆致蔡奇璋黃健維王潔瑜 3 柯朝元 1 屏東寶建醫院胃腸肝膽科 2 員生醫院胃腸肝膽科 3 國軍高雄總醫胃腸肝膽科 4 屏東寶建醫院護理部個管師

Background: The hepatitis C virus (HCV) infects up to 150 million people worldwide. Chronic HCV infection causes progressive liver fibrosis, which can lead to cirrhosis, hepatic decompensation, and hepatocecullar carcinoma. In the era of using pangenotypic regimens, simplified HCV treatment algorithm could provide to the clinician. Aims: We presented the results to assess the efficacy and safety of a fixed-dose combination tablet of sofosbuvir/ velpatasvir for 12 weeks, glecaprevir/pibrentasvir for 8 weeks in patients infected with HCV genotype 1 through 6 and grazoprevir/elbasvir for 12 weeks in patients infected with HCV genotype 1b. Methods: We conducted a retrospective cohort study involving both previously treated and previous untreated patients infected with HCV genotype 1 through 6 including those with compensated cirrhosis treated according to the treatment guideline and reimbursed by the current Nation Taiwan Health Insurance payment. The primary end point was a sustained virological response (SVR) at 12 weeks after the end of therapy. Results: We enrolled patients at Pao-Chien hospital, PingTung between Jan and Nov, 2020. Of the 41 patients who received treatment, 31.7% had HCV genotype 2a, 26.8% had genotype 1b, 12.2% had 6a, 9.8% had genotype 2b, 9.8% had genotype 3a, 7.3% had genotype 1a and 2.4% had mixed infection (genotype 1b + 2a). The rate of SVR among patients was 100% in per-protocol population (PP) and 100% in intent-to-treat (ITT) population. Serious adverse events occurred in 34% of patients. The most common events were headache (14.6%), fatigue (9.8%), insomnia (4.9%), skin rash (2.4%), arthralgia (2.4%), back pain (2.4%) and diarrhea (2.4%).

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P.017 Conclusions: With the widely used pan-genotypic regimens, sofosbuvir/velpatasvir and glecaparevir/ pibrentasvir and specific genotypic 1b, grazoprevir/elbasvir, we are able to cure 100% of HCV patients with very high safety profiles.

全基因型抗病毒藥物與混和基因型 C 型肝炎感染之療效 PANGENOTYPIC DIRECT-ACTING ANTIVIRAL AGENTS FOR MIXED GENOTYPE HEPATITIS C INFECTION: A REAL-WORLD EFFECTIVENESS ANALYSIS 1

1,2

丁元捷盧重光陳慰明董水義魏國良沈建亨 1 1 1 3 1 1,2 謝詠諭顏志維張國基邱文南洪肇宏盧勝男 1,2 張德生 1 嘉義長庚紀念醫院胃腸肝膽科 2 長庚大學醫學院 3 雲林長庚紀念醫院胃腸肝膽科

Background & Aims: Pangenotypic direct-acting antiviral agents (DAAs) glecaprevir/pibrentasvir (GLE/PIB) and sofosbuvir/velpatasvir (SOF/VEL) are effective against all hepatitis C virus (HCV) genotype infections. However, data on pangenotypic DAA treatment for mixed genotype HCV infection are sparse. Methods: All patients with mixed HCV genotype infections treated with GLE/PIB or SOF/VEL from August 2018 to August 2020 in Chiayi Chang Gung Memorial Hospital, Taiwan, were analyzed. The primary study endpoint was sustained virologic response (SVR) 12 weeks after treatment cessation. We also reported adverse events (AEs). Results: A total of 108 patients with mixed infections of any two or three genotypes of 1a, 1b, 2, 3, and 6 received pangenotypic DAAs during the study period. A total of 67 patients received GLE/PIB and 41 received SOF/VEL. The evaluable population analysis revealed SVR rates of 94% (63/67) and 95.1% (39/41) for SOF/VEL and GLE/ PIB therapy, respectively, and the per-protocol analysis revealed an SVR of 100% for both regimens. Four patients in the GLE/PIB group and two patients in the SOF/VEL were lost to follow-up. The most common AEs for GLE/ PIB versus SOF/VEL therapy included pruritus (14.9% vs 2.4%), abdominal discomfort (6.0% vs 7.3%), fatigue (4.5% vs 7.3%), and acid reflux (3.0% vs 4.9%). DAArelated significant laboratory abnormalities occurred in three patients with >1.5× elevated bilirubin level in the GLE/PIB group. None of the above AEs resulted in DAA discontinuation. Conclusions: Pangenotypic DAAs are well tolerated by and yield high SVR rates in patients with mixed genotype HCV infection.

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P.018

P.019

慢性 C 型肝炎患者在非干擾素全口服新藥成功治療結束後第十二週腎功能改善之預測因子 THE PREDICTIVE FACTORS OF RENAL FUNCTION IMPROVEMENT IN CHRONIC HEPATITIS C PATIENT TREATED SUCCESSFULLY BY DIRECTACTING ANTIVIRAL AGENTS

以長效型干擾素合併雷巴威林治療之慢性 C 型肝炎長期追蹤下肝臟組織變化的預測因子 FACTORS PREDICTING PAIREDBIOPSY-ASSESSED LIVER HISTOLOGICAL CHANGES IN LONGTERM FOLLOWED UP CHRONIC HEPATITIS C TREATED WITH PEGYLATED INTERFERON-ALPHA PLUS RIBAVIRIN: A PROSPECTIVE COHORT STUDY

1,2

陳彥均曾志偉曾國枝 1 佛教慈濟醫療財團法人大林慈濟醫院 2 慈濟大學醫學系 Background: Hepatitis C virus (HCV) causes chronic kidney disease (CKD) and even end-stage renal disease (ESRD). Interferon (IFN)-based therapy for chronic hepatitis C infection (CHC) is associated with reduced risk of CKD and ESRD. But the change of renal function after DAA treatment for CHC was controversial. Aims: To investigate the predictive factors of renal function improvement after DAA treatment. Methods: The patients with chronic hepatitis C (CHC) infection who underwent direct-acting antiviral agents (DAA) treatment between 2016 to 2019 were enrolled from the Dalin Tzu Chi Hospital in this retrospective study. Clinical and baseline laboratory data were analyzed for correlation with significant eGFR improvement at SVR12. Results: A total of 232 patients were included in the analysis. This population included 83 men (35.8%) and the mean age was 64.02 ± 10.65 years. Most patients were infected with the HCV genotype 1 (n=154, 66.4%). Of the patients in this study, 153 had advanced fibrosis (65.9%). The overall mean eGFR was 78.94 ± 17.82 ml/min/1.73m2 at BL and decreased to 76.41 ± 18.25 ml/min/1.73m2 and 77.32 ± 18.48 ml/min/1.73m2 at EOT and P12, respectively (EOT vs. BL, P<0.001; P12 vs. BL, P=0.005). Thirty-nine patients (16.8%) showed significant eGFR improvement after DAA treatment at SVR12 and their mean eGFR was 68.89 ± 15.70 at baseline and increased to 73.82 ± 15.58 at EOT and 82.29 ± 15.73 ml/min/1.73m2 at SVR12. After multivariate analysis, age (OR: 0.954, 95% CI: 0.9110.999, P=0.043) and baseline eGFR (OR: 0.938, 95% CI: 0.913-0.964, P<0.001) were associated significant eGFR improvement at SVR12. Conclusions: Age and baseline eGFR were negatively associated with eGFR improvement at SVR12.

1,2

2,3

1,2

謝明翰高子淯謝婷卉高群棋彭成元賴學洲 2 1,2 莊伯恒高榮達 1 中國醫藥大學醫學院醫學系 2 中國醫藥大學附設醫院內科部消化系 3 國立陽明大學學士班大一大二不分系

Background: Before direct-acting antivirals are recommended as the standard treatment for hepatitis C virus (HCV) infection, a great number of chronic hepatitis C (CHC) patients were treated with pegylated interferon (pegIFN)-alpha plus ribavirin. However, among these patients it remains unclear regarding those at a higher risk of liver fibrosis progression during long-term follow-up. Aims: To investigate the predictors of liver histological changes assessed by paired biopsies in long-term followed up CHC patients receiving pegIFN-alpha/ribavirin. Methods: From August 2008 to May 2017 at our hospital, 85 CHC patients were prospectively enrolled to receive pegIFN-alpha/ribavirin therapy and undergo long-term follow-up thereafter. To assess hepatic histological changes, paired liver biopsies were performed at baseline and the end of follow-up. Results: In the entire study cohort, mean duration between paired biopsies was 7.01 ± 1.60 years. Factors independently predicting fibrosis regression include pretreatment fibrosis stage ≥2 (F≥2) [odds ratio (OR) = 3.831, p = 0.033], activity response (defined as decreased or permanently absent necroinflammatory activity) (OR = 12.928, p = 0.047), baseline anti-HCV antibody titer ≥14.3 S/CO (OR = 3.268, p = 0.040) and baseline lowdensity lipoprotein ≥135 mg/dL (OR = 25.486, p = 0.011). Besides, among all factors activity response was independently associated with fibrosis progression [OR = 0.072 (inverse correlation), p = 0.002]. Furthermore, independent predictors of activity response include baseline glucose ≤105 mg/dL (OR = 7.316, p = 0.030) and sustained virological response (OR = 12.843, p = 0.006).

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P.020 Conclusions: Among CHC patients previously treated with pegIFN-alpha/ribavirin, those with pretreatment F≥2 or activity response are more likely to reverse liver fibrosis during long-term follow-up. Therefore, those with pretreatment F<2 or activity nonresponse should be continuously monitored instead of being discharged from the surveillance of fibrosis changes.

在偏鄉的 C 型肝炎篩檢及治療 ─ 信義鄉衛生所為例 HEPATITIS C SCREENING AND TREATMENT IN REMOTE AREAS: USING XINYI TOWNSHIP HEALTH CENTER AS AN EXAMPLE 1,2

1,2

史皓偉石薪雅史萬秋鄭銹錦黃昭郎 1 南投縣政府衛生局 2 信義鄉衛生所

Background: Chronic hepatitis C often results in worsening liver disease over time and progresses to cirrhosis or liver cancer. In the last 3 years, the National Health Insurance has allowed payment for direct-acting antivirals (DAAs). Not only are there few side effects during the treatment course but treatment success rate is more than 95%. Xinyi Township is a Taiwanese indigenous people township. In that township, chronic hepatitis or liver disease has always been the top 5 causes of death. The inconvenience in seeking medical attention and lack of medical knowledge that chronic hepatitis C can be treated often leads to delayed treatment in Xinyi Township. In 2020, Xinyi Township was given a part of the money donated by Rotary International to Nantou County for hepatitis C screening. Therefore, the health center conducted hepatitis C screening for registered residents of Xinyi Township from 1 January 2020 to 30 November 2020. It was hoped that the health bureau-health center-hospitalprimary medical clinic screening scheme can detect patients with hepatitis C and provide them with treatment to achieve the goal of hepatitis C-free Xinyi Township by 2025. Aims: To employ diverse community screening and intervention strategies to increase the detection rate and treatment rate of hepatitis C patients and to assess the incidence of hepatitis C in Xinyi Township through this screening project. Patients who tested positive for anti-HCV antibodies underwent retesting for hepatitis C viral load and DAAs were provided for patients with hepatitis C virus while periodic follow-up was conducted for those without hepatitis C virus. Methods: The health center tallied all registered residents of Xinyi Township from 1 January 2020 to 30 November 2020: (1) Number of people who underwent hepatitis C screening in Nantou County that was a donation by Rotary International; (2) Number of healthy subjects who underwent adult health examination in Xinyi Township Health Center (hepatitis B and C screening); (3) All subjects who participated in latent pulmonary tuberculosis treatment

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P.021 in Xinyi Township Health Center (hepatic function, HBsAg, and anti-HCV were tested before treatment); (4) Screening stations were set up in the villages. The ages of the subjects ranged from 12 to 75 years old. Screening sites were in the villages. The health center set up stations for hepatitis C screening during large-scale events in the village. County hospitals provided free hepatitis C screening for Xinyi Township residents when they sought medical attention in Nantou county and met the criteria for hepatitis C screening in Nantou county under the Rotary International donation. Patients who tested positive for anti-HCV antibodies underwent retesting for hepatitis C viral load and antiviral treatment was provided for patients with hepatitis C virus. The antiviral drugs were provided by the Ministry of Health and Welfare (Hepatitis C treatment project in remote areas) in which Harvoni was given as treatment for 12 weeks. Results: Health center statistics showed that 1056 people were screened from 1 January 2020 to 30 November 2020 and there were 32 who tested positive for anti-HCV. The incidence of HCV was 3.03% (32/1056). Among these 32 anti-HCV-positive people, 29 underwent HCV RNA test and HCV RNA was not tested in 3 people. Subsequently, 11 people tested HCV RNA(+) and 18 people tested HCV RNA(-). The persistent virus infection rate was 37.9% (11/29). Following that, 9 HCV RNA(+) patients received Harvoni treatment at our health center . One patient was referred to the hospital for treatment due to uncompensated cirrhosis and another patient was under follow-up. At 4 to 5 days of treatment, 4 patients developed headache and fatigue, which spontaneously resolved during the DAAs treatment. Conclusions: The total population of Xinyi Township is 15874. Based on this year’s screening results, we calculated that the incidence of HCV infection in Xinyi Township to be around 3.03%. From this, we extrapolated that there were 476 people who were infected with HCV and HCV may still be present in 180 people. We hope that the health bureauhealth center-hospital-primary medical clinic screening scheme can detect patients with hepatitis C promptly so that antiviral treatment can be provided. At present, DAAs have few side effects and high treatment success rate. If onsite screening and onsite treatment can be carried out similarly as that in Xinyi Township, treatment inconvenience can be improved for residents in remote regions, which can increase treatment rate. This will block hepatitis C transmission and decrease the occurrence of cirrhosis or liver cancer due to worsening liver disease and also decrease mortality rate.

傳統轉介失敗後，在美沙冬門診驗 C 肝病毒之作法可增加美沙冬患者 C 肝治療 ON-SITE HCV RNA TESTING INCREASES HCV TREATMENT UPTAKE IN METHADONE MAINTENANCE PATIENTS AFTER CONVENTIONAL REFERRAL FAILURE 1

戴啟明陳子皓蔡英楠曾政豪黃俊凱張簡德璋 4 顏永杰 1 義大醫院胃腸肝膽科 2 義大癌治療醫院胃腸肝膽科 3 義大醫院感染科 4 義大醫院精神科

Background: Although hepatitis C virus (HCV) seroprevalence rate is >90% among methadone maintenance treatment (MMT) patients in Taiwan, the majority of patients do not receive anti-HCV treatment. Aims: We aimed to evaluate the effectiveness of an integrated referral model especially on-site HCV RNA testing on the HCV cascade of care among MMT patients in direct-acting antiviral (DAA) era. Methods: Our referral model comprised four steps including screening (HCV Ab), linkage to care, confirmation (HCV RNA), and DAA treatment. Conventional referral (stage one) and on-site HCV RNA testing (stage two) were performed in this study. In stage one, anti-HCV was checked at MMT clinic. After successful referral, HCV RNA testing and DAA treatment were performed at liver or ID clinic. In stage two, on-site HCV RNA testing was applied to all patients after conventional referral failure. Both anti-HCV and HCV RNA were checked at MMT clinic. DAA was prescribed at first visit to liver or ID clinic after successful referral. Results: Between February 2020 and December 2020, 307 MMT patients were enrolled in this prospective observation study and 278 patients (90.6%) tested positive for anti-HCV. Before referral, HCV RNA was available in 85 patients (30.4%) out of the 278 patients, including undetectable HCV RNA, PEG‐IFN/RBV-treated and DAA-treated in 12 (4.3%), 22 (7.6%) and 51 (18.5%), respectively. After referral, accumulative percentage of patients receiving HCV RNA testing at stage one and stage two was 63.8% and 90.3%, respectively. Difference of proportion between two stages was 26.5 (95% CI: 18.6-32.0; P<0.001) and the increased response rate of HCV RNA testing at stage two was 41.5%. Accumulative

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P.022 percentage of patients receiving DAA treatment at stage one and stage two was 64.0% and 84.3%, respectively. Difference of proportion between two stages was 20.3 (95% CI: 18.6-32.0; P<0.001) and the increased response rate of treatment uptake at stage two was 31.7%. Conclusions: Our referral model can achieve good effectiveness on HCV RNA testing and HCV treatment uptake in MMT patients. On-site HCV RNA testing can simplify model of care and significantly increases HCV treatment uptake in MMT patients after conventional referral failure.

全基因型直接作用抗病毒藥對台灣 C 型肝炎病毒感染的真實療效和安全性 REAL-WORLD EFFICACY AND SAFETY OF PANGENOTYPIC DIRECT-ACTING ANTIVIRALS AGAINST HEPATITIS C VIRUS INFECTION IN TAIWAN 1

1,2

張國基張德生董水義魏國良陳慰明沈建亨 1,2 1 1 1 1 1 謝詠諭陳奕行陳俊憲許晃維顏志維童威霖 1 嘉義長庚紀念醫院肝膽胃腸科 2 長庚大學醫學院

Background: Clinical trials have demonstrated excellent effectiveness and safety of pangenotypic direct-acting antivirals (DAAs) for hepatitis C virus (HCV) treatment. However, there is a dearth of large-scale real-world data on these pangenotypic DAAs. Aims: This study examined the treatment results of two pangenotypic regimens, glecaprevir/pibrentasvir (GLE/ PIB) and sofosbuvir/velpatasvir (SOF/VEL), in a realworld setting in Taiwan. Methods: All HCV patients treated with GLE/PIB or SOF/ VEL from August 2018 to April 2020 in Chiayi Chang Gung Memorial Hospital were analyzed. The primary treatment outcome was sustained virologic response 12 weeks after treatment cessation (SVR12). Adverse events (AEs) were also reported. Results: A total of 1,356 HCV patients received pangenotypic DAA treatment during the study period: 742 received GLE/PIB and 614 received SOF/VEL. The rates of SVR12 for GLE/PIB vs. SOF/VEL were 98.9% (710/718) vs. 99.5% (581/584) by per-protocol analysis and 95.7% (710/742) vs. 94.6% (581/614) by evaluable population analysis. Eleven patients (eight received GLE/PIB and three received SOF/VEL) did not attain SVR12. The most common AEs for GLE/PIB vs. SOF/VEL included pruritus (17.4% vs. 2.9%), abdominal discomfort (5.8% vs. 4.4%), dizziness (4.2% vs. 2%), and malaise (3.1% vs. 2.9%). Laboratory abnormalities were uncommon, with less than 1% of the patients having elevated total bilirubin or aminotransferase in both regimens. Only five drug discontinuations resulted from AEs, three due to bilirubin elevation and two due to dermatological complaints. Conclusions: In real-world practice, pangenotypic DAAs GLE/PIB and SOF/VEL are well tolerated and achieve high SVR12 rates for patients with all HCV genotypes.

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P.023 全基因型全口服抗病毒藥物的真實世界治療經驗：針對一北部醫學中心參與 C 型肝炎召回計畫之病患 REAL WORLD EXPERIENCE OF PAN-GENOTYPIC DAAS FOR HCV PATIENTS: A CALL BACK PROGRAM IN ONE TAIWAN NORTH MEDICAL CENTER 1,2

齊振達李懿宬藍耿欣朱啟仁蘇建維侯明志 1,2 黃怡翔 1 臺北榮民總醫院內科部胃腸肝膽科 2 國立陽明大學臨床醫學研究所

Background: The treatment of chronic hepatitis C (CHC) has evolved from genotype-specific to pan-genotypic direct acting antivirals (DAAs) with high efficacy and safety. But the link between the diagnosed hepatitis C virus (HCV) infected patients to treat remained a gap. Aims: We conducted a hospital-based HCV patient call back program in Northern Taiwan, a low prevalence of HCV infection area. We aimed to access the index of call back program and the efficacy of pan-genotypic DAAs treatment. Methods: From September 2013 to December 2019, a total of 4938 patients with positive anti-HCV antibody in Taipei Veterans General Hospital were retrospectively enrolled into the call back program. The rates of call back, test of HCV-RNA, and positive RNA were analyzed. Additionally, 329 patients who have been treated with pan-genotypic DAAs before the call back program in Taipei Veterans General Hospital from August 2019 to Febuary 2020 were also enrolled for comparison. Results: After prescreening, 2501 patients could be called back. There was no significant difference between call back (n=444) and non-call back (n=2057) patients in age and sex. There was a significant difference between call back and non-call back patients in anti-HCV test date, address and main follow-up outpatient department (OPD). The call back rate was 17.8% (444/2501) and HCV-RNA test rate was 70.5% (313/444). The main reason of the 131 patients without further HCV-RNA testing after coming back to OPD was that previous undetectable HCV-RNA was found at OPD. Finally, HCV-RNA positive rate was 52.7% (165/313). Of them 149 patients were treated with pan-genotypic DAAs. By adding 329 genotypic DAAs treated patients before the call back program, the rates of viral response at the end of treatment (ETVR) and

sustained virologic response at 12 weeks post treatment (SVR12) were 98.8% (402/407) and 97.1% (335/345), respectively. All of the patients with GT 1 and 1a had ETVR and SVR12. The rates of ETVR and SVR12 were 98.8% and 97.7% in GT 1b; 98.8% and 97.4% in GT 2; 87.5% (7/8) and 71.4% (5/7) in GT 3; 100% and 94.4% in GT 6, respectively. For patients receiving SOF/VEL (n=238), the rates of ETVR and SVR12 were 98.5% and 97.0%, respectively. For patients receiving GLE/PIB (n=240), the rates of ETVR and SVR12 were 99.0% and 97.2%, respectively. Thirty-two patients had HCCs before DAA treatment, and the rates of ETVR and SVR12 were 96.3% (26/27) and 95.5% (21/22), respectively. Of the 149 patients from call back program treated with pan-genotypic DAAs, the rates of ETVR and SVR12 were 96.7% (117/121) and 94.6% (88/93), respectively. Conclusions: The in-hospital referral platform is feasible in a low-prevalence region of HCV. The real world experience of pan-genotypic DAAs showed good efficacy in HCV treatment.

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P.024

P.025

直接作用抗病毒藥物在慢性 C 型肝炎合併巴塞隆那臨床肝癌分類 B 期接受肝動脈栓塞化學療法的病人的效果及預後 DIRECT-ACTING ANTIVIRAL THERAPIES FOR CHRONIC HEPATITIS C IMPROVE THE OUTCOME OF BCLC STAGE B HEPATOCELLULAR CARCINOMA TREATED BY CHEMOEMBOLIZATION

Sofosbuvir/Velpatasvir 對晚期肝纖維化的 C 型肝炎患者的使用是有效且安全的：來自台灣單一醫療中心分析 SOFOSBUVIR/VELPATASVIR IS EFFECTIVE AND SAFE FOR HEPATITIS C PATIENTS WITH ADVANCED FIBROSIS: A SINGLE CENTER ANALYSIS IN TAIWAN

1,3

邵昶瀚 Paul P Shao 陳威廷林成俊林蔚然 1,3 葉昭廷 1 林口長庚紀念醫院肝膽胃腸科 2 加利福尼亞大學洛杉磯分校戴衛格芬醫學學院 3 林口長庚紀念醫院肝臟研究中心

Background: Chronic hepatitis C virus (CHC) infection is a one of the major causes of Hepatocellular carcinoma (HCC). With the development of direct-acting antiviral (DAA) combination regimens, the risks of CHC related HCC occurrence have been reduced. However, whether the use of DAA for CHC improves the outcome of patients with intermediate stage HCC under chemoembolization therapy is unclear. Aims: This study aims to evaluate the associations between the use of DAA and the prognosis of CHC patients with Barcelona Clinic Liver Cancer (BCLC) stage B HCC treated by chemoembolization and the overall outcomes. Methods: A retrospective cohort study of 113 CHC patients with BCLC stage B HCC receiving transarterial chemoembolization (TACE) between 2010 to 2019 was conducted. Kaplan-Meier curve, univariate and multivariate Cox regression analyses were used to identify factors survival outcomes. Results: The overall median survival of the cohort was 25.1 months. Among 113 patients, 14 received DAA therapy for CHC (12.3%), and the sustained virological response (SVR) rate was 92.9% (13/14). The median survival of DAA treated group and non-treated group were 40.1 months vs 22.9 months respectively. Multivariate analysis showed that ECOG, DAA treatment, and serum albumin are key independent factors associated with overall survival (HR = 1.982, 95% CI: 1.0823.630, p = 0.027; HR = 0.133, 95% CI: 0.018–0.976, p = 0.047; HR = 0.457, 95% CI: 0.229–0.912, p = 0.026; respectively). Moreover, the time-to-complete remission was improved in DAA treated group (HR = 3.137, 95% CI: 1.334-7.378, p = 0.009). Conclusions: ECOG performance status, DAA therapy, and serum albumin level were independent prognostic factors for CHC infected intermediate-stage HCC patients. DAA therapy was also a beneficial factor for time-to-complete response.

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1,2

黃宇庭陳慰明董水義魏國良沈建亨張國基 1 1 3 1,2,3 謝詠諭顏志維邱文南張德生 1 嘉義長庚紀念醫院肝膽胃腸內科 2 長庚大學醫學院 3 雲林長庚紀念醫院肝膽胃腸內科

Background: Liver fibrosis is an important factor associated with decreased chance of sustained virologic response 12 weeks after treatment cessation (SVR12) for direct-acting antiviral drugs especially for sofosbuvir-based regimens. Aims: However, data regarding the impact of hepatic fibrosis on the efficacy of sofosbuvir/velpatasvir (SOF/ VEL) is limited in the Asians. Methods: We analyzed all 633 HCV patients of various genotypes treated with SOF/VEL from June 2019 to April 2020 in Chang Gung Memorial Hospitals, Chiayi, Taiwan. The fibrosis degree was determined by fibrosis index based on four factors (FIB4) score with advanced fibrosis or cirrhosis being defined as FIB4 score > 3.25. Results: The primary treatment outcome was the rate of SVR12. Adverse events (AEs) were also evaluated. The SVR12 rates of FIB-4 score ≦ 3.25 vs. > 3.25 were 99.2% (485/489) vs. 100% (144/144) by the per-protocol analysis and 95.3% (485/509) vs. 93.5% (144/154) by the evaluable population analysis. Four patients with FIB-4 score ≦ 3.25 did not attained SVR12, with 1 relapsed and 3 had no response. The most common AEs for FIB-4 score ≦ 3.25 vs. > 3.25 included abdominal discomfort (3.9% vs. 6.5%), skin itching (3.5% vs. 3.9%), and fatigue (2.8% vs. 3.2%). Two patients with FIB-4 score >3.25 had total bilirubin elevation > 1.5-3× upper normal limit. No any AE resulted in treatment discontinuation. Conclusions: SOF/VEL are well tolerated and achieve high SVR12 rates for HCV patients regardless of fibrosis status.

2021 消化系聯合學術演講年會

P.026

P.027

以直接作用抗病毒藥物治療監獄中 HIV 併 HCV 感染之病患結果 THE CLINICAL OUTCOME OF DAA TREATING INCARCERATED HCV WITH HIV CO-INFECTION PATIENTS

Sofosbuvir-Velpatasvir 合併 RBV 用於纖維化階段慢性 C 型肝炎患者之療效與安全性 ─ 南台灣五家醫院之真實世界案例 THE EFFECTIVENESS AND SAFETY OF SOFOSBUVIR-VELPATASVIR WITH/ WITHOUT RBV FOR CHRONIC HCVINFECTED PATIENTS BY FIBROSIS STAGE ‒ A REAL-WORLD SETTING OF FIVE HOSPITALS IN SOUTH AREA OF TAIWAN

林群峰林連豐阮盛豪屏東基督教醫院肝膽胃腸科 Background: Direct-acting antiviral agent (DAA) is the new generation treatment of chronic hepatitis C (CHC) and achieved favored result. However there is no data describing the treatment of the incarcerated CHC with HIV co-infection patients in Taiwan. Aims: this work is to investigate the clinical outcome of DAA treating incarcerated CHC with HIV co-infection patients. Methods: Retrospective case control study was conducted with 57 CHC and HIV co-infection incarcerated patients who receiving DAA therapy during Jan. 2019 to Dec. 2019. These data were collected to analyze the viral response rate, HIV viral load change, CD4 count change, Fibrosis-4 (FIB-4) score variation before and after DAA therapy. Results: All of these 58 incarcerated CHC/HIV coinfection patients received DAA therapy achieved SVR12, no one withdrawl from the treatment course. Nine patients (15.5%) developed adverse effect. No one had severe adverse events. The paired t-test showed significant decreasing level of FIB-4 score and significant increasing level of CD4+ T cell count after DAA treatment. Conclusions: These data confirmed the high sustained virologic response (SVR) rate and clinical effectiveness of DAA therapy, even with HIV con-infection. Furthermore, after DAA therapy, elevated CD4 count may imply the increasing of patient’s immunity.

4,5

陳柏岳羅清池陳志州曾國枝黃嘉生陳啟益 1 嘉義基督教醫院內科部 2 天主教聖馬爾定醫院內科部 3 柳營奇美醫院內科部 4 大林慈濟醫院內科部 5 花蓮慈濟醫院 6 嘉義陽明醫院

Background: Sofosbuvir-velpatasvir (SOF/VEL, Epclusa) is a direct active antiviral agent with the distinctive features of pangenotypic, protease inhibitor-free and suitable for chronic HCV-infected patients regardless of fibrotic stage. In clinical trials, SOF/VEL combined with ribavirin for 12 weeks could even achieve more than 90% sustained virologic response (SVR) rate for HCV-infected patients with decompensated cirrhosis. Aims: The aim of our study is to evaluate the effectiveness and safety of SOF/VEL with or without ribavirin for chronic HCV-infected patients in a real-world setting. Methods: We retrospectively enrolled chronic HCVinfected patients who ever received Epclusa with/without ribavirin for 12 weeks in five hospitals which located in south area of Taiwan since Jul. 2019 to Mar. 2020. The SVR12 rate was defined as the percentage of undetectable HCV RNA (HCV RNA < 15 IU/ml) at week 12 after ceasing Epclusa treatment. The adverse effects and safety were reviewed by electrical medical record. Results: A total of 922 HCV-infected patients were enrolled. The median age was 61.4 years old and 54.6% of patients were female. Among 922 patients, 209 patients (22.7%) had advanced fibrosis which defined as FiB-4 ≥ 3.25 and 43 patients (4.7%) had decompensated cirrhosis. Only 4 patients had detectable HCV RNA at SVR12 and 36 patients had non-virologic failure (death = 13, lost to follow or poor adherence = 23). The overall SVR12 rate was 99.5% (882/886) and 95.7% (882/922) in perprotocol and intention-to-treat analysis, respectively.

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P.028 Among 154 patients with advanced fibrosis (FiB-4 ≥ 3.25), one patient had detectable HCV RNA at SVR12 and the SVR12 rate was 99.4% (153/154). The SVR12 rate of decompensated cirrhotic patients was 100% (43/43). In the safety profile, Improved ALT level (67 to 21 U/L), FiB4 value (2.81 to 2.28) and non-significant eGFR change (92.1 to 93.0 ml/mins/1.73m2) were noted from baseline to SVR12 in all patient’s analysis. Four patients (0.4%, 4/992) had premature discontinuity due to adverse effect or drug-drug interaction and there was no death related to Epclusa. Decreased treatment adherence was found to be correlated with advanced fibrosis stage (p = 0.01, 1.68% vs 4.89% vs 6.97% in FiB-4 < 3.25, advanced fibrosis and decompensated cirrhosis, respectively). Conclusions: Sofosbuvir-velpatasvir with or without ribavirin for 12 weeks is effective and safe for chronic HCV-infected patients.

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林口長庚醫學中心主動召回 C 型肝炎抗體陽性患者並給予治療的臨床經驗 THE EXPERIENCE OF CALL BACK SYSTEM FOR ANTI-HCV POSITIVE PATIENTS AND LINKAGE TO CARE IN CHANG GUNG MEMORIAL HOSPITAL, LIN-KOU 1

1,2,3

黃永信許朝偉林成俊張明鈴沈一嫻 1,2,3 1,2,3 1,2,3 謝森永林俊彥簡榮南 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膽胃腸科系肝臟科 3 長庚大學醫學院

1,2,3

Background: Chronic hepatitis C virus (HCV) infection poses a risk of liver cirrhosis and liver cancer. The treatment of chronic HCV infection becomes easy and effective with direct antiviral agents (DAAs). In Taiwan, an estimated 4 hundred thousand people showed chronic HCV infection and viremia. In addition, half of them are unaware or ignoring the HCV infection. The ministry of health and welfare has claimed to eliminate HCV by 2025, 5 years prior to the mission by World Health Organization (WHO). Clearly, to overcome the barrier of unawareness or ignoring the HCV infection is important. Aims: We conduct a call back program for patients with seropositive for anti-HCV and linkage to care in our hospital. Methods: From 2004 to 2017, a database of electronic medical record showing seropositive for anti-HCV were retrieved by department of intelligent technology of our hospital Retrospective chart review was used to construct the patient database and both descriptive statistics and inferential statistical tools were utilized to for data analysis. Results: In a period of 14 years, there were 31275 antiHCV positive patients. Call back system was performed since April 2019 till October 2020. We contacted 4524 patients (14.5%) successfully and excluded others by age, poor patient condition, demise, no available contact phone number, no response to our call and previous history of successful ribavirin ± pegylated interferon therapy. Among the 4524 patients, 1600 patients (35.4%) sought help at other hospitals. 747 patients (16.5%) had already been cured by DAAs. 597 patients (13.2%) refused treatment and 393 patients (8.7%) still had doubt for treatment. 507 patients (11.2%) decided to arrange outpatient clinic appointments by themselves. We arranged outpatient clinic appointments for the rest 680 patients (15%). Of them, 322

2021 消化系聯合學術演講年會

P.029 patients (47.3%) showed HCV RNA positivity. All 322 patients received one of the 4 DAAs (elbasvir/grazoprevir, sofosbuvir/ledipasvir, glecaprevir/pibrentasvir, sofosbuvir/ velpatasvir) therapy. The overall sustained virological response rate at off-treatment 12 weeks (SVR12) was 98.6%. There was no significant relationship between the DAAs and SVR 12 rate (p=0.667). Conclusions: In the hospital care setting, DAAs are safe, effective with high SVR. Call back system can expand our reach to those unaware or ignoring chronic HCV infection patients and linkage to treatment.

代償失調之慢性 C 型肝炎病毒感染肝硬化患者使用全口服直接抗病毒藥物治療其療效、安全性與耐受性分析 EFFICACY, SAFETY AND TOLERABILITY OF ALL ORAL DIRECTACTING ANTIVIRALS FOR CHRONIC HEPATITIS C PATIENTS WITH DECOMPENSATED CIRRHOSIS 1,2

1,2

2,3

朱啟仁蘇品碩吳思賢蘇建維林崇祺李發耀 1,2 1,2 黃怡翔侯明志 1 臺北榮民總醫院胃腸肝膽科 2 國立陽明大學醫學系 3 臺北榮民總醫院健康管理中心

1,2

Background: Chronic hepatitis C virus (HCV) infection is one of major liver diseases which can progress to cirrhosis decades after the infection and finally lead to liver-related death. In particular, patients with decompensated cirrhosis have extremely poor prognosis due to higher likelihood to develop hepatocellular carcinoma and portal hypertension related complications such as jaundice, refractory ascites, variceal bleeding, and hepatic encephalopathy. Historically, pegylated interferon (IFN)-based therapy is less effective and contraindicated in liver decompensated patients with a high frequency of adverse events. Fortunately, the invention of all oral direct-acting antivirals (DAAs) has revolutionized the treatment of HCV, including these special population. Aims: At present, real world data evaluating the efficacy, safety and tolerability of IFN-free all oral DAAs in HCVrelated decompensated liver cirrhosis are scarce in Taiwan. Therefore, we conducted this study to address the above important issues. Methods: Between December 2015 to June 2020, a total of 50 consecutive HCV related decompensated cirrhosis patients who started therapy with all oral DAAs (sofosbuvir/ daclatasvir: 7, sofosbuvir/ledipasvir: 32, sofosbuvir/ velpatasvir: 10, sofosbuvir/ledipasvir then sofosbuvir/ velpatasvir: 1) plus low dose ribavirin (600 mg/day) were enrolled for analyses. SVR12 was defined by undetectable HCV RNA (< 15 IU/mL) at the end-of-treatment and 12 weeks after the completion of therapy. Results: Mean age of enrolled patients was 68 ± 11.2 years, 68% of them was female, and nine (18%) patients has Child-Turcotte-Pugh (CTP) C cirrhosis. Nine (18%) of them failed to previous IFN. Genotype distribution was as follows: 1a: 3; 1b: 34; 2: 9; 6: 3; and one patient with

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P.030 an unclassified HCV genotype. Baseline HCV RNA level before treatment was 5.42 ± 1.2 log10 IU/mL and 28% of them with a baseline HCV RNA > 2,000,000 IU/mL. After DAAs therapy, 36 patients with available HCV RNA data at week 4 and 32 (88.9%) of them had undetectable HCV RNA (< 15 IU/mL). The rates of undetectable HCV RNA (< 15 IU/mL) at end-of-treatment was 96%. 40% patients reported subjective adverse events during therapy but the grades were generally mild and could be symptomatic relieved by medications. Only one patient did not finish therapy due to sepsis. After post-treatment follow up, the SVR12 rate for enrolled patients by intent-to-treat analysis was 96%. Conclusions: For patients with HCV related decompensated cirrhosis which identified as a contraindication by IFN-based therapy in the past, highly effective treatment response and well tolerability could be achieved by sofosbuvir-based DAA regimens.

142

口服直接作用抗病毒藥物對於慢性 C 肝併美沙冬患者的治療效果 EFFICACY OF DIRECT-ACTING ANTIVIRAL AGENTS FOR PEOPLE WHO INJECT DRUGS WITH CHRONIC HEPATITIS C 陳美蓁王嗣仁陳錫榮蔡青陽阮綜合醫院消化內科 Background: Chronic hepatitis C (CHC) causes liver cirrhosis, hepatocellular carcinoma (HCC), and longterm morbidity and mortality. Hepatitis C virus (HCV) eradication would significantly improve long-term outcomes. There are different direct-acting antiviral agents (DAAs), including Sofosbuvir (SOF) -based DAAs, and glecaprevir/pibrentasvir (GLE/PIB), that have been approved for treating CHC patients in Taiwan. However, there is limited data regarding effectiveness of different agents, especially in the patients with people who inject drugs (PWID) and under Methadone maintenance treatment. Therefore, we managed to evaluate the efficacy in patients with CHC who received these DAAs treatment. Aims: There is limited data regarding effectiveness of different agents, especially in the patients with PWID and under Methadone maintenance treatment. Therefore, we evaluated the efficacy in patients with CHC who received these DAAs treatment. Methods: The patients under Methadone treatment with HCV infection were retrospectively selected. They were treated with DAAs of either SOF/VEL for 12 weeks or GLE/PIB for 8 weeks at a single regional teaching hospital during 2019 to 2020. Total 109 PWID patients under Methadone treatment were registered and baseline characteristics were collected including underlying diseases and biochemical data. Total 64 patients were combined with HCV infection, and 7 patients ever received peginterferon (Peg-IFN) ± RBV treatment for HCV before (10.9%). We evaluated the efficacy by whether sustained virological response (SVR) was achieved. Results: Finally, 24 patients were enrolled for evaluation. In which, 14 patients were treated with SOF/VEL, and 10 patients with GLE/PIB. The overall SVR rate was 95.8%. Only one patient still had detectable HCV RNA under SOF/VEL for 12 weeks due to poor drug compliance. The hepatitis C RNA genotyping revealed GT-3,5. Conclusions: For PWID patients under Methadone maintenance treatment with CHC, current DAAs, including

2021 消化系聯合學術演講年會

P.031 SOF/VEL and GLE/PIB, achieved excellent SVR rate. Under good drug compliance, high efficacy was achieved regardless of underlying cirrhosis, HBV co-infection, CKD status, HIV co-infection, or previous treatment for HCV. Possible management for the treatment failure of this patient included SOF/VEL + Ribavirin for 12 weeks for NS5A Y93H resistance-associated substitution (RAS) in HCV genotype 3. Besides, avoidance of sharing needles or unprotected sexual contact should be educated and with regular follow-up.

在北部一醫學中心進行 SOF/VEL 治療 C 肝炎輕度和重度纖維化分期的實際療效和安全性比較 REAL-WORLD EFFICACY AND SAFETY COMPARISON BETWEEN MILD AND SEVERE FIBROSIS STAGES DURING SOF/VEL TREATMENT IN ONE NORTH MEDICAL CENTER 陳銘仁陳志仁林慶忠張經緯潘為鏡馬偕紀念醫院胃腸肝膽科 Background: Some non-invasive tests are valuable in evaluating hepatic fibrosis prior to HCV therapy. The use of these measures in monitoring HCV eradication efficacy and safety is currently limited at real-world practice. Aims: We investigated the real-world efficacy and safety of sofosbuvir/velpatasvir (SOF/VEL) in the treatment of hepatitis C virus patients regarding mild and severe fibrosis stages in one north medical center. Methods: A total of 216 patients treated for HCV infection with SOF/VEL are included in the intent-to-treat (ITT) analysis at MacKay Memorial Hospital (MMH)-Taipei. Among them, 209 patients were included in the per protocol (PP) analysis with 167 F0-F2 patients and 42 F3-F4 patients. In this study, liver fibrosis was measured using the fibrosis 4 index (FIB-4), which is calculated using age, aminotransferases, and platelets. An FIB-4 index higher than 3.25 was considered as a severe fibrosis (F3-F4). Results: The main genotypes were GT1b (41%) and GT2 (38%) in these patients. The overall rates of sustained virologic response at 12 weeks post treatment (SVR12) were 98.6% (206/209) in the PP analysis and 95.4% (206/216) in the ITT analysis. The SVR12 (PP) rates were 98.8% (165/167) in F0F2 patients and 97.6% (41/42) in F3-F4 patients. The levels of alanine aminotransferase and aspartate aminotransferase were decreased in both groups after 4 weeks of treatment. FIB-4 scores were decreased in F3-F4 patients and the levels of total bilirubin were within normal range in all patients at the timepoint of SVR. The estimated glomerular filtration rates were decreased slightly after treatment, and a significant difference was not observed between F0-F2 and F3-F4 patients. Conclusions: The real-world experience at MMH-Taipei shows SOF/VEL has very high efficacy in GT1, 2, 3, 6, and mixed types and whether in mild liver fibrosis (F0-F2) or severe liver fibrosis (F3-F4), (P=0.64). Liver functions improve soon and sustain after treatment in the two population. The renal function decreases slightly after treatment but is not significant.

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P.032

P.033

C 型肝炎患者接受 EPCLUSA 治療後糖尿病和非糖尿病之肝纖維化和脂肪肝的變化 CHANGES OF LIVER STIFFNESS AND STEATOSIS IN DIABETIC AND NONDIABETIC HEPATITIS C PATIENTS AFTER EPCLUSA TREATMENT

從 2017 年到 2020 年口服抗病毒藥治療 3477 位慢性 C 型肝炎病人有高 SVR 成功率及低死亡率 3477 HCV WITH DAA TREATMENT: HIGH SVR 96.4% AND LOW MORTALITY 1.2%

徐友春蘇培元顏旭亨蘇維文陳洋源吳順生彰化基督教醫院胃腸肝膽科

陳啟益周莒光陳柏岳張力仁許銘澤陳盛煊嘉義基督教醫院胃腸肝膽科

Background: Prior studies found that reduces both liver stiffness and steatosis in patients with chronic HCV who received direct-acting anti-viral therapy. Aims: To evaluate changes in liver stiffness and steatosis in diabetic and non-diabetic hepatitis C patients after EPCLUSA treatment. Methods: From June 2019 to March 2020, 164 patients were treated with EPCLUSA in Changhua Christian Hospital. Excluded One withdrawal, four deaths and one SVR loss f/u. Finally, the clinical data of 158 patients with 54 DM and 104 non-DM were retrospectively analyzed. Liver stiffness as evaluated with TE and steatosis as evaluated with CAP were assessed before treatment (baseline) and 12 weeks after end of treatment (SVR12). A total of 64 patients with complete data, including 22 diabetic patients and 42 non-diabetic patients. Results: The overall SVR12 (PP) is 98.7%, 96.3% for DM patients, and 100% for non-DM patients. The levels of total bilirubin, direct bilirubin and creatinine were within normal ranges during and after treatment in both DM and non-DM groups. The overall median liver stiffness at baseline and SVR12 were 6.5 and 5.3 kPa, respectively (p < 0.001). The DM group was 6.7 and 5.7 kPa (p = 0.077), and the nonDM group was 6.4 and 5.2 kPa (p < 0.001). The overall median CAP values at baseline and SVR12 were 225 and 246 dB/m, respectively (p = 0.008). The DM group was 234 and 254 dB/m (p = 0.054), and the non-DM group was 219 and 231 dB/m (p = 0.065). Changes in liver stiffness and steatosis was no significant difference between the two groups. Conclusions: The clinical effectiveness and safety of EPCLUSA in DM patients are still good. EPCLUSA therapy can reduce liver fibrosis but increase steatosis in chronic hepatitis C patients. Compared with non-diabetic patients, diabetic patients have significantly increased steatosis. Limited by the number of cases, large-scale research is required to further confirm.

Background: There were great improvements in DAA treatment SVR in HCV patients. The real world effectiveness and mortality rate of DAA in patients with chronic HCV hepatitis has not been investigated in Taiwan. Aims: We evaluated the real-world effectiveness and mortality of DAA treatment in chronic HCV patients. Methods: From 2017 to 2020, all patients admitted to our institution with positive HCV-RNA were examined to determine the types and outcome of DAA therapy, modalities of HCC treatment, status of HCC before and after DAA treatment, change of liver function and mortality rate. Results: There were 3477 patients with positive HCVRNA received oral DAA from 2017 to 2020. The total SVR per protocol was 96.4%. The average SVR were Zepatier 97.0%, Maviret 97.9%, and Epclusa 95.7% separately. The SVR of 261 HCV with previous history of HCC was 96.8%. There were 36 patients developed HCC after SVR of DAA. Fortunately, there was no mortality in these 36 HCC patient till now. There were 43 patients died, 37 patients after DAA therapy and 6 patients during DAA therapy. The mortality rate was 1.2%. The causes of death were 14 (32.5%) liver related death and 29 (67.5%) nonliver related death. HCC related death was the major cause of liver related death (10/14, 71.4%). Three major nonliver related death were uremia with dialysis (8/29, 27.5%), cardiovascular disease (7/29, 24.1%) and infection with sepsis (5/29, 17.2%). Conclusions: From 2017 to 2020, DAA treatment of chronic HCV hepatitis had achieved excellent improvements with high SVR rate and low mortality rate.

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P.034

P.035

Epclusa（Sofosbuvir/Velpatasvir）治療慢性Ｃ型肝炎代償性肝病真實世界的療效與安全性：一個台灣地區醫院之研究 REAL-WORLD EFFECTIVENESS AND SAFETY OF SOFOSBUVIR/ VELPATASVIR FOR PATIENTS WITH CHRONIC HEPATITIS C VIRUS INFECTION AND COMPENSATED LIVER DISEASE: ONE TAIWAN DISTRICT HOSPITAL STUDY

探討 Sofosbuvir/Velpatasvir 於東台灣治療慢性 C 型肝炎之療效：單一山地原鄉經驗 REAL-WORLD EFFECTIVENESS OF SOFOSBUVIR/VELPATASVIR FOR TREATMENT OF CHRONIC HEPATITIS C IN EASTERN TAIWAN: A SINGLE ABORIGINAL TOWNSHIP EXPERIENCE

1,2

葉欣榮方冠傑高偉育唐瑞祥張君照蘇宜輝 1,2 甘育安 1 臺北醫學大學附設醫院消化內科 2 枋寮醫院肝膽腸胃內科

Background: Epclusa (sofosbuvir/velpatasvir) has been reimburse by Taiwan health insurance since 2019 July. Data regarding the real-world effectiveness and safety of sofosbuvir/velpatasvir for patients with chronic hepatitis C virus (HCV) infection and compensated liver disease in Taiwan are limited. Aims: We aimed to evaluate the performance of sofosbuvir/ velpatasvir for 12 weeks for HCV-infected patients with compensated liver disease in one Taiwan district hospital. Methods: We collected 89 patients receiving Ecplusa in Pingtung Fangliao Hospital from September 1, 2019 to September 1, 2020. We also monitored adverse events during treatment period. We analyzed virologic and biochemical responses and monitored adverse events. Results: Of these patients, the median age was 70 years (range 35-90) and 41 (46%) were men. Forty-one were genotype type 1 (46.1%), 41 were genotype type 2 (46.1%), one was genotype type 3 (1.1%), and 6 were genotype type 6 (6.7%). Three patients discontinued treatment due to headache, septic shock and non-compliance. Among 86 patients who had the sustained virologic response at off-treatment week 12 (SVR12), the SVR12 rates by per-protocol populations analyses were 100% (86 of 86 patients). Twelve patients (13.5%) had adverse events. Two patient (2.2%) had headache, 8 patients (8.99%) had pruritus and symptom relieved after taking Cyproheptadine, 3 patients (3.4%) had fatigue and poor appetite. Two patients (2.2%) developed hepatocellular carcinoma. Conclusions: Sofosbuvir/velpatasvir for 12 weeks is efficacious and well-tolerated for chronic HCV-infected patients with compensated liver disease in Taiwan.

陳頎叡田惠文陳雅雲陳健麟雷尉毅 1 佛教慈濟醫療財團法人花蓮慈濟醫院內科部 2 花蓮縣秀林鄉衛生所 3 佛教慈濟醫療財團法人花蓮慈濟醫院內科部肝膽腸胃科 Background: Aboriginal people is a group with a high prevalence of HCV infection in Taiwan. Reducing HCV incidence and increasing access to HCV therapy are priorities of national hepatitis C strategies, which highlight aboriginal people as a priority population. Clinical trials have shown high efficacy of sofosbuvir/velpatasvir (SOF/ VEL) for the treatment of patients with chronic HCV, but there are still limited data from real-world settings. Aims: The aim of this study was to evaluate SOF/VEL effectiveness and safety in aboriginal population in Eastern Taiwan. Methods: Patients who received SOF/VEL for chronic hepatitis C were retrospectively recruited in Hualien Xiulin township from Jan. 2019 to Aug. 2019. The baseline characteristics of patients were recorded, and sustained virologic response 12 weeks after end-of treatment (SVR12) were assessed. Data of non-aboriginal HCV patients treated with SOL/VEL in Hualien Tzu-Chi hospital during the same period of time were also collected. We compared the baseline characteristics, virologic and biochemical response between aboriginal patients from Xiulin township and nonaboriginal individuals in the hospital. Results: Totally, twenty-four patients treated with SOF/ VEL in Xiulin township and 55 patients in Hualien TzuChi hospital were analyzed. For the genotype distribution, 62% of aboriginal patients were GT1b and 51% of nonaboriginal patients were GT2. In Fibrosis-4 (FIB-4) defined advanced fibrosis, 17% of patients in aboriginal group and 29% of patients in non-aboriginal group had FIB4 > 3.25. The overall SVR12 rates at per protocol were 100% in both groups. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) normalization were achieved in both groups after 4 weeks of treatment. FIB4 scores improved after SVR12 with SOF/VEL treatment in both groups. The estimated glomerular filtration rates

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P.036 (eGFR) were slightly decreased in non-aboriginal patients after treatment, compared to the baseline eGFR. No patients discontinued therapy due to adverse effect or poor adherence in both groups. Conclusions: Our study demonstrated that the overall SVR12 rates in Taiwanese aboriginal patients with chronic HCV who received SOF/VEL were comparable with those in previous clinical trials and real-world data. SOF/VEL achieved high efficacy and well-tolerated for treatment of chronic hepatitis C. More real-world experience need to be obtained in the future.

以直接作用抗病毒藥物治療 C 型肝炎病毒與人類免疫缺乏病毒共同感染之病患 DIRECT-ACTING ANTIVIRAL THERAPIES IN PATIENTS WITH HIV/ HCV COINFECTION 1

1,3

朱家聲林伯昌高榮達陳浤燿許鈺銓蕭望德 5 1,3 1 4 5 1 曾晟恩許偉帆卓富讚余承儒陳政國舒敬軒 1,3 1,3 1,3 1,6 彭成元林俊哲林肇堂賴學洲 1 中國醫藥大學附設醫院消化醫學中心 2 中國醫藥大學附設醫院內科部感染科 3 中國醫藥大學醫學院 4 長安醫院肝膽腸胃科 5 亞洲大學附設醫院內科部肝膽腸胃科 6 中國醫藥大學中醫學院 Background: Hepatitis C virus (HCV) infection is one of the most frequent causes of comorbidity and mortality in the human immunodeficiency virus (HIV) population. In recent years, direct-acting antiviral (DAA) therapies has dramatically transformed HCV treatment with high efficacy (>90%) across all genotypes and special populations. However, there are limited studies to demonstrated real-world characteristic and efficacy in HIV/HCV coinfected patients. Aims: To demonstrated the clinical characteristics of the patients with HIV/HCV coinfection and the efficacy of DAA therapies in this population. Methods: We identified 165 patients with HIV/HCV coinfection who completed DAA therapy from November 29, 2017 to December 31, 2020 and analyzed the clinical characteristics and assessed the efficacy of DAA therapies. Efficacy was evaluated as sustained virologic response (SVR) 12 weeks after DAA completion. Results: Totally, 139 males and 26 females were enrolled. The mean age was 42.4 (21 to 80) years old. Only 19 patients had cirrhosis, one of them was in Child-Puge B and two of them were in Child-Pugh C. HCV genotype 1a accounted for 28.3%, followed by genotype 6 (27.1%). One patient had mixed-type HCV infection (genotype 1a and 1b) only. 10 patients lost to follow-up and didn’t receive the blood test 12 weeks after completion. In 155 patients who completed the whole DAA therapeutic course and received follow-up blood test, only 3 patients experienced virologic failure. The efficacy of DAA therapies in HIV/HCV coinfected patients was 98.1%. Conclusions: Our results supported that DAA therapies has good efficacy in HIV/HCV coinfected patients. 98.1% of the patients achieving SVR12 and only 3 patients experienced virologic failure.

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P.037 艾百樂對於慢性 C 型肝炎患者的療效與安全性評估 ─ 單一中心的真實數據 THE EFFECTIVENESS AND SAFETY OF GLECAPREVIR/PIBRENTASVIR FOR CHRONIC HCV-INFECTED PATIENTS ‒ A REAL-WORLD EXPERIENCE OF SINGLE HOSPITAL 陳柏岳周莒光張力仁許銘澤蔡崇榮蘇昶昭方建忠林玉玲陳啟益嘉義基督教醫院胃腸肝膽科 Background: Maviret is a direct acting antiviral agent which is composed of the NS3/4A protease inhibitor glecaprevir and the NS5A inhibitor pibrentasvir. Regardless of genotypes, Maviret has been proved to be effective and safe for chronic HCV-infected patients without decompensated cirrhosis. In clinical trials, glecaprevir/ pibrentasvir (G/P) could achieve 98% sustained virologic response (SVR) rate for HCV-infected patients with severe renal impairment. Aims: The aim of our study is to evaluate the effectiveness and safety of glecaprevir/pibrentasvir for 8 or 12 weeks in chronic HCV-infected patients without decompensated cirrhosis. Methods: We retrospectively enrolled chronic HCVinfected patients who ever treated by glecaprevir/ pibrentasvir for 8 or 12 weeks in Chia-Yi Christian Hospital since Jul. 2018 to Jul. 2020. The SVR12 rate was defined as the percentage of undetectable HCV RNA (HCV RNA < 15 IU/ml) at week 12 after ceasing Maviret treatment. The adverse effects and safety were reviewed by electrical medical record. Results: A total of 562 HCV-infected patients were enrolled retrospectively. The median age was 60.8 years old and 54.1% of patients were female. Among 562 patients, 112 patients (19.9%) had advanced fibrosis which defined as FiB-4 ≥ 3.25. A total of 72 patients (12.8%) received dialysis treatment and 22 patients were classified as severe renal impairment (chronic kidney disease stage 4 or 5 without dialysis). 447 and 115 patients received 8 and 12 weeks Maviret treatment, respectively. Most patients were infected by genotype 2 HCV (66.4%, 373/562), and followed by genotype 1b (21.7%, 122/562). Of 562 enrolled patients, one patient had detectable HCV RNA at SVR12 and 14 patients were defined as non-virologic failure. The overall SVR rate was 99.8% (547/548) and 97.3% (547/562) by per protocol and intention to treat analysis,

respectively. The SVR rate was consistently effective to the patients with ESRD (100%, 72/72) or severe renal impairment (100%, 22/22). Among 435 and 112 patients who completed 8 weeks and 12 weeks of Maviret treatment respectively, the SVR rate was 100% (435/435) and 99.1% (111/112). Among 14 patients with non-virologic failure, 4 patients (0.7%, 4/562) had premature discontinuity due to adverse effects and no death was found during treatment. A total of 18 patients’ serum bilirubin level rose to more than 2.0 mg/dl, none of them progressed to hepatic decompensation and all achieved undetectable HCV RNA at SVR12. The incidence of risen bilirubin level during Maviret treatment was not associated with fibrosis stage (FiB-4 < 3.25 vs FiB-4 ≥ 3.25, 3.10% vs 7.00%, p = 0.09). Conclusions: Glecaprevir-pibrentasvir given for 8 or 12 weeks is effective and safe for chronic HCV-infected patients without decompensated cirrhosis.

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P.038

P.039

南台灣 GT6 型之 C 型肝炎患者使用 EPCLUSA 之真實世界經驗調查 EPCLUSA IN GT6

阿里山鄉居民使用 EPCLUSA 治療 C 型肝炎之經驗分析 EPCLUSA IN ABORIGINAL POPULATION OF ALISHAN TOWNSHIP

陳志州董宏達李佩倫郭行道許銘仁侯佳儀 4 吳麗卿 1 柳營奇美醫院胃腸肝膽科 2 永康奇美醫院胃腸肝膽科 3 柳營奇美醫院病理中心 4 永康奇美醫院病理中心

Background: Genotype 6 (GT6) HCV is the most diverse genotype and comprised of up to 31 subtypes and 19 unassigned subtypes. GT6 HCV is mainly geographically restricted in Southeast Asia and South China. In Taiwan, GT6 HCV infection has been reported scarcely except in intravenous/injection drug user (IDUs), mostly subtype 6a. Aims: Recently, a global collective study of HCV patients treated with different Sofosbuvir-based regimens, including over 14,000 patients, a new GT6 subtype closely related with 6g and 6w was identified from Tainan. Thus, subtype 6g and 6w might have be the indigenous HCV subtypes in Tainan for centuries. The prevalence of GT6 where more than 30% are located between Jishui and Zengwen rivers, and the local endemic infection with geographic restriction by two rivers could be caused by indigenous subtype 6g/6w. Methods: To analysis the Epclusa Real world data, in Chi Mei-Liouying Hospital, the baseline patient characteristic had examined their prior HCC history, FIB-4 score, eGFR, HCV RNA amount, hemoglobin and so on among all the 39 GT6 patients and 156 non-GT6 patients. SVR12 was also analyzed to observe the efficacy of Epclusa. Results: In our research, we analyzed the efficacy of EPCLUSA in treating HCV patients with GT6 and nonGT6. Then analyze the liver function by FIB-4, most of the patient had FIB-4 < 3.25 (90% of non-GT6 and 79% of GT6). Notably, decompensated cirrhosis was 7% in GT6 but having no case found in non-GT6. EPCLUSA real world experience in Chi Mei-Liouying performed very high efficacy SVR12 = 100% in GT6. Conclusions: The liver and kidney function by laboratory data showed improved after EPCLUSA treatment in the two population, GT6 and non-GT6.

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羅清池天主教聖馬爾定醫院內科部 Background: ccording to a hepatitis C treatment program of aboriginal population, people in Alishan township has a hepatitis C potential risk of 7. Aims: In order to deal with the hepatitis C patient at Alishan township, we have started hepatitis C outpatient department since December, 2018. Methods: In the EPCLUSA real world data in Alishan aboriginal population which compared with patient in St. Martin De Porres Hospital (STMH), the major genotype of these two population were GT1b and GT2. Notably, genotype of GT6 was higher than STMH. Results: As for the fibrosis stage estimation, 50% of Alishan aboriginal population had FiB-4 ≥ 3.5. After treat with EPCLUSA, the sustained virologic response (SVR) was 100% in Alishan population, 99.45% of SVR12 in STMH population at the same time. Based on the laboratory data after EPCLUSA treatment in the two populations, liver and kidney function was significantly improved. Conclusions: In conclusion, it showed high efficacy of EPCLUSA in both Alishan aboriginal population and STMH population.

2021 消化系聯合學術演講年會

P.040 彰化縣在社會邊緣族群之 C 型肝炎微根除 HEPATITIS C MICRO-ELIMINATION IN MARGINALIZED POPULATION OF CHANGHUA COUNTY TAIWAN 1

clinical settings. Table 1 shows the result of HCV testing and treatment in HIV-positive patients. There are 791 HIVpositive patients receiving care in five major hospitals in Changhua county. The overall anti-HCV antibody testing rate is 99.87% and the positive rate is 46.71%. Furthermore, RNA results are also provided and the overall testing rate and positive rate are 94.58% and 75.07%. Among these people who are HCV RNA positive, the overall treatment rate is 84.73% and 81.53% of them completed the treatment within the end of follow-up time. The HIV transmission route (ratio of PWID/MSM) are different among these 5 hospital patients, which make a difference between the HCV co-infected rates ranged from 28.57% to 94.29%. The same situation applied to the result of HCV RNA testing. PWID patients in Methadone clinics have the highest seroprevalence of HCV testing (88.41%) shown in Table 2 compared to other 3 groups. The seroprevalence of HCV antibody are 38.15% for prisoners (Table 3) and 15.77% for other high-risk groups (Table 4), respectively. The proportions of RNA testing and treatment are similar among HIV-positive cases, PWID patients in Methadone clinics and prisoners. The group 4 patients who had HCV diagnosed were not sure if linked to care due to failed subsequently follow-up. Inadequate education about disease awareness and difficult access to these patients on subsequently followup are the major barriers since they were incidentally found to have hepatitis C Antibody under transient judiciary only. There are no law or regulation to promptly render these patients to access HCV care for eliminate the disease. We still need more efforts to overcome these barriers to help these patients. Conclusions: Our study demonstrated that this collaborative care model increased the rates of diagnosis and achieved substantially higher linkage to care which will help for HCV elimination. Apply this model for marginalized population to other part of Taiwan may help to achieve 2025 Taiwan goal.

蘇維文胡琮輝蘇培元楊智超楊基滐葉永祥 6 7 8 9 10 郭武憲葉彥伯陳秀熙許文郁劉尊榮 1 彰化基督教醫院胃腸肝膽內科 2 高雄長庚紀念醫院胃腸肝膽內科 3 衛生福利部彰化醫院胃腸肝膽內科 4 秀傳紀念醫院胃腸肝膽內科 5 彰濱秀傳紀念醫院胃腸肝膽內科 6 員生醫院胃腸肝膽內科 7 彰化縣衛生局 8 國立臺灣大學公衛學院 9 彰化基督教醫院精神科 10 彰化基督教醫院感染科

Background: Toward 2025 Taiwan goal of hepatitis C elimination, marginalized population would be the difficult part to accomplish this goal. Aims: We aimed to report the experience of Changhua county via integrated hepatitis C elimination task force in this difficult population. Methods: The Changhua HCV micro-elimination for marginalized population adopted a multidisciplinary care approach targeted at patients attended HIV clinic; methadone substitution therapy clinic; correctional institution in prison; and other high-risk patients under judiciary in the county. This model incorporated rigorous HCV screening into a robust infection control program. HCV diagnosis was linked to direct-acting antiviral (DAA) treatment enabled by active collaboration between different teams with gastroenterologists (GIs) and nursing coordinators. Results: The result enrolled patients from early 2019 to 2020 Dec and can be divided into four groups from different Table 1. HCV testing and treatment of HIV-positive patients Number of Hospital HIV cases

Testing Anti-HCV antibody testing N

Positive

Treatment

RNA testing N

Positive

Complete

129

100.00

65.12

96.43

86.42

84.29

86.44

404

100.00

118

29.21

116

98.31

61.21

92.96

68.18

100.00

28.57

60.71

70.59

91.67

81.82

100.00

36.84

85.71

83.33

100.00

60.00

141

140

99.29

132

94.29

129

97.73

104

80.62

77.88

90.12

Total

791

790

99.87

369

46.71

349

94.58

262

75.07

222 84.73

181

81.53

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Table 2. HCV testing and treatment of PWID patients in Methadone clinics Number of Hospital PWID cases

Testing Anti-HCV antibody testing N

Treatment

RNA testing

Positive

Complete

223

100.00

202

90.58

200

99.01

163

81.50

157 96.32

142

90.45

100.00

73.91

100.00

76.47

76.92

80.00

102

100.00

84.31

98.84

76.47

93.85

95.08

100.00

71.43

90.00

72.22

95.35

95.12

97.44

86.84

93.94

87.10

Total

442

440

99.55

389

88.41

385

98.97

307

79.74

287 93.49

256

89.20

Table 3. HCV testing and treatment in correctional institutions Testing Anti-HCV antibody testing N

Treatment

RNA testing

Positive

Complete

2019

2180

83.69

865

39.68

724

83.70

578

79.83

528 91.35

497

94.13

HIV

143

100.00

133

93.01

131

98.50

105

80.15

78.10

89.02

2020

294

88.29

20.41

93.33

51.79

29 100.00

34.48

Prison

2617

84.94

1058

40.43

911

86.11

712

78.16

639 89.75

580

90.77

81.69

24.14

100.00

78.57

11 100.00

100.00

Youth detention center 135

61.36

0.00

Total

83.33

1072

38.15

925

86.29

723

78.16

Detention house

2810

650 89.90

591

90.92

Table 4. HCV testing and treatment among other high-risk groups Anti-HCV antibody testing

Type

Positive

PWID

461

100.00

165

35.79

Sex worker

100.00

8.14

Whoremonger

100.00

0.00

Probation Officer (People under protective control, parole)

249

100.00

144

57.83

People who attend lectures of Class III & IV hazardous drugs

168

100.00

2.38

Named

100.00

Anonymous

330

100.00

Others

627

100.00

14.19

Sports Center

690

100.00

0.72

Total

2676

100.00

422

15.77

People found by the police officer

MSM

150

2.19

2021 消化系聯合學術演講年會

P.041 宜譜沙（Epclusa）治療 C 肝的現實世界療效與不良反映 ─ 雲林一區域醫院經驗 REAL-WORLD EFFECTIVENESS AND ADVERSE EFFECT OF EPCLUSA FOR PATIENTS WITH HEPATITIS C IN A REGIONAL HOSPITAL 1

黃克章陳達位許貝池吳奕霆湯昇曄 1 中國醫藥大學北港附設醫院腸胃肝膽科 2 臺南市立安南醫院消化內科

Background: Sofosbuvir/velpatasvir (Epclusa) is used for adults with genotype 1–6 chronic hepatitis C (CHC) virus (HCV) infection. It was developed by the pharmaceutical company Gilead Sciences and approved by the U.S. Food and Drug Administration (FDA) in June 2016. In Taiwan (CDC) it was approved and used in 2019, for the treatment of chronic hepatitis C virus infection in adults. The Epclusa had high effects and lower adverse effect, but the real-world data of Epclusa in Taiwan are limited. Aims: This study aimed to investigate the effectiveness and adverse effects of the pan-genotypic DAA (Epclusa) for CHC patients in a regional hospital. Methods: We performed a retrospective study on 107 CHC patients. CHC patients received Epclusa from September of 2019 to June of 2020. All patients had received completed courses for 12 weeks and with data of HCV viral load at 12 weeks after completion of DAA therapy (SVR12). The primary endpoint was undetectable HCV RNA (HCV RNA < 15 IU/mL) at 12 weeks posttreatment (SVR12). The adverse effects were also evaluated. Results: From Sep. 2019 to June. 2020, a total of 107 HCV patients received Epclusa treatment, there were 106 patients who complete this treatment course, but one patient discontinued the treatment due to an adverse event. The mean age was 63.43 ± 12.95 years, Male to female ratio was 52/55 (48.60%/51.40%); combined HBV coinfection was 10 (9.3%); HIV co-infection was 1 (0.9%); Fib-4 ≧ 3.25 was 35 (32.7%) and with decompensated cirrhosis was 7 (6.5%); eGFR < 60 ml/min/1.73m 2 was 9 (8.4%); HCV RNA (log10 IU/ml) mean (SD) was 6.54 (6.88); ALT mean was 66.03 (68.34); Total bilirubin mean was 0.96 (0.69); the genotypes were type 1 (2), type 1a (7), type 1b (51), type 1b+2 (2), type 2 (42), type 6 (3). After Epclusa treatment, ALT & AST showed declining at wk4, EOT & SVR12; Total bilirubin showed declining at wk4, EOT; the Fib-4 showed declining at SVR12; the GFR showed declining at wk4 & EOT, but it elevated at

SVR12. The rate of undetectable HCV RNA (<15 IU/ ml at EOT and SVR12 were 100% and 100%. The main adverse events are headache (11.2%), fatigue (9.3%), insomnia (8.4%), pruritus (8.4%), dizziness (5.6%), cough (5.6%), constipation (2.8%), mylagia (1.9%), depression (1.9%), arthralgia (0.9%) and oral ulcer (0.9%). The grade of adverse events were generally mild and most patients completed treatment except 1 patient with early withdrawal. Conclusions: 1. Major genotypes for EPCLUSA® realworld experience in the two populations are GT1b, GT2. 2. EPCLUSA ® perform very high efficacy SVR12 = 100% (PP), even higher proportion severe liver fibrosis patients compared the normal population in the two population. 3. Liver function improved by laboratory data after EPCLUSA® treatment. 4. The kidney function after EPCLUSA ® treatment declined at wk 4 & EOT, but recovered at SVR12. 5. The main adverse events are headache, fatigue, insomnia, pruritus, dizziness & cough.

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P.042 併有腎功能不全和慢性 C 肝病人在使用 Sofosbuvir 後發生末期腎臟疾病的風險 RISK OF END-STAGE RENAL DISEASE AMONG HEPATITIS C PATIENTS WITH CHRONIC KIDNEY DISEASE TREATED WITH AND WITHOUT SOFOSBUVIR 1,2

Laura Telep , Meghan Sise , Lindsey Force , 1 1,2 Anuj Gaggar , Anand Chokkalingam 1 Gilead Science, Foster City, CA, USA School of Public Health, University of California, 2 Berkeley, CA, USA Department of Medicine, Division of Nephrology, 3 Massachusetts General Hospital, Boston, MA, USA Background: Sofosbuvir (SOF) is a prodrug inhibitor of the hepatitis C virus (HCV) NS5B polymerase. The predominant circulating metabolite of SOF, GS-331007, is renally eliminated. Whether SOF affects kidney function is not well described. Aims: Using administrative claims data, we sought to characterize the risk of end-stage renal disease (ESRD) or dialysis among patients with chronic kidney disease (CKD) and HCV treated with SOF- and non-SOF-containing direct acting antiviral (DAA) regimens. Methods: 2,359 adult patients with evidence of interferon (IFN) -free DAA-treated HCV infection and claims indicating diagnosis of CKD were identified from a large US administrative claims database. All included patients had at least 1 year of continuous enrollment prior to cohort entry. Exclusion criteria were 1) prior claim for ESRD, dialysis, or kidney transplant, 2) simultaneous exposure to SOF and non-SOF DAA regimens, and 3) concomitant receipt of IFN. Patients were observed from initiation of the most recent DAA regimen to the first of: a claim for ESRD or dialysis, kidney transplant, discontinuation of insurance enrollment, or last date of data availability (September 2018). Absolute rates per 100 person-years (PYs) were calculated with exact 95% Poisson confidence intervals (CIs) at all stages of CKD combined and stratified for those patients with staging identified. Adjusted hazard ratios (HRs) estimating ESRD/dialysis risk associated with SOFvs non-SOF-containing DAA regimens were calculated using Cox proportional hazards methods, after adjustment for baseline health status and treatment propensity score weighting. Results: Overall, the unadjusted incidence of ESRD or dialysis was 3.88 (95% CI: 3.24-4.62) per 100 PY, with

152

rates highest for patients with severe CKD (18.26; 95% CI: 12.79 – 25.28 per 100 PY). For the 1,976 SOF and 383 non-SOF DAA regimens, the unadjusted rates of ESRD or dialysis were 3.53 (95% CI: 2.89 – 4.28) and 7.41 (95% CI: 4.65 – 11.22) per 100 PY respectively. After covariate adjustment and treatment propensity score weighting, there was no significant difference in risk of ESRD or dialysis with vs. without SOF (adjusted HR = 0.77, 95% CI: 0.431.36). Similar results were observed when stratified by CKD stage. Conclusions: The results of this analysis of real world data indicate no difference in risk of ESRD or dialysis in HCVinfected CKD patients treated with SOF- vs. non-SOFcontaining DAA regimens.

2021 消化系聯合學術演講年會

P.043

P.044

輕度與重度纖維化使用 EPCLUSA 之真實世界經驗 EPCLUSA REAL WORLD EXPERIENCE WITH MILD AND SEVERE FIBROSIS STAGE

Sofosbuvir/Velpatasvir 在青少年和 3 至 17 歲兒童的慢性 C 型肝炎感染治療後 24 週內的安全和有效性評估 SAFETY AND EFFICACY OF SOFOSBUVIR/VELPATASVIR FOR THE TREATMENT OF CHRONIC HEPATITIS C INFECTION IN ADOLESCENTS AND CHILDREN AGED 3 TO 17 YEARS OLD THROUGH 24 WEEKS POSTTREATMENT

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: A total of 152 patients had ever exposure to EPCLUSA treatment for hepatitis C infection in Taichung Veterans General Hospital till November 2020. Aims: Among them, 25 patients had ongoing EPCLUSA treatment course and the clinical data of 127 patients were collected and analyzed. Methods: Among 127 patients, 2 patients did not complete the treatment course with an incomplete ratio of 1.57%. Finally, end of treatment (EOT) data and sustained virologic response at 12 weeks after treatment (SVR12) data were available in 125 patients and 96 patients, respectively. Results: Stages of liver fibrosis according to FIB-4 scores were F0 in 34 (27.2%), F1 in 23 (18.4%), F2 in 39 (31.2%), F3 in 21 (16.8%) and F4 in 8 (6.4%) patients. For genotyping data, 43% of patients were GT2 and 39% of patients were GT1b. EOT response and SVR12 were 100% in both F0-2 and F3-4 patients. EOT response and SVR12 were also 100% regardless of genotypes. Both F0-2 and F3-4 patients had improvement in alanine aminotransferase and no deterioration in estimated glomerular filtration rate after 12 weeks of treatment. Conclusions: EPCLUSA performed good efficacy and safety for treatment of hepatitis C infection in both F0-2 and F3-4 patients.

Etienne M. Sokal , Kathleen B. Schwarz , Philip Rosenthal , 4 5 6 Gabriella Verucchi , Chuan-Hao Lin , William F. Balistreri , 7 8 9 Jessica Wen , Suzanne Whitworth , Daniel H. Leung , 10 2 11 Stanjay Bansal , Wikrom Karnsakul , Alessandra Mangia , 12 13 13 Girish S. Rao , Jiang Shao , Chia-Hsiang Hsueh , 13 13 13 Bandita Parhy , Anuj Gaggar , Kathryn Kersey , 14 15 Michael R. Narkewicz , Regino P. Gonzalez-Peralta , 16 17 18 Karen F. Murray , Rene Romero , Maureen M. Jonas Cliniques Universitaires Saint-Luc, Université Catholique 1 de Louvain, Bruxelles, Belgique Johns Hopkins University School of Medicine, Baltimore, 2 MD, USA University of California San Francisco, San Francisco, CA, 3 USA 4 DIMEC, Università di Bologna, Bologna, Italy Children’s Hospital Los Angeles, University of Southern 5 California, Los Angeles, CA, USA Cincinnati Children’s Hospital. University of Cincinnati, 6 Cincinnati, OH, USA University of Pennsylvania and The Children’s Hospital of 7 Philadelphia, Pennsylvania, PA, USA Cook Children’s Health Care System, Fort Worth, TX, 8 USA Baylor College of Medicine, Texas Children’s Hospital, 9 Houston, TX, USA 10 Kings College Hospital, London, UK Ospedale Casa Sollievo della Sofferenza, San Giovanni 11 Rotondo, Italy Riley Hospital for Children, Indiana University School of 12 Medicine, Indianapolis, IN, USA 13 Gilead Sciences, Inc, Foster City, CA, USA University of Colorado School of Medicine and Children’s 14 Hospital of Colorado, Aurora, CO, USA AdventHealth for Children and AdventHealth Transplant 15 Institute, Orlando, FL, USA Cleveland Clinic Children’s Hospital, Cleveland Clinic, 16 Cleveland, OH, USA

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P.045 Children’s Healthcare of Atlanta and Emory University 17 School of Medicine, Atlanta, GA, USA 18 Boston Children’s Hospital, Boston, MA, USA Background: Sofosbuvir/velpatasvir (SOF/VEL) is a pangenotypic, fixed-dose combination of 2 direct acting antivirals for the treatment of hepatitis C. Aims: The current study evaluated the safety, and efficacy of SOF/VEL in pediatric patients 3 to 17 years old. Methods: Patients aged 3 to 17 years with chronic HCV of any genotype (GT), with or without cirrhosis, were enrolled sequentially by age group into this open‐label study (NCT03022981) to receive SOF/VEL once daily for 12 weeks. The dose and formulation (standard or lowdose tablet or oral granules) were based on age and weight. Sustained viral response was assessed at 12- and 24-weeks post-treatment (SVR12 and SVR24). Safety was assessed by adverse events (AEs), and laboratory data and effects on growth. Intensive pharmacokinetic (PK) sampling on Day 7 in a subgroup of patients in each age group was done to confirm the appropriateness of the chosen dose and select the dose for the next age group. Results: A total of 216 patients were enrolled: 102 aged 12 - 17 years, 73 aged 6 - 11 years, and 41 aged 3 - 5 years. Overall, 76% had GT1, 6% GT2, 12% GT3, 3% GT4, 3% GT6 HCV; 53% were female, 80% were white, 88% were treatment naïve, and 93% had been vertically infected. PK confirmed the doses selected resulted in exposures within the range observed in adults. SVR12 rates are in the table; in total, only 2 (<1%) patients had virologic failure. SVR24 concordance with SVR12 was 100%. Most AEs were mild or moderate in severity. Five patients had serious AEs, one of whom had a SAE of auditory hallucinations the investigator assessed as treatment-related and that resulted in treatment discontinuation. Two other patients discontinued treatment due to AEs. The most common AEs (>15% of patients) were headache, fatigue, and nausea in adolescents; vomiting, cough and headache in 6 to 11 year olds; and, vomiting in 3 to 5 year olds. No relevant effects on growth were observed. Conclusions: Treatment with SOF/VEL for 12 weeks resulted in high SVR12 rates in patients aged 3 to 17 years with chronic HCV regardless of genotype and was well tolerated overall. A smaller, low-dose tablet and oral granule formulations have been developed to facilitate dosing in younger children. SOF/VEL is a simple, pangenotypic, fixed dose combination regimen that promises to be a beneficial treatment option for children as young as 3 years of age.

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GLE/PIB 治療 8 週用於 C 型肝炎患者及併有物質使用疾患之真實世界研究：彙整多項上市後觀察研究的分析 REAL-WORLD OUTCOMES IN PATIENTS WITH CHRONIC HEPATITIS C VIRUS INFECTION AND SUBSTANCE ABUSE DISORDERS TREATED WITH GLECAPREVIR/PIBRENTASVIR FOR 8 WEEKS: A POOLED ANALYSIS OF MULTINATIONAL POST-MARKETING OBSERVATIONAL STUDIES 1

Giuliano Rizzardini , Michael Gschwantler , 3 4 5 Stefan Bourgeois , Beat Müllhaupt , Włodzimierz Mazur , 6 6 7 Mark Bondin , Zhenzhen Zhang , Fiona Marra , 8 9 10 Ella Veitsman , Konstantinos Mimidis , Nuno Marques , 11 Juliette Foucher 11st Division of Infectious Diseases, ASST 1 Fatebenefratelli-Sacco, Milan, Italy Department of Internal Medicine IV, Wilhelminenspital, 2 Vienna, Austria 3 Stuivenberg ZNA, Antwerp, Belgium Department of Gastroenterology and Hepatology, University Hospital Zürich and University of Zürich, 4 Zurich, Switzerland Clinical Department of Infectious Diseases, Medical 5 University of Silesia, Katowice, Poland 6 Abbvie Inc., North Chicago, IL, USA 7 Liver Unit, Rambam Health Care Campus, Haifa, Israel University of Liverpool Hepatology Drug Interactions 8 Group, Liverpool, UK First Department of Internal Medicine, Democritus University of Thrace Medical School, Alexandroupolis, 9 Greece Infectious Diseases Service, Hospital Garcia De Orta EPE, 10 Almada, Portugal 11 Hôpital Du Haut-Lévêque, Preesac, France Background: Hepatitis C Virus (HCV) affects > 50% of people who inject drugs. To meet World Health Organization 2030 HCV elimination targets, people who use drugs (PWUD) are a critical population to reach and provide access to treatment. Glecaprevir/pibrentasvir (G/ P) is approved for treatment of adults with chronic HCV genotype (GT) 1–6 infection, with a label now including 8-week treatment for treatment-naïve (TN) patients with compensated cirrhosis (CC). Despite data demonstrating G/P effectiveness in PWUD, barriers to treatment persist,

2021 消化系聯合學術演講年會

P.046 including stigma, risk of reduced treatment compliance, and thus, effectiveness. Shorter therapy durations could potentially improve outcomes in such patients. Aims: To examine the real-world effectiveness and safety of 8-week G/P in PWUD and other historically underserved patient groups. Methods: Data from TN patients (without cirrhosis/ with CC) prescribed 8-week G/P were pooled from 9 countries (13 Nov 2017 - 02 Oct 2019). The percentage of patients who achieved sustained virologic response at post-treatment Week 12 (SVR12) was assessed overall/by subgroup. Illicit drug use was patient reported. Results: Of 1423 patients prescribed G/P for 8 weeks, 452 (31.8%) had a self-reported history of any illicit drug use (PWUD), 120 (8.4%) had psychiatric disorders, 192 (13.5%) had a history of alcohol use (≥ 2 drinks/day), 363 (25.5%) were unemployed, 312 (21.9%) reported lowto-no education. The most commonly used prescribed psychotropic drugs with a potential interaction with G/P were quetiapine (0.5%), haloperidol (0.3%), and aripiprazole (0.3%). The most commonly used illicit drugs in PWUD were heroin (58.7%), cocaine (22.8%), and marijuana (12.8%). SVR12 rate was 98.1% (1198/1221) overall, 97.0% (357/368) in PWUD and ≥ 95.6% across subgroups. There was 1 G/P-related serious adverse event. Conclusions: Across a variety of real-world clinical settings, 8-week G/P treatment was highly effective and well tolerated in HCV-infected PWUD and other historically underserved patients.

肝細胞癌患者中以 Sofosbuvir/Velpatasvir 治療 C 型肝炎感染：單一醫學中心的真實經驗 REAL-WORLD EXPERIENCE OF SOFOSBUVIR/VELPATASVIR THERAPY FOR HEPATITIS C VIRUS RELATED HEPATOCELLULAR CARCINOMA ‒ A SINGLE CENTER DATA 1

2,3

黃永信林成俊許朝偉林錫銘沈一嫻謝森永 2,3 2,3 林俊彥簡榮南 1 林口長庚紀念醫院胃腸肝膽科系 2 林口長庚紀念醫院胃腸肝膽科系肝臟科 3 長庚大學醫學院

Background: Sofosbuvir/velpatasvir (SOF/VEL) therapy has been demonstrated good efficacy in treating chronic hepatitis C virus (HCV) infection. However, the treatment experience on the patients with HCV related hepatocellular carcinoma (HCC) is few, and the results are still equivocal. Aims: We retrospectively evaluated the treatment efficacy and safety of SOF/VEL ± ribavirin in treating HCV related HCC patients. Methods: This study enrolled all the HCV related HCC patients who received SOF/VEL ± ribavirin therapy for a period of 12 weeks between June 2019 to October 2020 in Lin-Kou Chang Gung Memorial Hospital. A total of 58 patients were included in the intent-to-treat (ITT) analysis. Among them, 50 patients were included in the per-protocol (PP) analysis and 8 patients were excluded. Those 8 patients passed away during the treatment period due to HCC progression, sepsis and suicide. Results: Within the ITT analysis group, the average age of the patients was 66.3 years old, and 38 patients (65.5%) were male. 39 patients (67.2%) patients were diagnosed as liver cirrhosis by abdomen echo, fibroscan, FIB-4 or biopsy. The average viral load was 2.199368 IU/L. HCV genotype 2 was the predominant genotype with overall frequency of 51.7% followed by genotypes 1b (39.8%), 6 (3.4%), 1a (3.4%) and 1a+1b+6 (1.7%). The overall sustained virologic response rate at 12 weeks post-treatment (SVR12) were 98.0% (49/50) in the PP analysis and 84.5% (49/58) in the ITT analysis. The SVR12 (PP) rates were 97.1% (34/35) and 100% (15/15) in patients with cirrhosis and without cirrhosis, respectively. The levels of alanine aminotransferase was decreased in both cirrhosis groups (from 103.6 ± 85.4 U/L to 39.2 ± 35.2 U/L) and noncirrhosis groups (from 186.5 ± 284.5 U/L to 34.6 ± 28.5 U/ L after treatment. The estimated glomerular filtration rate

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P.047 was decreased slightly in both cirrhosis groups (from 98 ± 35.7 cc/ml to 90.7 ± 27.1 cc/ml) and non-cirrhosis groups (from 95.7 ± 31.4 cc/ml to 84 ± 28.4 cc/ml after treatment. Conclusions: The real-world experience of SOF/VEL ± ribavirin showed very good efficacy in HCC patients with hepatitis C infection, both in cirrhosis and non-cirrhosis condition. SOF/VEL ± ribavirin improved liver function and did not affect renal function.

評估 GLE/PIB 第二期及第三期臨床試驗中達到 SVR12 的病患之 SVR4 陽性預測值 POSITIVE PREDICTIVE VALUE OF SVR4 IN PATIENTS WHO ACHIEVED SVR12 FROM PHASE 2 AND 3 CLINICAL TRIALS WITH GLECAPREVIR/ PIBRENTASVIR 1

Edward J. Gane , Victor De Ledinghen , Douglas E Dylla , 4 5 Giuliano Rizzardini , Mitchell L Shiffman , 6,7 8 Stephen T. Barclay , Jose Luis Calleja Panero , 3 3 9 Zhenyi Xue , Margaret Burroughs , Julio A. Gutierrez 1 University of Auckland, Auckland, New Zealand Centre d’Investigation De La Fibrose Hépatique, Bordeaux 2 University Hospital, Pessac, France 3 AbbVie Inc., North Chicago, IL, USA 1st Division of Infectious Diseases, ASST Fatebenefratelli4 Sacco, Milan, Italy Liver Institute of Virginia, Bon Secours Mercy Health, 5 Richmond, VA, USA Life Sciences, Glasgow Caledonian University, Glasgow, 6 Scotland Gastroenterology, Glasgow Royal Infirmary, Glasgow, 7 Scotland Department of Gastroenterology and Hepatology, Hospital 8 Universitario Puerta De Hierro, Madrid, Spain Scripps Center for Organ and Cell Transplantation, La 9 Jolla, CA, USA Background: The population with hepatitis C virus (HCV) is increasingly younger and can be less compliant with long-term follow-up. Providers prescribing HCV treatment now come from diverse specialties, and many practice in nontraditional settings. Consequently, patients and/or providers may not adhere to the monitoring and long-term testing algorithms used to confirm HCV cure. Aims: To determine the positive predictive (PPV) of achieving SVR12 in patients with HCV without cirrhosis or with compensated cirrhosis receiving glecaprevir/ pibrentasvir (G/P) in clinical trials who achieved SVR at post-treatment Week 4 (SVR4). Methods: Two separate integrated datasets from 20 Phase 2 and 3 clinical trials of G/P were evaluated: (1) patients with G/P treatment duration (8, 12, or 16 weeks) consistent with the current label (label-consistent group), and (2) all patients, regardless of consistency of the treatment duration with the current label (overall group). SVR4 PPV, negative predictive value (NPV), sensitivity, and specificity were

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P.048 calculated for achieving SVR12 in both groups, and by treatment duration in the label-consistent group. SVR was defined as HCV RNA < lower limit of quantification (LLOQ). Results: A total of 2890 patients were included in the label-consistent group and 4390 in the overall group. PPV after achieving SVR4 was >99% in both groups and did not differ by treatment duration. Not achieving SVR4 had 100% NPV and sensitivity for all groups and >79% specificity for groups with >2 patients with week 12 HCV RNA ≥ LLOQ. Conclusions: Achieving SVR4 was highly predictive of SVR12 for patients treated with G/P regardless of treatment duration in clinical trial settings. These data provide reassurance that long-term follow-up to confirm SVR may not be necessary. For patients with ongoing risk behaviors or more advanced liver disease, follow-up for reinfection and/ or disease progression still remains important.

接受 C 型肝炎口服抗病毒藥物治療達 SVR 患者可獲得肝臟硬度的改善 REGRESSION IN LIVER STIFFNESS IN CHRONIC HEPATITIS C PATIENTS WITH SUSTAINED VIRAL RESPONSE AFTER DIRECT-ACTING ANTIVIRAL THERAPIES 楊昇勳魏克承郭明正王俊雄林瑞昌牟聯瑞台南市立醫院肝膽腸胃科 Background: The treatment of hepatitis C virus infection was revolutionized with the introduction of direct-acting antiviral (DAA) agents. However, the impact of these therapies on liver stiffness is not well known. Aims: This study aims to evaluate the dynamic change of liver stiffness measurement (LSM) by shear wave elastography (SWE) in HCV-infected patients with sustained viral response (SVR) after DAA treatment. Methods: From Jan 2018 to June 2019, a total of 213 patients with chronic HCV hepatitis and SVR after DAA treatment were enrolled and received measurement of Toshiba shear imaging (Aplio 500). Liver stiffness was measured at baseline (BL), end of treatment (EOT), 12 weeks after EOT (FU12) and 48 weeks after EOT (FU48) by SWE. A mixed model was utilized to identify the factors associated with the dynamic change of liver stiffness after HCV elimination. Results: Improvement of LSM was found in 191 of 213 (89.7%) patients assessed by SWE between BL and FU48. Median values of LSM for baseline, EOT, FU12, FU48 were 2.01 m/s (Range 1.26-10.2 m/s), 1.91 m/s (Range 1.22-4.36 m/ s), 1.82 m/s (Range 1.19-3.93 m/s) and 1.79 m/s (Range 1.186.65 m/s), respectively. This finding is statistically significant and equals median LSM regression of 0.11 m/s (IQR, -0.010.22 m/s, p=0.0045), 0.16m/s (IQR, 0.04-0.29 m/s, p<0.0001) and 0.25m/s (IQR, 0.09-0.36 m/s, p<0.0001) between BL and EOT, BL and FU12, and BL and FU48, respectively. A positively significant linear trend between time and LSM reduction was also found (p=0.0004). After multivariate analysis with random intercept model, patients with advanced fibrosis (Fibrosis-4 ≥ 3.25) at baseline (P<0.001) were positively associated with significant LSM reduction after DAA treatment. Conclusions: HCV eradication after DAA treatment is associated with liver stiffness regression that can be detected as early as EOT and lasts over time. The improvement of liver stiffness seems to be positively influenced by baseline advanced fibrosis status..

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P.049 慢性 C 型肝炎病人接受 Glecaprevir/ Pibrentasvir 治療其病毒量與療效之相關性：一多中心匯總分析 THE ASSOCIATION OF VIRAL LOAD AND EFFICACY IN GLECAPREVIR/ PIBRENTASVIR FOR CHRONIC HEPATITIS C: A MULTICENTER POOLED ANALYSIS 1

3,4

洪肇宏沈一嫻張德生胡琮輝陳建宏林俊彥長庚醫療財團法人高雄長庚紀念醫院胃腸肝膽科系暨 1 長庚大學醫學系 2 長庚醫療財團法人林口長庚紀念醫院胃腸肝膽科系 3 長庚醫療財團法人嘉義長庚紀念醫院胃腸肝膽科 4 長庚醫療財團法人雲林長庚紀念醫院胃腸肝膽科 Background: Glecaprevir/pibrentasvir (GLE/PIB) is a highly effective pan-genotypic direct antiviral agent to treat chronic hepatitis C. However, our previous study has shown that high viral load (≥107 IU/ml) may predict treatment failure in non-cirrhotic genotype (GT) 2 patients receiving 8 weeks GLE/PIB therapy. Aims: The aim of this study was to evaluate the association of viral load and sustained virological response 12 weeks off therapy (SVR12) in chronic hepatitis C GT1-6 patients treated with GLE/PIB based on a multicenter pooled database. Methods: From 2018 to 2020, data were pooled from four hospitals (the Linkuo, the Chiayi, the Yunlin and the Kaohsiung Chang Gung Memorial Hospital) including 1669 patients treated with 8-16 weeks GLE/PIB therapy. Results: A total of 1622 patients were finally enrolled after excluding the cases of early withdrawal (n = 21), reinfection (n = 1) and loss of follow-up (n = 25). At baseline, 249 (15%) had cirrhosis and median HCV RNA level was 6.24 ± 1.02 log IU/ml with high viral load ≥ 10 7 IU/ml in 150 (9.2%). The SVR12 rate was 99.1% (1320/1332), 99.6% (283/284), and 100% (6/6) in GLE/PIB 8-week, 12week and 16-week group, respectively. For patients with HCV GT 1 (n = 378), 2 (n = 1061), 3 (n = 31), 6 (n = 71) and mixed type (n = 81), the SVR12 rate was 99.7%, 99.1%, 96.8%, 100%, and 98.8%, respectively (p = 0.320). There were 13 patients with virologic failure. The mean serum HCV RNA level at baseline was borderline lower in the SVR12 patients than those without (5.95 ± 1.02 log IU/mL vs. 6.49 ± 0.76 log IU/ml, p = 0.058). Pretreatment higher viral load (≥107 IU/ml) was significantly associated with lower SVR12 rate (96.7% vs. 99.5%, p = 0.004); whereas

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the difference was only significant in G2 patients receiving 8 weeks GLE/PIB therapy (94.7% vs. 99.4%, p = 0.005) by subgroup analyses. Multivariate analyses showed that HCV RNA ≥ 107 IU/ml was the independent factor (odds ratio = 0.113, 95% confidence interval = 0.003–0.428; p = 0.001) associated with SVR12 in this subgroup patients. Conclusions: In a pooled analysis of multicenter data, we found that high viral load (≥107 IU/ml) might be associated with treatment failure in GT 2 patients receiving 8 weeks GLE/PIB therapy.

2021 消化系聯合學術演講年會

P.050 以 Sofosbuvir 為主的 DAA 治療在慢性 C 型肝臟相關之肝臟移植病人上之治療結果 SOFOSBUVIR BASED THERAPIES FOR HCV RELATED LIVER TRANSPLANT 1

葛振瑜胡琮輝林志哲王植熙陳肇隆 1 高雄長庚紀念醫院胃腸肝膽科系 2 高雄長庚紀念醫院一般外科

showed no serious adverse events (AE) and less percentage of drug-drug interaction when compared to other protease inhibitor contained regimens in other 12 patients (other than 96 SOF based therapies) (glecaprevir/pibrentasvir in 2; viekirax/dasabuvir in 5; and elbasvir/grazoprevir in 5). Conclusions: SOF/VEL represents both efficacy and safety among the sofosbuvir based therapies for liver transplant patients.

Background: The efficacy of antiviral C therapy using new direct-acting antiviral (DAA) agents without PEGIFN, leading to sustained virologic response (SVR) rates over 90% in non-transplant patients. Results available for transplant patients showed a better efficacy and tolerability and less drug-drug interactions of sofosbuvir (SOF) based regimens than with protease inhibitors (PIs) regimens. However, Asian experience of new wave DAA (especially for living donor transplant and genotype 2/3) was very rare. Aims: To evaluate the results of new wave DAA on HCV related liver transplant patients. Methods: A pilot study to investigate effectiveness of sofosbuvir based therapies with or without ribavirin for recurrent hepatitis C (genotype 1, 2, 3, 6) in living donor liver transplantation recipient in Taiwan. There were 96 living donor liver transplantation recipients with recurrent hepatitis C were enrolled, with Sixty-three (63) genotype 1 (57 for 1b and 6 for 1a), twenty-nine (29) genotype 2, two (2) genotype 3, and two (2) genotype 6. Therapeutic regimens were sofosbuvir/ledipasvir (Harvoni) ± ribavirin (RBV) 12 weeks for genotype 1, and sofosbuvir + RBV or sofosbuvir/daclatasvir ± RBV 12 weeks for genotype 2, 3; and sofosbuvir/velpatasvir (SOF/VEL) for pan-gynotypic patients. The Endpoint is sustained virological response 4 (SVR4) and 12 and 24 weeks (SVR12, 24) after cessation of therapy. Results: For the efficacy result, SOF/VEL showed 100% (10/10) of undetectable HCV RNA at SVR12. However, the SVR rate for other SOF based DAA except SOF/VEL was only 93.02% (80/86). They were six patients did not reach SVR12, two in SOF/LDV (type 1b and 2); two in SOF/DCV (type 1b and 2); and two in SOF/RBV (type 1b and 2). It seems like that genotype 2 regimens (SOF/DCV, SOF/LDV, SOF/RBV) before SOF/VEL era might lead to a higher relapse rate. In addition, there was no failure of treatment with regimens of SOF/DCV/RBV or SOF/ LDV/RBV. It might indicate that ribavirin may be needed for patients treated before pan-genotypic agent SOF/VEL is available. As for safety profile, SOF based regimens

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P.051

P.052

在台灣美沙冬替代療法中心以宜譜莎治療 C 型肝炎注射藥癮者 PWID HCV CARRIERS TREATED BY EPCLUSA IN TAIWAN ONE OST CENTER

單一醫學中心 C 型肝炎治療與第三期慢性腎病變腎功能變化因素之探討 LONG-TERM RENAL FUNCTION CHANGE AFTER ELIMINATION OF HCV INFECTION BY DIRECTACTING ANTIVIRAL AGENT IN CKD STAGE 3 PATIENTS: A REAL WORLD RETROSPECTIVE STUDY IN A SINGLE MEDICAL CENTER

張智皓衛漢庭 1 臺北市立聯合醫院忠孝院區消化內科 2 臺北市立聯合醫院林森中醫昆明院區心身醫學科 Background: The prevalence of hepatitis C virus (HCV) is high among people who inject drugs (PWID) worldwide. Aims: ASTRAL Phase 3 studies showed that there was no significant difference between opioid substitution treatment (OST) and non-OST participants in sustained virologic response at 12 weeks post treatment (SVR12) rate, adherence rate and proportion of adverse events. In an international phase 4, open-label study, the majority of patients continued drug use throughout HCV therapy. Despite ongoing drug use, SVR12 rate of EPCLUSA was 94% in the intent-to-treat analysis in patients with recent injecting drug use. Methods: From January to November 2020, among patients referred from the methadone clinic to the gastroenterology clinic for HCV assessment and treatment with direct-acting antiviral agents, 57 patients were treated with EPCLUSA in Taipei City Hospital, Kunming Branch. Results: The major genotypes were GT-6 (39%), GT-1a (23%), GT-1b (21%) and GT-3 (12%). The SVR12 rate in the per protocol analysis was 90% (9/10). The one with detectible HCV RNA at SVR12 has different genotype. The levels of alanine aminotransferase and aspartate aminotransferase were decreased after treatment. Conclusions: The real world experience of EPCLUSA showed good efficacy in patients addicted to methadone. Liver function was improved in all patients. In PWID, EPCLUSA showed good efficacy and simple to treat.

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胡彥佶藍耿欣黃怡翔侯明志臺北榮民總醫院胃腸肝膽科 Background: Background –Chronic HCV infection is related not only to chronic kidney disease (CKD) but also accelerates renal deterioration. Treatment with Directacting antiviral (DAA) could slow renal function decline in some trials, but the long-term outcomes of renal function changes following HCV elimination by DAA remained inconclusive. Aims: The aim of the study is to identify the factors associated with eGFR change in HCV patients with chronic kidney disease stage 3 (CKD 3) who received the DAA treatment. Methods: This retrospective study analyzed the data of HCV infection patients with CKD stage 3 who were treated with DAA and achieved sustained virologic response at 12 weeks after treatment (SVR12) during 2017-2020 at a single medical center. Results: Among 130 HCV infection and CKD stage 3 patients treated with DAA, 77 patients had no eGFR decline at SVR 12, and 53 patients had eGFR declined at SVR 12. Patients with Diabetes Mellites (DM) (p = 0.016, OR: 2.6) is highly associated with eGFR decline after DAA treatment. Conclusions: Among patients with HCV infection and CKD stage 3, comorbidity with DM has less benefit in renal function improvement after HCV treatment with DAA.

2021 消化系聯合學術演講年會

P.053 以口服直接抗病毒藥物治療慢性 C 型肝炎第 1 型之成效 REAL-WORD EXPERIENCE OF DIRECTACTING ANTIVIRAL THERAPY IN CHRONIC HEPATITIS C GENOTYPE-1 PATIENTS IN TAIWAN

of treatment for HCV infection, several kinds of DAAs have become available over the past few years for genotype 1 patients. DAA therapy can achieve a high SVR rate among CHC GT-1 patients in southern Taiwan, regardless of whether the patient were treatment experienced, had history of HCC, liver cirrhosis or advanced CKD.

羅寧黃釧峰梁博程徐成鼎許博堯陳信成林子堯黃志富莊萬龍余明隆戴嘉言高雄醫學大學附設中和紀念醫院肝膽胰內科 Background: Chronic hepatitis C (CHC) is a major cause of cirrhosis, hepatocellular carcinoma (HCC), and mortality. Eliminating hepatitis C virus (HCV) can greatly improve long-term outcomes. Several direct-acting antiviral agents (DAAs) have been approved for treating CHC genotype-1 (GT-1) patients in Taiwan. Aims: We aimed to evaluate the real-world efficacy in CHC GT-1 patients who underwent these DAA regimens in southern Taiwan. Methods: This multicentre, retrospective study enrolling 1375 CHC GT-1 patients treated with either Elbasvir/ Grazoprevir (EBR/GZR), Sofosbuvir/Ledipasvir (SOF/ LDV), glecaprevir/pibrentasvir (GLE/PIB) or sofosbuvir/ velpatasvir (SOF/VEL) with or without ribavirin from December 2013 to June 2020 in three hospitals. Therapeutic efficacy was evaluated by whether sustained virological response (SVR) were achieved at 12 weeks after finishing DAAs treatment. Intention-to-treat (ITT) analyses enrolled all patients treated with the regimens. Per-protocol analyses (PPA) were performed after excluding patient with treatment discontinuation or loss of follow up. Results: The overall SVR rate at week 12 (SVR12) by ITT and PPA were 95.3% and 99.1%, respectively. The SVR12 rates were similar in four DAAs regimen by ITT (97.2%, 95.0%, 94.5% and 94.5% respectively) and by PPA (99.7%, 98.6%, 99.5% and 99.3% respectively). All eleven patients without SVR12 were relapsers: one was IFN-experienced (by EBR/GZR), four were previous injection drug users (PIWD) (one by SOF/LDV, one by GLE/PIB, other two by SOF/VEL), two were HIV co-infected (by GLE/PIB and SOF/VEL), one with HCC (by SOF/LDV). In the subgroup analysis, the SVR12 rate by PPA was significantly lower in genotype 1a (96.6%), which was noted in SOF/VEL group (94.6%), HIV co-infection (95.1%) which was noted in GLE/PIB group (90% vs 100%), PIWD (95.3%) which was noted in SOF/VEL group (92% vs 100%). Conclusions: In the era of rapidly evolving landscape

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P.054

P.055

C 型肝炎抗病毒藥物對腸道菌的影響 THE EFFECTS OF DIRECT ANTI-VIRAL AGENTS ON GUT MICROBIOTA IN PATIENTS WITH CHRONIC HEPATITIS C

以 Sofosbuvir 為基底的直接作用抗病毒藥對 C 型肝炎病毒感染患者低密度脂蛋白變化的影響：一統性文獻回顧與統合分析 EFFECT OF SOFOSBUVIR-BASED DIRECT-ACTING ANTIVIRALS ON CHANGES IN LOWER-DENSITY LIPOPROTEIN IN PATIENTS WITH HEPATITIS C VIRUS INFECTION: A SYSTEMATIC REVIEW AND METAANALYSIS

1,2

黃寳源陳建宏姚志謙王心明張國欽蔡成枝 1,2 蔡明釗 1 高雄長庚紀念醫院胃腸肝膽科系 2 長庚大學臨床醫學研究所

Background: Gut microbiology is associated with liver disease because of gut-liver circulation via the gutmicrobial-liver axis. There is a paucity of data regarding the effects of the cure of hepatitis C virus (HCV) infection on the gut-liver axis. Aims: The aim of our study is to evaluate the fecal microbiota before and after direct anti-viral agents (DAA) treatment in patients with HCV infection. Methods: This is a prospective study at Kaohsiung ChungGung memorial hospital, Taiwan, from December 2019 and November 2020. We recruited patients with chronic hepatitis C (CHC) patients receiving DAA treatment. Fecal samples were collected twice from CHC patients, at baseline (start DAAs treatment) (CHC group) and 6 months after end of treatment (EOT) (CHC-SVR group), and once from health controls at baseline (health group). The taxonomic composition of gut microbiota was determined using 16S ribosomal RNA gene sequencing of stool samples. Results: A total of 60 CHC patients and 60 healthy controls matched by age and gender were enrolled. All patients achieved sustained viral response (SVR). The alpha diversity showed no significant difference in all groups. Principal coordinates analysis showed mild clustering of samples between health group and CHC group (ANOSIM, Analysis of Similarity, R = 0.0146, P = 0.098) and scant clustering between CHC group and CHC-SVR group (ANOSIM, R = -0.0139; P = 0.94). Four phyla, 20 genera and 6 bacterial species resulted differentially abundant among health group and CHC group. Conclusions: In summary, there is no significant difference of gut microbiota in individuals with CHC, and HCV eradication by DAA is not associated with a modification of gut microbiota.

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王盈文李偉平黃怡翔侯明志藍耿欣 1 臺北榮民總醫院健康管理中心 2 臺北榮民總醫院醫學研究部 3 臺北榮民總醫院內科部胃腸肝膽科

Background: Previous studies reported worsened lipid profiles in patients infected with hepatitis C virus (HCV) during direct-acting antivirals (DAAs) treatment. Aims: This study aimed to investigate the effect of sofosbuvir (SOF)-based DAAs on changes in low-density lipoprotein (LDL) in HCV patients. Methods: A systematic review of articles published before 15 May 2020 was conducted by searching MEDLINE, Cochrane Library, EMBASE, and CINAHL Plus. Eligible studies were those comparing SOF-based DAAs and nonSOF DAAs for HCV patients and providing numerical data for changes in LDL. Risk Of Bias In Non-randomized Studies- of Interventions was used for assessing risk of bias, and meta-analysis was performed for changes in LDL. Results: Five studies comprising 1127 patients were included, 755 patients treated with SOF-based DAAs and 372 patients with non-SOF DAAs. SOF-based DAAs group had significantly greater increases in LDL from baseline to week 4 (P = 0.001) than non-SOF DAAs group. However, changes in LDL from baseline to the end of treatment (P = 0.060), to post-treatment week 12 (P = 0.263), and to post-treatment week 24 (P = 0.321) did not significantly differ between the two groups. Further comparison of SOF/ ledipasvir with asunaprevir/daclatasvir revealed a similar trend in changes in LDL. Conclusions: For HCV patients, SOF-based DAA regimens were associated with rapid and significant increases in LDL during the initial 4 weeks of treatment, and the changes did not sustain after the end of treatment. Potential mechanism might be related to the phosphoramidate side chain of SOF.

2021 消化系聯合學術演講年會

P.056 口服直接作用抗病毒藥物對於慢性 C 肝基因型第 6 型的治療效果 EFFICACY OF DIRECT-ACTING ANTIVIRAL AGENTS FOR CHRONIC HEPATITIS C GENOTYPE-6 1

1,2

許峻麒梁博程黃釧峰葉明倫黃駿逸林子堯 1,2 1,2 1,2 1,2 1,2 陳信成黃志富戴嘉言莊萬龍余明隆 1 高雄醫學大學附設醫院肝膽胰內科 2 高雄醫學大學醫學系

Background: Chronic hepatitis C (CHC) is one of main causes of liver cirrhosis, hepatocellular carcinoma (HCC), and mortality. Eradicating hepatitis C virus (HCV) would improve long-term outcomes prominently. There are different direct-acting antiviral agents (DAAs), including Sofosbuvir (SOF) plus different NS5A inhibitors, as well as non-SOF-based DAAs, including glecaprevir/pibrentasvir (GLE/PIB), that have been approved for treating CHC genotype-6 (GT-6) patients in Taiwan. Aims: There is limited data regarding effectiveness of different agents for treating CHC genotype-6 (GT-6) patients in Taiwan. Therefore, we managed to evaluate the efficacy in patients with CHC GT-6 who received these DAAs treatment. Methods: We retrospectively selected patients with CHC GT-6 who started to be treated with SOF-based DAAs or GLE/PIB at a single medical center during 2018 to 2020. Total 98 patients were registered and baseline characteristics were collected including underlying diseases and biochemical data. And 8 patients ever received peginterferon (Peg-IFN) ± RBV (ribavirin) treatment for HCV before. Eleven patients lost follow-up and 12 patients are still under treatment or within 12 weeks follow-up period currently. All of the patients were treated with either SOF/LDV (Ledipasvir) ± RBV for 12 weeks, SOF/VEL (Velpatasvir) for 12 weeks, or GLE/PIB for 8 or 12 weeks. We evaluated the efficacy by whether sustained virological response (SVR) were achieved at 12 weeks after finishing DAAs treatment. The primary endpoint was clearance of the HCV RNA at 12 weeks after treatment (SVR12). Results: Finally, 75 patients were enrolled for evaluation. In which, 21 patients were treated with SOF/LDV ± RBV for 12 weeks, 27 patients with SOF/VEL for 12 weeks, 27 patients with GLE/PIB (22 patients for 8 weeks and 5 patients for 12 weeks). The overall SVR rate were 100%. All of these regimens achieved SVR whether the patients had underlying cirrhosis (32.0%), hepatitis B virus (HBV)

co-infection (10.7%), chronic kidney disease (CKD) (24.0%), end-stage renal disease (ESRD) (4.0%), human immunodeficiency virus (HIV) co-infection (17.3%), or previous treatment for HCV (10.7%). There were also significant improvement of liver enzymes and liver fibrosis score (FIB-4) at 12 weeks after treatment compared with baseline data. Conclusions: For patients with CHC GT-6, SOF in combination with LDV, or VEL, as well as GLE/PIB may reach high efficacies regardless of underlying cirrhosis, HBV co-infection, CKD status, HIV co-infection, or previous treatment for HCV.

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P.057 C 型肝炎全口服藥物用於基因型第 3 型 C 型肝炎患者之療效 THE EFFICACY OF DIRECT ANTIVIRAL AGENTS IN PATIENTS WITH GENOTYPE 3 HEPATITIS C 1

1,2,3

王崧維戴嘉言黃釧峰黃志富余明隆 1,2,3 1,2,3 1,2,3 1,2 莊萬龍陳信成林子堯黃駿逸 1 高雄醫學大學附設中和紀念醫院內科部 2 高雄醫學大學附設中和紀念醫院肝膽胰內科 3 高雄醫學大學醫學系

Background: Hepatitis C is chronic viral infection that related to liver cirrhosis and hepatocellular carcinoma. Genotype 3 makes a small proportion of the patients with hepatitis C in Taiwan. Since the direct acting antivirals (DAAs) developed, they provides satisfactory treatment efficacy and tolerability in the past studies. To reach the elimination of hepatitis C virus by 2030, the Ministry of Health and Welfare lower the threshold for DAAs prescription. Aims: This study aims to investigate the effectiveness and outcomes of DAAs in patients with genotype 3 hepatitis C. Methods: 53 patients were enrolled but 4 patients lost follow-up during or after treatment. 49 patients with genotype 3 hepatitis C were investigated retrospectively in 3 hospitals. The patients were treated with Sofosbuvir/ Daclatasvir (SOF/DCV), Glecaprevir + Pibrentasvir (GLE/ PIB), Sofo-sbuvir/Velpatasvir ± Ribavirin (SOF/VEL ± RBV) for 8~16 weeks based on patient’s characteristic according to the guideline. The laboratory test and fibrosis score were collected before treatment, in end of treatment and at the 12 weeks post treatment. SVR (sustained virologic response) is defined as undetectable HCV RNA at 12 weeks following completion of treatment and is an important endpoint. Adverse effects are also recorded in this study. Results: In SOF/VEL ± RBV group, patients with genotype 3 HCV have higher FIB-4 score, serum bilirubin, liver cirrhosis and hypertriglyceridemia. Totally 46 patients (93.9%) reached the SVR (1 patient in SOF/DCV, 30 patients (93.8%) in GLE/PIB group and 15 patients (93.8%) in SOF/VEL ± RBV group). 3 patients had relapsed disease (2 treated with Glecaprevir/Pibrentasvir and 1 with Sofosbuvir/Velpatasvir + Ribavirin). In patients who reached the SVR, marked improvement was found in AST, ALT, rGT and FIB-4 score. Fatigue were the most common adverse effects (14 patients). No patients had

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severe adverse effects and there was no significant decrease in renal function. Conclusions: Compared to other genotype of hepatitis C, treatment of genotype 3 is challenging though the pangenotypic DAAs has short treatment courses, good safety and high success rates. More cases are needed to investigate the difference between patients who reach SVR or not.

2021 消化系聯合學術演講年會

P.058 老年 C 型肝炎患者治療後之生化與血液變化 BIOCHEMISTRY AND HEMATOLOGIC CHANGES AFTER HCV TREATMENT IN ELDERLY 1,2,3

1,2,3

章振旺張經緯林煒晟王蒼恩 1,2,3 陳銘仁 1 馬偕紀念醫院內科部肝膽腸胃科 2 馬偕醫護管理專科學校 3 馬偕醫學院

1,2,3

王鴻源

non-elderly patients in the biochemistry and hematologic changes after HCV treatment. The improvement of albumin is more predominant in the elderly. There is no significant difference in the Hb and WBC count. However, the elderly had improvement of platelet, but not in non-elderly groups. Conclusions: In conclusion, elderly patients tolerated DAA (G/P) treatment. After HCV treatment, some biochemistry and hematologic improvement were better in the Elderly than non-elderly.

Background: Elderly patients with chronic HCV infection are likely to have an advanced liver disease including cirrhosis of the liver and related complication. Glecaprevir plus pibrentasvir (G/P) is a pangenotypic, once-daily, ribavirin-free direct-acting antiviral (DAA) treatment for hepatitis C virus (HCV) infection. G/P demonstrated a favourable safety and tolerability profile from the previous studies. However, the evidence of G/P in treating the elderly was still controversial. Aims: The aim of this study was to identify the biochemistry and hematologic changes after HCV treatment in elderly. Methods: This is a retrospective observational study. Patients who had received G/P for chronic HCV between Aug 2018 and Mar 2020 were recruited. Patients were divided into two groups: non-elderly < 65 years and elderly ≥ 65 years. Patients’ gender, HCV genotype, changes in biochemistry and hematologic data before and after treatment, sustained virologic response 12 weeks (SVR12) after the cessation of drug administration, side effects, and interaction effects were recoreded. Results: A total of 237 chronic HCV patients were enrolled in this study and there were 117 (49.4%) male. In the study, there were 136 (57.4%) non-elderly patients and 101 (42.6%) elderly patients. In the genotype, most elderly were type 2 with significant difference (non-elderly vs elderly: 41.2% vs 69.3%, p<0.01). Discontinue treatment was found in 10 patients, and more in the non-elderly group. (non-elderly vs elderly: 4.4% vs 4.0%, p=0.03) After treatent, only two cases without SVR (99.2%) and all in the non-elderly group. In the baseline biochemistry and hematologic findings, the level of albumin, Hb, and platelet were low in elderly patients. After treatment with G/P, in all of the patients, there was a significant change in the laboratory, which included improvement of hepatitis, increased albumin level, increased WBC, and platelet count. There are also differences between elderly and

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P.059

P.060

病態性肥胖病人非酒精性脂肪肝炎與肝纖維化的血漿與肝臟三酸甘油酯亞類 THE PLASMA AND LIVER TRIGLYCERIDE SUBCLASS OF NONALCOHOLIC STEATOHEPATITIS AND FIBROSIS IN MORBIDLY OBESE PATIENTS

乙醛去氫酶 ALDH2*2 等位基因突變可以追溯到一萬年前 THE ALDEHYDE DEHYDROGENASE ALDH2*2 ALLELE DATES BACK TO 10,000 YEARS AGO

1,2,3

7,8

6,7

高偉育董德璿張宜崴陳志榮唐瑞祥 1,2,3 4,5 9 張君照王偉黃士懿 1 臺北醫學大學臨床醫學研究所 2 臺北醫學大學附設醫院內科部胃腸科 3 臺北醫學大學醫學院內科學科 4 臺北醫學大學附設醫院外科部消化外科 5 臺北醫學大學醫學院外科學科 6 臺北醫學大學附設醫院病理部 7 臺北醫學大學醫學院病理學科 8 臺北醫學大學萬芳醫院病理實驗部 9 臺北醫學大學代謝與肥胖科學研究所

2,3

Background: The prevalence rate of nonalcoholic steatohepatitis (NASH) has been reported in 50% to 70% of morbidly obese patients. Aims: This study aims to use lipidomic analysis to investigate triglyceride (TG) subclass between healthy obesity (HO) and NASH with advanced liver fibrosis in morbidly obese patients. Methods: Lipidomics was performed using ultra-highperformance liquid chromatography–tandem mass spectrometry on plasma and liver samples from a prospective cohort study involved morbidly obese patients who underwent bariatric surgery at Taipei Medical University Hospital. Wedge liver biopsy was performed during surgery, and advanced liver fibrosis was defined as a fibrosis score 3. We selected HO (n=8) and NASH with advanced liver fibrosis (n=8) patients. Results: 94 and 64 TG species were identified in plasma and liver, respectively. In plasma, the fold changes of TG (50:1), (52:2), (54:3), and (54:4) were significant higher and TG (55:2) was significant lower in the NASH with advanced liver fibrosis than HO group (p < 0.05). In liver, the fold changes of TG (48:3), (50:3), (50:4), and (54:2) were significant higher in the NASH with advanced liver fibrosis than HO group (p < 0.05). Furthermore, these TG species in plasma and liver had several highly positive correlation with parameters related to hepatic steatosis and fibrosis and liver functions, especially TG (50:1). Conclusions: TG subclass were associated with NASH and liver fibrosis. Among the TG species in plasma and liver, TG (50:1) may be proposed as a lipid metabolite to predict NASH with liver fibrosis in morbidly obese patients.

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1,2

3,4,5

1,2

劉玉瑛梁恭豪陳立偉陳碩為胡瀞之錢政弘 1 1 1 1 2,6 1,2 余佳穎鄒騰信林書廷吳克轅徐于喬林志郎 1 基隆長庚紀念醫院胃腸肝膽內科 2 基隆長庚紀念醫院社區醫學科研中心 3 臺北榮民總醫院醫學研究部 4 陽明大學食品安全與健康風險評估研究所 5 陽明大學生物醫學資訊研究所 6 中央研究院分子生物研究所

Background: Alcohol has been an important part of life in the long human history. The consumption of alcohol has health, economic and social issues. Previous studies revealed that the personal consumption quantity is partly determined by genetics. Aims: In this study, the drinking behaviors of the residents in Keelung, a vibrant harbor city on the northern coast of Taiwan, were evaluated using the Alcohol Use Disorder Identification Test (AUDIT) score for identifying residents who drink hazardously (AUDIT score ≧ 8, referred to as heavy-drinkers) and who does not drink on their daily life (AUDIT score = 0, referred to as non-drinkers). Methods: We performed a genome-wide association study comparing 126 non-drinkers and 71 heavy-drinkers. Among the ~750,000 genomic variants evaluated, the rs671 G>A single nucleotide polymorphism (SNP) manifests the highest significance of association (Fisher’s exact P = 8.75 × 10-9). Results: This is a pleiotropic, non-synonymous variant in the aldehyde dehydrogenase 2 (ALDH2). The minor allele “A”, also known as the ALDH2*2 allele, is associated with non-drinkers. Identity-by-descent haplotypes with a median length of 0.361 centiMorgans were found consistently in all included persons with the ALDH2*2 alleles. Using the length distribution of the haplotypes in ALDH2*2 carriers, we estimated the age of the ALDH2*2 as ~10000 years ago, much longer than ages shown in prior literature. Conclusions: In conclusion, the SNP rs671 G>A is the leading genomic variant associated with the drinking quantity in Keelung, Taiwan. The ALDH2*2 allele dates back to ~10000 years ago.

2021 消化系聯合學術演講年會

P.061

P.062

血中尿酸與非酒精性脂肪肝在基隆長庚醫院社區患者的關聯性 ASSOCIATION BETWEEN SERUM URIC ACID AND NONALCOHOLIC FATTY LIVER DISEASE IN THE COMMUNITY PATIENT OF KEELUNG CHANG GUNG HOSPITAL

ALBI Score 於預測嚴重酒精性肝病患者短期及長期預後的實用性 UTILITY OF THE ALBI SCORE IN PREDICTING SHORT-TERM AND LONG-TERM PROGNOSIS IN PATIENTS WITH SEVERE ALCOHOLIC LIVER DISEASE

1,2

謝承翰陳立偉李宗實張家昌林志郎錢政弘 1 基隆長庚紀念醫院胃腸肝膽科 2 基隆長庚紀念醫院社區醫學科研中心

Background: Several experimental and observational studies suggest high serum uric acid (SUA) is a risk factor in non-alcoholic fatty liver disease (NAFLD). Aims: In this study, we aim to examine the association between serum uric acid levels and NAFLD in community patients of Keelung Chang Gung hospital. Methods: A cross-sectional analysis of total 1107 adults who participated in healthy exam from 201812 -201909 in Keelung Chang Gung hospital. The participants were divided into 3 groups according to the SUA quartiles for both sexes. The SUA quartiles were defined into three group: ≤4.8, 4.8–6.0 and ≥6.0 mg/dL for both sex. Hepatic steatosis presence and severity were defined by ultrasonographic finding. We modeled the probability that more severe NAFLD would be associated with the higher quartiles of SUA. Results: Compared to the quartile 1, the odds ratio for NAFLD were 1.541 (1.274 - 1.86, p < 0.001) and 1.828 (1.488 - 2.244, p < 0.001) for the quartile 2 and the quartile 3, respectively. After adjusting for potential confounders of age, gender and BMI, the adjusted odds ratio (95% CI) for the subjects in the quintile 2, 3 versus the quintile 1 were 1.391 (1.145 - 1.689) and 1.348 (1.105 - 1.644), respectively. Conclusions: In this cross-sectional observational study, we showed that elevated SUA levels is independently associated with increased risk of NAFLD.

李政祺黃仁杰辛政憲陳季宏陳鄭弘堯溫奕志澄清綜合醫院中港分院胃腸肝膽科 Background: Alcoholic liver disease is characterized by acute or acute-on-chronic hepatic failure and associated with a high mortality. Increasing alcohol consumption has resulted in an increasing number of cases of alcoholic liver disease in Taiwan. There are several scoring systems available to evaluate the severity of liver dysfunction and predict the prognosis of patients with liver failure. The ALBI score is a new model for assessing the severity of liver dysfunction and to predict the outcome of patient s with acute-on-chronic liver failure. Aims: To investigate the utility of the ALBI score in assessing short-term and long-term prognosis of patients with severe alcoholic liver disease. Methods: A retrospective study of 162 mortality patients with severe alcoholic liver disease between Jan. 2006 and Dec. 2016 at the Cheng-Chin General hospital ChungGang branch was performed. After exclusion of 32 patients with incomplete data, ALBI scores (data obtained from the date of last admission) were calculated. And after exclusion of 71 patients with incomplete data, initial ALBI scores (iALBI, data obtained from the date of diagnosis) were calculated separately. The ALBI scores were classified as grade 1 (Gr1 ≦ -2.6), grade 2 (Gr 2, ≦ -1.39 and > -2.6), grade 3 (Gr 3, > -1.39) to predict short term prognosis. The iALBI scores were classified as low ALBI group (Gr1 & Gr 2, ≦ -1.39) and high ALBI score group (Gr 3, ALBI > -1.39) to predict long term prognosis. Patients were evaluated on the basis of age, gender, laboratory data. Data were statistically analyzed using the chi-squared test & student’s t-test. Analysis of survival was performed using the Kaplan-Meier method. Results: Demographic data including average age, sexuality, complications and coexistence of malignancy of the low ALBI and high ALBI groups was comparable. The higher ALBI score group (Gr3) was found to have poor short term prognosis than those of other two groups (Gr2 & Gr1) but it was not significant. The high iALBI scores

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P.063 group prone to poorer long term prognosis than that of the low iALBI group. Conclusions: Severe alcoholic liver disease is associated with high ALBI scores. ALBI score seems to be useful in predicting long-term but not short-term prognosis of severe alcoholic liver disease patients. The ALBI score may be used as a simple, reliable prognostic score to predict the long-term mortality in patients of hepatic failure due to severe alcoholic liver disease.

以肝纖維儀探討飲食及運動調控在肥胖病人脂肪肝代謝之影響 SHORT-TERM EFFECTS OF EXERCISE AND DIET MODIFICATION ON FIBROSCAN VALUES IN OBESE PATIENTS WITH METABOLIC ASSOCIATED FATTY LIVER DISEASE 1

林霖雷尉毅王仁宏劉作財易志勳翁銘彣梁書瑋 1 1 洪睿勝陳健麟 1 佛教慈濟醫療財團法人花蓮慈濟醫院內科部肝膽腸胃科 2 佛教慈濟醫療財團法人花蓮慈濟醫院醫學研究部 Background: Metabolic associated fatty liver disease (MAFLD) represents a growing problem in the world in parallel with the increasing incidence of obesity. It is a major health problem because of the associated risk of progression to cirrhosis and liver cancer. Exercise and diet modification is a recommended therapy for MAFLD. Fibroscan device can be used to estimate the degree of liver scarring present and steatosis. Aims: The aim of this study was to evaluate the effect of exercise and diet modification on Fibroscan values in an obese population with MAFLD. Methods: All study participants were recruited from Hualien Tzu Chi Hospital by screening to identify individuals with central obesity (waist circumference ≥90 cm in men and ≥85 cm in women). Individuals with central obesity who had ultrasonography- diagnosed MAFLD were invited to confirm the diagnosis by Fibroscan device. Thirty-two consecutive patients (38.7 ± 8.9 years, 10 male) were included in this prospective follow-up study. All participants were instructed to participate in a 6-month exercise and diet modification program. We compared the physical parameters, biochemical testing and Fibrocan values before and after the 6-month program. Results: After 6 months of exercise and diet program, body weight, body mass index, waist circumference, hip circumference, waist-to-hip ratio, body weight and blood pressure were significantly reduced compared with preintervention data. In addition, AST, ALT, creatinine, uric acid, cholesterol, GGT, LDL cholesterol, urine creatinine, urine albumin and fatty liver index also showed improvement after 6-month program intervention. Liver steatosis values were found to be significantly decreased compared to the preintervention data (Controlled Attenuation Parameter (dB/m): 255.0 ± 50.0 versus 297.5 ± 48.4, P < 0.001). There was no significant difference in

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P.064 liver stiffness values between pre- and postintervention (5.24 ± 1.41‒kPa versus 4.82 ± 1.58‒kPa, P = 0.090). Conclusions: This study indicates that exercise with diet modification can have benefits in reducing weight, body fat, metabolic profile and liver steatosis among patients with MAFLD. Our study may support the notion that Fibroscan could therefore serve as monitoring tools for therapeutic intervention in obese patients with MAFLD.

手柄區域胜肽可減輕非酒精性脂肪肝疾病小鼠的脂肪變性，炎症和纖維化 HANDLE REGION PEPTIDE ATTENUATES STEATOSIS, INFLAMMATION AND FIBROSIS IN MICE WITH NON-ALCOHOLIC FATTY LIVER DISEASE 1,2

1,2

李癸汌謝昀蓁吳佩珊黃怡翔侯明志林漢傑 1 臺北榮民總醫院胃腸肝膽科 2 國立陽明大學醫學院內科學科

Background: The prevalence of nonalcoholic fatty liver disease (NAFLD) in Taiwan is gradually increasing. Especially, liver fibrosis is the most important prognostic indicator for these NAFLD patients. However, the drug to treat NAFLD is limited. We had found that inhibiting hepatic (pro)renin receptor (PRR) expression can reduce fibrosis in mice chronically injured by thioacetamide. Importantly, in patients with NAFLD and fibrosis, expression of PRR in the fibrotic livers was high. Additionally, inhibiting PRR in hepatocytes was found to reduce its fat accumulation. Aims: Hence, we aimed to investigate whether PRR blockage via a (pro)renin receptor blocker peptide (NH2IPLKKMPS-COOH, the so-called handle region peptide (HRP) of prorenin) could improve steatosis and liver fibrosis in mice with NAFLD. Methods: A mouse model with NAFLD was made by feeding mice with fast food diet (FFD) for 24 weeks. HRP (0.1 mg/kg/day) or placebo were administered to the mice by minipumps since 12 weeks following FFD feeding. Results: FFD mice receiving placebo exhibited severe steatosis with moderate inflammation, hepatocyte b a l l o o n i n g a n d f i b r o s i s i n l i v e r. H R P t r e a t m e n t decreased liver weight, epidydymal fat weight without change of systemic insulin resistance in FFD-fed mice. Importantly, HRP significantly reduced the degrees of severity of steatosis, inflammation, ballooning and fibrosis with decreased hepatic triglyceride levels, hepatic hydroxyproline content and serum alanine aminotransaminase levels in FFD mice. HRP treatment in FFD mice activated genes regarding fatty acid oxidation, such as peroxisome proliferators activated receptor alpha (ppara), carnitine palmitoyltransferase 1 alpha, cytochrome P450/family 4/subfamily a/polypeptide 10 (cyp4a10) and acyl-CoA oxidase and lowered total acetyl-CoA carboxylase protein levels, which both contributed to the

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P.065 decreased hepatic steatosis. Moreover, HRP treatment decreased oxidative stress levels, p38 phosphorylation, recruitment of inflammatory cells, and the expression of tissue inhibitor of metalloproteinase-1, collagen 1 alpha 1, alpha smooth muscle actin, tissue growth factor beta, SMAD3 phosphorylation in livers of FFD fed mice, which could contribute to the improvement of inflammation and fibrosis. In AML12 cells, HRP was found to inhibit prorenin-induced steatosis with increased transcript expression of ppara and cyp4a10. Conclusions: HRP mitigates non-alcoholic steatohepatitis and fibrosis in mice with NAFLD. Prorenin inhibition might be a pharmacologic therapeutic strategy to treat NAFLD.

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水蒸金針花之水萃物可保護 L-02 細胞株免受酒精引致的氧化損傷 AQUEOUS EXTRACT OF STEAMED DAYLILY FLOWER PROTECT L-02 CELLS AGAINST ALCOHOL INDUCED OXIDATIVE INJURY 1

顏聖烈王智弘殷媚晶 1 彰濱秀傳紀念醫院肝膽腸胃科 2 亞洲大學食品營養與保健生技學系 Background: Daylily flower (Hemerocallis fulva L.) is consumed as a vegetable in many Asian countries. Aqueous and ethanol extracts of daylily flower have been proved to have protective effects on HUVE cells against high glucose. Aims: In present study, L-02 cells were used to evaluate the protective effects of aqueous extract prepared from steamed daylily flower (DAE) against ethanol. Methods: L-02 cells are human normal hepatic cells. L-02 cells were pretreated with DAE at 0.25, 0.5 or 1% for 48 hr at 37°C, and followed by ethanol treatment of 150 mM. Effects of DAE pretreatment upon L-02 cells were evaluated, including cell viability, mRNA expression of Bcl-2 and Bax, the levels of ROS, 8-OHdG, GSH, the activity of GPX and catalase, and the activity of CYP2E1. Results: DAE treatments at 0.25, 0.5 and 1% enhanced the survival of L-02 cells. DAE at 0.5 and 1% upregulated Bcl-2 mRNA expression and down-regulated Bax expression. Ethanol increased reactive oxygen species level, decreased glutathione content, and glutathione peroxidase and catalase activities in L-02 cells. DAE at 3 concentrations reversed these changes. DAE at 3 concentrations reduced CYP2E1 activities. Conclusions: The results of this study suggested that aqueous extract of steamed daylily flower might be a potent agent to prevent alcoholic liver injury.

2021 消化系聯合學術演講年會

P.066

P.067

蛹蟲草菌絲體發酵液改善小鼠非酒精性脂肪肝並促進腸道乳酸桿菌生長 IMPROVEMENT OF NONALCOHOLIC FATTY LIVER AND PROMOTION OF INTESTINAL LACTOBACILLUS IN MICE WITH CORDYCEPS MILITARIS MYCELIUM FERMENTATION BROTH

白藜蘆醇對非酒精性脂肪肝相關肌肉萎縮症的可能治療及 SIRT1 媒介機轉的探討 SIRT1-DEPENDENT MECHANISMS AND EFFECTS OF RESVERATROL FOR PREVENTION OF MUSCLE WASTING IN NASH MICE

顏聖烈王俊偉許文光 1 彰濱秀傳紀念醫院肝膽腸胃科 2 大葉大學食品暨應用生物科技學系 Background: It has been shown that the formation of non-alcoholic fatty liver disease (NAFLD) by longterm consumption of high fat diet in mice will lead to the reduction or disappearance of the normal dominant flora in the intestine. Aims: In this study, the Cordyceps militaris mycelium fermentation broth (CMFB) was used to investigate the improvement of liver function, and to study the changes in the intestinal flora of NAFLD mice. Methods: Fifty male BALB/cByJNarl mice were randomly divided into negative control group, control group, and three test groups. Mice in the negative control group were fed with ordinary diet and the control group fed with the high-fat diet. Mice in three test groups were fed with highfat diet and three different doses of CMFB, at 6.15 gm/ kg/d, 12.3 gm/kg/d, 24.6 gm/kg/d, respectively. The mice were sacrificed on the 16th week of the experiment. Serum levels of glucose, insulin, adiponectin, IL-6, TNF-α, ALT, AST, total cholesterol, and triglyceride were determined. The number of Escherichia coli and Lactobacillus in the mouse feces was determined by the microbial plate culture method. Results: The results of our study showed that serum levels of TNF-α, ALT, AST, total cholesterol, and triglyceride in three test groups were significantly lower than that in control group (P<0.05). CMFB in three test groups can significantly promote the growth of intestinal Lactobacillus and significantly inhibit the growth of E. coli (P<0.05). Conclusions: CMFB can improve the liver function of NAFLD mice and promote the growth of intestinal Lactobacillus and inhibit the growth of E. coli.

4,5

4,6

劉志偉黃加璋黎子豪楊盈盈謝昀臻黃怡翔 4 4 侯明志林漢傑 1 臺北榮民總醫院內科部風濕免疫科 2 臺北榮民總醫院內科部內分泌新陳代謝科 3 新光吳火獅紀念醫院內科部風濕免疫科 4 臺北榮民總醫院內科部胃腸肝膽科 5 臺北榮民總醫院教學部臨床技術訓練科 6 陽明大學臨床醫學研究所

Background: In NASH, progressive muscle wasting was an aggravating factor for the progression of hepatic steatosis. This study explores the potential benefits of chronic treatment with resveratrol, a strong activator of SIRT1 on the muscle wasting of NASH mice. Methods: In vivo and in vitro study, we evaluate the SIRT1-dependent mechanisms and effects of resveratrol administration for 6 weeks with high-fat (HF)-methionine and choline deficient (MCD) diet-induced NASH mice (NASH-resv) and palmitate-pretreated C2C12 myoblast cells. Results: Resveratrol treatment increased grip strength and muscle mass of limbs, increased running distance and time on exercise wheels in NASH mice. There is a negative correlation between muscular SIRT1 activity and 3-nitrotyrosine levels of NASH and NASH-resv mice. SIRT1-dependent protection of muscle wasting was associated with the suppression of oxidative stress, up-regulation of anti-oxidants, inhibition of protein degradation, activation of autophagy, suppression of apoptotic activity, up-regulation of lipolytic genes and the reduction of fatty infiltration in limb muscle of NASH mice. In vitro, resveratrol alleviated palmitate acid-induced oxidative stress, lipid deposition, autophagy dysfunction, apoptotic signals, and subsequently reduced fusion index and myotube formation of C2C12 cells. The protective effects of resveratrol were abolished by EX527. Conclusions: Our study suggests that chronic resveratrol treatment is a feasible strategy for amelioration of hepatic steatosis, metabolic abnormalities, and muscle wasting in NASH mouse model.

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P.068

P.069

接受肝癌切除手術且 > 3 cm 分化良好的肝細胞癌患者之臨床特徵和預後 CHARACTERISTICS AND PROGNOSIS OF PATIENTS WITH LARGE WELLDIFFERENTIATED HEPATOCELLULAR CARCINOMA WHO HAVE UNDERGONE RESECTION

保疾伏（Nivolumab）併用酪氨酸激酶抑制劑與否在治療無法切除的肝細胞癌患者療效差別 NIVOLUMAB THERAPY WITH OR WITHOUT COMBINATION OF TYROSINE KINASE INHIBITOR FOR PATIENTS WITH UNRESECTABLE HEPATOCELLULAR CARCINOMA

林淑賢王植熙鄭汝汾王景弘顏毅豪 1 高雄長庚紀念醫院胃腸肝膽科系 2 高雄長庚紀念醫院肝臟移植中心暨一般外科 3 高雄長庚紀念醫院肝臟移植中心暨放射診斷科系 Background: Large well-differentiated hepatocellular carcinoma (HCC) ≥ 3 cm (defined as atypical HCC) is uncommon. Aims: We evaluated the characteristics and outcomes of atypical HCC patients underwent liver resection (LR). Methods: This retrospective study enrolled patients who underwent LR for HCC from 2007-2017. Patient characteristics, overall survival (OS), and recurrencefree survival (RFS) were compared between patients with atypical HCC and patients with typical HCC (moderate-toundifferentiated HCC ≥ 3 cm). Results: Among 598 patients, 51 (8.5%) had atypical HCC. Patients with atypical HCC had higher rates of nonviral infections (43% vs. 23%, p = 0.02) and American Joint Committee on Cancer T1 pathology (74.5% vs. 27.4%, p < 0.001), a lower rate of alpha-fetoprotein >20 ng/ml (5.9% vs. 47.5%, p < 0.001). Patients with atypical HCC had a longer RFS (5-year RFS: 62.5% vs. 43.8%, p = 0.02) and OS (5-year OS: 86.1% vs. 63.7%, p < 0.001) than those with typical HCC. Multivariate analysis showed that atypical HCC was not associated with RFS; however, it was associated with OS (HR = 0.50, 95% CI = 0.27 – 0.91, p = 0.02). Conclusions: Patients with atypical HCC have a higher rate of non-viral etiologies and a lower rate of aggressive tumor biologic behavior. Furthermore, atypical HCC is an independent predictor of OS.

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1,3

王楚評許偉帆莊伯恒陳政國王鴻偉蔡明宏 1 1 1 1,3 1,3 1,3 蘇文邦陳浤燿楊其穎林俊哲黃冠棠林肇堂 1,6 1,3 賴學洲彭成元 1 中國醫藥大學附設醫院內科部消化醫學中心 2 中國醫藥大學生物醫學研究所 3 中國醫藥大學醫學系 4 亞洲大學附屬醫院內科部腸胃肝膽科 5 中國醫藥大學附設醫院內科部血液腫瘤科 6 中國醫藥大學中醫學系

Background: Immune checkpoint inhibitors (ICIs) are emergent therapeutic options for hepatocellular carcinoma (HCC). The treatment efficacy of ICIs with or without tyrosine kinase inhibitors (TKIs) for patients with unresectable HCC is unknown. Aims: To investigate whether the combination of nivolumab with TKI yielded better progression-free survival (PFS) and overall survival (OS) than did nivolumab monotherapy in patients with unresectable HCC. Methods: This retrospective study enrolled 52 consecutive patients with unresectable HCC from May 2017 to December 2019 at China Medical University Hospital and Asia University Hospital. Patients with Barcelona Clinic Liver Cancer (BCLC) stage D, or who received concurrent transarterial chemoembolization or radiotherapy were excluded. Results: Of the 52 patients, 6, 5, and 41 patients had BCLC stages A, B, and C, respectively, and 32 and 18 patients were of Child–Pugh class A and B, respectively. The median nivolumab treatment duration was 2.45 (1.78–4.17) months, and 27 (51.9%) patients received combination therapy with TKIs (15, 8, 1, 2, and 1 patients received sorafenib, lenvatinib, regorafenib, sequential sorafenib and regorafenib, and sequential sorafenib and lenvatinib, respectively). Fourteen patients did not reach the time of first radiological imaging assessment at data analysis (10 patients died and 4 patients were lost to follow-up). Objective response (OR) and disease control rates were

2021 消化系聯合學術演講年會

P.070 23.1% and 36.5%, respectively. Patients who received combination therapy with TKIs had a higher proportion of BCLC stage C compared to those received nivolumab monotherapy (92.6% vs. 64.0%, p=0.013). Combination therapy (hazard ratio [HR]: 0.439, 95% confidence interval [CI]: 0.119–0.650, p=0.003) and OR (complete response and partial response, HR: 0.267, 95% CI: 0.088–0.812, p=0.020) were predictors of short PFS. Higher Cancer of the Liver Italian Program (CLIP) score (≥3) (HR: 3.615, 95% CI: 1.214–10.769, p=0.021) was a predictor of poor OS. Conclusions: Patients who received combination therapy with TKIs had a higher proportion of advanced HCC. Combination therapy with nivolumab and TKI yielded better PFS, but not OS for patients with unresectable HCC. OR was a predictor for longer PFS, and higher CLIP score (≥3) was a predictor for poor OS.

十種非侵入性模型預測中期肝細胞癌患者整體生存期的比較 COMPARISON OF TEN NONINVASIVE MODELS TO PREDICT OVERALL SURVIVAL IN PATIENTS WITH INTERMEDIATE-STAGE HEPATOCELLULAR CARCINOMA 1

1,2,3,9

4,9

5,9

6,9

張凱智許偉帆陳德鴻林建宏林膺峻 7,9 8,9 1,3,9 1,9 1,3,9 蔡明宏陳旆聿王鴻偉朱家聲彭成元 1 中國醫藥大學附設醫院內科部消化醫學中心 2 中國醫藥大學生物醫學科學研究所 3 中國醫藥大學醫學院 4 中國醫藥大學附設醫院外科部 5 中國醫藥大學附設醫院影像醫學部 6 中國醫藥大學附設醫院放射腫瘤部 7 中國醫藥大學附設醫院血液腫瘤部 8 中國醫藥大學附設醫院病理部 9 中國醫藥大學附設醫院肝癌多專科照護團隊 Background: Intermediate-stage hepatocellular carcinoma (HCC) is a heterogeneous tumor in terms of tumor size, number, and liver function. Various noninvasive models have been proposed to assess the liver functional reserves or fibrosis severity, including Child-Pugh score (CPS), model for end-stage liver disease (MELD), albuminbilirubin (ALBI) grade, platelet-albumin-bilirubin (PALBI) grade, FIB-4, aspartate aminotransferase-to-platelet ratio (APRI), Lok index, cirrhosis discriminant index (CDS), Göteborg University cirrhosis index (GUCI), and King’s score. Aims: To assess the feasibility and compare the prognostic role of these ten noninvasive models in patients with intermedicate-stage HCC. Methods: From January 2012 to November 2018, 612 consevutive patients with intermedicate-stage HCC from China Medical University Hospital were enrolled in this retrospective study. Patients who received radiofrequency ablation (n = 19), liver transplantation (n = 13), systemic therapy (n = 5), radiotherapy (n = 5), and hospice care or visited other hospitals (n = 77) were excluded. Finally, 493 patients were included in the finaly analysis. Demographic data, virological features, and factors associated with overall survival (OS) were recorded at baseline. The ten noninvasive models were calculated according to previous studies. The predictive performance of these ten models for OS was examined using receiver operating characteristic (ROC) curve analysis with the DeLong test.

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P.071 Results: Of 493 patients, 373 (75.7%) were male and 275 (55.8%) had liver cirrhosis (LC). The median age was 64 (55–72) years (first quartile–third quartile). Most patients had tumor volume ≤50% (n = 424, 86.0%), and the maximum tumor size was 6.0 (4.0–8.5) cm. The median α-fetoprotein (AFP) was 36.25 (6.13–552.91) ng/mL. Patients received trans-arterial chemoembolization (TACE, n = 349) or surgery (n = 144). The median follow-up period was 26.07 (9.77–48.27) months. Among the ten models, ALBI score had the highest area under ROC (AUROC) value (0.644 [95% confidence interval 0.595–0.693]) in all patients. In the subgroup analysis, Lok index, PALBI score, ALBI score, and Lok index had the highest AUROC values in patients without cirrhosis (n = 218), with cirrhosis (n = 275), receiving TACE (n = 349), and receiving surgery (n = 144), respectively. In the multivariate Cox regression analysis, ALBI grade 1, Lok index grade 1, ALBI grade 1, ALBI grade 1, and Lok index grade 1 were independent predictors of longer OS in all patients, patients without LC, patients with LC, patients receiving TACE, and patients receiving surgery, respectively. Conclusions: Among these ten noninvasive models, ALBI grade exhibited the highest diagnsotic value in predicting OS for all patients, cirrhotic patients, and those receiving TACE, and Lok index grade exhibited the highest diagnostic value in predicting OS in non-cirrhotic patients and those receiving surgery.

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糖尿病與高血壓在以索拉非尼治療之晚期肝細胞癌預後的角色 PROGNOSTIC ROLES OF DIABETES MELLITUS AND HYPERTENSION IN ADVANCED HEPATOCELLULAR CARCINOMA TREATED WITH SORAFENIB 1,2

2,3

1,2

Background: It remains limited whether diabetes mellitus (DM) and hypertension (HTN) affect the prognosis of advanced hepatocellular carcinoma (HCC) treated with sorafenib. Aims: Our study attempted to elucidate the roles of DM/HTN and the effects of diabetes medications among advanced HCC patients receiving sorafenib. Methods: From August 2012 to February 2018, 733 advanced HCC patients receiving sorafenib were enrolled at China Medical University, Taichung, Taiwan. According to the presence/absence of DM or HTN, they were divided into four groups: control [DM(-)/HTN(-), n=353], DM-only [DM(+)/ HTN(-), n=91], HTN-only [DM(-)/HTN(+), n=184] and DM+HTN groups [DM(+)/HTN(+), n=105]. Based on the types of diabetes medications, there were three groups among DM patients (the combined cohort of DM-only and DM+HTN groups), including metformin (n=63), non-metformin oral hypoglycemic agent (OHA) (n=104) and regular insulin (RI)/ neutral protamine hagedorn (NPH) groups (n=29). We then assessed the survival differences between these groups. Results: DM-only and DM+HTN groups significantly presented longer overall survival (OS) than control group (control vs. DM-only, 7.70 vs. 11.83 months, p=0.003; control vs. DM+HTN, 7.70 vs. 11.43 months, p=0.008). However, there was no significant OS difference between control and HTN-only group (7.70 vs. 8.80 months, p=0.111). Besides, all groups of DM patients showed significantly longer OS than control group (control vs. metformin, 7.70 vs. 12.60 months, p=0.011; control vs. non-metformin OHA, 7.70 vs. 10.80 months, p=0.016; control vs. RI/NPH, 7.70 vs. 15.20 months, p=0.026). Conclusions: Rather than HTN, DM predicts better prognosis in advanced HCC treated with sorafenib. Besides, metformin, non-metformin OHA and RI/NPH are associated with longer survival among DM-related advanced HCC patients receiving sorafenib.

2021 消化系聯合學術演講年會

P.072 肝腫瘤組織中脂質過氧化衍生的 DNA 化合物 γ-OHPDG 水平可預測肝癌的術後結果 THE LIPID PEROXIDATION DERIVED DNA ADDUCT γ-OHPDG LEVELS IN PARANEOPLASTIC LIVER TISSUES PREDICT POSTOPERATIVE OUTCOMES OF HEPATOMA 1

馮揚毅林暘翔葉昭廷 1 林口長庚紀念醫院肝膽胃腸科 2 林口長庚紀念醫院肝臟研究中心 Background: Hepatocellular carcinoma (HCC) ranks the third most frequent cause of cancer-related mortality in the world. In Taiwan, viral hepatitis accounts for more than 90% of HCC etiologies. About 3.50 million people are hepatitis B virus (HBV) carriers and 1.70 million people have hepatitis C virus (HCV) infections in Taiwan. To date, neonatal vaccination, nucleoside analogue therapy, direct acting antiviral and pegylated interferon treatment together have significantly reduce the prevalence of viralrelated HCC. Metabolic syndromes, including obesity, dyslipidemia and diabetes, have been correlated with an increased risk of liver diseases and HCC. All of them can trigger chronic necroinflammation, a pivotal factor for development of HCCs. Aims: Recently, many advanced therapeutics, including target therapy and immunotherapy have been developed. These therapies combining with the other traditional treatments such as radiofrequency ablation and transcatheter arterial chemoembolization may improve the outcomes of patients with HCC. DNA damage response has been proposed to be a crucial event in oncogenesis and promising strategies against tumor formation can be developed. However, few studies, particularly in liver cancer, have been conducted regarding its clinical relevance. Our objective in this study was to determine the association between the DNA damage indicator, γ-OHPdG, and postoperative outcomes in a retrospective cohort of HCCs. Methods: Statistical analysis was performed by SPSS version 25 (SPSS Inc., Chicago, IL, USA). Survival outcomes were evaluated based on Kaplan–Meier survival analysis. Kaplan-Meier survival curves for overall survival (OS), intrahepatic recurrence-free survival (RFS) and distant metastasis-free survival were compared using the log-rank test. P values < 0.05 were considered significant. Univariate and multivariate Cox’s proportional hazard

models were used to calculate the hazard ratio (HR) and confidence interval (CI) in survival analysis, for all patients and for subgroups. Results: γ-OHPdG is an independent prognostic factor for distant metastasis-free survival. Expression of γ-OHPdG in noncancerous tissues is an effective prognosis predictor in subgroups of HCC. Hydrogen peroxide inhibits cell viability and migration in vitro. Conclusions: In conclusion, assessment of γ-OHPdG expression in paraneoplastic noncancerous and cancerous liver tissues is helpful in predicting the postoperative outcomes of HCC, especially for HBV-related HCC patients.

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P.073

P.074

整合 ALBI Grade 及 Up-to-7 來預測肝癌中期病患之預後 INCORPORATING ALBUMINBILIRUBIN GRADE AND UP-TO-SEVEN CRITERIA TO PREDICT OUTCOMES OF PATIENTS WITH INTERMEDIATE STAGE HEPATOCELLULAR CARCINOMA

對於肝癌合併腫瘤破裂之患者，切除手術能提供較佳的預後 SURGICAL RESECTION COULD PROVIDE A BETTER OUTCOME FOR PATIENTS WITH HEPATOCELLULAR CARCINOMA AND WITH TUMOR RUPTURE

陳興曄盧勝男王景弘陳建宏洪肇宏紀廣明顏毅豪郭垣宏高雄長庚紀念醫院內科部肝膽胃腸科系 Background: Intermediate stage hepatocellular carcinoma (HCC) is a heterogenous disease in terms of liver function and tumor burden. Aims: To use albumin-bilirubin (ALBI) grade and upto-7 (UT7) criteria to assess outcomes of patients with intermediate stage HCC after transarterial embolization (TAE). Methods: Between January 2012 and January 2019, newly diagnosed intermediate HCC patients underwent TAE were enrolled and analyzed. The demographics, clinical characteristics and survival were obtained from medical chart reviews. Results: A total of 359 patients were enrolled and 30.4% of them were within UT7 criteria [UT7(-)]. There were 36.5%, 59.3%, and 4.2% of the patients with ALBI grade I, II, and III, respectively. Beyond UT7 [UT7(+)] and ALBI grade II/III were associated with overall mortality in multivariate analysis. Based on ALBI grade I/II/III and UT7 -/+, patients were classified into six groups as ALBI grade I plus UT7(-), II plus UT7(-), III plus UT7(-), I plus UT7(+), II plus UT7(+), and III plus UTI(+). Distributions of median survival were 47.5, 32.9, 15, 34.3, 16.7 and 14.3 months, respectively. Patients with statistically insignificant survivals were further combined. Patients with ALBI grade I plus UT7(-) were reclassified as ALBI-U class I, whereas ALBI grade II plus UT7(-) and I plus UT7(+) were ALBI-U class II , and the others were ALBI-U class III. There were 8.4%, 48.7%, and 42.9% of patients in ALBI-U class I, II, and III, respectively. The 5-year survival rate was 48.8%, 22.5%, and 13.7% in ALBI-U class I, II, and III, respectively (p<0.01). Conclusions: ALBI-U classification was useful in predicting outcomes of patient with intermediate stage HCC after TAE.

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1,2

2,3

3,4,5

1,5

1,3

李君陽蘇建維周嘉揚柳建安黃怡翔侯明志 1 臺北榮民總醫院內科部胃腸肝膽科 2 臺北榮民總醫院外科部一般外科 3 國立陽明大學醫學院醫學系 4 臺北榮民總醫院放射線部 5 國立陽明大學醫學院臨床醫學研究所

Background: The prognoses are poor for patients with hepatocellular carcinoma (HCC) and with tumor rupture at the time of diagnosis. The major treatment modalities for these patients include surgical resection (SR), transarterial chemoembolization (TACE), and supportive treatments. Aims: We aimed to investigate the outcomes of patients with HCC and with tumor rupture. Moreover, we aimed to identify the optimal treatment modality for such patients. Methods: We enrolled 91 patients with treatment-naive HCC and with tumor rupture while diagnosis between 2008 and 2019 at Taipei Veterans General Hospital. Overall survival (OS) was estimated using the Kaplan-Meier method and compared by Cox’s proportional hazard model. Results: In this study, 38 patients were received SR alone, 28 patients received TACE only, and 20 patients received TACE and then SR sequential therapy, and 5 patients receive supportive treatment. We divided the patients into two groups: SR group (SR alone and TACE/SR sequential therapy) and non-SR group (TACE alone and supportive treatment alone). After a median follow-up of 13.1 (interquartile range 2.9‒41.1) months, 54 patients had dead. The cumulative 1-year and 3-year OS rates were 71.7% vs. 24.2%, and 63.0% vs. 7.6%, in the SR group vs. nonSR group, respectively. (p < 0.001). A multivariate analysis showed that non-SR (hazard ratio [HR]: 6.173, 95% confidence interval [CI]: 3.436‒11.09, p < 0.001), serum alpha fetoprotein levels >100 ng/mL (HR: 3.124, 95% CI: 1.410‒6.922, p = 0.005), and serum albumin levels ≤ 3.5g/ dL (HR: 2.809, 95% CI: 1.397‒5.650, p = 0.004) were the independent risk factors associated with poor OS. Conclusions: For patient with HCC and with tumor rupture at the time of diagnosis, SR could provide better outcomes.

2021 消化系聯合學術演講年會

P.075

P.076

血小板增多症和肝癌病人較差的預後有關 THROMBOCYTOSIS IS ASSOCIATED WITH WORSE SURVIVAL IN PATIENTS WITH HEPATOCELLULAR CARCINOMA

局部治療在肝細胞肝癌接受免疫治療中病況惡化的角色 ADD-ON LOCAL REGIONAL THERAPIES IN HEPATOCELLULAR CARCINOMA WITH ISOLATED PROGRESSIVE DISEASE DURING IMMUNE CHECKPOINT INHIBITORS

1,2

1,3,4

1,3

2,5

柯智傑劉柏宏黃怡翔侯明志 Amit G. Singal 1 臺北榮民總醫院內科部 2 德克薩斯大學達拉斯西南醫學院 3 國立陽明大學醫學系 4 國立陽明大學臨床醫學研究所 5 德克薩斯大學達拉斯西南肝膽腸胃科

Background: Thrombocytosis is associated with more aggressive tumor biology in many malignancies, however, there are limited data in patients with hepatocellular carcinoma (HCC), which often occurs in patients with cirrhosis and portal hypertension. Aims: The prognostic value of thrombocytosis in two cohorts of patients with HCC. Methods: 3,561 patients from Taiwan and 1,145 patients from the United States. Thrombocytopenia was defined as platelet count < 150 x 109/L and thrombocytosis as ≥ 300 x 10 9/L at HCC diagnosis. We used multivariable Cox proportional hazard models to identify independent predictors of survival. Results: Compared to patients with normal platelet counts and those with thrombocytopenia, patients with thrombocytosis had larger tumors, increased vascular invasion and a higher proportion had extra-hepatic metastases in both cohorts. In multivariable analysis, thrombocytosis was associated with worse survival in the Taiwan (aHR: 1.79, 95% CI: 1.56–2.07) and U.S. (aHR: 1.74, 95% CI: 1.30-2.33) cohorts after adjusting for age, gender, liver disease etiology, model for end-stage liver disease (MELD) score, Barcelona Clinic Liver Cancer (BCLC) stage, and alpha-fetoprotein level. Patients with thrombocytosis had a median survival of 6 and 4 months in the Taiwan and U.S. cohorts, compared to 32 and 14 months for those with normal platelet counts, and 38 and 16 months for thrombocytopenic patients. Conclusions: Thrombocytosis is independently associated with increased tumor burden and worse overall survival among HCC patients.

劉玠晏姜學謙蔡宏名王昊宸林毅志陳炯瑜 1 1 1,5 1 1,3 1,3 莊喬雄陳柏潤陳威穎康瑞文謝名宗郭欣瑜 1 成大醫院內科部 2 成大醫院放射診斷科 3 國立成功大學臨床醫學研究所 4 成大醫院外科部 5 國立成功大學公共衛生研究所 Background: Traditionally, progression under immunotherapy using the programmed cell death protein-1 (PD-1) inhibitors leads to withdrawal of agents, which indicate treatment failure in cancer treatment. However, recent studies showed that progression confined to a single site of disease and amenable to a local therapy may indicate a favorable biology and may not necessitate a change in systemic therapy. Aims: This study aimed to study the feasibility of local treatments for progressing lesions during PD-1 inhibitors treatment in advanced HCC (aHCC). Methods: We retrospectively reviewed medical records of patients with aHCC treated with PD-1 inhibitors from 2015.12.01 to 2020.10.31 at the National Cheng Kung University Hospital, Tainan, Taiwan. Patients receiving treatment of PD-1 inhibitors and further add-on localregional therapies of an isolated site of progressive disease were enrolled. The treatment response was assessed with the modified Response Evaluation Criteria in Solid Tumors 1.1 criteria. The time to progression (TTP), additional progression-free survival (PFS), and overall survival (OS) were analyzed by Kaplan-Meier method. Results: A total of 158 aHCC patients treated with PD-1 inhibitors were identified. Among these patients, 6 underwent local therapies for progressing lesions and continued on immunotherapy despite objective progression, in whom 3 had new lesions, and 3 had progression of target lesions. Of the 6 patients, 2 received surgeries, 1 received radiofrequency ablation, 2 received radiotherapy and 1 received transarterial chemoembolization for progressing lesions. Median follow-up duration until 2020.10.31 was 25.6 months (interquartile range, 19.3 - 33.8). Median TTP was 1.9 months (95% confidence interval [CI], 1.2 - 15.0)

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P.077 and duration of usage of PD-1 inhibitors was 22.1 months (range, 4.1-47.5). At the end of the follow-up period, 4 of the patients were alive, and 3 remained progression-free following the local therapies for the progressing disease. The additional median PFS beyond the original TTP was not reached (95% CI, 3.2–not estimable) by the date of follow-up. There were no severe treatment-related adverse events from medical records. Conclusions: Regarding the focal progression to immunotherapy in HCC, loco-regional therapies may achieve additional survival benefit without significant adverse. Further investigation is needed to identify the patients who are more likely to benefit from the combination of immunotherapy and local therapies delivered to the area of the progression.

肝實質電腦斷層造影對比增強可預測肝細胞癌的經動脈導管栓塞術治療後之預後 COMPUTED TOMOGRAPHY CONTRAST ENHANCEMENT OF LIVER PARENCHYMA MAY PREDICT THE OUTCOME OF TRANSARTERIAL CHEMOEMBOLIZATION IN HEPATOCELLULAR CARCINOMA 1

林煊淮張維洲施宇隆謝財源 Francis Y.K. Yao , 3 Benjamin M. Yeh 1 三軍總醫院內科部胃腸科 2 三軍總醫院放射診斷部 3 加州大學舊金山分校 Background: Whether the heterogeneity of liver parenchymal enhancement related to cancer progression is unclear. Aims: The aim of this study to define the role of heterogeneity of liver parenchymal enhancement on computed tomography (CT) in the survival of patients with early and intermediatestage hepatocellular carcinoma (HCC) after transarterial chemoembolization (TACE). Methods: We retrospectively reviewed the medical records of the patients who had early and intermediate-stage HCCs, and undergone TACE as the initial HCC treatment modality. The heterogeneity of liver parenchymal enhancement was estimated using standard deviation (SD) of the enhanced values of CT scan. SD > 5.6 was heterogenous enhancement, and SD ≦ 5.6 was homogeneous enhancement. Results: 30 patients were heterogenous enhancement and 86 patients were homogeneous enhancement. The clinical characteristics, liver function reserve, and severity of liver fibrosis of these two groups were not different, but the KaplanMeier survival curve showed a longer survival in patients with heterogenous enhancement (Log-rank test, p = 0.001). 47 patients underwent liver transplants at the following years. The pathologic findings of liver explants showed 16 (44.4%) patients with homogenous enhancement had micronodular cirrhosis, but 11 (100%) patients with heterogenous enhancement had non-micronodular cirrhosis (p = 0.003). The patients with homogenous enhancement tended to have higher alpha-fetoprotein (AFP) compared with others (128.7 vs. 34.2 ng/ml), but it did not reach statistical significance (p = 0.086). Conclusions: The early and intermediate-stage HCC patients who had undergone TACE as the initial treatment modality with heterogeneity of liver parenchymal enhancement tended to have non-micronodular cirrhosis and associate a longer survival.

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P.078 肝動脈灌注化學藥物與質子束輻射合併治療肝細胞癌及門靜脈癌栓的療效評估 HEPATIC ARTERIAL INFUSION CHEMOTHERAPY COMBINATION WITH PROTON BEAM RADIOTHERAPY FOR HEPATOCELLULAR CARCINOMA WITH PORTAL VEIN TUMOR THROMBOSIS 1,5

2,5

3,5

4,5

1,5

林成俊黃炳勝潘廣澤吳宗翰林錫銘鄭雅婷 1,5 謝彝中 1 林口長庚紀念醫院胃腸肝膽科系 2 林口長庚紀念醫院質子暨放射中心 3 林口長庚紀念醫院胃腸影像診療科 4 林口長庚紀念醫院肝臟暨移植外科 5 長庚大學醫學系

to-progression (TTP) was 8.4 months (95% CI: 4.3-12.6 months). Vp4 PVTT did not affect the outcomes. Initial disease control according to the first image evaluation after combination therapy was the only prognostic factor associated with better OS and longer TTP (OS: P = 0.012, HR = 0.056; time-to-progression: P = 0.007, HR = 0.033). The patients with initial disease control after the combination therapy had a significantly better OS (29.4 vs. 6.8 months, P < 0.001) and a longer TTP (13.4 vs. 3.2 months, P < 0.001). Severe TEAE (grade 3 or 4) was found in 14 (47%) patients, including upper gastrointestinal bleeding (23%), thrombocytopenia (20%), and leukopenia (13%). No patients died due to the combination therapy. Conclusions: Combination with HAIC and PBT was safe and efficacy for treating HCC with PVTT. Initial disease control after combination predicted better outcomes of these advanced patients.

Background: Hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT) had a poor prognosis, even after the newly developed therapies. Hepatic arterial infusion chemotherapy (HAIC) combination with radiotherapy could have a synergistic antitumor effect. Proton beam therapy (PBT) can prescribe a large radiation dose into the tumor with little radiation exposure to peripheral non-tumor parts. HAIC plus PBT for treating HCC with PVTT has not been reported. Aims: Retrospectively review the therapeutic efficacy and safety for the HCC with PVTT patients who received HAIC plus PBT. Methods: From January 2016 to April 2019, 30 HCC patients with PVTT have received HAIC plus PBT therapy. Major PVTT (Vp3-4) was found in 25 (75%) patients. The treatment protocol was 2 cycles HAIC, followed by PBT, and then 2 cycles HAIC. Each HAIC cycle gave 5-hour 250 mg 5-fluorouracil and 1-hour 10mg cisplatin every day for 5 days, followed by 2-day therapeutic rest. PBT was planning to give the maximum radiation dose of 72.6 grays dividing into 20-25 fractions to cover the liver tumor and PVTT. A dynamic CT scan or MRI to evaluate the therapeutic response was done every 3 months after therapy initiation. Additional HAIC 1 cycle per month was given for the patients having disease control after the combination therapy. Results: The best objective response was found in 17 (57%) patients, including 6 (20%) complete responses. A total of 15 patients died during a mean follow-up period of 16.5 months. The median overall survival (OS) was 23.0 months (95% CI: 16.0-30.0 months) and median time-

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P.079 循序使用蕾莎瓦與樂衛瑪治療無法手術切除之肝癌病患的臨床實況 ─ 單一醫院經驗 SORAFENIB-LENVATINIB SEQUENTIAL THERAPY IN UNRECTABLE HEPATOCELLULAR CARCINOMA IN REAL WORLD PRACTICE ‒ A SINGLE INSTITUTE EXPERIENCE 1

1,2

莊伯恒王鴻偉 1 中國醫藥大學附設醫院消化醫學中心 2 中國醫藥大學醫學院醫學系 Background: Observational GIDEON study (Int J Clin Pract. 2014;68(5):609‒17) reported sorafenib to HCC patients in overall safety profile and dosing strategy are similar across Child-Pugh subgroups. Safety findings also appear comparable irrespective of initial sorafenib dose or BCLC stage. Lenvatinib and sorafenib are tyrosine kinase inhibitors (TKIs) with different pathways and both were reimbursed as first-line systemic therapy exclusively at present. Sequential therapy of sorafenib to lenvatinb was reported in the sorafenib arm 56/476 (11.8%) of the REFLECT trial (Liver Cancer. 2018;7:1‒19). Aims: We aimed to elucidate the sequential therapeutic efficacy of self-paid lenvatinib in their reimbursed sorafenib failure in different BCLC, Child-Pugh and initial lenvatinib dose subgroups. Methods: We enrolled 26 unresectable HCC patients treated with self-paid lenvatinib after their reimbursed sorafenib failure from June 2017 to January 2019 and the analysis was conducted at the end of 2020. They were 21 males (81%) and clinical findings at introduction of of sorafenib and lenvatinib were median age 66 and 67.5 years, Barcelona Clinic Liver Cancer (BCLC) stage B/C/ D (ECOG 4) = 3/22/1 and 2/23/1, Child-Pugh score (CPS) 5/6/7/8/9/10 = 19/6/0/1/0/0 and 3/5/10/3/1/3, alternatively. Clinical findings and Eastern Cooperative Oncology Group Performance Status (ECOG) at introduction of these two TKIs were retrospectively evaluated. Results: There are three patients alive (11.5%, all BCLC C) till the end of 2020. The median overall survival (OS) at introduction of of sorafenib and lenvatinib were: 13.8 and 5.9 months respectively. The median OS in different ChildPugh score at introduction of these two TKIs were A5/A6 = 20.5/9 (p = 0.083) and A/B/C = 31.7/14/5.2 (p = 0.003) respectively. The median albumin-bilirubin (ALBI) score at introduction of these two TKIs were -2.59 and -1.99 respectively but both were ALBI grade 2. The median OS

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in different ALBI grade 1/2/3 were 13.7/14/- (p = 0.079) and not reached/16.9/5.2 (p = 0.005) respectively. The median OS in different ECOG 0-1/2-4 were 14/3.7 (p < 0.001) and 20.5/3.8 (p = 0.002) respectively. The median OS in different initial weight and cost base lenvatinib doses 10/7-8/5 mg were 0.8/16.3/6.1 months (p = 0.402). Conclusions: Good liver function and better performance status in unresectable HCC patients will have better prognosis in the systemic sequential sorafenib and lenvatinib therapy and were more important in the timing of lenvatinib use. The initial weight and cost base lenvatinib dose did not show significant difference to prognosis.

2021 消化系聯合學術演講年會

P.080 使用非侵入性肝纖維化超音波檢查（ARFI）評估切肝手術之預後：中部家醫學中心的臨床經驗 ACOUSTIC RADIATION FORCE IMPULSE ELASTOGRAPHY FOR THE OUTCOME OF HEPATECTOMY: EXPERIENCE OF A MEDICAL CENTER IN CENTRAL TAIWAN 1,4

1,4

1,2

1,3

陳宣怡汪奇志李祥麟李原地蔡明璋 1 中山醫學大學附設醫院肝膽腸胃科 2 中山醫學大學附設醫院消化外科 3 中山醫學大學附設醫院感染科 4 中山醫學大學醫學系

1,4

Background: Due to development and health insurance reimbursement of antiviral treatment and the increasing frequency of nonviral-related hepatocellular carcinoma (HCC). The number of HCC patients with relatively preserved hepatic function has been increasing. Clinical practice guideline and outcomes of HCC are both significantly influenced by the underlying liver dysfunction, as well as by the stage and extent of the tumor size. Traditionally, the Child-Pugh classification and dynamic functional tests such as indocyanine green retention test (ICG) is an important assessment of preoperative liver function in Patients with HCC. Recent investigations have suggested that the albumin-bilirubin (ALBI) grade can also be used as an assessment tool for hepatic reserve function. Liver ultrasound is one of the main methods of non-invasive and cost-effective diagnosing diffuse liver disease as well as in our daily practice. The usefulness of liver stiffness evaluation, such as acoustic radiation force impulse elastography can provide a more detailed method of assessment of hepatic function and clinical outcomes. Aims: To evaluate the hepatic function and clinical outcomes of hepatectomy through non-invasive liver stiffness evaluation in HCC patients. Methods: We enrolled 36 newly diagnosed HCC patients (male/female: 22/14) scheduled to received hepatectomy. Pre-operative evaluation includes MELD score, mean fibrosis-4 (FIB-4) index, AST to platelet ratio index (APRI), indocyanine green retention test at 15 minutes (ICG-R15), liver stiffness evaluation through acoustic radiation force impulse elastography. We evaluated clinical outcomes through post-operation complication, intensive care unit stay and total hospital stay. We also evaluated correlation between our elastography (ARFI) scores and histological

fibrosis stage of Modified Ishak fibrosis score. Results: In multivariate comparisons between patients with hospital stays within or more than 20 days, higher MELD score (8.4 ± 2.6 vs. 7.4 ± 2.4, p = 0.277), FIB-4 index (4.59 ± 3.37 vs. 3.83 ± 3.88, p = 0.553), liver stiffness (1.94 ± 0.76 vs. 1.73 ± 0.46, p = 0.341) had higher incidence of more hospital stays and post-operation complications includes uncontrolled ascites, bile leakage, intra-abdominal infection, hepatic failure and mortality. But did not reach statistical significance in our limited data. However, higher APRI and ICG-R15 test did not showed higher incidence of more hospital stays and post-operation complications. 80% (p = 0.002) of hospital stays more than 20 days was due to post operation intra-abdominal infection. ARFI scores has strong correlation with histological fibrosis stage of Modified Ishak fibrosis score (p < 0.001). Conclusions: In our limited data, blood chemistry examinations combined with liver stiffness (fibrosis) elastography evaluation can provide more detailed methods of assessment of hepatic function and clinical outcomes.

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2021 消化系聯合學術演講年會

P.081 對早期肝細胞癌患者經射頻燒灼術術後療效評估，較短的 DCP（PIVKA II）半衰期是一個很好的預測因子 SHORT HALF-LIFE OF DESγ-CARBOXY PROTHROMBIN (PIVKA II) IS A GOOD FACTOR TO EARLY DETECT UNFAVORABLE TREATMENT IN PATIENTS WITH HEPATOCELLULAR CARCINOMA AFTER RADIOFREQUENCY ABLATION 姚志謙郭垣宏張國欽顏毅豪紀廣明陳建宏洪肇宏胡琮輝王景弘盧勝男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 clinical significance of des-γ-carboxy prothrombin (DCP) changes in patients undergoing radiofrequency ablation (RFA) for hepatocellular carcinoma need to be further clarify. Aims: To investigated whether the post-ablation halflives (HLs) of DCP can be a good predictor in monitoring treatment response of RFA and try to access the best cut-off value of HLs for predicting complete treatment response. Methods: A total of 36 HCC patients who had pre-ablation DCP concentrations ≥ 80 mAU/ml underwent RFA therapy were analyzed. We calculated the HLs of DCP from their values before and first day post-ablation. The efficacy of the ablation response is assessed by standard imaging modality, a computed tomography scan 1 month after RFA. We assessed the correlation between different HLs of DCP and treatment outcomes by standard imaging modality. Results: Of the 36 patients, 21 (58.3%) had complete radiological response post RFA. The ROC analysis showed that the optimal cut-off value of HLs of DCP for predicting complete treatment response is 47.5 hours (Area under the ROC curve: 0.708). So we further defined short HLs of DCP <48 hours as predictor of favorable RFA treatment response. Of the 21 RFA patients with a complete radiological response, 15 (71.4%) had short HLs of DCP and 6 (28.6%) had long HLs of DCP. In 19 patients with short HLs of DCP, 15 (78.9%) had complete radiologic response. However, among 17 patients with long HLs of DCP, only 6 patients had complete radiologic response (35.3%). Based on the standard image modality, the sensitivity, specificity, accuracy, positive predictive value, and negative predictive value were 71.4%, 73.3%, 72.2%, 78.9%, and 64.7%, respectively, for short HLs of DCP in

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the detection of favorable RFA treatment response. Besides, 19 patients with short HLs of DCP had better diseasefree survival curve then patients with long HLs of DCP in Kaplan-Meier estimation. (P = 0.034, log–rank test). Conclusions: This present study showed that short HLs of DCP (< 48 hours) is a useful predictive marker for treatment response and recurrent-free survival after RFA therapies. Those HCC patients who had long HLs calculated after RFA should be consider to have further image modalities study to early detection incomplete treatment and rescue management for residual HCC timely.

2021 消化系聯合學術演講年會

P.082 比較早期肝癌患者接受射頻燒灼術合併經動脈導管肝臟腫瘤注射化學栓塞或射頻燒灼術合併經皮穿刺腫瘤內酒精注射與外科手術切除的預後 COMBINATION THERAPY OF LOCAL ABLATION WITH TRANSCATHETER ARTERIAL EMBOLIZATION OR WITH PERCUTANEOUS ETHANOL INJECTION FOR PATIENTS WITH EARLY-STAGE HEPATOCELLULAR CARCINOMA: 5-YEAR EXPERIENCE AT A MEDICAL CENTER 1

1,2,3

林志杰張經緯洪建源王蒼恩陳銘仁 1 馬偕紀念醫院內科部肝膽腸胃科 2 馬偕醫護管理專科學校 3 馬偕醫學院

cumulative survival curves between RFA plus TACE group and resection group. There was also no difference in survival curves f between RFA plus PEI group and resection group. Conclusions: Combined RFA with TACE and RFA with PEI may have comparable therapeutic outcomes with surgical resection among patients with early-stage HCC. These need more patient data collection.

王鴻源

Background: Although radiofrequency ablation (RFA) combined with transcatheter arterial chemoembolization (TACE) or with percutaneous ethanol injection (PEI) has become important curative treatments for patients with hepatocellular carcinoma (HCC), the effect of combination of RFA withTACE or with PEI compared with surgical resection remains controversial. Surgical resection and liver transplantation are still the priority for early-stage HCCs. Aims: The aim of our study was to compare the effectiveness of RFA plus TACE or RFA plus PEI with hepatectomy in patients with early-stage HCC. Methods: We retrospectively reviewed the medical records of patients with HCC from June 2014 to September 2019 in the MacKay Memorial Hospital. Patients with early-stage HCC (single nodule ≤5 cm or multiple ≤3 nodules, each ≤3 cm) were enrolled. The treatment outcomes of RFA plus TACE or RFA plus PEI were compared with surgical resection. Results: A total of 398 patients with early-stage HCC were analyzed. The sex ratio (male to female) was 1:0.57. The ratio of BCLC stage (0/A) was 24.4/75.6%. All patient underwent treatment. The type of curative treatment was categorized into surgical resection (n=175), RFA (n=159), RFA plus TACE (n=11), and RFA plus PEI (n=8). The overall survival rate of treatment at 5 years was 63.47% (57.06~69.88). In subgroup analysis, the 5-years survival rate of resection, RFA, RFA plus TACE, and RFA plus PEI were 69.99% (60.74~79.23), 60.04% (49.89~70.20), 70.71% (42.70~98.71), and 50.00% (5.27~94.73), respectively. There was no significant difference in

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P.083

P.084

重新定義巴塞隆納中期肝癌病患之腫瘤負荷：7-11 規約 REDEFINING TUMOR BURDEN IN PATIENTS WITH INTERMEDIATE STAGE HEPATOCELLULAR CARCINOMA: THE 7-11 CRITERIA

持續病毒學反應對 C 型肝炎相關肝癌射頻燒灼術後之存活助益 SURVIVAL BENEFIT OF ACHIEVING SUSTAINED VIROLOGICAL RESPONSE IN PATIENTS WITH HCV-RELATED HEPATOCELLULAR CARCINOMA RECEIVING RADIOFREQUENCY ABLATION

1,2

1,2,3

1,2

1,2,3

洪雅文李懿宬齊振達李潤川侯明志黃怡翔 1 臺北榮民總醫院胃腸肝膽科 2 國立陽明大學醫學系內科學科 3 國立陽明大學臨床醫學研究所 4 臺北榮民醫院放射線部

Background: For patients with intermediate stage hepatocellular carcinoma (HCC), the definition of high tumor burden remains controversial. Aims: This study aimed to compare the prognostic value of different criteria of tumor burden in patients with intermediate HCC undergoing transarterial chemoembolization (TACE). Methods: From 2007 to 2019, 632 treatment-naïve patients with intermediate HCC undergoing TACE were retrospectively enrolled. We compared different criteria of tumor burden in discriminating radiologic response and survival, including up-to-7, up-to-11, 5-7, seven lesions criteria, and newly proposed 7-11 criteria. Results: Significantly different proportions of patients were classified as high tumor burden by different criteria. Among the five criteria, 7-11 criteria have the best performance to discriminate complete response (CR) and overall survival (OS) after TACE. In patients with low, intermediate, and high tumor burden classified by 7-11 criteria, the CR rate was 21%, 12% and 2.5%, respectively (p < 0.001), and the median OS was 33.1, 22.3 and 11.9 months, respectively (p < 0.001). By multivariate analysis, 7-11 criteria were significantly associated with CR (intermediate versus high burden, odds ratio = 4.617, p = 0.002; low versus high burden, odds ratio = 8.675, p < 0.001) and OS (intermediate versus high burden, hazard ratio = 0.651, p < 0.001; low versus high burden, hazard ratio = 0.524, p < 0.001). 7-11 criteria were also significantly associated with objective response, progressive disease after TACE, and recurrencefree survival after achieving CR. Conclusions: Conventional definitions of tumor burden were not optimal for patients with intermediate HCC. The new 7-11 criteria had the best discriminative power in predicting radiologic response and survival in patients with intermediate stage HCC undergoing TACE.

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1,2,3

胡果正李懿宬齊振達柳建安侯明志黃怡翔 1 臺北榮民總醫院胃腸肝膽科 2 國立陽明大學醫學系 3 國立陽明大學臨床醫學研究所 4 臺北榮民總醫院放射線部

Background: In patients with hepatitis C virus (HCV)related hepatocellular carcinoma (HCC) who received radiofrequency ablation (RFA), the benefit of achieving sustained virological response (SVR) on survival remains unclear. Aims: The aim of this study was to evaluate the impact of SVR on survival of patients with HCV-related HCC undergoing RFA. Methods: Consecutive 262 patients receiving RFA for HCV-related HCC were retrospectively enrolled, including 72 (27.5%) and 78 (29.8%) patients with interferon-based (IFN-based) and direct-acting antivirals (DAA) therapy, respectively. To minimize the risk of immortal time bias, we adjusted the overall survival (OS) from the date of antiviral therapy to death for patients who started antiviral therapy after RFA. Factors associated with OS with and without adjustment were evaluated. Results: The SVR rate was 50% and 93.6% in patients treated IFN-based and DAA therapy, respectively. During a median follow-up period of 46.8 months, 140 (53.4%) patients died. By multivariate analysis, tumor number > 1 (HR = 1.920, p = 0.046), bilirubin > 1.5 mg/dL (HR = 2.203, p = 0.009), albumin > 3.0 g/dL (HR = 0.351, p = 0.001), platelet count > 150 x 109/L (HR = 0.372, p = 0.007) and achieving SVR by either IFN-based treatment (HR = 0.115, p < 0.001) or DAA (HR = 0.232, p = 0.001) were independent predictors of OS before adjustment. The impact of achieving SVR remained significant in multivariate analysis of adjusted OS, as well as in subgroup patients with and without tumor recurrence. Conclusions: Achievement of SVR by either IFN-based or DAA therapy was associated with a significantly improved survival after RFA in patients with HCV-related HCC.

2021 消化系聯合學術演講年會

P.085 周產期及停經後的婦女患有原發性肝惡性腫瘤有較差的預後嗎？來自台灣全國性的世代研究證據 DO PERIPARTUM AND POSTMENOPAUSAL WOMEN WITH PRIMARY LIVER CANCER HAVE A WORSE PROGNOSIS? EVIDENCE FROM A NATIONWIDE COHORT IN TAIWAN 1

1,3

1,4

Conclusions: Peripartum females with PLC have no difference in survival rates compared with those patients without peripartum. Menopausal females with PLC have worse survival rates compared with those patients without menopause.

1,4

曾冠瑋林美辰賴世偉彭成元莊伯恒蘇文邦 1,4 1,4 1,4 1,4 1,5 高榮達林俊哲黃冠堂林肇堂賴學洲 1 中國醫藥大學醫學院醫學系 2 中國醫藥大學附設醫院健康資料中心 3 中國醫藥大學附設醫院家庭醫學部 4 中國醫藥大學附設醫院內科部消化醫學中心 5 中國醫藥大學中醫學院中醫學系

Background: Few large-scale population-based studies have been reported that evaluated the clinical survival outcomes among peripartum and postmenopausal women with primary liver cancer (PLC). Aims: This study aimed to investigate whether peripartum and postmenopausal women with PLC have lower overall survival rates compared with women who were not peripartum and postmenopausal. Methods: The Taiwan National Health Insurance claims data from 2000 to 2012 was used for this propensity-scorematched study. A cohort of 40 peripartum women with PLC and a reference cohort of 160 women without peripartum were enrolled. In the women with PLC with/without menopause study, a study cohort of 10752 menopausal females with PLC and a comparison cohort of 2688 women without menopause were enrolled. Results: Patients with peripartum PLC had a nonsignificant risk of death compared with the non-peripartum cohort (aHR = 1.40, 95% confidence intervals (CI) = 0.89– 2.20, p = 0.149). The survival rate at different follow-up durations between peripartum PLC patients and those in the non-peripartum cohort showed a non-significant difference. Patients who were diagnosed with PLC younger than 50 years old (without menopause) had a significant lower risk of death compared with patients diagnosed with PLC at or older than 50 years (postmenopausal) (aHR = 0.64, 95% CI = 0.61-0.68, p < 0.001). The survival rate of women <50 years with PLC was significantly higher than older women with PLC when followed for 0.5 (72.44% vs. 64.16%), 1 (60.57% vs. 51.66%), 3 (42.92% vs. 31.28%), and 5 year(s) (37.02% vs. 21.83%), respectively (p < 0.001).

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P.086 肝動脈化療對門靜脈栓塞的肝癌病患的療效 HEPATIC ARTERY INFUSION CHEMOTHERAPY FOR PATIENTS OF HEPATOCELLULAR CARCINOMA WITH MAIN PORTAL VEIN THROMBOSIS 1

1,2

陳順益蔡維倫孫煒智陳文誌蔡峯偉鄭錦翔 1 高雄榮民總醫院內科部肝膽胃腸科 2 國立陽明大學醫學院醫學系

Background: Hepatocellular carcinoma (HCC) ranks the 2nd cause of cancer death in Taiwan. Main portal vein thrombosis (MPVT) is not unusual in HCC. But MPV thrombosis remained a challenge for Hepatologists and had poor prognosis despite aggressive treatment. Hepatic artery infusion chemotherapy (HAIC) is a treatment recommendation for HCC with MPV thrombosis but treatment outcome required further investigation. Aims: to evaluate the treatment efficacy of HAIC for HCC with MPV thrombosis. Methods: From January 2005 to September 2018, 183 patients with MPVT and received HAIC in VGHKS were enrolled. Clinical characteristics and outcome were analyzed. Treatment response was evaluated by m-RECIST criteria. Logistic regression analysis was used to analyze factors associated with overall response. Cox-regression analysis was used to analyze the factors associated with mortality. Results: Among the 183 patients, 156 (85.2%) were male and 27 (14.8%) were female. The BCLC stages were: C = 177 (96.7%), D = 6 (3.3%), Child Score were: A = 135 (73.8%), B = 48 (26.2%). The treatment response showed: complete response (CR) = 18 (9.8%), partial response (PR) = 26 (14.2%), stable disease (SD) = 35 (19.1%), progression disease (PD) = 104 (56.8%). The rate of overall response (CR + PR) is 24%. The median survival time in patients with overall response was 34.8 ± 4.4 months vs. 10.9 ± 1.3 months in patients without overall response, p < 0.001. In uni-variate analysis under Logistic Regression, PLT (hazard ratio [HR]: 0.996, 95% confidence interval [CI]: 0.992-1.001, p = 0.034) and size of tumor (HR: 0.863, 95% CI: 0.788-0.945, p = 0.002) were related to response rate. In multi-variate analysis, only size of tumor (HR: 0.878, 95% CI: 0.797-0.967, p = 0.009) were independently related to response rate. In uni-variate analysis under COXregression for survival analysis, gender, size of tumor, total bilirubin, albumin, Child-Pugh Score, ALBI (Albumin-

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Bilirubin) Grade and AFP level were associated with mortality. Multi-variate analysis found that albumin (HR: 0.528 95% CI: 0.375-0.544, p < 0.001) and AFP level (HR: 1.002, 95% CI: 1.000-1.004, p = 0.001) were associated with mortality. Conclusions: In HCC patients with MVPT, the overall response rate is 24%. Albumin and AFP level were associated with survival and tumor size was associated with response rate.

2021 消化系聯合學術演講年會

P.087

P.088

抑制 STAT3 可促進放射性降低 HBV 肝腫瘤細胞遷移 INHIBITION OF STAT3 ENHANCES IRRADIATION TO SUPPRESS TUMOR MIGRATION IN HBV-INFECTED HEPATOCELLULAR CARCINOMA CELLS

肝硬化合併反覆肝性腦病變患者結合使用 Rifaximin 和 Lactulose 的一年療效優於單獨使用 Lactulose ONE-YEAR EFFICACY OF RIFAXIMIN ADD-ON TO LACTULOSE IS SUPERIOR TO LACTULOSE ALONE IN CIRRHOTIC PATIENTS COMPLICATED WITH RECURRENT HEPATIC ENCEPHALOPATHY

程俊嘉謝宗霖何愛生 1 長庚大學放射醫學研究院 2 振興醫院胃腸肝膽科 Background: HBV infection exacerbates hepatocellular carcinoma (HCC) progression. Irradiation is a promising therapeutic against HCC in clinical practice. However, resistance against radiotherapy (radioresistance) still occurs. Aims: This study aimed to investigate the mechanism causing radioresistance in HBV-infected HCC and search for potential agents improving radiotherapy against HCC. Methods: HBV-infected Hep3B, PLC5 and non-HBVinfected HepG2 were selected and investigated in this study. Cell proliferation and migration were investigated for the cells treated with irradiation. Meanwhile, a drug panel was used to search for potential therapeutic agents improving irradiation efficacy against HBV-infected HCC cells. Results: Irradiation significantly inhibited cell proliferation and migration in HBV-infected Hep3B and PLC5. The anti-tumor effect was also observed in use of Vemlidy, a HBV suppressor. We found that PLC5 expressing CD44 presented higher radioresistance compared to Hep3B, possessing higher proliferative and migratory capacity. As expect, Hep3B-derived tumorspheres led to radioresistance compared to parental Hep3B. In addition, we discovered SB1317, BBI608, Halofuginone significantly inhibited cell viability of both Hep3B and PLC5, particularly BBI608 targeting STAT3 caused remarkable inhibition against cell migration and tumorsphere formation. Moreover, knockdown of STAT3 reduced HBV gene expression and inhibited cell proliferation and migration in PLC5 cells. The inhibition of STAT3 by BBI608 significantly enhanced radiation-mediated anti-tumor effect in PLC5 cells. Conclusions: This study found that irradiation reduced cell viability and migration in HBV-infected HCC cell lines. In addition, targeting STAT3 such as BBI608 significantly inhibited tumorsphere-derived radioresistance and improved irradiation-mediated anti-tumor effect.

1,2

張靖黃建豪簡榮南 1 林口長庚紀念醫院胃腸肝膽科系 2 長庚大學醫學院 Background: Hepatic encephalopathy (HE), a neuropsychiatric complication of decompensated cirrhosis, is associated with high mortality and high risk of recurrence. Rifaximin add-on to lactulose for 3 to 6 months is recommended for prevention of recurrent episodes of HE after the second episode. However, whether the combination for more than 6 months is superior to lactulose alone in the maintenance of HE remission is less evident. In addition, the use of rifaximin for HE remains a new approach in Taiwan. Aims: The aim of this study is to evaluate the oneyear efficacy of rifaximin add-on to lactulose for the maintenance of HE remission in Taiwan. Methods: We conducted a single-center retrospective cohort study to compare the long-term efficacy of rifaximin add-on to lactulose (group R+L) versus lactulose alone (group L, control group). Furthermore, the treatment efficacy before and after rifaximin add-on to lactulose was also analyzed. The primary endpoint of our study was time to first HE recurrence (Conn score ≥ 2). All patients were followed up every three months until death, and censored at one year if still alive. Results: 12 patients were enrolled for rifaximin add-on to lactulose (group R+L). Another 31 patients received lactulose alone (group L). Sex, comorbidity, ammonia level, and ascites grade were matched while age, HE grade, and MELD score were adjusted in the multivariable logistic regression model. Compared with group L, significant improvement in the maintenance of HE remission and decreased episodes and days of HE-related hospitalizations were demonstrated in group R+L. The serum ammonia levels were significantly lower at the 3rd and 6th month in group1. Concerning changes before and after rifaximin add-on in group R+L, MMSE, episodes of hospitalization,

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P.089 and variceal bleeding also improved at 6 and 12 months. Days of hospitalization, serum ammonia levels also improved at 6th month. Except for concern over price, no patients discontinued rifaximin due to adverse events or complications. Conclusions: The above results provide evidence for the one-year use of rifaximin add-on to lactulose in reducing HE recurrence and HE-related hospitalization for patients with decompensated cirrhosis in Taiwan.

非專一性 β 型腎上腺素阻斷劑可減少肝硬化合併靜脈曲張的病患發生肝功能代償不全、肝細胞癌及死亡 NON-SELECTIVE BETABLOCKER REDUCED HEPATIC DECOMPENSATION, OCCURRENCE OF HEPATOCELLULAR CARCINOMA AND MORTALITY IN CIRRHOTIC PATIENTS WITH VARICES 1,2

3,4

1,2

李沛璋譚家惠蘇建維高偉育黃怡翔 1,2 侯明志 1 臺北榮民總醫院胃腸肝膽科 2 國立陽明大學醫學系 3 衛生福利部國家中醫藥研究所 4 國立陽明大學醫務管理研究所 5 臺北醫學大學附設醫院胃腸肝膽科 6 國立陽明大學臨床醫學研究所 7 臺北榮民總醫院醫學研究部

1,2,6

6,7

吳肇卿

Background: Non-selective beta-blockers (NSBB) can reduce portal hypertensive complications in patients with cirrhosis; however, its effects on tumor prevention and survival benefit are still controversial. Aims: In this study, we aimed to investigate the effects of NSBB on hepatic decompensation, occurrence of hepatocellular carcinoma (HCC) and survival in cirrhotic patients. Methods: Assessing data from the Taiwan National Health Insurance Research Database, we identified 14,906 cirrhotic patients between 2003 and 2013. Among them, patients with antecedent malignancy, short follow-up period less than 90 days, early development of HCC or death within 180 days, prior prescription of NSBB before the diagnosis of cirrhosis and those who underwent liver transplantation were excluded. The NSBB users (continuous using propranolol, nadolol or carvedilol for more than 180 days) without experience of esophageal variceal ligation (EVL), and non-users who underwent EVL were adjusted by inverse probability of treatment weighting using the propensity score. The Kaplan-Meier method and Cox proportional hazards models stratified by cumulative defined daily dose of NSBB were employed for analyses. Results: The study cohort comprised 1,394 NSBB users and 455 non-users who underwent EVL. Patients using NSBB had significantly better survival than the counterpart (3-year and 5-year overall survival rate: 85.6% vs. 69.0% and 76.1% vs. 45.4%, respectively; p

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P.090 < 0.001). Besides, NSBB significantly reduced the risk of hepatic decompensation (adjusted hazard ratio [aHR]: 0.22, 95% confidence interval [CI]: 0.12–0.40, p < 0.001) with a marginal benefit according to the cumulative dose of NSBB. In addition, the NSBB user had a significant reduction of the risk of HCC occurrence (aHR: 0.38, 95% CI: 0.20–0.71, p = 0.003). Conclusions: Non-selective beta-blocker significantly improved the overall survival, reduced the risk of HCC development, and dose-dependently reduced the risk of hepatic decompensation in cirrhotic patients with varices.

運輸蛋白 Transporter ABCC2（MRP2）基因變異與藥物引起高血膽紅素之關聯性 THE ASSOCIATION OF TRANSPORTER ABCC2 (MRP2) GENETIC VARIATION AND DRUG-INDUCED HYPERBILIRUBINEMIA 1

1,2

曾少譽黃以信張天恩彭清霖黃怡翔 1 臺北榮民總醫院內科部胃腸肝膽科 2 國立陽明大學醫學院內科學

1,2

Background: Hyperbilirubinemia is a predictor of severe drug-induced liver injury (DILI). Hepatobiliary ATPbinding cassette (ABC) transporters play an important role in the transportation of many drugs and bilirubin, however little is known about these transporters and the risk of DILI. Aims: The aim of this study was to explore associations between genetic variations in important ABC transporters and susceptibility to DILI, with a particular focus on hyperbilirubinemia. Methods: A total of 200 patients with DILI and 200 healthy controls were enrolled as the training dataset. Another 106 patients with DILI were recruited as the validation dataset. They were genotyped for ABCB11 (BSEP) rs2287622, ABCB1 (MDR1) rs1128503, rs1045642, ABCB4 (MDR3) rs2230028, ABCC2 (MRP2) rs1885301, rs717620, rs2273697, rs3740066 and rs8187710 using polymerase chain reaction-based TaqMan genotyping assays. Results: There were no statistical differences in any of the nine ABC transporter single nucleotide polymorphisms between the DILI and control groups. However, in the DILI group, the patients with hyperbilirubinemia had a higher frequency of the ABCC2 rs717620 C/T and T/T genotypes than those without hyperbilirubinemia (44.2% vs. 20.2%, p = 0.001). After adjusting for other confounding factors, the ABCC2 rs717620 T variant was still associated with an increased risk of hyperbilirubinemia (adjusted OR: 3.83, 95% CI: 1.73-8.48, p = 0.001). This association was confirmed by the validation dataset (adjusted OR: 3.92, 95% CI: 1.42-10.81, p = 0.015). We also found that the mortality group had higher frequencies of the ABCC2 (MRP2) rs717620 C/T and T/T genotypes than the survival group (50.0% vs. 27.9%, p = 0.048). Conclusions: Carriage of the ABCC2 (MRP2) rs717620 T variant may increase the risk of hyperbilirubinemia and mortality in patients with DILI. Screening for this variant may help to prevent and mitigate drug-induced hyperbilirubinemia.

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P.091 使用世界衛生組織身心障礙評估量表（WHODAS 2.0）評估台灣慢性肝病病患之失能及殘障程度 FUNCTIONING AND DISABILITY OF ADULTS WITH CHRONIC LIVER DISEASE IN TAIWAN: AN ASSESSMENT BY USING THE WORLD HEALTH ORGANIZATION DISABILITY ASSESSMENT SCHEDULE-WHODAS 2.0 1

1,2

甘育安粟慧嫻張君照 1 臺北醫學大學附設醫院消化內科 2 臺北醫學大學醫學系消化內科學科 Background: Chronic liver disease (CLD), liver cirrhosis (LC), and its complications, such as hepatocellular carcinoma (HCC), accounts for a significant burden of disease worldwide. Several studies have focused on functional assessment and evaluating disabilities in patients with CLD. Though few studies have demonstrated the difference of clinical outcome and cognitive deterioration between alcoholic LC and non-alcoholic LC patients, the comparison of functional decline in other domain between different etiologies of CLD is not well understood. To date, there was no study used World Health Organization Disability Assessment Schedule (WHODAS 2.0) to evaluate disability in patient with CLD. Aims: Herein, in the present study, we investigated the functional and disability status of adults with CLD by using a nationwide database in Taiwan. Methods: Data were obtained from the Taiwan Data Bank of Persons with Disability (TDPD) between July 2012 and October 2018. During the study period, we selected 6085 participants who received a diagnosis of HCC, alcoholrelated liver disease, viral hepatitis B, viral hepatitis C or liver cirrhosis and whose disability primarily caused by liver-related ICF body structure categories (s560). To determine the influence of sex on liver-related disability, we compared the male and female patients. We also classified the patients according to the severity of impairment (into three groups, mild/moderate, severe and extreme) and the etiology of liver disease (HCC, alcohol-related liver disease and non-alcohol-related liver disease). Results: The data on 4897 subjects disabled by CLD (men = 3741; women = 1156) were obtained from the TDPD. Larger proportion of alcohol-related liver disease was observed in male subjects (23.7%, vs 8.7% in female subjects). The domain-specific and summary scores of

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WHODAS 2.0 were significantly higher in female subjects. Regarding the severity of impairments of the subjects, there were higher domain-specific and summary scores of WHODAS 2.0 among subjects with increased severity. As categorized by etiology (divided to 3 groups: HCC, alcohol-related and non-alcohol-related), the subjects in alcohol-related group were much younger compared with the other two groups (mean age: 49.9 years, vs. HCC and non-alcohol-related group, 60.8 and 55.8 years) and, were more predominantly male (89.9% vs. 76.2% and 72.1%). Subjects in non-alcohol-related group had higher score in domain 1 (cognition), while subjects in alcoholrelated group had lower score in domain 4 (getting along). Otherwise, there was no significant differences in other domain-specific and summary scores of WHODAS 2.0. Conclusions: There was no consistent difference of functioning between different etiologies of CLD observed in present study. The severity of structural impairment might play a greater role than etiology in influencing the degree of functional decline and disability.

2021 消化系聯合學術演講年會

P.092

P.093

肝硬化病人之菌血症預測指標 FUNGEMIA IN PATIENTS WITH LIVER CIRRHOSIS

用深度卷積神經網路篩選及追蹤黃疸 JAUNDICE SCREENING AND MONITORING BY DEEP CONVOLUTIONAL NEURAL NETWORK

1,2

張宇辰陳文誌鄭錦翔李沅融 1 高雄榮民總醫院胃腸肝膽科 2 國立陽明大學醫學系

Background: Patients with liver cirrhosis are at risk of bacterial infections with the deterioration of liver reserve. Multi-drug resistant bacterial infections had increased in these decades. Moreover, fungus infections usually indicate a worsening immune status and resulted in prolonged hospital stay and increased mortality. However, fungus/ fungemia is rarely investigated in patients with liver cirrhosis. Aims: The aim of this study is to evaluate the incidence and fungus infections/fungemia in patients with liver cirrhosis. Methods: The patients diagnosed with liver cirrhosis and complicated with bacteremia or fungemia between 2011 and 2020 were enrolled. The demographic characteristics and previous antibiotics records were collected. Baseline biochemistry data among these patients were compared, and we try to find the difference between the fungemia and bacteremia group, which divided into gram-positive group and gram-negative group, then compared the variable outcomes between each groups. Results: During the study period, 5292 patients with liver cirrhosis were enrolled. 520 patients were positive for blood culture sampling prior to antibiotics use. Forty patients had fungemia, 78 patients yielded CoNs, and another 5 patients developed anaerobic bacteremia. The 42-day mortality rate was about 83% in patients with fungemia and % in patients with bacteremia. Conclusions: Although the occurrence of fungemia was low in patients with liver cirrhosis, it can caused high mortality and multiple morbidity. The predictors of fungemia in patients with liver cirrhosis deserve further investigation.

2,3

2,3,5,6

李嘉瑋蘇東弘陳善青江佩穎高嘉宏 1 國立臺灣大學資訊工程學系暨研究所 2 台大醫院胃腸肝膽科 3 台大醫院肝炎研究中心 4 仁寶電腦公司 5 國立臺灣大學醫學院臨床醫學研究所 6 台大醫院醫學研究部

周承復

Background: Jaundice usually indicates severe hepatic or biliary diseases and prompt management is needed to reduce disease complications. The degree of jaundice correlates with the severity of illness, and jaundice is easily confirmed by checking serum total bilirubin (T-Bil) level. Practically, self-identification of jaundice is the key for its early detection, because a careful inspection may detect jaundice with a T-Bil > 2 - 3 mg/dL. However, selfmonitoring of jaundice is not easy for people without training, so a correct diagnosis is usually delayed. Aims: To investigate the capability of early jaundice detection by smartphones. Methods: We conducted a prospective study to enroll healthy volunteers and patients with jaundice. They all have recent data of T-Bil level as reference standard. The facial images were taken by smartphones with a color checker. These images were first normalized for brightness and color temperature, and followed by deep convolutional based facial landmark detection and scleral segmentation methods. The average sRGB color of sclera were measured, and the color was converted to CIE LAB. A Support Vector Machine model using the LAB color of patient’s both sclera was used to classify the presence of jaundice determined by a T-Bil 2 or 3 mg/dL, respectively. Overall, 80% of the images were used as the training set, and a 10-fold crossvalidation was applied in the training phase. The remaining 20% of the images were used as the testing set. Results: A total of 108 patients had been enrolled with 146 facial images being collected. There were 105, 10, and 31 scleral images with a T-Bil level <2, 2-3, and ≥3 mg/ dL, respectively. At the training phase, if the T-Bil level was set at 3 mg/dL, the area under the receiver operating characteristics (AUROC), sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) on validation set are 0.983, 0.883, 0.978, 0.933,

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P.094 and 0.968, respectively. If the T-Bil level set at 2 mg/dL, these values are 0.988, 0.867, 0.965, 0.925, and 0.959, respectively. At the testing phase, if the T-Bil level set at 3 mg/dL, the AUROC, sensitivity, specificity, PPV, and NPV on testing set are 0.979, 0.833, 0.958, 0.833, and 0.958, respectively. If the T-Bil level set at 2 mg/dL, these values are 0.986, 0.909, 0.947, 0.909, and 0.947, respectively. Conclusions: Our data demonstrate the capability of jaundice detection by smartphone captured images with good performance. This platform may be applied in the scenario of self-monitoring or telemedicine.

新診斷 2 型糖尿病患者化膿性肝膿瘍的風險：台灣全國性的世代研究 THE RISK OF PYOGENIC LIVER ABSCESS IN NEWLY DIAGNOSIS TYPE 2 DIABETIC PATIENTS: A NATIONWIDE, POPULATION-BASED COHORT STUDY 1,2

5,6

6,7

王子源林則成王美玲賴世偉彭成元林俊哲 6,7 6,7 1,6 黃冠棠林肇堂賴學洲 1 中國醫藥大學附設醫院內科部新陳代謝科 2 中國醫藥大學中醫學院中醫系 3 中國醫藥大學附設醫院健康資料中心 4 弘光科技大學護理學系 5 中國醫藥大學附設醫院家庭醫學部 6 中國醫藥大學中醫學院中醫系 7 中國醫藥大學附設醫內科部消化醫學中心

6,7

Background: To date, there is no comprehensive epidemiologic study for risk of pyogenic liver abscess (PLA) in newly diagnosed diabetic patients in the world. Aims: In the present study, we conducted a retrospective cohort study using National Health Insurance database to examine the association between newly diagnosed diabetes mellitus (DM) and PLA. Methods: The DM cohort was enrolled the newly diagnosed diabetic patient (ICD-9-CM 250) during from 2000 to 2009, with follow-up until 31 December 2011. We randomly frequency matched up to 4 controls. Adjusted hazard ratio of PLA associated with the DM cohort was compared to the comparison cohort. The cohort included 44728 patients with DM and 178912 patients without DM during the study period. Results: 166 patients in DM cohort were diagnosed as having PLA (incidence rate: 5.87 per 10000 person-years). The DM cohort had a 2.83-fold increased risk of PLA than the comparison cohort (HR = 2.83, 95% CI = 2.32-3.46). Furthermore, we also found that the adjusted hazard ratio of PLA risk in DM cohort was the highest in the youngest age groups, males and the first 2 years after the diagnosis of DM. The most frequent microorganism was Klebsiella pneumoniae in diabetes patients in our present study. In addition, we observed that PLA risk in patients with diabetes was increased in the individual with gallstone and cholecystitis. Compared to comparison cohort, the DM patients prescribing acarbose might be associated with a risk reduction of PLA, while glyburide have a significantly increased risk of PLA in diabetes patients. Conclusions: This study did find a statiscally significantly increased risk of PLA in a newly diagnostic diabetic patients and acarbose may have beneficial effect to reduce PLA.

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P.095 Obeticholic Acid 可以改善肝硬化併腹水小鼠的相關肝腎症候群 OBETICHOLIC ACID AMELIORATES CHRONIC HEPATORENAL SYNDROME IN ASCITIC CIRRHOTIC RATS 1

5,6

蔡友蓮劉志偉黃加璋黎子豪李癸汌楊盈盈 5,7 5 5 5 謝昀臻黃怡翔侯明志林漢傑 1 臺北榮民總醫院內科部 2 臺北榮民總醫院內科部風濕免疫科 3 臺北榮民總醫院內科部內分泌新陳代謝科 4 新光吳火獅紀念醫院內科部風濕免疫科 5 臺北榮民總醫院內科部胃腸肝膽科 6 臺北榮民總醫院教學部臨床技術訓練科 7 國立陽明大學臨床醫學研究所

stress (8-iso-PGF2α)-activated COX-TXA2 pathway, apoptosis, and tubular injury accompanied by a decrease in hyper-responsiveness to the vasoconstrictor 8-iso-PGF1α in perfused kidneys. In vitro experiments revealed that 8-iso-PGF1α induced oxidative stress, release of reactive oxygen species, and cell apoptosis, which were reversed by concomitant incubation with the FXR agonist. Conclusions: Through the inhibition of renal 8-iso-PGF2α production and the downregulation of the COX-TXA2 pathway, our study suggests that chronic OCA treatment can ameliorate the chronic HRS in ascitic cirrhotic rats. Thus, OCA is an agent with anti-oxidative stress, antivasoconstrictive, anti-apoptotic properties which benefit ascitic, cirrhotic rats with systemic, hepatic, and renal abnormalities.

Background: Advanced cirrhotic patients with ascites often suffer from chronic hepatorenal syndrome (HRS), thus requiring liver and renal transplantation, due to a high recurrence rate after the withdrawal of standard treatment of albumin plus vasoconstrictor. The systemic and hepatic benefits of normalization of hepatic Foresaid X receptor (FXR) expression and oxidative stress have been reported in patients with cirrhosis. In cirrhosis-related chronic HRS, increased renal oxidative stress (such as 8-iso-PGF2α) and upregulated cyclooxygenase-thromboxane A2 [COXTXA2] pathway are the main pathogenic factors for persistent intrarenal vasoconstriction and renal damage. Aims: This study explores the potential of chronic treatment with the FXR agonist obeticholic acid (OCA), which inhibits oxidative stress-related pathogenesis, in ascitic cirrhotic rats with chronic HRS developed 6 weeks after chronic bile duct ligation (BDL). Methods: Systemic, splanchnic, and renal hemodynamics; and pathogenic cascades were measured in ascitic BDL and sham rats receiving 2-weeks of either vehicle (BDL and sham groups) or FXR agonist (OCA, sham-OCA and BDL-OCA groups) treatments. Furthermore, various measurements were performed in rat kidneys and NRK52E cells, a rat kidney tubular epithelial cell line. Results: Chronic OCA treatment significantly normalized cardiac output, glomerular filtration rate, urine output, renal blood flow; decreased ascites, renal vascular resistance, serum creatinine; suppressed plasma volume expansion, and the release of renal tubular damage markers, including urinary neutrophil gelatinase-associated lipocalin (uNGAL) and kidney injury moleculae-1 (uKim-1) in BDL-OCA rats. In the BDL group, inhibition of the renal oxidative

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第二部分：消化道及膽胰疾病 P.096

P.097

上消化道內視鏡檢查：口、咽、喉常見的異物與非預期物體 FOREIGN BODIES AND UNEXPECTED OBJECTS ENCOUNTERED DURING UGI ENDOSCOPY WITH ORAL-PHARYNXLARYNX EXAMINATION

應用各國間死亡對發病比之改變評估胃癌處理進展 USING THE CHANGE OF MORTALITYTO-INCIDENCE RATIO TO EVALUATE GASTRIC CANCER MANAGEMENT IMPROVEMENT

周益霆楊志偉陳保中黃天祐許剛張維國 1 國防醫學院三軍總醫院胃腸科 2 國防醫學院三軍總醫院牙科部

Background: Foreign bodies and unexpected objects can be accidentally identified in the oral cavity during upper gastrointestinal (UGI) endoscopy. Aims: We aimed to describe the types, locations, symptoms, and interventions of foreign bodies or unexpected objects during routine UGI endoscopy with oral-pharynx-larynx examination. Methods: Patients who underwent UGI endoscopy with oral-pharynx-larynx examination were analyzed. Foreign bodies or unexpected objects were categorized into removable dentures, tongue piercing, medical devices, intra-oral hair, and tenacious mucus plugs. Patients’ demographic characteristics, clinical symptoms, and the foreign bodies or unexpected objects were recorded. Results: Among the 2,567 patients, 53 (2.0%) had foreign bodies or unexpected objects in the oral cavity, pharynx, and larynx, with tenacious mucus plugs (n = 29) being the most common, followed by removable dentures (n = 15), nasogastric tube coiling (n = 3), intra-oral hair (n = 3), tongue piercing (n = 2), and suction tube fragment (n = 1). Removable dentures, tongue piercing, nasogastric tube coiling, and suction tube fragment required immediate removal. Intra-oral hair in the pharynx can be removed by forceps and hair follicles can be destroyed. Tenacious mucus plugs required immediate removal before UGI endoscopy. Conclusions: Knowledge and procedural skill are prerequisites for UGI endoscopy with oral-pharynx-larynx examination.

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1,2

1,4

楊子緯汪奇志洪瑋成宋文瑋蔡明璋 1 中山醫學大學醫學系 2 中山醫學大學附設醫院肝膽腸胃科 3 中山醫學大學附設醫院醫學教育部 4 中山醫學大學附設醫院泌尿科

1,2

Background: The survival of gastric cancer improved greatly by the screen and surveillance program and the introduction of multidisciplinary management in recent years. The mortality-to-incidence ratio (MIR) is widely used to evaluate the efficacy of cancer management outcomes for individual countries. However, the association between the health expenditure and change of MIR is unknown. Aims: To analyze the association between the level of economic development, health expenditure, MIRs of gastric cancer in different countries in 2012 and 2018. Methods: We conducted an analysis using the GLOBOCAN 2012 and 2018 database of gastric cancer incidence and mortality statistics of 59 countries. The association among human development index (HDI), current health expenditure (CHE), CHE as percentage of GDP (CHE/GDP, %), MIR, and the change of MIR between 2012 and 2018 (δMIR) were evaluated. Results: Among regions, Asia had the highest numbers of new gastric cancer cases (769,728), gastric cancer-related deaths (584,375), cumulative risk of incidence (1.67), and mortality (1.23). Japan had the highest age-standardized ratio (ASR) for gastric cancer incidence and the lowest MIR of 0.17 for gastric cancer. To analyze the crude rate of mortality, only CHE per capita showed a negative association (correlation coefficient, CC = -0.262, P = 0.045). There was no association between health expenditure and the crude rate of incidence. MIR was negatively associated with HDI, CHE per capita, and CHE/GDP % (CC, -0.741, -0.764, and -0.672, all P < 0.001). In addition, δMIR from 2012 to 2018 was positively associated with CHE/GDP (CC = 0.292, P = 0.025). Conclusions: Increased HDI index, CHE per capita, and CHE/GDP is associated with better gastric cancer outcome. The δMIR can be an indicator to evaluate the improvement of cancer management outcomes over time.

2021 消化系聯合學術演講年會

P.098

P.099

以內視鏡氣球擴張術治療胃繞道術後吻合處狹窄 ENDOSCOPIC BALLOON DILATION FOR GASTROJEJUNAL ANASTOMOTIC STRICTURE AFTER ROUX-EN-Y GASTRIC BYPASS: A CASE SERIES

台灣東部地區醫院 14 天反轉式混合療法與 14 天三合一療法於一線治療幽門螺旋桿菌感染的比較 FOURTEEN-DAY REVERSE HYBRID THERAPY VERSUS 14-DAY TRIPLE THERAPY FOR FIRST-LINE TREATMENT OF HELICOBACTER PYLORI INFECTION IN A DISTRICT HOSPITAL IN EASTERN TAIWAN

吳翊綝陳文旭陳溢松蔡英楠戴啟明 1 義大醫院胃腸肝膽科 2 義大癌治療醫院胃腸肝膽科

Background: Roux-en-Y gastric bypass (RYGB) is an effective bariatric procedure. Gastrojejunal (GJ) anastomotic stricture is one of the most common complications after RYGB. Aims: We evaluated the efficacy and complications of endoscopic balloon dilation in the management of the GJ anastomotic stricture after RYGB. Methods: Patients who underwent balloon dilatation for GJ anastomotic stricture secondary to RYGB between March 2009 and April 2013 in E-Da hospital were retrospectively reviewed. A small balloon size (8 mm) was routinely chosen initially and increased balloon size gradually. Dilation was stopped if the patients felt abdominal pain or up to 15 mm. Results: Thirteen patients (nine men and four women) with a median age of 26 years (range 20–42 years) and a median body mass index of 41.5 kg/m2 (range 35.3–65.4 kg/m2) were enrolled. Anastomotic size ranged from 1mm to 4mm. Median interval between surgery and first dilation was 43 days (range 20–112 days). Nine patients (69.2%) required only one dilation, three (23.1%) required two dilations, and one (7.7%) required three dilations. Seven patients (53.8%) had anastomotic ulcers. Two patients had perforation and were treated conservatively. Twelve patients (92.3%) were successfully treated by balloon dilation. One patient was found to have total obstruction 4 months after the first dilation and received operation. Conclusions: Our study suggests that endoscopic balloon dilation is effective in the management of GJ anastomotic stricture after RYGB and most patients response to one dilation session. Although perforation occurred, it can be treated conservatively in our series.

吳大中鄧志敦馬堅毅 1 台東基督教醫院肝膽腸胃內科 2 台東基督教醫院檢驗科 3 台東基督教醫院腎臟內科 Background: Helicobacter pylori (H. pylori) infections are critical factors in chronic gastritis, peptic ulcer disease, gastric cancer, and gastric mucosa-associated lymphoid tissue lymphoma. According to the consensus statement of the Gastroenterological Society of Taiwan, in areas of low clarithromycin resistance (≤15%), a 14day clarithromycin-based therapy (hybrid, sequential, concomitant, or triple therapy) is the first-line treatment of choice; 14-day bismuth quadruple therapy is a suitable alternative to first-line therapy. Hu et al. reported a 13.5% resistance to clarithromycin in eastern Taiwan. Lin and Hsu et al reported that reverse hybrid therapy exhibited high eradication rates of 96.4% through intention-to-treat (ITT) analysis and 96.6% through preprotocol (PP) analysis. However, whether 14-day reverse hybrid therapy can achieve a high eradication rate in eastern Taiwan remains unclear. Aims: The aim of this study was to compare the efficacy of 14-day reverse hybrid therapy and 14-day triple therapy as first-line treatment for H. pylori infection. Methods: A total of 143 patients with H. pylori infection between June 2017 and May 2020 were retrospectively enrolled from a district hospital in eastern Taiwan. Diagnoses of H. pylori infection were based on a positive result from a rapid urease test, histology, a stool antigen test, or a urea breath test (UBT). All patients were recommended to undergo endoscopy before treatment. Patients received either 14-day reverse hybrid therapy (lansoprazole 30 mg plus amoxicillin 1 g twice daily for 14 days and clarithromycin 500 mg plus metronidazole 500 mg twice daily for the first 7 days) or 14-day triple therapy (lansoprazole 30 mg plus amoxicillin 1 g plus clarithromycin 500 mg twice daily for 14 days). Patients

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P.100 with previous eradication treatment, a history of antibiotic use within 4 weeks, and allergies to antibiotics were excluded, as were patients who were pregnant. Eradication was confirmed by a negative UBT. It was performed 4 or more weeks after completion of H. pylori therapy. Proton pump inhibitor therapy should be withheld 2 weeks prior to testing. Results: A total of 107 patients with H. pylori infection received 14-day reverse hybrid therapy, and 36 patients received 14-day triple therapy. The two therapies exhibited comparable eradication rates according to ITT (79.4% vs 80.6%, P = 0.885) and PP analysis (83.3% vs 82.9%, P = 0.948). No difference in adverse events (9.3% vs 8.3%, P = 0.866) or drug compliance (95.3% vs 97.2%, P = 1.000) was detected. Conclusions: In this study conducted in eastern Taiwan, both 14-day reverse hybrid therapy and 14-day triple therapy achieved poor eradication as first-line treatments for H. pylori infection.

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影響洛杉磯分類 A/B 級糜爛性食道炎患者症狀復發之危險因子 RISK FACTORS FOR SYMPTOM RELAPSE IN PATIENTS WITH LOS ANGELES GRADE A/B EROSIVE ESOPHAGITIS 施長碧吳登強蔡成枝高崧碩蔡坤峰郭立夫 1 1 1 1 吳奕霆湯昇曄黃文威許秉毅 1 臺南市立安南醫院內科部消化內科 2 高雄醫學大學附設醫院內科部胃腸內科 3 高雄長庚紀念醫院內科部胃腸肝膽科 4 高雄榮民總醫院內科部胃腸肝膽科 1

Background: Recurrence of reflux symptoms following discontinuing proton pump inhibitor therapy is a common problem in the treatment of gastroesophageal reflux disease. Aims: (1) to examine the rate of symptom relapse following 8-week proton pump inhibitor therapy in patients with mild erosive esophagitis (Los Angeles grade A/B erosive esophagitis) and (2) to search the risk factors predicting symptom relapse in the treatment of mild erosive esophagitis. Methods: Patients with Los Angeles Grade A/B erosive esophagitis who received esomeprazole therapy (40 mg qd) for 8 weeks and had complete symptom resolution at the end of treatment were recruited. They didn’t receive proton pump inhibitor therapy following initial treatment, and their reflux symptoms were regularly followed up for 3 months. The 3-month cumulative rate of symptom relapse was assessed, and the risk factors predicting symptom relapse were analyzed by multivariate analysis. Results: In total, 175 patients with Los Angeles Grade A/ B erosive esophagitis who had complete symptom resolution following 8-week esomeprazole therapy were recruited for the study. After discontinuing proton pump inhibitor therapy, 104 patients (59.4%) developed symptom relapse within 3 months. Univariate analysis showed male gender, smoking, alcohol consumption, spy food consumption, and middle-type insomnia were associated with symptom response (P = 0.017, 0.007, 0.017, 0.013, and 0.019, respectively). Multivariate analysis with stepwise logistic regression revealed that only male gender (95% confidence interval [CI]: 1.17 – 5.79), smoking (95% CI: 3.07 – 40.36), alcohol constipation (95% CI: 0.15 – 0.95) and middle-type insomnia (95% CI: 1.26 – 5.79) were independent factors predicting symptom relapse with odds ratios of 2.60, 11.13, 0.38, and 2.70, respectively. Conclusions: The 3-month symptom relapse rate in patients with Los Angeles grade A/B erosive esophagitis following 8-week esomeprazole therapy is 59.4%. The independent factors related to symptom relapse include male gender, smoking, alcohol constipation and middle-type insomnia.

2021 消化系聯合學術演講年會

P.101

P.102

腫瘤微環境中 HOXA9-IGFBP2 Axis 參與胃癌之進展 HOXA9-IGFBP2 AXIS PARTICIPATES IN THE PROGRESSION OF GASTRIC CANCER IN THE TUMOR MICROENVIRONMENT

過敏性鼻炎是胃食道逆流的風險之一 ALLERGIC RHINITIS IS ONE OF RISK FACTORS OF GASTRO-ESOPHAGEAL REFLUX DISEASE

1,2

2,4

1,2,4

朱能生陳逸琪劉忠榮郭富珍許文鴻郭昭宏 1 高雄市立小港醫院內科 2 高雄醫學大學附設中和紀念醫院胃腸內科 3 義守大學義大醫院學士後醫學系 4 高雄醫學大學醫學系

Background: Gastric cancer is one of the most common cancers worldwide, and is also the second leading cause of cancer-related mortality. The poor prognosis of gastric cancer may be partly attributed to the complicated molecular networks operating the aggressiveness of gastric cancer. Aims: Although a large body of studies has revealed the deregulation of certain genes in gastric carcinogenesis, the molecular mechanisms behind gastric tumor development are not yet fully understood. Methods: We explored the role of HOXA9/IGFBP2 by analyzing HOXA9 protein expression in human gastric cancer tissues and transfecting HOXA9-overexpressing vector into human AGS cells. We further co-cultured human gastric cancer cells and human mesenchymal stem cells (HBMMSCs), and then observed these cells interaction by measuring the motility of human gastric cancer cells and HBMMSCs in the co-culture system. Results: In the present study, we found that IGFBP2 is upregulated by HOXA9 in human gastric cancer tissues. Human gastric cancer cells recruited more HBMMSCs through HOXA9/IGFBP2 pathway. Recruited HBMMSCs then enhanced cell motility in human gastric cancer cells. Conclusions: Human gastric cancer cells with high activity of HOXA9/IGFBP2 signaling pathway recruited more HBMMSCs. HBMMSCs then enhanced the motility of human gastric cancer cells.

1,2

謝易倫王耀廣謝孟書吳政毅吳登強郭昭宏 1 高雄醫學大學附設中和紀念醫院胃腸內科 2 高雄醫學大學醫學系 3 高雄市立小港醫院內科

1,2,3

Background: Gastroesophageal reflux disease (GERD) can cause several upper airway symptoms and alter the physiology of nasopharyngeal mucosa, while upper airway diseases in turn might also exacerbate GERD symptoms. For a long time, asthma was considered a risk factor of GERD in the literature. Asthma and allergic rhinitis (AR) are usually identified as united airway disease according to similar epidemiology and pathophysiology; however, the association between AR and GERD is less elucidated. Aims: We aimed to evaluate whether AR would increase the development of GERD. Methods: Patients diagnosed as AR were identified from the National Health Insurance Research Database between January 1, 2000 and December 31, 2005 without prior history of gastroesophageal reflux disease. The outcome of interest was new-onset GERD. Cox regression models were applied to calculate the hazard ratio (HR) of GERD. Results: We analyzed the data of 193,810 AR patients aged 18 years or older and being free of AR at baseline. The AR cohort (n = 96,905) had a significantly increased risk of GERD over a non-AR cohort (n = 96,905) (adjusted HR (aHR) 1.94; 95% CI = 1.88-1.99, p < 0.001). Conclusions: AR may have stronger correlation with GERD than does asthma, although asthma might increase GERD risk by means of certain pathways shared with AR.

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P.103

P.104

內視鏡胃瘜肉冷切除與熱切除皆為安全的處理方式：一個高雄醫學中心的經驗 ENDOSCOPIC COLD AND HOT SNARE POLYPECTOMY ARE BOTH SAFE FOR REMOVING GASTRIC POLYPS WITHOUT SIGNIFICANT ADVERSE EVENT: A SINGLE MEDICAL CENTER REPORT IN KAOHISUNG

對於高風險性消化性潰瘍出血在釋腎上腺素注射術後，比較併用氬氣電漿凝固術或止血夾兩者之止血療效 RANDOMIZED CONTROLLED TRIAL OF ARGON PLASMA COAGULATION PLUS DILUTED EPINEPHRINE INJECTION VERSUS HEMOCLIPPING PLUS DILUTED EPINEPHRINE INJECTION FOR TREATMENT OF HIGH-RISK PEPTIC ULCER BLEEDING: AN INTERIM REPORT

馬德齡楊世正吳鎮琨梁志明盧龍生胡銘倫周業彬邱逸群吳耿良戴維震高雄長庚紀念醫院胃腸肝膽內科

Background: Endoscopic polypectomy has become standard in the management of most polyps in the gastrointestinal tract. However, bleeding is the most common adverse event (AE) of snare polypectomy. Polypectomy with a cold snare (CSP) has been increasingly utilized in recent years, but further evidence is required to establish its safety of gastric polypectomy. Aims: The aim of this study was to compare intraprocedure and postprocedure AEs in patients who underwent CSP versus hot snare polypectomy (HSP) of gastric polyps. Methods: Electronic medical records and endoscopy reports of all patients who underwent gastric polypectomy for Paris Is or Ip gastric polyps between December 2019 and December 2020 at a tertiary center were retrospectively reviewed. Data on patient demographics, polyp characteristics, method of polypectomy, and intraprocedural and postpolypectomy AEs were collected. Results: A total of 78 patients (mean age 59.5, 30.8% male) had 115 polyps removed. Histologically most were FDPs 60/115 (52.2%) and the rest were reported as either hyperplastic polyps 39/115 (33.9%), or non-specific (inflammatory changes) in 16/115 (13.9%). Of these, 92 polyps were removed from 58 patients by HSP, compared to 23 polyps that were removed from 20 patients by CSP. The mean polyp size was 11.3 mm in the HSP group and 7 mm in the CSP group (P < 0.001). 10 patients (17.2%) from HSP group and 3 (15%) from CSP group presented with intraprocedural bleeding that required treatment (P = 0.817). There was neither dalayed postpolypectomy bleeding nor perforation, death in this series. In multivariate logistic regression, we did not find any independent risk factor of immediate postpolypectomy bleeding. Conclusions: In this study, both HSP and CSP techniques were not associated with serious postpolypectomy adverse events and appeared to be effectively used for gastric polypectomy. A prospective multicenter study has been commenced to verify these findings and to assess the efficacy of CSP for the complete resection of gastric polyps.

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王惠民彭南靖蔡峯偉陳文誌 1 高雄榮民總醫院胃腸肝膽科 2 高雄榮民總醫院核醫部

Background: Endoscopic treatment is recommended for initial hemostasis in nonvariceal upper gastrointestinal bleeding. Many endoscopic devices have been demonstrated to be effective in the hemostasis of bleeding ulcers. However, the additional hemostatic efficacy of argon plasma coagulation (APC) after endoscopic injection therapy has not been widely investigated. Aims: The study aim is to compare APC plus diluted epinephrine injection with clipping plus diluted epinephrine injection in treating high-risk peptic ulcer bleeding. Methods: From Jan. 2019 to Oct 2020, consecutive patients with high-risk bleeding ulcers, characterized by active bleeding, non-bleeding visible vessels and adherent clots, were admitted to our hospital. They prospectively randomly underwent either APC therapy plus diluted epinephrine injection or hemoclipping plus diluted epinephrine injection. Pantoprazole infusion was conducted during the fasting period after endoscopy and orally for 8 weeks to encourage ulcer healing. Episodes of rebleeding were retreated with endoscopic combination therapy. Patients who did not benefit from retreatment underwent emergency surgery. The data were expressed as mean±SD. Quantitative variables were compared according to Student t-test, and qualitative variables were compared using the Chi-square test and Fisher’s exact test when appropriate to compare the location of the bleeding lesions, initial hemostasis, rebleeding, emergency surgery and mortality of both treatment groups. The Cox regression model was employed to measure risk factors for the development of failure of initial hemostasis, rebleeding and mortality on univariate and/or multivariate analysis. All hypothesis tests were performed against a two-sided alternative,

2021 消化系聯合學術演講年會

P.105 where appropriate. A p < 0.05 was viewed as statistically significant. Analyses were undertaken using SPSS software (SAS, SPSS Inc., Chicago, Ill., USA). Results: In all, 85 eligible patients were analyzed. Hemostatic efficacy in 41 patients treated with APC plus diluted epinephrine injection (APC group) was prospectively compared with 44 patients treated with hemoclipping plus diluted epinephrine injection (Hemoclip group). The two treatment groups were similar with respect to all baseline characteristics. Initial hemostasis was accomplished in 40 patients treated with APC combined with diluted epinephrine injection therapy, and 43 patients with hemoclipping plus diluted epinephrine injection therapy (97.6% vs. 97.7%, P = 1.000). Bleeding recurred in 2 patients in the APC group, and in 6 patients in the Hemoclip group (4.9% vs. 13.6%, P = 0.268). The transfusion requirements is lesser in APC group than Hemoclip group (2.0 ± 1.8 vs. 5.1 ± 6.1 units, P = 0.002). No significant differences were observed between the 2 groups in hospital stay, surgery/arterial embolization and mortality. Conclusions: Endoscopic therapy with APC plus diluted epinephrine injection is similarly effective as hemoclipping plus diluted epinephrine injection for preventing rebleeding in the treatment of high-risk bleeding ulcers. Both treatment methods also have similar safety during therapeutic endoscopy. Nevertheless, APC group requires less blood transfusion requirements, compared with Hemoclip group.

內視鏡醫師經由傳統白光內視鏡影像診斷幽門螺旋桿菌感染之準確率 PERFORMANCE OF ENDOSCOPISTS IN THE DIAGNOSIS OF H. PYLORI INFECTION BY IMAGE FINDINGS OF CONVENTIONAL WHITE LIGHT ENDOSCOPY 1

吳奕霆石志安簡泰隆沈昌平郭立夫湯昇曄 1 2 1 1 1 3 黃文威鄭一中吳坤輝施長碧蔡坤峰陳彥樺 1 許秉毅 1 臺南市立安南醫院消化內科 2 安泰醫院內科部胃腸肝膽科 3 高雄榮民總醫院內科部胃腸肝膽科 Background: The endoscopic appearance of the gastric mucosa may change as a consequence of H. pylori infection, providing useful diagnostic information to the endoscopist. Several studies demonstrated that the judgement of H. pylori infection by the conventional white light endoscopy could be based on the presence of either diffuse redness, rugal hypertrophy, or thick and whitish mucus. Aims: To investigate the performance of endoscopists in the diagnosis of H. pylori infection by the images of conventional white light endoscopy. Methods: Upper gastrointestinal image sets from 200 consecutive subjects receiving of conventional white light endoscopy with confirmation of H. pylori status by rapid urease test were reviewed and retrieved. The images from the subjects with any of the following criteria are excluded: (a) previous eradication therapy, and (b) previous gastrectomy. Seven endoscopists were invited to read the endoscopic images and recorded their impression of H. pylori status according to the image findings of endoscopy. The performances of the endoscopists in the diagnosis of H. pylori infection by image findings of conventional white light endoscopy were assessed and compared. Results: The endoscopic images from 104 subjects with H. pylori infection and 96 subjects without H. pylori infection were retrieved for the study. The sensitivity of diagnosis of H. pylori infection according to endoscopic findings of the seven endoscopists ranged from 33.7% to 74.0% (P < 0.001; mean: 54.3%). The specificity of diagnosis of H. pylori infection by endoscopic images ranged from 67.7% to 97.9% (P < 0.001; mean: 82.7%). Overall, the accuracy of diagnosis of H. pylori infection ranged from 55.5% to 76.0% (P < 0.001; mean: 67.9%).

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P.106 Conclusions: The mean accuracy of diagnosis of H. pylori infection by the images of conventional white light endoscopy in this study is 68%. Significant differences in the diagnostic performances of endoscopists on the assessment of H. pylori status by endoscopic images exist. Whether artificial intelligence with convolutional neural network for analysis of endoscopic images can improve diagnostic accuracy and replace current diagnostic modalities for H. pylori infection merit further investigation.

內視鏡黏膜下剝離術治療早期食道腫瘤的臨床療效：南台灣單一中心回溯性研究 CLINICAL OUTCOMES OF ENDOSCOPIC SUBMUCOSAL DISSECTION FOR EARLY ESOPHAGEAL NEOPLASMS: A SINGLECENTER EXPERIENCE IN SOUTH TAIWAN 1

楊適宇姚志謙李育麒盧龍生周業彬胡銘倫 1,2 1,2 邱逸群戴維震 1 高雄長庚紀念醫院胃腸肝膽科系 2 長庚大學醫學院

Background: Endoscopic submucosal dissection (ESD) is accepted as the major treatment modality for early gastrointestinal neoplasm including the esophagus. It is an advanced endoscopic procedure and poses technically difficult and risky. Aims: We aimed to analyze the clinical outcomes of ESD for early esophageal neoplasms in our hospital, retrospectively. Methods: From June 2011 to October 2020, 80 patients with the diagnosis of early esophageal neoplasm and received ESD procedure are enrolled in this study. All patients underwent chromoendoscopy with narrow-band imaging and Lugol staining before ESD for peripheral margin detection. Endoscopic ultrasound was also performed for invasion depth evaluation before ESD. Results: A total of 101 lesions in 80 patients were enrolled and 3 patients with 3 lesions were loss follow-up. 71 patients were men (92.2%). The mean age was 58.1 ± 9.3 years. The mean size of tumors was 13.2 ± 10.6 cm2. 98 lesions in 77 patients were treated by ESD. En bloc resection rate was 99% (97/98). The mean operation time was 89.7 ± 81.3 minutes. There were 25 ESD-related complications, including 3 with intra-procedure perforation and 22 with post-ESD stricture. 7 patients received additional esophagectomy due to deep submucosal invasion. During a mean of 25.4 months of follow-up, 1 local recurrence (1%) and 6 metachronous recurrences (6%) were noted. There was no procedure-related mortality. Tumor size (≥ 10 cm2) (p = 0.002) and circumference of the lumen (≥ 3/4) (p < 0.001) were associated with post-ESD stricture. Conclusions: ESD is a successful and relatively safe treatment for early esophageal neoplasms. Larger tumor size (≥ 10 cm2) and circumference of the lumen (≥ 3/4) should be aware of post-ESD stricture.

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P.107

P.108

針對早期胃部腫瘤執行內視鏡黏膜下剝離術分析：單一醫學中心經驗分享 ANALYSIS OF ENDOSCOPIC SUBMUCOSAL DISSECTION FOR EARLY GASTRIC NEOPLASM: A SINGLE CENTER EXPERIENCE

食道顆粒細胞瘤的診斷與治療：一醫學中心之經驗 DIAGNOSIS AND TREATMENT OF ESOPHAGEAL GRANULAR CELL TUMORS: A SINGLE MEDICAL CENTER EXPERIENCE

方信為姚志謙李育麒盧龍生周業彬胡銘倫 1,2 1,2 邱逸群戴維震 1 高雄長庚紀念醫院胃腸肝膽科系 2 長庚大學醫學院

Background: Endoscopic submucosal dissection (ESD) has developed as a curative treatment for patients with early gastric neoplasm. However, the complexity of ESD varies with the characteristics of the lesion. Aims: This study is conducted to investigate the complexity of ESD for early gastric neoplasm. Methods: A total of 54 patients diagnosed with early gastric neoplasm are enrolled in this study. A total of 60 lesions are undergone ESD between August 2010 to October 2020 at Kaohsiung Chang Gung Memorial Hospital. Results: Among the 54 patients and 60 gastric lesions, 95% achieve En bloc resection and 4% develop local recurrence during the follow-up, respectively. 6 cases have procedurerelated complications (10%), including 5 delayed bleeding needs endoscopic hemostasis and 1 Mallory-Weiss tear. Based on the pathology reveals submucosal layer invasion, 2 cases receive additional surgical intervention. The 1-way analysis of variance for mean time and mean speed (cm2/ mins) of ESD identifies decreasing time (p < 0.001) and increasing speed (p = 0.003) during the 11-year period. Further independent t-test reveals lesion size more than 10 cm2 have significance on ESD speed (p = 0.015), while the Paris classification II influences the procedure time (p = 0.021) and speed (p = 0.002) both. The endoscopic ultrasound (EUS) exam before ESD has a good prediction in the mucosal lesion (Sensitivity = 0.83); however, a poor detection in submucosal invasion (Specificity = 0.33), separately. Conclusions: ESD is an effective treatment of early gastric neoplasm with a 95% En bloc resection rate. The EUS exam has a good prediction in mucosal gastric neoplasm.

1,2

曹國良黃柏儒黃文信彭成元林俊哲林肇堂 1 中國醫藥大學附設醫院內科部 2 中國醫藥大學附設醫院消化醫學中心

Background: Granular cell tumor (GCT) is predominantly located in the oral cavity, skin, and breast tissues and less common in the GI tract. Most gastrointestinal GCTs are found in the esophagus and are regarded as benign neoplasms. At present, the gold standard for its diagnosis is based on histopathologic examination of endoscopic biopsies. However, because of its rarity, the management of esophageal GCT is still controversial. Aims: The aim of this study is to present the clinical manifestations, EUS images, endoscopic treatment and clinical outcome of our patients with esophageal GCTs. Methods: The patients with pathologically confirmed esophageal GCTs between 2004 and 2020 in a medical center were studied. All patients’ characteristics, presentation, endoscopic and EUS appearance, treatment and clinical outcome were analyzed. Results: Of 11 patients with pathologically confirmed esophageal GCTs, the mean age was 46.2 years old (range from 30 to 62) at time of diagnosis. Gender differences showed female is predominant (7/11, 64%). The pathologic reports were almost benign except one malignant GCT (1/11, 9%). Most patients were asymptomatic or presented with non-specific symptoms. Only the patient with malignant GCT had progressive dysphagia. The GCTs were located in the upper third (3), middle third (4) and lower third (4), respectively. EUS was performed in 7 patients. The images of EUS were variable, including hypoechoic (n=4), hypoechoic to hyperechoic (n=3), homogenous (n=3), heterogenous (n=4), and distinct-edged tumors restricted to deep mucosal and submucosal layers (n=5). Two cases with tumor invasion into muscular and even adventitia layers. Endoscopic ultrasonography was valuable to assess the tumor size, location, and depth of invasion. The size of the benign tumors ranged from 4 to 7.5 mm in diameter and the malignant tumor showed more than 10 cm in size. Four patients with benign esophageal GCTs received endoscopic resection including two endoscopic

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P.109 mucosal resection and two endoscopic submucosal dissection. One patient with malignant GCT received chemotherapy and esophageal stenting because of lumen stricture. The other six patients received follow up. The clinical outcome of our patients with benign esophageal GCTs has good prognosis. One patient with malignant GCT and multiple organs metastasis (liver, bone, back skin, and lung) died 6 months later. Conclusions: Patients with esophageal GCTs are almost asymptomatic and are incidentally found during endoscopic examination. The overwhelming majority of esophageal GCTs are benign. However, malignant change may occur. Therefore, endoscopic follow-up is necessary, and endoscopic tumor resection should be considered.

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食道胃接合處阻塞之惡性腫瘤病人接受金屬支架置放之預後 OUTCOMES IN PATIENTS WITH MALIGNANT ESOPHAGO-GASTRIC JUNCTION OBSTRUCTION RECEIVING METALLIC STENT PLACEMENT 潘鈺聆吳佩珊李癸汌黃怡翔侯明志臺北榮民總醫院內科部肝膽腸胃科 Background: The malignant obstruction at esophagogastric junction is uncommon in patients with gastric cancer, esophageal cancer or other cancer with gastric metastasis. These patients are often inoperable in the TNM stages III or IV and have poor outcomes. Metallic stent insertion is one of the options of palliative treatment to improve life quality in these patients. However, the outcomes in these patients is unclear to date. Aims: This study aimed to investigate the outcomes of the patients receiving metallic stent insertion for esophagogastric junction obstruction. Methods: Forty consecutive patients with malignant inoperable esophagogastric junction obstruction receiving metallic stent placement in Taipei Veterans General Hospital from January 2008 to August 2020 were enrolled and analyzed retrospectively. The outcomes, complications, durations of metallic stent patency and survival were analyzed. Among them, 29 (72.5%) had gastric cancer, 8 (20%) had esophageal cancer, and 3 (7.5%) had other cancers with gastric metastasis. Thirty-three (82.5%) patients were in stage IV, 6 (15%) were in stage III, and 1 (2.5%) was in stage II. Five of them (12.5%) had received surgical intervention before stent insertion. Twentytwo patients received uncovered stent placement, and 18 patients received partially covered stent placement. Results: Between patients receiving uncovered or partially covered metal stents, there was no difference in age, TNM stages, stenosis length, stent length, complications, survival and stent patency time. Twenty-five (62.5%) males and 15 (37.5%) females received metallic stent insertion, with mean age of 75.58 year-old (dev, 15.81). The technical success rate was 100%. Infection (aspiration pneumonia or sepsis) occurred in 7 (17.5%) patients after the procedure. No procedure related death was noted. The oral intake improved significantly 7 days and 30 days following stent placement (p < 0.001 and p = 0.007, respectively). Stent dysfunction developed in 5 (12.5%) patients, with restenosis in all. The overall survival was 184.23 ± 238.99

2021 消化系聯合學術演講年會

P.110 days and the patency time were 155.75 ± 204.69 days, respectively. Only radiotherapy after stent placement predicted lower mortality rate (HR: 0.169, 95% CI: 0.0360.794, p = 0.024). Conclusions: Metallic stent placement is effective and safe to keep better oral intake for patients with malignant esophagogastric junction outflow obstruction. Radiotherapy may be suggested to these patients following the stent placement.

食道阻抗及酸鹼值檢測應用於反覆性胃食道逆流患者：在一個醫學中心 16 個月的經驗 MULTICHANNEL INTRALUMINAL IMPEDANCE AND PH MEASUREMENT FOR EVALUATION THE PATIENT WITH REFRACTORY GASTROESOPHAGEAL REFLUX DISEASE: 16 MONTHS EXPERIENCE IN A SINGLE MEDICAL CENTER 蕭望德楊其穎張安迪蔡宗佑朱家聲高榮達丁俊夫賴學洲中國醫藥大學附設醫院消化內科 Background: Gastroesophageal reflux disease (GERD) is associated with a set of typical (esophageal) symptoms, including heartburn, regurgitation, and chest tightness. The esophagogastroduodenoscopy (EGD) is a powerful examination to evaluation of erosive reflux disease. However, there was nonerosive reflux disease (NERD) phenotype, in that they have typical reflux symptoms without any oesophageal mucosal lesion visible at endoscopy. Multichannel intraluminal impedance and pH (MII-pH) measurement constitutes an important development in reflux monitoring. It enables measurement of nonacid reflux and acid reflux. Aims: The objective of the study was to evaluation of the necessary of MII-pH in refractory gastroesophageal reflux disease. Methods: In this retrospective study, we reviewed all patients who underwent proton pump inhibitors over eight weeks but recurrent symptom of GERD. The MII-pH measurement for this patient in China Medical University Hospital from August 2019 to December 2020. Results: A total 63 patients with refractory GERD were enrolled. Two patients were excluded because total examination times were less than 8 hours. The subgroups were defined under the findings of EGD to four grounds as NERD, GERD A, GERD B and GERD C. Post MIIpH measurement, we separated two major part as acid respond (AR) and non-acid respond (NAR). The AR group contained true GERD, true NERD and hypersensitivity to acid. The NAR group contained functional heart burn, hypersensitivity to weakly acid and non-acid. There were 27 patients in NERD group, the AR was nine (33.3%) and the NAR was eighteen (66.6%). GERD A had 29 patients with eleven (37.9%) in AR and eighteen (62.1%) in NAR. The GERD B were four patients with three (75%) in AR

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P.111 and one (25%) in NAR. Only one patient was in GERD C and the MII-pH also showed true GERD. Conclusions: The erosive findings of oesophageal mucosa in EGD is less accuracy for GERD, especially the minor mucosa break as GERD LA grade A or even GERD LA grade B. The MII-pH measurement is an important examination for GERD especially the group of NERD and minor mucosa break in EGD.

食道疾病中，食道壓力計及酸度測試的比較 A COMPARISON OF ESOPHEGEAL MANOMETRY AND PH-IMPEDANCE FINDINGS IN PATIENTS WITH ESOPHAGEAL ORIGIN DISEASES 1

1,2

張宇辰陳文誌許秉毅鄭錦翔蔡峯偉林恭弘 1,2 1,2 蔡騌圳高崧碩 1 高雄榮民總醫院胃腸肝膽科 2 國立陽明大學醫學系 3 臺南市立安南醫院消化內科

Background: Esophageal manometry currently is commonly used on evaluation in patients with symptoms of esophageal origin such as dysphagia, heartburn or lump sensation, while recently developed PH-impedance is utilized for further evaluation on gastro-esophageal reflux disease. For those symptoms not compatible with upper gastrointestinal endoscopic findings, esophageal manometry and PH-impedance is suggested for further examination. Aims: To evaluate the distribution of patients who received esophageal manometry exam without significant endoscopic findings, and the difference on manometry findings between patients with and without dysphagia. Methods: From 2019 to 2020, the patients in VGHKS who received esophageal manometry were enrolled. We collect the demography of patients’ age, gender, and the presence of symptoms such as acid reflux, heartburn, chest pain, food regurgitation, lump, cough, hoarseness, epigastric pain, dysphagia, and odenophagia. The findings of esophageal manometry and PH-impedance also were collected. Results: 33 patients were enrolled in. The most common clinical symptom is acid reflux (63%), followed by dysphagia (39%), and lump sensation (33%). Among 21 of 33 patients with acid reflux symptom, the distribution of gender were 11:10 on male:female, and the mean age was 52.2 ± 9.8 years old. The other 11 patients free from acidreflux, male:female were 7:5, and the mean age was 62 ± 12.4 years old. Among the patients who has dysphagia, the distribution of gender was 11:10 on male:female, and the mean age was 59.4 ± 13.7 years old; among the patients negative from dysphagia, the distribution of gender was 12:8 on male:female, and the mean age was 53.2 ± 9.8 years old. As for the esophageal manometry findings on patients with dysphagia, 8 of 13 patients (61%) had major findings of achalasia or GE junction obstruction; the other 5 patients had negative or ineffective finding. Among the

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P.112 patients free from dysphagia, 17 of 20 patients had minor or negative finding, while achalasia was disclosed in only 3 patients. We collected the finding of PH-impedance on the 21 patients who had acid-reflux sensation. Only 3 patients met the criteria of acid exposure (pH<4, >5% of the exam time), and 6 patients had positive findings on symptom association. Among 11 patients negative from acid-reflux sensation, only 1 patient was positive on symptom association, and no patient met the criteria of acid exposure. Conclusions: In patients with dysphagia, the esophageal manometry findings were predominantly compatible with achalasia or gastric-esophageal outflow junction obstruction. The positive findings on acid exposure of PHimpedance only revealed in part of patients who had acidreflux sensation, which revealed that functional heartburn might be considered in those who were negative on PHimpedance while positive on symptoms. Esophageal manometry and PH-impedance could be suggested as further diagnostic examination for patients with nonerosive reflux disease or symptoms of esophageal origin disease.

探討功能性心灼熱合併胃食道逆流病患的臨床、食道壓力及心理特徵 CLINICAL, MANOMETRICAL AND PSYCHOLOGICAL CHARACTERISTICS IN PATIENTS WITH FUNCTIONAL HEARTBURN OVERLAPPING WITH GASTROESOPHAGEAL REFLUX DISEASE 1,2,3

葉秉威陳建全吳嘉峯李慧娟李宜家王秀伯 4 4 吳明賢曾屏輝 1 臺安醫院內科部胃腸肝膽科 2 臺北榮民總醫院內科部胃腸肝膽科 3 國立陽明大學醫學院醫學系 4 國立臺灣大學醫學院附設醫院內科部 5 國立臺灣大學醫學院附設醫院小兒部

Background: Functional heartburn (FH) is a complex disorder with poor response to proton pump inhibitors (PPIs) and it is crucial to distinguish FH from gastroesophageal reflux disease (GERD). However, some patients may have overlap between FH and GERD as defined by the updated Rome IV criteria and have been rarely investigated. Aims: We aimed to investigate the clinical, manometrical and psychological characteristics in patients with FH overlapping with GERD (overlap FH). Methods: From November 2014 to December 2019, consecutive patients who had proven GERD but refractory symptoms despite of PPIs use >= 8 weeks were prospectively enrolled at a tertiary center. All patients received validated questionnaires, including Reflux Disease Questionnaire (RDQ), Patient Assessment of Gastrointestinal Symptom Severity Index (PAGI-SYM), Brief Symptom Rating Scale (BSRS-5), and Pittsburgh Sleep Quality Index (PSQI). All patients underwent highresolution impedance manometry (HRIM), and ambulatory multichannel intraluminal impedance-pH testing (MII-pH) tested on PPI therapy. Esophageal motility was evaluated based on the Chicago Classification v3.0 and GERD was further categorized according to the Rome IV criteria. Ageand sex- matched healthy volunteers were also enrolled for comparison of esophageal motility. Results: A total of 54 patients with refractory GERD symptoms were identified. Thirty-three patients (61%) were diagnosed as overlap FH while the other 21 patients with refractory symptoms were found to have residual acid reflux (n=3), weakly acid reflux (n=13), and reflux

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P.113 hypersensitivity (n=5). The clinical characteristics, symptom profiles and HRIM parameters were similar between the overlap FH and the other refractory GERD patients. Compared with the healthy volunteers, patients with overlap FH had lower distal contractile integral values, larger peristaltic break size and more hiatal hernia. Among the patients with overlap FH, 12 (36.4%) had psychiatric comorbidity (BSRS-5 ≥ 10) and 26 (78.4%) had poor sleep quality (PSQI ≥ 6). In the subgroup analysis, those with overlap FH and normal motility was associated with high proportion of psychiatric comorbidity than those with ineffective motility disorder (58.8% vs. 12.5%, p=0.006). Conclusions: The clinical and psychologic characteristics are similar between overlap FH and the other refractory GERD patients. Patients with overlap FH had weaker esophageal contractility, more hiatal hernia, a high proportion of psychiatric comorbidity, and sleep dysfunction. Further studies to elucidate the pathophysiology of overlap FH are warranted.

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Brunner’s Gland Hyperplasia 和 Brunner’s Gland Hamartomas 的內視鏡超音波診斷、臨床病理特徵及內視鏡治療 ENDOSCOPIC ULTRASONOGRAPHIC AND CLINICOPATHOLOGICAL FEATURES OF BRUNNER’S GLAND HYPERPLASIA AND HAMARTOMAS DIAGNOSED AND REMOVED BY ENDOSCOPIC MANAGEMENT 1

吳宜樺黃文信楊其穎張凱博 1 中國醫學大學附設醫院消化系內科 2 中國醫學大學附設醫院病理科 Background: Brunner’s glands (BGs) are branched acinotubular glands and they are most common in the duodenal bulb. The size of BG hyperplasia lesions is up to 5 millimeters (mm) according to some sources and up to 10 mm according to other sources. Larger lesions were called BG hamartomas, adenomas, or brunneromas. However, Brunner ’s gland hamartoma, a rare gastrointestinal subepithelial lesion, located almost between the pylorus and the ampulla of Vater, with an unknown pathogenesis and prevalence, is widely recognized as a benign lesion. Its clinical presentation varies greatly. Histologic diagnosis is difficult without surgical or endoscopic resection. The endoscopic ultrasonographic (EUS) characteristics of Brunner’s gland hamartomas were only reported on few sporadic case reports because of its rarity. The differential diagnosis and optimal treatment remain a challenge to endoscopists. Furthermore, this study examined the characteristics of the proliferative lesions of BG and examined their association with H. pylori. Aims: To evaluate the EUS and clinical pathological features of Brunner’s gland hyperplasia and Brunner’s gland hamartoma. Methods: This retrospective study included patients who underwent an upper gastrointestinal system endoscopy in the endoscopy unit of our hospital during 2005–2020. We reviewed the patient characteristics, clinical presentation, outcomes of treatment, and endoscopic and EUS findings of Brunner’s gland hyperplasia and Brunner’s gland hamartoma, which were diagnosed by endoscopic resection or biopsy removal. Results: Fifty-nine patients (38 men, 21 women; age range 18-78, average 54.38 years) were evaluated by EGD at our institute before undergoing endoscopic removal of the lesions. The initial presentations were abdominal pain

2021 消化系聯合學術演講年會

(20), GI bleeding (8) and dyspepsia (31). Lesions were mostly sessile (58) but one was pedunculated in contour, which were located in duodenal bulb (45), junction of 1st and 2nd portion (15) and pylorus (1). Its size ranged 10 mm to 30 mm, average 14 mm. Additionally, H. pylori was detected in Brunner’s gland hyperplasia and Brunner’s gland hamartoma in our study at rates of 65.6%. Initial endoscopic biopsies revealed Brunner’s gland hamartoma in 2 of 59 lesions, Brunner’s gland adenoma in 1 of 59 lesions, and others were Brunner’s gland hyperplasia. There were thirteen of all the lesions (59) could be safely removed by endoscopic resection after EUS confirmation of the layer origin within the submucosa. Of the EUS studies, all (13) were located in the second and third sonographic layers, with features of indistinct outer margins. Internal echo texture of the lesions appeared to be hyperechoic/ heterogeneous (8), and mixed/heterogeneous (5). All were diagnosed pathologically with hamartomas or hyperplasia. One lesion revealed Brunner’s gland hamartoma with dysplasia. Two lesions had anechoic foci. The thirteen lesions were successfully removed endoscopically (12 by polypectomy or EMR, and 1 by ESD). One patient with post-EMR bleeding needed endoscopic hemostasis therapy. Additionally, only one Brunner’s gland hyperplasia is at the ampulla of Vater and removed by endoscopic papillectomy. Conclusions: Brunner’s gland hyperplasia (BGH) presents sporadically and is accompanied by abdominal pain, hemorrhage, jaundice, or obstruction. Endoscopically, BGH may appear as solitary or multiple and mucosal or submucosal nodules, and may manifest as a heterogenous hypoechoic mass located in the mucosal and submucosal layers on EUS. The EUS features of Brunner’s gland hamartomas were hyper/mixed and heterogenous echogenicity, 2nd and 3rd layers origins, indistinct margins, and anechoic foci in some lesions, which provide more valuable information before tissue proof and help differentiation from other subepithelial lesions. Additionally, two Brunner’s gland hamartomas were pathologically diagnosed before endoscopic resection, which might mean routine endoscopic biopsies are still needed. Endoscopic resection is a safe and feasible method for the treatment of Brunner’s gland hyperplasia and Brunner’s gland hamartomas, especially concerning one case illustrating malignant potential due to dysplasia. For treatment, surgical resection has been used to treat ampullary BGH. Nevertheless, by offering a safe and effective alternative to surgery that enables a correct diagnosis, EP could be considered to be the first-line

treatment in patients with benign ampullary masses. Furthermore, in our study, we found that BG hyperplasia and hamartomas were associated with a high rate of the presence of H. pylori. H. pylori may play an important role in the etiology of BG proliferative lesions. We propose that H. pylori should also be considered in the pathogenesis and treatment of BG hyperplasia and hamartomas.

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P.114 Codeine 對食道收縮的影響 INFLUENCE OF CODEINE ON ESOPHAGEAL PERISTALSIS IN HUMANS: STUDIES WITH HIGH RESOLUTION MANOMETRY 洪睿勝易志勳劉作財雷尉毅翁銘彣梁書瑋林霖陳健麟佛教慈濟醫療財團法人花蓮慈濟醫院內科部肝膽腸胃科 Background: Inhibition of descending relaxation properties of esophageal peristaltic reflex has been shown in animal models by activating opioid receptors. Morphine has been demonstrated to impair lower esophageal sphincter (LES) relaxation in healthy volunteers and dysphagia patients probably mediated with opioid receptors. Codeine, an opioid receptors agonist, has been shown to alter esophageal peristalsis during deglutition, but little was known for distension-induced secondary peristalsis. Aims: We aimed to evaluate the hypothesis whether acute administration of codeine can influence esophageal peristalsis in healthy adults. Methods: Eighteen healthy adults (men 13, mean age 27, 20-43 years) underwent high resolution manometry (HRM) with a catheter containing 22 pressure transducers with one injection port located in mid-esophagus. Secondary peristalsis was performed with rapid air injections of 10 and 20 mL after ten wet swallows for primary peristalsis. Two different sessions including acute administration of placebo or codeine (60 mg) were randomly performed to test the effects of codeine on esophageal peristalsis. Esophageal peristaltic frequencies as well as relevant HRM parameters were evaluated and compared. Results: Codeine significantly increased 4-second integrated relaxation pressure (IRP-4s) of secondary peristalsis for the injections of 10 mL (7.1 vs. 4.6 mmHg, p = 0.04) and 20 mL (6.4 vs. 4.2 mmHg, p = 0.02), but didn’t alter the frequency of secondary peristalsis for 10 mL (p = 0.09) or 20 mL (p = 0.07). There was no statistical difference in distal contractile integral (DCI) of secondary peristalsis between codeine and the placebo during air injection of 10 mL (p = 0.35) or 20 mL (p = 0.57). Codeine significantly increased IRP-4s of primary peristalsis (4.7 vs. 3.0 mmHg, p = 0.01), but decreased distal latency of primary peristalsis (6.2 vs. 6.9 seconds, p = 0.003). DCI of primary peristalsis was significantly increased with the administration of codeine (1243 ± 172.2 vs. 899.4 ± 123.5

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mmHg.s.cm, p = 0.04). No difference was found for other parameters of primary peristalsis. Conclusions: In healthy adults only LES relaxation of secondary peristalsis was influenced by codeine. Codeine has distinct effects on primary peristalsis in terms of increasing LES relaxation pressure and contractile vigor, while decreasing distal latency. Our findings suggest in human esophagus that activation of opioid receptors from codeine might has certain role in the modulation of esophageal peristalsis; however, peristaltic physiology subsequent to codeine administration probably differs between primary and secondary peristalsis.

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P.115 薄荷醇對食道收縮的影響 EFFECTS OF MENTHOL INFUSION ON ESOPHAGEAL PERISTALSIS IN HUMAN 劉作財易志勳雷尉毅洪睿勝翁銘彣梁書瑋陳健麟林霖佛教慈濟醫療財團法人花蓮慈濟醫院內科部肝膽腸胃科

The data suggest that the triggering of secondary peristalsis is probably modulated by TRPM8-sensitive mechanoreceptors; however, the activation of TRPM8 from menthol has no effect on motility change in primary peristalsis or secondary peristalsis.

Background: The cold receptor, TRPM8 (transient receptor potential melastatin 8), has been reported to be expressed in esophageal vagal afferents. Recent work has shown that the infusion of menthol into the esophagus can modulate esophageal perception in reflux patients via TRPM8, but the effects of menthol on esophageal motility are not well investigated. Aims: This study was therefore aimed to test the hypothesis whether the infusion of menthol into the esophagus could affect esophageal peristaltic characteristics in healthy adults. Methods: Eighteen healthy adults (men 10, mean age 30, 22-42 years) underwent high resolution manometry (HRM) with a catheter containing 22 pressure transducers with one injection port located in mid-esophagus. Primary peristalsis was performed with ten water swallows, while rapid air injections of 10 mL and 20 mL was performed for secondary peristalsis. Two different sessions including acute administration of placebo or menthol (3 mM) were randomly performed to test the effects on primary and secondary peristalsis. Frequency of primary and secondary peristalsis as well as relevant HRM parameters were evaluated and compared. Results: Menthol infusion didn’t change distal contractile integral (DCI) (p = 0.33) or distal latency (p = 0.86) (Table 1). Menthol infusion had no effects on basal lower esophageal sphincter pressure (p = 0.19), esophagogastric junction contractile integral (p = 0.25), or integrated relaxation pressure (p = 0.75) of primary peristalsis (Table 1). Infusion of menthol significantly decreased the frequency of secondary peristalsis for air injects of 10 mL (46.7% vs. 63.3%, p = 0.02) and 20 mL (70.6% vs. 80.6%, p = 0.04) (Table 2). There was no difference in DCI of secondary peristalsis for air injections of 10 mL (p = 0.34) or 20 mL (p = 0.87) between menthol infusion and the placebo (Table 2). Conclusions: Esophageal infusion of menthol inhibits peristaltic frequency of secondary peristalsis as induced by rapid intra-esophageal air distension, but has no effect on peristaltic characteristics in response to deglutition.

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P.116 食道警覺度及臟器性焦慮程度正相關於逆流症狀及心理困擾之嚴重度但不受二十四小時酸鹼阻抗測定參數影響 ESOPHAGEAL-SPECIFIC HYPERVIGILANCE AND VISCERAL ANXIETY ARE SIGNIFICANTLY ASSOCIATED WITH REFLUX SYMPTOM BURDEN AND PSYCHOLOGICAL DISTRESS BUT NOT WITH AMBULATORY 24-HR IMPEDANCE-PH 翁銘彣洪睿勝梁書瑋林霖雷尉毅劉作財易志勳陳健麟佛教慈濟醫療財團法人花蓮慈濟醫院內科部肝膽腸胃科 Background: The pathogenesis of gastroesophageal reflux disease (GERD) symptoms is complex and multifactorial. The esophageal hypervigilance and anxiety (EHAS) scale is a novel cognitive-affective approach of visceral sensitivity for GERD and dysphagia. EHAS has been shown to be associated with reflux symptom severity, but its association with psychological distress or reflux burden has not been examined. Aims: The aim of this study was to investigate whether EHAS correlates with psychological stress, phenotypes of GERD, and reflux parameters in GERD patients. Methods: Adult patients with chronic reflux symptoms were prospectively evaluated with esophagogastroduodenoscopy and ambulatory pHimpedance monitoring for GERD phenotyping: erosive esophagitis (EE), non-erosive reflux disease (NERD), reflux hypersensitivity (RH), functional heartburn (FH). All participants were required to complete questionnaires including EHAS, gastroesophageal reflux disease questionnaire (GERDQ), reflux symptoms index (RSI), Taiwanese Depression Questionnaire (TDQ) score, and State-Trait Anxiety Inventory (STAI) score. Correlations among EHAS, GERDQ, RSI, TDQ, STAI, and acid exposure time (AET) were assessed using Pearson’s correlation. Results: We enrolled 63 patients, aged 21–67 years (mean 48), 56% female, of whom 14 patients had EE, 7 patients had NERD, 23 patients had RH, and 19 patients had FH. EHAS (including subscales of anxiety and hypervigilance) correlated significantly with GERDQ, TDQ, and STAI (P < 0.05); however, there were no significant correlations between GERDQ and TDQ, as well as STAI (P = NS).

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Patients with EE were more likely to have high values of TDQ and STAI as compared to RH and FH (P < 0.05). There were no significant group differences among GERD phenotypes regarding EHAS, GERDQ, and RSI (P = NS). In addition, there was no significant correlation between EHAS and pH-impedance parameters (P = NS). Conclusions: We have demonstrated that esophageal hypervigilance and anxiety correlated well with reflux symptom burden and psychological distress, but not with the phenotypes of GERD or individual reflux parameters. This work indicates that EHAS appears to have important clinical utility for outcome measurements across GERD phenotypes.

2021 消化系聯合學術演講年會

P.117 抬腿誘發之短暫裂口分離可預測逆流合併食道無效性蠕動病人之酸負荷 TRANSIENT HIATAL SEPARATION DURING STRAIGHT LEG RAISE CAN PREDICT ACID BURDEN IN GERD PATIENTS WITH INEFFECTIVE ESOPHAGEAL MOTILITY 1

雷尉毅林霖梁書瑋洪睿勝翁銘彣劉作財易志勳 2 1 張維娟陳健麟 1 佛教慈濟醫療財團法人花蓮慈濟醫院內科部肝膽腸胃科 2 佛教慈濟醫療財團法人花蓮慈濟醫院醫學研究部

higher acid reflux events (p = 0.037) and longest acid reflux episodes (p = 0.006), as well as a higher DeMeester score (p = 0.019). Conclusions: The evaluation of transient hiatal separation with SLR during esophageal HRM allows direct assessment of potential disruption of EGJ barrier, and helps predict acid reflux burden in IEM patients. Our work supports the notion that abnormal EGJ remains to be one of the most important pathophysiological mechanisms leading to pathological acid reflux in GERD.

Background: Straight leg raise (SLR) while supine increases intra-abdominal pressure, and can assess the integrity of the esophagogastric junction (EGJ) barrier during high-resolution manometry (HRM). Aims: The aim of this study was to evaluate the implications of transient hiatal separation during SLR in symptomatic gastroesophageal reflux disease (GERD) patients. Methods: Consecutive patients presenting for evaluation of reflux symptoms with esophageal physiological testing were included. Demographic information, GERD questionnaires, HRM, and reflux monitoring studies were analyzed. EGJ morphology was evaluated based on lower esophageal sphincter and crural diaphragm location. Esophageal motor diagnosis and peristaltic patterns were identified according to Chicago Classification version 3.0. Transient hiatal separation (determined as 1 cm or more) during SLR was assessed using on-screen software tools. We compared reflux monitoring parameters and esophageal motor patterns between patients with and without transient hiatal separation during SLR, and hiatal hernia. Results: Of 85 patients who completed SLR (47.1 ± 11.9 years, 48 female), 35 (41%) had hiatal hernia, 19 (22%) had transient hiatal separation during SLR, and the remaining 31 had no separation. Hiatal hernia patients were more likely to have a higher mean total acid exposure time (AET) (p = 0.016), higher total acid reflux events (p = 0.145), higher longest acid reflux episodes (p = 0.024) and a higher DeMeester score (p = 0.016) compared to patients in the non-separation group (Table 1). There were no differences in reflux parameters between patients with transient hiatal separation and no separation groups. However, within ineffective esophageal motility (IEM) patients, the presence of transient hiatal separation during SLR significantly correlated with a higher total AET (p = 0.014) (Figure 1),

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2021 消化系聯合學術演講年會

P.118 以高解析度咽部功能檢查儀探討 Baclofen 對口咽吞嚥生理功能之影響 EFFECT OF BACLOFEN ON OROPHARYNGEAL SWALLOWING: STUDY WITH HIGH RESOLUTION PHARYNGEAL MANOMETRY 梁書瑋洪睿勝林霖翁銘彣雷尉毅劉作財易志勳陳健麟佛教慈濟醫療財團法人花蓮慈濟醫院內科部肝膽腸胃科 Background: The GABAB (gamma-aminobutyric acid B receptor) agonist, baclofen, has been shown to affect gastrointestinal motility, lower esophageal sphincter (LES) tone and transient LES relaxation. However, the impact of baclofen on oro-pharyngeal swallowing has not been elucidated in human. Aims: This study aimed to investigate the effect of baclofen on pharyngo-esophageal motor function. Methods: Twenty two healthy volunteers (13 male, 29 years, [21-41]) were included. High resolution impedance manometry studies were performed at Hualien Tzu Chi Hospital. A solid-state catheter (Laborie, Solar GI acquisition unit, MMS) recorded pressure and bolus flow along the pharyngo-esophageal segment. Studies were performed on two occasions, on one occasion oral 5 mg baclofen was administered one hour before study. After catheter placement and accommodation to the catheter, participants swallowed triplicate standardized bolus challenges (SBMkit, Trisco Foods) of 5, 10 and 20 mL thin liquid and viscous liquid (total 18 swallows). The manometric data were analyzed on the online platform SwallowGatewayTM (swallowgateway.com, Flinders University). Metrics derived included pharyngeal contractile integral, pre-deglutitive upper esophageal sphincter (UES) basal pressure, post-deglutitive UES contractile integral, UES maximum opening admittance, mean hypopharyngeal peak pressure, bolus presence time, distention contraction latency, hypopharyngeal intra-bolus pressure and the global swallow-risk-index. Piecemeal swallowing was defined when the orally administered bolus was divided into two or more portions. Results: All participants completed the protocol. Preand Post-deglutitive UES contractility was lower during exposure to baclofen. These effects were most significant for viscous swallows. Other pharyngeal metrics were not affected by baclofen. Piecemeal swallowing behavior was more prevalent at larger volumes. Baclofen reduced the

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proportion of swallows that were piecemeal. Conclusions: Oral baclofen reduces UES contractility and the incidence of piecemeal swallowing. These effects may suggest disruption of pathways that induce reflex activation of the UES as well as the neuroregulatory mechanisms that modify volitional swallowing behavior to accommodate large bolus size.

2021 消化系聯合學術演講年會

P.119

P.120

胃癌和第 2 型糖尿病腸道微生物相之相關性 RELATIONSHIP BETWEEN GASTRIC CANCER AND TYPE 2 DIABETES INTESTINAL MICROBIOTA

喝酒對於胃食道逆流患者食道機能的影響：高解析食道機能壓力測定之新觀點 EFFECTS OF ALCOHOL CONSUMPTION ON ESOPHAGEAL MOTILITY OF GERD PATIENT: NEW PERSPECTIVES FROM ESOPHAGEAL HIGH-RESOLUTION MANOMETRY

1,2

1,2,3

張景翔劉忠榮王俊偉許文鴻吳登強郭昭宏 1 高雄醫學大學附設醫院胃腸內科 2 高雄醫學大學醫學系 3 高雄巿立小港醫院內科

Background: Diabetes mellitus (DM) is a major risk factor of several other chronic diseases, including cancer. The pathologic conditions of diabetes, such as hyperinsulinemia, hyperglycemia, and fat-induced chronic inflammation, were demonstrated to favor tumorigenesis. Hyperglycemia, a lower HDL level, a low HOMA-IR level, which was demonstrated associated with early gastric cancer (GC) risk (2019 Gut liver, 13(2):154). Of note, dysbiosis of the gut microbiome, which accounts for about 90% of all diabetes cases worldwide, is reported in GC. Aims: In this study, we further investigates the relationship of intestinal microbiota between gastric cancer and type 2 diabetes. Methods: Gastric diseases: 34 samples analyzed w/ 16s rRNA gene NGS so far – 5 gastric cancer positive and 29 gastric cancer negative. Chronic kidney disease/ Diabetes patients: 95 samples analyzed w/ 16s rRNA gene NGS so far – 23 CKD, 35 DM, 35 DM-CKD and 2 None. Results: In our preliminary study, we have analyzed the gut microbiome of patients with diabetes (DM, n = 93; nonDM, n = 2) and gastric cancer (cancer, n = 5; non-cancer, n = 29) with 16S rRNA sequencing. The composition % of phylum Proteobacteria, Verrucomicrobia, Fusobacteria, which were belong to gram-negative bacteria, were increased in patients with DM or gastric cancer. Conclusions: The results imply the endotoxemia may be one of the common culprits between GC and DM.

1,2

王俊偉王崧維謝易倫吳秉儒張景翔蘇育正 1 高雄醫學大學附設中和紀念醫院胃腸內科 2 高雄醫學大學醫學系

1,2

Background: Alcohol ingestion is commonly associated with gastrointestinal symptoms and disorders by inducing a cascade of inflammatory mechanisms. Symptoms of gastroesophageal reflux disease (GERD) could be triggered by alcohol consumption, but the definite pathophysiology has not been well established. Although some studies have demonstrated that alcohol consumption could affect peristaltic movement of the esophagus body and pressure of esophageal sphincters, there was little available objective data to validate the result. Aims: We aimed to evaluate effects of alcohol consumption on esophageal motility of recurrent and refractory GERD patients by esophageal high-resolution manometry (HRM). Methods: In the retrospective single-center trial, 63 patients diagnosed with recurrent and refractory GERD were recruited, and were divided into 21 alcohol users and 42 nonalcohol users. A total of 630 wet swallows were reviewed and analyzed in all patients who underwent an esophageal HRM test according to the Chicago classification v3.0. Results: The ratio of esophageal motility dysfunction was higher in the alcohol users than non-alcohol uses (71.4% vs. 45.2%, respectively, P = 0.049). The average esophageal distal contractile integral (DCI) and 4-second integrated relaxation pressure (IRP4) both showed no differences between alcohol users and non-alcohol users (P > 0.05). Subgroup analysis between current and ever alcohol users presented that there might be an increasing trend in DCI and decreasing trend in IRP4 after quitting alcohol drinking. Furthermore, multivariate analysis revealed that alcohol consumption was a strong risk factor contributing to esophageal weak peristalsis (HR: 4.66, 95% CI: 1.05–20.65, P = 0.043). Conclusions: Alcohol consumption is associated with esophageal motility disorders, especially on esophageal peristalsis, in GERD patients, and esophageal motility dysfunction might be improved after alcohol abstinence.

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2021 消化系聯合學術演講年會

P.121 阿斯匹靈用於胃癌術後的病患，可以降低復發率和增加存活率嗎？ ASPIRIN USER DOES NOT DECREASE RECURRENCE RISK NOR INCREASE SURVIVAL IN PATIENTS WITH GASTRIC CANCER AFTER SURGERY 1,2

1,2

2,4

林弘恩宋寬益王彥博郎慧珠盧俊良 1 臺北榮民總醫院胃腸肝膽科 2 臺北榮民總醫院內視鏡診斷暨治療中心 3 國立陽明大學醫務管理研究所 4 國立陽明大學腦科學研究所

Background: Gastric cancer is the third most common cancer worldwide with around 6.8% of total cancer incidence. And gastric cancer had a poor prognosis with a 5-year survival rate of around 29% in Western countries. Aspirin, as an antiplatelet to prevent cardiovascular disease, may play a role in preventing cancer growth and metastasis. Epidemiological studies have also associated aspirin use with decreased risk of gastric cancer incidence and survival, though controversial results still present. To date, it remained unknown whether aspirin use will have any impact on the recurrence risk and survival in the patients who underwent surgical intervention. Aims: We tried to observe whether aspirin use will have any impact on the recurrence risk and survival in patients with gastric cancer who underwent surgical intervention. Methods: We performed a population study base on Taiwan Cancer Registry and Taiwan National Health Insurance Database. A total of 13,447 patients with gastric cancer between 2008 and 2016 and taking surgical intervention were identified in the cancer registry Aspirin prescriptions and associated comorbidities were identified from linkages to the Taiwan National Health Insurance database. The recurrence risk, cancer-related mortality rate, and 5-year survival rate were determined. Results: There were 1,285 aspirin users among patients with gastric cancer. The recurrence rate is similar between aspirin users and nonusers (14.4% vs 14.7%, p=0.84). Subgroup analysis also the aspirin use did not affect the recurrence in different stages of gastric cancer (stage 0: 0 vs. 3.3%, p=0.58, stage I: 4.03% vs 4.13%, p=0.93; stage II: 11.8% vs 16.2%, p=0.07; stage III: 31.6% vs 29.6%, p=0.42). In all-cause mortality, the aspirin user group has significantly higher than the non-user group (54.6% vs 44.5%, p<0.0001). However, the aspirin user and nonuser showed similar cancer-related mortality (38.91%

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vs 37.72%, p=0.40). After matching of sex, age, surgical intervention year, and the comorbidities, the 5-year survival rate was also showed no difference between the aspirin user and non-user group (49.8% vs. 47.2%, p=0.37). Conclusions: Aspirin use changes neither the recurrence risk nor the survival rate in patients with gastric cancer after surgical intervention.

2021 消化系聯合學術演講年會

P.122 在酒癮患者藉由碘液染色內視鏡偵測食道鱗狀上皮細胞病變：一個橫斷及觀察性研究 DETECTION OF ESOPHAGEAL SQUAMOUS CELL NEOPLASM IN HEAVY ALCOHOL DRINKERS BY LUGOL CHROMOENDOSCOPY: A CROSS-SECTIONAL AND OBSERVATIONAL STUDY 1,2

1,2

1,3

陳以勳林大雅陳彥成王耀廣許文鴻吳宜珍 1 高雄醫學大學附設中和紀念醫院胃腸內科 2 衛生福利部旗山醫院內科 3 高雄醫學大學醫學系

LVL classification, there was 7 patients (23.3%) with LVL classification A, 15 patients (50%) with LVL classification B, 1 (3.4%) patient with LVL classification C, and 7 patients (23.3%) with LVL classification D. Within patient with LVL classification D group, 4 patients had esophageal squamous cell carcinoma, and 2 patients had esophageal low-grade dysplasia. Conclusions: Alcoholic patients had the potential risk to develop ESCN. Lugol chromoendoscopy screening among these alcoholic patients seems a practical method to detect ESCN.

Background: Alcohol is one of the most important carcinogens to induce synchronous or metachronous esophageal squamous-cell neoplasm (ESCN) among the patients with head and neck squamous cell carcinoma, and Lugol chromoendoscopy is a practical and reliable tool to detect the ESCN. However, little is known for the alcoholic patients without cancers to develop ESCN. Aims: We aimed to evaluate the incidence of ESCN for alcoholic patients without cancers by the Lugol chromoendoscopy. Methods: We initiated a cross section cohort at Chi-San hospital. The inclusion criteria were adults who drank alcohol above two times per week and continued for more than 20 years, no known cancer history, and with some gastrointestinal symptoms such as dyspepsia, acid reflux sensation or epigastric pain. Exclusion criteria was patients with previous cancer history, allergic to Iodine, or refused the esophagogastroduodenoscopy (EGD) survey. All patients agreed with the EGD with Lugol chromoendoscopy and signed the inform consent. This cohort was performed during January 2019 to September 2020. Results: 53 patients were recruited initially, and 20 patients received medication treatment and refused EGD screening. The rest 33 patients received EGD screening, and we excluded 3 patients due to previous head and neck cancer history (2 hypopharyngeal cancer, 1 buccal cancer). Total 30 patients were included to our study. Among these patients, there was only one female, and the average age was 53.9 ± 8.7 years. Most of the patients presented with epigastralgia (18/30, 60%), and the following symptoms were acid reflux sensation (10/30, 33%), and dysphagia (3.3%) as well as black stool passage (3.3%). There were 5 patients to have squamous cell carcinoma or aplastic carcinoma and 3 patients had low grade dysplasia. For the

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P.123 吞嚥困難的不同病因與社會負擔之間的關係：全國性回溯性研究 RELATIONSHIP BETWEEN DIFFERENT ETIOLOGIES OF DYSPHAGIA AND SOCIAL BURDEN: A NATIONWIDE COHORT STUDY 粟慧嫻張君照臺北醫學大學附設醫院消化內科 Background: Dysphagia is one of important health problems related to patient’s quality of life, poor nutritional status and life threatening complications. We want to evaluate different etiologies of dysphagia and their disease severity, incidence of institutionalization and unemployment status. Aims: Dysphagia is one of important health problems related to patient’s quality of life, poor nutritional status and life threatening complications. We want to evaluate different etiologies of dysphagia and their disease severity, incidence of institutionalization and unemployment status. Methods: Our study is a large cross-sectional study based on medical records from Taiwan Data Bank of Persons with Disability (TDPD) enrolled for dysphagia from July 2012 to October 2018. We totally enrolled 18608 patients with dysphagia (aged above 18 year-old). We excluded education level refused to answer or missing (2,755), persons with multiple underlying diseases unable to classified (1,816), remaining 14037 patient were studied. We categorized these patients into three groups; dysphagia related to neurologic cause, oropharyngeal cause and obstructive cause. We compared their disease severity, institution residence, unemployment status. Results: We analyzed total 14037 participants with dysphagia (9458 man and 4578 women) from July 2012 to October 2018 (Figure 1). The distribution of demographic variables of population was in Table 1. Of these patients, 6336 (45.1%) were 18- 64-year-old and 7701 (54.9%) were 65 and above, 13581 (96.8%) were unemployment, 11377 (81.1%) had multiple disability, with statistical difference of older age (P < 0.0001), male gender predominant (P < 0.0001), unemployment (P < 0.0001), with multiple disability (P < 0.0001). Again categorized them into three groups according to etiology; dysphagia due to neurologic disease (n = 9479, 67.5%), dysphagia due to obstruction problems (n = 939, 6.7%), dysphagia due to disease of oropharyngeal cavity (n = 3619, 25.8%). We found that majority of dysphagia was due to neurologic disease,

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most of them were associated with multiple disabilities, more severe impairment, higher unemployment and institutionalization compared with other two groups. Conclusions: Diseases like stroke, dementia, Parkinson’s disease were associated with aging and may result dysphagia. These patients end up with institutionalization due to burden of care at home as family members and care giver no longer cope their demands. In our study, neurological cause of dysphagia was associated with highest multiple disability, unemployment status and institutionalization.

2021 消化系聯合學術演講年會

P.124 後 REAP-HP 調查：2020 年針對台灣胃腸科醫師對於幽門螺旋桿菌除菌之臨床實踐以及期待之臨床調查 POST REAP-HP SURVEY: THE 2020 SURVEY FOR THE REAL-WORLD PRACTICE AND EXPECTATION IN HELICOBACTER PYLORI ERADICATION OF THE GASTROENTEROLOGISTS IN TAIWAN 1

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4,8

5,8

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蔡元榮許秉毅吳登強蔡成枝陳冠仰陳健麟 2,8 7 施長碧石志安 1 屏東基督教醫院內科部胃腸肝膽科 2 臺南市立安南醫院消化內科 3 高雄醫學大學附設醫院內科部胃腸科 4 高雄長庚紀念醫院內科部胃腸肝膽科 5 臺北市立聯合醫院仁愛院區內科部胃腸肝膽科 6 花蓮慈濟醫院醫學部 7 安泰醫院肝膽腸胃內科 8 台灣胃酸相關疾病暨微菌叢聯盟

Background: With the rising prevalence of antimicrobial resistance, the treatment success of standard triple therapy has declined to 66.5% in Japan and less than 80% in most other Asia-Pacific countries. In addition to traditional standard triple regimens, several treatment regimens have emerged to cure H. pylori infection recently. These novel first-line anti-H. pylori therapies include sequential therapy, concomitant quadruple therapy, hybrid therapy, high-dose dual therapy and bismuth-containing quadruple therapy. REAP-HP study was the pioneer study investigating the expectation and preference of physicians across Asia-Pacific in H. pylori eradication in 2015. This study is a followup study of REAP-HP exploring the possible changes of expectation and preference of gastroenterologists in Taiwan in 2020. Aims: (1) To investigate the preference in regimens for the first-line anti-H. pylori therapy among gastroenterologists in Taiwan. (2) To survey the minimal eradication rate of a first-line regimen accepted by gastroenterologists in different districts in Taiwan, and (3) To further investigate the most concerned factors of gastroenterologist when prescribing anti-H. pylori regimens in clinical practice. Methods: In the Taiwan Digestive Disease Week (TDDW) 2020, a questionnaire for H. pylori eradication survey of physicians was distributed to the gastroenterologist who attended the meeting and had prescribed anti-H. pylori therapy before. The key questions included the most

commonly used therapy, minimal accepted eradication rate of a first-line anti-H. pylori regimen in clinical practice, and the most concerned factors during anti-H. pylori therapy. Results: A total of 258 physicians from different districts of Taiwan participated in the post REAP-HP Survey. The top three most commonly used anti-H. pylori regimens in Taiwan were 14-day standard triple therapy (36.8%; n = 95), 7-day standard triple therapy (17.8%; n = 46) and 14day reverse hybrid therapy (14.7%; n = 38) respectively. The minimal accepted eradication rate in northern, central, southern and eastern districts of Taiwan was 86.7%, 87%, 86.5% and 88.1% respectively. The average minimal accepted eradication rate for first line regimen is 86.7%. The top two most concerned factors during prescribing anti-H. pylori therapy by gastroenterologists were eradication rate (81.7%) and side effect (10.4%). Conclusions: 14-day standard triple therapy is the most commonly used first-line anti-H. pylori therapy among gastroenterologists in Taiwan. The minimal accepted eradication rate of anti-H. pylori therapy expected by gastroenterologists is 86.7% which is less than 90%. An unmet treatment need for H. pylori eradication therapy exists among gastroenterologists in Taiwan if to fulfilling the Kyoto consensus recommendation.

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P.125 接受治療的成年腐蝕性患者來預測住院死亡率新評估分數：林口長庚紀念醫院 20 年的經驗 NEW SCORE FOR PREDICTING INHOSPITAL MORTALITY IN ADULT PATIENTS WITH CAUSTIC INGESTION AND TREATED AT CGMH, 1999-2018: THE 20-YEAR EXPERIENCE OF A LARGEST MEDICAL CENTER IN TAIWAN 1,2,3

鄭浩材黃書偉陳品錚蘇銘堯謝森永史麗珠新北市立土城醫院（委託長庚醫療財團法人興建經營） 1 胃腸肝膽科 2 林口長庚紀念醫院胃腸肝膽科系 3 長庚大學臨床醫學研究所 4 長庚大學公共衛生學科 Background: Caustic agent ingestion is constantly lifethreatening. Endoscopy is the gold standard diagnosis of the severity of the corrosive injury. Studies combining endoscopy with other risk factor to predict the mortality of caustic patients were rare. Aims: This study aimed to provide a new score to predict 1-year mortality in adults with caustic ingestion by analyzing the 20-year data from our hospital, a largest medical center in Taiwan. Methods: The retrospective study analyzed adults treated for caustic agent ingestion at Chang Gung Memorial Hospital, Taiwan, between January 1999 and December 2018. Uniformly strict inclusion/exclusion criteria and a double-checked process during chart review were adopted. All patients underwent urgent esophagogastroduodenoscopy (EGD) within 24 hours after admission. Caustic mucosal damage was graded using Zargar’s modified endoscopic classification. The univariate analysis (log-rank test and the Kaplan-Meier curve) and multivariate analysis (Cox’s proportional hazard model) was made to examine the association between various risk factors and the survival. Receiver operating characteristic (ROC) curve and the area under the ROC curve (AUC) was made to generate a composite score to predict the mortality. Results: Among 665 patients admitted with caustic injuries, 414 (62.3%) required hospitalization. Among those who required hospitalization, the mortality during admission was 6.5% and the 1-year mortality after discharge was 2.3% after discharge. Among those who did not require hospitalization, the 1-year mortality was 0.4%.

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Among those who required hospitalization, multivariate analysis reveals that shock and respiratory failure were important and significant factors associated with in-hospital mortality of these patients. The adjusted hazard ratio (aHR) was 4.59 (95% CI = 1.98-10.62) for shock and 7.79 (95% CI = 2.69-22.56) for respiratory failure, respectively. The area under the receiver operating characteristic curve (AUC) was high (89.3%, 95% CI = 81.1%-97.4%), indicating an excellent predictability of the in-hospital mortality of the composite score of these two factors. The best cutoff was either having shock or respiratory failure with a high sensitivity (85.2%) and specificity (89.1%). Conclusions: Shock and respiratory failure were important factors associated with in-hospital mortality of the caustic patients. The composite score of these two factors demonstrated an excellent predictive ability of the inhospital mortality for the caustic patients.

2021 消化系聯合學術演講年會

P.126 補充羅伊氏乳酸桿菌對於根除胃幽門螺旋桿菌感染之比較功效：一項隨機對照試驗的薈萃分析 COMPARATIVE EFFECTIVENESS OF LACTOBACILLUS REUTERI SUPPLEMENTATION IN ERADICATING HELICOBACTER PYLORI INFECTION: A META-ANALYSIS OF RANDOMIZED CONTROLLED TRIALS

Conclusions: Lactobacillus reuteri supplementation significantly give a rise to the improvement of H. pylori eradication therapy and reduce the incidence of gastrointestinal symptoms associated with antibiotic therapy.

劉芳辰黃天祐陳鵬仁陳宣位楊志偉林榮鈞林煊淮黃瑋琛施宇隆張維國謝財源陳保中三軍總醫院胃腸肝膽科 Background: Helicobacter pylori (H. pylori) infection is a worldwide disease causing many disease, including peptic ulcer disease, gastric neoplasm (carcinoma and mucosa-associated lymphoid tissue-lymphoma), non-ulcer dyspepsia. In some countries, the prevalence of H. pylori is about 80–90%. However, the rate of H. pylori eradication therapy declined in recent decades owing to the escalating antibiotic resistance. Thus, it is needed to apply new agents to improve the efficacy of H. pylori eradication. Aims: Lactobacillus reuteri (L. reuteri) have been demonstrated to reduce H. pylori bacterial load and suppress the binding of H. pylori to gastric epithelialium. The aim of our research is to explore the effectiveness of L. reuteri supplementation for helping H. pylori eradication. Methods: A systematic search of studies on L. reuteri for combination in H. pylori eradication was conducted mainly in PubMed, Embase, Web of Science and Cochrane Library (up to December, 2020). Our investigations were limited to RCTs and controlled clinical trials. The odds ratio of H. pylori eradication rate of L. reuteri supplementation versus placebo was treated as the primary outcome, whereas the odds ratio of gastrointestinal symptoms of L. reuteri supplementation versus placebo comprised the secondary outcome. Results: The meta-analysis included five randomized controlled trials comprising 387 participants in total. The pooled odds ratio of H. pylori eradication rate in the L. reuteri supplementation arm compared with the placebo arm was 1.90 (95% confidence level [CI]: 1.15 to 3.15, p=0.013), indicating a improvement in L. reuteri for combination in H. pylori eradication. The quantitative analysis showed a significantly lower GSRS of L. reuteri supplementation versus placebo after H. pylori eradication (SMD: -0.79; 95% CI: -0.21 to -0.36).

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P.127

P.128

Wnt 抑制劑 2,4-Diamino-Quinazoline 可抑制胃癌發展和轉移 2,4-DIAMINO-QUINAZOLINE, A WNT SIGNALING INHIBITOR, SUPPRESSES GASTRIC CANCER PROGRESSION AND METASTASIS

培養人胃癌類器官的基準方法 BENCHMARKED METHOD OF CULTURING HUMAN GASTRIC CANCER ORGANOIDS

1,2

張德生盧重光謝詠諭魏國良陳慰明董水義 1 3 3 吳正雄陳永恩江明格 1 嘉義長庚紀念醫院胃腸肝膽科 2 長庚大學醫學院 3 國立中正大學生物醫學科學系

Background: Gastric cancer (GC) is among the most treatment-refractory epithelial malignancies. Aberrant activation of Wnt/β-catenin-signaling has been implicated in a variety of human cancers, including gastric cancer. Aims: To explore if Wnt-signaling pathway is a druggable therapeutic target in the treatment of GC. Methods: We established GC organoids and nonneoplastic gastric organoids from surgically resected tissue of patients with gastric adenocarcinoma and its adjacent gastric epithelium. Next, we set out to analyze the response of these organoid lines to 2,4-DAQ treatment. Results: Elevated expression of Wnt pathway transcription factor lymphoid enhancer binding factor 1 (Lef1) is associated with the TNM (tumor– node–metastasis) stage of gastric cancer. Subsequently, 2,4-diamino-quinazoline (2,4-DAQ), a selective inhibitor of Lef1, was identified to suppress the expression of Wnt/β-catenin target genes such as AXIN2, MYC and LGR5 and result in the suppression of gastric cancer cell growth through the apoptotic pathway. The 2,4-DAQ also exhibited an inhibitory effect on the migration/invasion of gastric cancer cells. Importantly, the treatment of human gastric tumor xenograft with 2,4DAQ suppressed tumor growth in a nude mouse model. Furthermore, 2,4-DAQ appears effective on patient-derived organoids (PDOs). Transcriptome sequencing analysis also revealed that 2,4-DAQ are more effective on the gastric cancers that exhibit higher expression levels of Wntsignaling pathway-related genes than their adjacent normal gastric tissues. Conclusions: Our results indicate that 2,4-DAQ exerts its potent, selective antitumor effect primarily through inhibition of the Wnt/β-catenin-signaling pathway on GC cells, suggesting the potential therapeutic usage of 2,4-DAQ in clinical applications.

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2,3,4

1,3

林志豪潘佳彬古家禎劉忠榮橫山一成 1,2,3,4 吳登強 1 高雄醫學大學附設醫院胃腸內科 2 高雄醫學大學醫學研究所 3 高雄醫學大學再生醫學與細胞治療研究中心 4 高雄醫學大學醫學院

2,3,4

Background: Gastric cancer is heterogenous featuring different histological and molecular subtypes, including the microsatellite heterogeneity (MSI), Epstein-Barr virus (EBV), intestinal chromosome instability (CIN), and diffuse genomic stable (GS) subtypes. Each key genetic alteration is clarified such as the increase of RNF43 and ARID1A mutations in MSI, the increase of ARID1A and PIK3CA mutations in EBV, TP53 mutation and oncogenic amplification in CIN, and the mutations of CDH1, RHOA or ARHGAP fusion in GSs. To confirm these heterogeneity we have developed the 3D-organoids from human stomach cancers. Aims: To confirm these heterogeneity we have developed the 3D-organoids from human stomach cancers. Methods: Gastric cancer is heterogenous featuring different histological and molecular subtypes, including the microsatellite heterogeneity (MSI), Epstein-Barr virus (EBV), intestinal chromosome instability (CIN), and diffuse genomic stable (GS) subtypes. Each key genetic alteration is clarified such as the increase of RNF43 and ARID1A mutations in MSI, the increase of ARID1A and PIK3CA mutations in EBV, TP53 mutation and oncogenic amplification in CIN, and the mutations of CDH1, RHOA or ARHGAP fusion in GSs. To confirm these heterogeneity we have developed the 3D-organoids from human stomach cancers. Results: To clarify the fidelity of human organoid models, we have noticed several key issues for cultivation and differences between normal and cancerous organoids. (1) Effect of ROCK inhibitor; Rho kinase inhibitor was added to the primary cultures to inhibit anoikis and apoptosis were previously observed in purified colonic epithelial cells. (2) Effect of GSK inhibitor CHIR-99021; Treatment with CHIR-99021 ubiquitously and strongly activated beta-catenin-mediated transcription, induced discordant phenotypic alterations in intestinal organoids. Of note,

2021 消化系聯合學術演講年會

P.129 CHIR treatment, in combination with histone deaceylase inactivation via valproic acid, comprised an effective procedure for the enrichment of Lgr5+ cells in intestinal organoids. Thus, we used only for 3 days and removed. (3) Dose of niche factors; R-spondin concentration of normal and cancer organoids are the same as 10%, but Wnt3a in cancer case is 10% and normal organoids required 20%. Conclusions: We develop the precise culture conditions of the gastric organoids in vitro to improve the accuracy of generation of organoid models to apply the therapeutic and medical use in a future, especially to investigate the molecular interaction between the environmental niche and the gastric cancer stem cells to develop the gastric cancer phenotypes.

探討 LRRK2 在胃癌進展和活化細胞自噬活動的機制作用 THE POTENTIAL ROLES OF LRRK2 IN THE REGULATION OF TUMOR PROGRESSION AND AUTOPHAGY ACTIVITY IN GASTRIC CANCER 1,2

1,2

2,4

吳宗勳鄭光宏胡晃鳴吳孟杰盧建宇吳登強 1 高雄巿立大同醫院內科 2 高雄醫學大學附設中和紀念醫院胃腸內科 3 國立中山大學生物醫學研究所 4 高雄醫學大學醫學系

Background: Gastric carcinoma (GC) is one of the most prevalent cancers worldwide and is the secondary leading cause of cancer-related mortality because of the poor prognosis of GC patients. Mutations in the leucine-rich repeat kinase 2 (LRRK2) were first identified as a cause of Parkinson’s disease (PD). Recent association studies have linked LRRK2 with a variety of biological processes such as autophagy or mitophagy. Thus, LRRK2 gene is generally shown to play critical roles in development, pattern formation during embryogenesis and in the maintenance and cellular homeostasis of neural and other tissues in the adult. However, the oncogenic signals and regulatory mechanisms for LRRK2 in tumorigenesis are not yet full characterized. Aims: To investigate the role of LRRK2 in the regulation of tumor progression and autophagy activity in gastric cancer. Methods: The clinical impact of LRRK2 was first evaluated in The Cancer Genome Atlas (TCGA) GC cohort. The biological function of LRRK2 was studied in vitro, in vivo, and in GC mouse models and murine GC cell lines. LRRK2 downstream effector and pathways were identified by RNA sequencing, qRT-PCR, western blots, immunefluorescence (IF), immunohistochemical (IHC) staining and immunoprecipitation (IP) analysis. Results: We found that LRRK2 is overexpressed in gastric carcinoma (GC), and this increased expression is associated with GC progression through western blots and immunohistochemistry analyses. Furthermore, we also observed that LRRK2 modulates cell growth rates of gastric cancer, and affects gastric cancer cell migration and invasion. Conditional knockout of LRRK2 in H/K ATPase Cre/Ptenloxp/loxp /LKB1loxp/loxp P53loxp/loxp prometastatic GC mouse models significantly reduces GC invasion and metastasis.

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P.130 Conclusions: Thus, we proposed that the LRRK2 signaling pathway as a therapeutic target for the treatment of GC and hope to identify its major downstream effector genes that regulate cell survival, proliferation and motility. In the long term, the understanding of the modes of LRRK2 signaling cascades and its biological roles in GC could undoubtedly provide ideal nodal points of therapeutic intervention in addition to aiding in the diagnosis and prognosis of this devastating disease.

白藜蘆醇類似物 4'-BROMORESVERATROL 透過調控 JNK-SIRT3 訊息傳遞抑制胃癌幹細胞化 4’-BROMO-RESVERATROL INHIBITS GASTRIC CANCER STEMNESS THROUGH JNK-SIRT3 SIGNALING PATHWAY 1,2

3,4

2,4,6

胡晃鳴吳孟杰林明瑋蔡忻誼黃耀斌吳登強 1 高雄巿立大同醫院內科 2 高雄醫學大學醫學系 3 義大癌治療醫院醫學研究部 4 高雄醫學大學再生醫學與細胞治療研究中心 5 高雄醫學大學藥學系 6 高雄醫學大學附設中和紀念醫院胃腸內科

Background: Chemotherapy is the treatment of choice for gastric cancer, but the currently available therapeutic drugs for the treatment have limited efficacy. Recent studies suggested that gastric cancer stem cells may play an important role in drug resistance of chemotherapy. Therefore, new agents that selectively target gastric cancer stem cells in gastric tumor are urgently needed. SIRT3 is a key NAD+-dependent protein deacetylase in the mitochondria of mammalian cells, functioning to prevent cell aging and transformation via regulation of mitochondrial metabolic homeostasis. SIRT3 in glioma stem cells GSC increases mitochondrial respiratory capacity and maintained stemness. Aims: The investigate the role of the stemness inhibition by 4BR in gastric cancer. Methods: The protein expressions were performed by western blotting. The stemness-related receptors were evaluated by flow cytometry, and stemness characteristics were evaluated by the ability to form spheroids and colonies. Cell viability was measured by CCK8 assay. Results: 4 BR inhibited human gastric cancer cells stemness thorough JNK-SIRT3 signaling pathways. Combination of 4BR with 5FU enhanced chemo-toxicity to human gastric cancer MKN45 and AGS cells. Conclusions: Targeting the metabolic mechanisms regulating SIRT3 may provide a novel therapeutic option for intractable patients with gastric cancer. Small molecule inhibitor of SIRT3, 4’-bromo-resveratrol (4BR), is an analog of resveratrol.

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P.131 胃癌細胞移植異源性粒線體的分泌體學研究 THE MITOCHONDRIAL PROTEOME REGULATED BY HETEROLOGOUS MITOCHONDRIA TRANSPLANTATION IN GASTRIC CANCER 1,2

2,4

陳彥成葉俊余郭富珍許文鴻黃斌吳登強 1 衛生福利部旗山醫院內科 2 高雄醫學大學附設中和紀念醫院胃腸內科 3 義守大學學士後醫學系 4 高雄醫學大學醫學系 5 高雄醫學大學生物醫學暨環境生物學系

Background: Mitochondria affects the Mitochondria transplantation been attempted to be applied in rescuing the aging cells or reversing the malignance of cancer cells. Based on the hypothesis of endosymbiosis, cells can uptake mitochondria either purified from autologous or heterologous cells. In the cardiophathy mice, the transplanted mitochondria enhances the function of cardiomyocytes. Transplanted with the autologous mitochondria, the malignance of breast cancers were reduced. In the present study, the AGS gastric cancer cell transferred with mitochondria extracted from gastric epithelial cells of normal tissue (GES-1) showed a attenuated malignance, however, transferred with vascular endothelial cells (EAhy) showed an increased malignance. Further elucidating the molecular signaling cascade, the exosomes purified from these treatments were subjected to quantitative proteomics analysis Aims: With this study, the role of exosome in regulating cancer metastasis after mitochondrial transplantation can be further elucidate. Methods: The current experiment was designed as three groups: AGS only, AGS+GES Mito, AGS+EAhy Mito. Mitochondria was extracted from GES-1 and EAhy two donor cells separately. The mitochondria was incubated with acceptant cell AGS for 1 hour and the medium was replaced by serium free medium. The exosomes were collected by the commercialized kit with precipitation for 24 hours. The exosomes were lysed and the protein amounts were measured. Ten nano grams of exosomal proteins were trypnized and then analyzed by nLC-MS/MS with the algorithm against human database. Results: The present result showed that 134 proteins from AGS, 123 proteins from AGS+EAhy and 131 proteins from AGS+GES Mito were identified. 8 proteins with identical elevated expression and 11 proteins with decreased

expression were identified specifically in the group of AGS+GES Mito as compared to AGS group. 9 proteins with increased expression and 10 proteins with decreased expression were identified in the group of AGS+EAhy. Further investigation showed that these proteins were involved in ERK, TGF-beta and VEGF signalings. As a result, transplantation with heterologous mitochondria showed a possible implications in regulating carcinogenetic response of AGS. Conclusions: Mitochondria transplantation showed a significant regulation in the migration and malignance of AGS. These secretomic exosomes provide a valuable reference for discussing the signal transmission between the cancer cells.

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P.132

P.133

肝癌衍生生長因子調節纖維母細胞分化在胃癌進程之角色 THE ROLE OF HEPATOMADERIVED GROWTH FACTOR (HDGF)-REGULATED FIBROBLAST DIFFERENTIATION IN THE GASTRIC CANCER PROGRESSION

實際發炎性腸道疾病治療時，兩種不同機轉之生化製劑定位 POSITIONING OF ANTI-TNF OR ANTI-INTEGRIN THERAPY FOR INFLAMMATORY BOWEL DISEASES IN REAL-WORLD PRACTICE

1,2

1,3

1,2,3

施翔耀李佳容劉忠榮朱能生蘇育正郭昭宏 1 高雄醫學大學附設中和紀念醫院胃腸內科 2 高雄巿立小港醫院內科 3 高雄醫學大學醫學系

Background: Gastric cancer, as one of the most prevalent cancers worldwide, is the second leading cause of cancer-related mortality in the world for the prognosis of gastric cancer is generally poor, especially in patients with advanced stage. Helicobacter pylori (H. pylori) infection causes the chronic inflammation of stomach as well as the development of gastric cancer, with a three to six-fold increased risk of gastric cancer. Carcinomaassociated fibroblasts (CAFs) are myofibroblasts in tumor microenvironment, which possess various abilities to promote the progression of cancer by stimulating neoangiogenesis, proliferation, migration, invasion and therapy resistance of tumor cell. Hepatoma-derived growth factor (HDGF) plays a critical role in tumor cell proliferation, anti-apoptosis, VEGF expression, lymph node metastasis and poor prognosis in human gastric cancer. Aims: In the present study, we will investigated the effect of HDGF on differentiation of human bone marrow mesenchymal stem cells (HBMMSCs) in to CAFs. Methods: AGS cells are infected with Helicobacter pylori strain ATCC 49503 in the co-culture experiments. Myofibroblast markers are detected by reverse transcription and real-time PCR. Results: In the present study, human AGS gastric cancer cells infected with H. pylori show high expression of HDGF. HBMMSCs treated with HDGF have properties of CAF-like myofibroblastic phenotypes with increased expression of myofibroblast markers (α-smooth muscle actin [α-SMA], procollagen α1, tropomyoson I, desmin, fibroblast activation protein [FAP]), and fibroblastmarkers (prolyl-4-hydroxylaseA1 [PHA1] and fibroblast specific protein-1 [FSP-1]/S100A4). Conclusions: These findings suggest that HDGF might play a critical role in gastric cancer progress through stimulation of HBMMSCs differentiation to CAF-like cells.

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林煒晟章振旺陳銘仁許自齊王鴻源 1 台北馬偕紀念醫院胃腸肝膽科 2 台北馬偕紀念醫院大腸直腸外科

Background: For any biologic agent, it is likely that a patient will respond best when the agent is used as the first-line option. Adalimumab (ADA) is the first biological therapy approved for moderate-to-severe inflammatory bowel disease (IBD) patients not responding to conventional therapy in Taiwan since 2011, while Vedolizumab (VDZ) is available in June 2017. Anti-TNF or anti-integrin therapy could be reimbursed as the first line of biologics. Aims: The aim of this study is to provide the clinical characteristics of IBD patients receiving biologics in the real world practice. Methods: This retrospective one center study collected data from a cohort of 58 consecutive IBD biologic naïve patients who received biologics treatment between August 2011 and December 2019. Results: There were 41 patients under ADA treatment and 17 patients received VDZ in our hospital. There were no significant differences in age and gender. VDZ was more frequently prescribed (58.8%) for UC patients in comparison with ADA (36.6%), but the difference was not statistically significant (P=0.12). There were no significant different in the disease location of ulcerative colitis (UC) and Crohn’s disease (CD). The penetrating type CD received more ADA but without statically difference (46.2% vs. 28.6%, P=0.40). In the comorbidity of HBV, HCV carrier or latent TB, there were no different in the both groups. The operation history was common in ADA group but without statistical significance. In the combined therapy, there were no difference of 5-ASA, steroid and immunomodulators in both groups. Conclusions: VDZ was commonly used in UC and ADA was used in penetrating type CD patients. However, there was no statistically significant. Both anti-TNF and antiintegrin therapy were considered to be the first-line choice of IBD patients in this real-world clinical practice.

2021 消化系聯合學術演講年會

P.134 透明套輔助換水式大腸鏡失敗時運用透明套輔助換水式胃鏡，無氣囊小腸鏡之經驗 TRANSPARENT CAP-ASSISTED GASTROSCOPE, ENTEROSCOPE (WITHOUT BALLOON) WATER EXCHANGE METHOD IN FAILED TRANSPARENT CAP-ASSISTED, WATER-EXCHANGE COLONOSCOPY

time of 19 minutes. The remaining 2 cases were performed directly with CAE without balloon. The cecum intubation rate was 100%, one ascending colon cancer was found in a young 45 year-old male patient, whose cancer staging was IIIA after surgery. There were no complications. Conclusions: Cap-assisted gastroscope, enteroscope (without balloon) water exchange method was a simple and cheap rescue method in failed transparent cap assisted water exchange colonoscopy.

林連福童綜合醫院內科部肝膽腸胃科 Background: Colonosocopy with polypectomy has been shown to reduce the incidence of colonrectal cancer (CRC), and its associated mortaility [Gastrointest Endosc. 2017;85: 59–66]. Repeated successful colonoscopy can detect lesions in up to 53% of failed colonoscopy [Gastrointest Endosc. 2016;83:1239–1244]. Transparent cap-assisted, waterexchange colonoscopy (TCWEC) can achieve a cecum intubation rate (CIR) of 99.7% in our previous report [Adv Dig Med. 2020;7:118–123]. Aims: The aim of this study is to report our experience using the water exchange cap-assisted gastroscope (CAG), cap-assisted enteroscope without balloon (CAE) in failed TCWEC. Methods: From Nov 2018 to Sep 2020, a total number of 911 cases of colonoscopy using TCWEC performed by a single endoscopist were analyzed. The inclusion criteria were: 1) Failure to reach the cecum using TCWEC. The exclusion criteria were: 1) Poor colon bowel preparation 2) colon cancers with strictures. The rescue methods were water exchange technique as described previously [Adv Dig Med. 2020;7:118–123], but using CAG, CAE without balloon instead of colonoscope. The instruments used in CAG, CAE were GIF-H290, SIF-Q260, Olympus Optical Co., Ltd., Tokyo, Japan, water infusion pump with room-temperature water, and Olympus distal attachment (transparent cap) D-201-10704. Pethidine and midazolam or intravenous propofol sedation were used. Results: There were 4 failed TCWEC cases (3 female, and 1 male patients), with the mean age of 55 (45-63 yr) after excluding six cases of colon cancers with stricture, and 4 with poor bowel preparation. The mean intubation time in failed TCWEC was 16.3 (6-30 minutes), and the mean cecum intubation time with the rescue methods was 15.5 (12-19 minutes). The first case was successful with CAG. In the second case, CAG was tried for 20 minutes, but only successful with CAE without balloon with intubation

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P.135 Vedolizumab 及 Adalimumab 對潰瘍性大腸炎之比較：南臺灣單一醫學中心經驗 VEDOLIZUMAB VERSUS ADALIMUMAB FOR CROHN’S DISEASE: A SINGLE-CENTER EXPERIENCE OF SOUTHERN TAIWAN 1

1,2

陳建宏郭行道許銘仁孫啟書林育民馮意哲 1 奇美醫療財團法人奇美醫院胃腸肝膽科 2 奇美醫療財團法人奇美醫院內科部

Background: Biologic therapies are widely used in patients with Crohn’s disease. A new head-to-head trials of Vedolizumab versus Adalimumab for Moderate-to-Severe Ulcerative Colitis has been studied recently which showed vedolizumab was superior to adalimumab with respect to achievement of clinical remission and endoscopic improvement. However, data of Crohn’s disease are lacking. Aims: We would like to compare Vedolizumab versus Adalimumab for Crohn’s disease by a single-center experience of Southern Taiwan. Methods: The study enrolled the biologic-naive Crohn’s disease patients who received biological therapy at least two doses of vedolizumab (4 patients) or adalimumab (4 patients) in Chi-mei hospital from November 2018 to November 2020. All patients receiving biologics therapy followed the rule of the National Health Insurance Administration. We used CDAI score for clinical response (defined as a >100-point decrease in CDAI score) at Week6 and clinical remission (defined as a Crohn’s Disease Activity Index [CDAI] score <150 points) at Week24 and used MaRIA index for MR enterography (MRE) improvement evaluation. The MaRIA index was calculated using the previously published formula: 1.5 × wall thickening (mm) + 0.02 × RCE (relative contrast enhancement) + 5 × oedema + 10 × ulcers. We defined deep MRI remission as no segmental MaRIA > 7 and MRI remission was defined as no segmental MaRIA > 11 according to Barcelona criteria. Results: Total 8 patients who were enrolled received at least two doses of vedolizumab (4 patients) or adalimumab (4 patients). At week6, clinical response was observed in all of 8 patients. In addition, 1 patients achieved clinical remission at W24 in the vedolizumab group and 2 patient in the adalimumab group (25% vs. 50%; difference, 25 percentage points; 95% confidence interval [CI], -2.5 to 15.0; P=0.6). 1 patient (Case1) with poor response to

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maintenance therapy of Vedolizumab and the endoscopic biopsy confirmed diagnosis of CMV reactivation (Figure 1). After Ganciclovir therapy for CMV reactivation, the clinical condition had improved and without switching biologics. The other 3 patients received Vedolizumab showed good response and achieved mucosal healing and MRI remission but 1 of them deteriorated later due to suspension by the rule of National Health Insurance Administration. On the other hand, 1 patient (Case7) of the Adalimumab group accepted ileum-segment resection due to segmental stricture of ileum during induction therapy but improved condition after operation. The other 3 patients showed good response to maintenance therapy of Adalimumab and 2 patients achieved mucosal healing and MRI remission (Table 1). Conclusions: In this retrospective experience involving patients with Crohn’s disease, all the patients receiving either vedolizumab or adalimumab had good clinical response early and about half of patients achieved mucosal healing of clinical remission, MRI remission and endoscopic improvement during maintenance therapy. Although biologic therapies provided good control of the disease’s progression and improved the patient’s quality of life. Nevertheless, their use can cause an increased risk of new infectious events and/or reactivation of latent infectious diseases such as cytomegalovirus coinfection. In addition, our case number is too small, resulting in a difference that was not statistically significant. More included cases and further prospective study are needed.

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P.136

P.137

大腸癌 MIR 與醫療保健支出的 GDP 佔比之間的相關性 FAVORABLE COLORECTAL CANCER MORTALITY-TO-INCIDENCE RATIOS IN COUNTRIES WITH HIGH EXPENDITURES ON HEALTH AND DEVELOPMENT INDEX

發炎性腸道疾病：單一醫院之回溯性研究 CLINICAL FEATURE AND TREATMENT OF INFLAMMATORY BOWEL DISEASE IN LOW INCIDENCE AREA A HOSPITAL BASED RETROSPECTIVE COHORT STUDY IN TAIWAN

1,2,3

2,3,4

2,5

1,2,3

汪奇志宋文緯顏佩怡柯博允蔡明璋 1 中山醫學大學附設醫院肝膽腸胃科 2 中山醫學大學醫學系 3 中山醫學大學醫研所 4 中山醫學大學附設醫院泌尿科 5 馬偕紀念醫院醫學教育部

Background: Global variation in the incidence and outcomes of colorectal cancer (CRC) is associated with many factors, among which screening policies and early treatment play substantial roles. However, screening programs and intense treatment are expensive and require good health care systems. For CRC, no clear association has yet been established between clinical outcomes and health care disparities before. Aims: The association between health care disparities and mortality-incidence ratio (MIR) of colon cancer. Methods: We used the MIR of CRC as a measure of clinical outcomes for comparison with the Human Development Index (HDI), current health expenditure (CHE), and current health expenditure as a percentage of gross domestic product (CHE/GDP) using linear regression analyses. Results: We included 171 countries based on data from the GLOBOCAN 2018 database. We found that the regions with the lowest MIRs for CRC are Oceania and North America. A significant correlation was observed between incidence, mortality and HDI, CHE, and CHE/GDP among the countries enrolled. Furthermore, lower MIRs of CRC significantly correlated with higher HDI, CHE, and CHE/ GDP (p < 0.001, p < 0.001, and p < 0.001, respectively). Conclusions: CRC MIRs tend to be most favorable in countries with high health care expenditures and a high HDI.

顏旭亨許翠純陳洋源蘇培元楊佳偉彰化基督教醫院胃腸科 Background: Inflammatory bowel disease (IBD) has emerged in the Asia–Pacific area over the past two decades. There is a paucity of clinical data regarding the real-world experience of IBD patients from low-endemic areas such as Taiwan. Aims: The present study aimed to review the clinical features of IBD patients in a tertiary center in Taiwan. Methods: A total of 163 IBD patients were identified from the electronic clinical database of Changhua Christian Hospital. Demographic data of the patients and clinical features of disease patterns were retrospectively reviewed. Results: There is a higher proportion (62.6%) of patients with a diagnosis of UC. Both CD and UC patients have a male predominance. The median age of diagnosis is younger among CD patients compared with UC patients (CD vs UC: 31 vs 40-year-old, p=0.0423). The disease distribution of UC was as follows: E1 (15.7%), E2 (47.1%), and E3 (37.3%). The disease distribution of CD was as follows: L1 (36.1%), L2 (14.8%), L3 (42.6%), and L4 (6.5%). The majority of CD patients had a complicated presentation with B2 (32.8%) and B3 (32.8%). CD patients have a higher bowel resection rate compared with UC patients. Patients with CD are more likely to be treated with immune modulators and biologics and UC are more likely to be treated with 5-ASA. Conclusions: UC with male predominance was the predominant type of IBD in the study. CD patients are likely to have a complicated disease course requiring a higher demand for biologic therapy than UC patients.

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P.138

P.139

以內視鏡切除 PT1 大腸腺癌之預後分析 OUTCOME OF PT1 COLORECTAL ADENOCARCINOMA TREATED BY ENDOSCOPIC RESECTION

大腸鏡對於 90 歲以上病患相關的安全性和重要性 SAFETY AND IMPORTANCE OF COLONOSCOPY IN NONAGENARIANS

1,2

陳紹宇張允亮張麗文劉玉華孫灼基楊國卿 1,2 林裕民 1 新光吳火獅紀念醫院胃腸肝膽科 2 輔仁大學醫學系

Background: Endoscopic management of colorectal neoplasm is common practice in our clinical work, however, its application for the treatment of pT1 colorectal cancer (CRC) remains controversial. Aims: This study aims to understand the outcome of pT1 CRC treated by endoscopic resection. Methods: We retrospectively evaluated CRCs reported in a single hospital between 2014 and 2018 from the cancer registry database. Records of age, gender, characteristics of tumor and treatments were acquired in patients with pT1 CRC. Those with the initial treatment of endoscopic resection were enrolled for analysis. The treatment outcome was accessed according to the resected margin of tumor (adequate or inadequate), lymph node metastasis (yes or no), recurrence of CRC (yes or no) and mortality (yes or no). Results: A total of 1249 colorectal cancers were identified in the registry database. Among them, 173 were reported as pT1. The mean age was 63.7y. Male to female ratio was 1.47. Endoscopic resection was applied as the initial treatment in 31 cases (17.9%) of pT1 CRCs, including: polypectomy (n=2), endoscopic mucosal resection (EMR, n=25), endoscopic submucosal dissection (ESD, n=4). The morphology of the pT1 tumors revealed polypoid (Paris classification: Ip, Isp and Is) and non-polypoid (Paris classification: IIa, IIb and IIc) in 15 (48.4%) and 16 (51.6%) patients respectively. The resected margin revealed inadequate in 8 of 15 polypoid tumors (53.3%). They were either rescued by surgical resection (n=5), ESD (n=1) or close observation (n=2). The surgical specimen showed residual tumor in 3 of these 8 CRCs (37.5%). The resected margin revealed inadequate in 9 of 16 non-polypoid tumors (56.3%), and all were rescued by surgical resection. The surgical specimen showed residual tumor in one of these 9 CRCs (11.1%). There were no cases presented with lymph node metastasis, recurrence of CRC and mortality after a median follow-up of 2.8 years. Conclusions: Our results suggest endoscopy resection was effective for the treatment of pT1 CRC. Residual tumor was estimated in about 13% (4/31) of pT1 CRC treated by endoscopic resection, accordingly, their utilization should be applied with caution.

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1,2,4,5

2,4,5

1,3,4

3,4

宋寬益王彥博張天恩王煥昇姜正愷 1,2,4,6 2,5 1,2,4 1,2,4,5 羅景全李發耀侯明志盧俊良 1 臺北榮民總醫院內視鏡診斷暨治療中心 2 臺北榮民總醫院肝膽腸胃科 3 臺北榮民總醫院大腸直腸外科 4 臺北榮民總醫院內科部 5 陽明醫學大學腦科學研究所 6 衛生福利部基隆醫院腸胃肝膽內科

Background: With the growth of aging population, the need of colonoscopies on nonagenarians is rising. However, few data on colonoscopies for the extremely elder are available. For better acknowledgement of colonoscopies’ role in this specific group of patients, we conducted this study to evaluate its safety and clinical impact. Aims: To evaluate the safety and clinical impact of colonoscopy in nonagenarian patients. Methods: We performed a retrospective cohort study comparing nonagenarians who received colonoscopy in a tertiary medical center in Taiwan in 2016 with 1:1 matched 76-80 year-old patients (relative elderly patients) as a control. The post-colonoscopy 30-day adverse events, mortality and long-term survival were recorded. Results: A total of 137 nonagenarians and 137 relative elderly patients were included. Nonagenarians receiving colonoscopy were more likely to be hospitalized (40.1% vs. 19.0%, P < 0.001) and the adjusted colonoscopy completion rates were comparable in both groups (92.0% vs. 97.1%, P = 0.063). The overall adverse events rate and post-colonoscopy 30-day mortality rates were low in both groups (2.9% vs. 1.5%, P = 0.409 and 2.2% vs. 1.5%, P = 0.652, respectively). A total of 18.2% of nonagenarians were diagnosed with advanced neoplasia. Among the nonagenarians diagnosed with colorectal cancer, patients receiving surgery had a significantly lower risk of death compared to patients receiving conservative management (hazards ratio 0.1044, 0.01275-0.8529, P = 0.038). Conclusions: Colonoscopy in patients older than 90 years is generally safe. Colonoscopy findings that led to surgery in nonagenarians diagnosed with colorectal cancer were associated with survival benefits.

2021 消化系聯合學術演講年會

P.140 加護病房內床邊大腸鏡：一個醫學中心之經驗 BEDSIDE COLONOSCOPY IN THE INTENSIVE UNIT: EXPERIENCE IN A MEDICAL CENTER 吳東龍顏旭亨彰化基督教醫院肝膽腸胃科

Conclusions: In this study, the higher GCS level and higher albumin level have signigicant lower mortality rate. The higher platelet level may reduce mortality rate but had significant different (P-value = 0.074). The result of study shows the mortality who received colonoscopy in ICU had relationship with baseline condition insteade of colonoscopy finding.

Background: Colonoscopy is rarely performed in the intensive care unit (ICU) because of the high risk of the procedure. Colonoscopy is generally performed in ICU for suspected ischemic colitis, decompression of colonic distension and lower gastrointestinal hemorrhage. The bowel preparation and the patient condition are different from routine colonoscopy practice. Patients in the ICU usually have more co-morbidities and have a mortality rate. Aims: The result of urgent or emergency colonoscopy in ICU is rarely reported in the literature. We would like to review the medical record and colonoscopy reports in ICU. Collecting lab data and reports then figure out the relationship between who received colonoscopy in ICU and mortality risk during the hospital course. Methods: From Jan 2019 to June 2020 all patients in our medical center who received colonoscopy examination were enrolled. Patients with pending cardiac transplant and who received colonoscopy out of ICU were excluded. Univariate and multivariate analysis were performed. Results: A total of 79 patients were enrolled and included in the analysis (46 Alive, 33 Death). The median age was 78-year-old. The patients had Angiodysplasia (n=3, 3.8%), Colitis (n=17, 21.5%), Colonic ulcer (n=2, 2.5%), Diverticulosis (n=3, 3.8%), Hemorrhoid (n=10, 12.7%), Rectal ulcer (n=16, 20.3%), Tumor (n=10, 12.7%), Volvulus (n=1, 1.3%), Unknown Bleeding origin (n=4, 5.1%) and Non-diagnostic (n=13, 16.5%). The survival group (n=47) had ststaticlly different higher GCS score (average 11, range from 9 to 11, P-value = 0.05, adjusted OR P-value = 0.025) compared to mortality group (n=33, average 10, range from 7 to 11) and significant different higher albumin level (average 2.42, range from 2.2 to 3, P-value = 0.005, adjusted OR P-value = 0.008) than mortality group (average 2.2, range from 1.9 to 2.5). The platelet level in survival group (13.9k/mm3) is higher than mortality group (10.3K/ mm 3) but the ststaticlly different boarderline (adjusted OR P-value = 0.074). The major finding with rectal ulcer and colitis who had 5.44 time higher mortality risk than others but no statistically significant diffierent (adjusted OR P-value = 0.154).

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P.141

P.142

針對 40-49 歲族群以糞便潛血檢查進行精準化大腸直腸癌篩檢 ─ 初步成果 PRECISE COLORECTAL CANCER SCREENING WITH FECAL IMMUNOCHEMICAL TEST IN THE POPULATION AGED 40-49 YEARS: A PRELIMINARY RESULT

使用 Adalimumab 治療中度至重度潰瘍性結腸炎：單一中心治療經驗 EXPERIENCE OF ADALIMUMAB THERAPY FOR MODERATE TO SEVERE ULCERATIVE COLITIS

1,2,3

1,3

張鴻俊張麗文劉玉華陳瑞灝朱光恩孫灼基 1,3 1 林裕民楊國卿 1 新光吳火獅紀念醫院胃腸肝膽科 2 新光吳火獅紀念醫院癌症防治中心 3 輔仁大學醫學系

Background: The incidence of colorectal cancer among young adults less than 50 years is increasing in Taiwan in recent ten years. However the efficient screening strategy for this population is still unclear. Aims: Our study is aimed to provide precise colorectal cancer screening program with fecal immunochemical test (FIT) in the population, aged 40‒49 years and to early detect colorectal cancer and to reduce the colorectal cancer incidence in this population. Methods: We provide the FIT screening for persons visiting the gastroenterology outpatient clinic, who are aged 40‒49 years with the possible risk factors of colorectal cancer, including family history of colorectal cancer, hypertension, diabetes, hyperlipidemia, fatty liver, obesity, and smoking habit. If the person has positive result of FIT examination, we will arrange further colonoscopy for further confirmation. Results: Until November 30, 2020, a total of 288 patients who met the inclusion criteria, attended this screening project. 227 (78.8%) patients finally returned the fecal collection tube and completed FIT examination. 8 patients (3.5%) reported positive FIT results. 7 patients had received colonoscopy examination for further confirmation. 4 (57.1%) patients among those patients with positive FIT were found to have neoplastic polyps including 3 patients with adenomatous polyps and one patient with adenocarcinoma. The patient with colorectal cancer received treatment of surgical operation and finally staged at early stage of T1N0M0. Conclusions: Although the limitation of small sample size of current study, our preliminary results had showed potential promising effects of the FIT screening focusing in the population aged 40‒49 years, and with risk factors of colorectal cancer. Our findings provided the evidence and supported aggressive precise screening policy among younger adults needed to be considered in the future.

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顏旭亨陳洋源許翠純蘇培元楊佳偉彰化基督教醫院胃腸肝膽科 Background: The anti-TNF agent was reimbursed for the treatment of moderate to severe ulcerative colitis in Taiwan since 2016. Studies on treatment outcomes of adalimumab therapy in non-Caucasian patients with ulcerative colitis (UC) are lacking. Aims: Evaluate the treatment outcome of adalimumab therapy in a single medical centre Methods: A total of 163 IBD patients were identified from the electronic clinical database of Changhua Christian Hospital. Demographic data of the patients and treatment outcome were retrospectively reviewed. Results: Between Jan 2015 and June 2020, adalimumab therapy was started in a total of 18 patients with UC (8 males [50.0%]; median age, 42.5 years [interquartile range, 36 to 51 years]; and median disease duration, 8.1 years [interquartile range, 3.9 to 9.8 years]). Five of 18 patients (27.7%) received induction therapy only due to primary non-response. Of 13 patients who received adalimumab maintenance therapy, 3 (23.1%) stopped adalimumab therapy due to loss of response and one patient (7.7%) hold due to cutaneous reaction to adalimumab. Because the use of adalimumab was limited for one year in Taiwan. Two (20%) of 10 patients finished the 1st course of therapy didn’t experience a relapse during follow-up. Seven patients required a 2nd course of adalimumab with a median time to relapse of 31 weeks [interquartile range, 19 to 43.75 weeks]). Conclusions: The treatment response of adalimumab therapy in our UC patients appear to be comparable to those in previously published Western studies. The majority of responded patients will have disease relapse after a limited duration of adalimumab therapy in Taiwan.

2021 消化系聯合學術演講年會

P.143

P.144

小於 50 歲患者的高風險大腸瘜肉的危險因子 RISK FACTORS OF ADVANCED COLORECTAL POLYP WITH SMALL AND INTERMEDIATE SIZE IN INDIVIDUALS YOUNGER THAN 50 YEARS OLD

換水大腸鏡使用生理食鹽水灌注入鏡法可以減少左側大腸黏液的生成：一項先導觀察性研究 SALINE INFUSION DURING WATER EXCHANGE COLONOSCOPY REDUCES LEFT COLON MUCUS PRODUCTION: A PILOT OBSERVATIONAL STUDY

1,2

2,3

1,2

陳俊瑋林蔚然林淳榮蘇銘堯邱正堂 1 林口長庚紀念醫院胃腸肝膽科 2 長庚大學醫學院 3 新北市立土城醫院胃腸肝膽科

Background: Colonoscopy screening for colorectal neoplasm is recommended at the age of 50 years old. Limited data on the characteristics of colorectal neoplasm less than 50 years old is available. Aims: The aim of this study is to investigate the characteristics of colorectal neoplasm and identify the risk factor of advanced colon polyp in individuals less than 50 years old. Methods: This study was performed in Linkou Chang Gung Memorial Hospital. From Jan, 2015 to Jan, 2017, patients who performed polypectomy with polyp size between 6 to 20 millimeters and younger than 50 years old were enrolled in this study. The demography of patients and the polyp characteristics including polyp pathological findings, size, location and morphology were collected. Descriptive statistics and frequency were calculated. Univariate and multivariate logistic regression analyses were performed for the risk factors of polyp with villous component and high grade dysplasia. Statistical significance was defined as p value < 0.05. Results: A total of 264 patients with 323 polyps were included in this study. The male patients were 183 (69.3%). The demography of patients and polyps were listed in Table 1. In advanced colorectal adenoma, there were 171 (52.9%) polyps ≥ 10 mm, 58 (18%) polyps with villous component and 2 (0.6%) polyps with high grade dysplasia. In multivariate analysis, the polyp size with increasing 1 mm and pedunculated shape were associated with villous component and high grade dysplasia in patients younger than 50 years old (Table 2). For polyp sized ≥ 10 mm, the pedunculated shape was the only risk factor (ORs: 7.62, 95% CI: 3.32-17.49, p < 0.001). Conclusions: Increased polyp size and pedunculated polyp shape are the independent risk factors of advanced colorectal polyps in individuals younger than 50 years old.

鄭吉良郭彥麟蘇怡佳唐瑞祥連昭明謝毓錫 4 Felix W. Leung 1 中壢長榮醫院胃腸科 2 臺北醫學大學附設醫院胃腸肝膽科 3 大林慈濟醫院胃腸肝膽科 4 美國加州大學洛杉磯分校醫學院

Background: Water exchange (WE) colonoscopy improves several colonoscopy outcomes. However, water filling during WE insertion can result in mucus production in the left colon, which may impair mucosal inspection. An observation study reported the substitution of water with saline reduced mucus production (Endoscopy 2020;52:1118-21). Aims: To test the hypothesis that saline filling during WE insertion reduces left colon mucus production. Methods: We performed an observational study and used either normal saline (saline group 1), mixed saline and water at 1:1 ratio (saline group 2), or mixed saline and water at 1:3 ratio (saline group 3) during WE insertion in patients undergoing screening, surveillance or diagnostic colonoscopies. We compared these findings with the reference water group which was video recorded during our previous randomized controlled trial (RCT) comparing right colon adenoma miss rate using WE and carbon dioxide insufflation (J Clin Gastroenterol 2020 [in press]). The amount of mucus in the left colon was scored on a six-point scale by colonoscopists (score 0: nil; score 1: trace clear mucus in thin streaks; score 2: minimal clear mucus in thin strands; score 3: mild opaque mucus in thin strands; score 4: moderate opaque mucus in thicker clumps covering one side of surface; score 5: more opaque mucus in thicker clumps covering more sides of surface). Results: A total of 68 patients (17 patients in each group) completed the study. Demographic features, procedure indications, volumes of fluid infused and aspirated during insertion, cecal intubation time, and withdrawal time were similar in the four groups. Saline groups 1 and 2 were associated with less mucus production compared to saline group 3 and water filling (median score 0 [saline 1]

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P.145 vs. 1 [saline 2] vs. 2 [saline 3] vs. 2 [water]; P < 0.0001, Kruskal-Wallis test). The proportion of patients with left colon mucus score ≤2 were significantly higher in saline groups 1 and 2 compared to saline group 3 and water group (100% [saline 1] vs. 100% [saline 2] vs. 88% [saline 3] vs. 65% [water]; P = 0.003, Fisher exact test). Fifteen patients (7 in saline group 1, 4 in saline group 2, 4 in saline group 3) had blood tests 20 minutes before and 60 minutes after colonoscopy and no acute electrolyte (including sodium, potassium, chloride) abnormality was found in any patient. Conclusions: Normal saline filling during WE insertion is associated with less mucus production by the left colon compared to water filling. A 50% diluted saline solution achieves similar effects as normal saline on mucus reduction. The provocative data warrant confirmation in a RCT.

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利用微晶腸胃道病原體多標的核酸檢測評估發炎性腸道疾病病患之腹瀉 MULTIPLEX GASTROINTESTINAL PATHOGEN PANEL FOR EVALUATION OF DIARRHEA IN PATIENTS WITH INFLAMMATORY BOWEL DISEASES 1,2,3

1,2

2,4

林敬斌王賀立陳善銘 1 中山醫學大學附設醫院內科部肝膽腸胃科 2 中山醫學大學醫學系 3 中山醫學大學微生物免疫研究所 4 中山醫學大學附設醫院兒科部 Background: Gastrointestinal infections, in particular Clostridium difficile (CDI), are common in patients with IBD, a flare of IBD may be indistinguishable from acute infectious gastroenteritis with patients presenting with diarrhea, rectal bleeding and abdominal pain; gastrointestinal infections as well as antibiotic use may themselves trigger a flare of IBD. Aims: To evaluate an IBD patient presenting with symptoms of a flare using multiplex gastrointestinal pathogen panels (GPPs). Methods: We performed a retrospective cohort study in 42 patients with IBD between January 1, 2020 to December 31, 2020, and underwent stool testing for suspected symptoms of IBD flare (diarrhea, rectal bleeding, and/or abdominal pain). infectious evaluation for diarrhea was performed exclusively using conventional stool testing (stool culture and C. difficile PCR, detects C. difficile toxin A gene (tcdA), and GPP, BioFire FilmArray GI Panel®, This test detects nucleic acid from 22 pathogens including 13 bacteria, 5 viruses, and 4 parasites, including C. difficile genes for both toxins A (tcdA) and B (tcdB). Results: We performed 32 stool cultures tests and 32 GPPs, in both inpatient and outpatient setting in all patients. Approximately 4.2% stool cultures tested positive, and ~10% C. difficile PCR tests were positive. Of all GPPs test performed, overall positivity is 36% (including C. difficile 16.3%). Median time from collection to result was 18 hours for FilmArray and 47 hours for culture. Patients diagnosed by FilmArray were more likely to receive targeted rather than empirical therapy, compared to those diagnosed by culture. Conclusions: In patients with suspected flare of IBD, GPPs have higher pathogen detection rate and lead to lower rate of IBD treatment modification. A diagnostic testing strategy based on GPPs is associated with higher hospital-related healthcare utilization as compared to conventional stool testing.

2021 消化系聯合學術演講年會

P.146

P.147

無色素沉著在類黑色素沉著大腸症是檢查診斷腺瘤的指標 THE PIGMENTATION SPARING SIGN: A DIAGNOSTIC MARKER OF ADENOMA ON MELANOSIS COLI

專人清腸衛教可降低大腸鏡之盲腸到達時間 ─ 單一機構的回顧性研究 DEDICATED STAFF FOR PATIENT EDUCATION ON BOWEL PREPARATION REDUCES THE CECAL INTUBATION TIME OF COLONOSCOPY ‒ A SINGLE INSTITUTION RETROSPECTIVE STUDY

詹宜學洪建源謝子鈺林煒晟章振旺陳銘仁馬偕紀念醫院胃腸肝膽科 Background: The appearance of melanosis coli during colonoscopy is largely due to pigment granule deposition in macrophages located in the colonic mucosa. Our observation from the boundary between the adenomatous and normal mucosa supports the theory that pigment-laden macrophages are found to be absent in the adenomatous epithelium. Aims: The study is aimed to know could the pigmentation sparing sign be a colonoscopic marker of adenoma on melanosis coli. Methods: A consecutive of patients scheduled colonoscopy for cancer screening and diagnosed as melanosis coli with polyps during 2020 were retrospectively analysed. The following data were collected including gender, age, endoscopic characteristics including polyp location, number, color, size, surface morphology, surrounding mucosa. For patients with multiple polyps, all polyps were evaluated histologically. Results: During the study period, 35 polyps in 16 patients (5 males and 11 females, aged 22 to 72 years [mean, 49.1 years]) who were diagnosed with colonic polyps on melanosis coli were retrospectively reviewed. These included 24 polyps with pathologically confirmed adenoma and 14 polyps with hyperplasia polyps. The average size of adenoma was 3.9 mm (range, 2–10 mm) and the size of hyperplasia polyp was 2.9 mm (range, 2–6 mm). The sensitivity was 95.2%, the specificity was 78.6 and the positive predict valve was 87.0% and the negative predict calve was 91.0% for the pigmentation sparing sign to predict adenoma. Conclusions: The overall accuracy is 88.6% for a pigmentation sparing sign to predict adenoma on melanosis coli fore. If detected, removal and further histopathologic analysis of the polyps may be facilitated.

邱毓澤郭震亞李輔仁張吉仰天主教輔仁大學附設醫院胃腸肝膽內科 Background: Colorectal cancer (CRC) is the leading cause of death in Taiwan. Colonoscopy played an important role in the CRC screening program. Adequate bowel preparation is essential for successful colonoscopy screening. Nevertheless, about one-quarter of colonoscopies are associated with inadequate bowel preparation. There are several high-quality formulations available worldwide, including Bowklean (sodium picosulfate/magnesium citrate (PSMC) preparation). However, its split-dose regimen is sometimes confusing. Besides, another reason of inadequate bowel preparation is because that some patients didn’t adhere to the low residual diet owing to inadequate patient education. To promote Bowklean, dedicated staff for patient education on bowel preparation was provided by Universal Integrated Corporation (Taiwan), but not in every time period because of the clinic room availability. This provided us an opportunity to compare the quality of colonoscopy between the two groups with and without the dedicated patient education. Aims: To compare parameters regarding the quality of colonoscopy between patients undergoing colonoscopy exam with Bowklean as the bowel cleansing agent who received patient education on bowel preparation by dedicated staff and those who didn’t, including cecal intubation time, withdrawal time, total procedure time, the bowel preparation quality, and adenoma detection rate. Methods: All patients who received colonoscopy from an outpatient setting with Bowklean as the bowel cleansing agent during October 2020 to November 2020 were recruited retrospectively through the database of the endoscopy department of Fu Jen Catholic University Hospital. Patients who had previous colonoscopy within three years, were referred from other medical facilities for polyp management, had not completed the procedure for any reason, or had colorectal cancer regardless of being treated or not were all excluded. We divided patients into two groups – those who received patient education on

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P.148 bowel preparation by dedicated staff and those who didn’t, and then compared parameters regarding the quality of colonoscopy between the two groups, including cecal intubation time, withdrawal time, total procedure time, the bowel preparation quality, and adenoma detection rate. Results: 337 patients receiving colonoscopy with Bowklean were found during October to November 2020. 63 patients were excluded. Total 274 patients were recruited, including 150 patients with patient education on bowel preparation by dedicated staff and 124 without. Cecal intubation time was significantly shorter in the patient education group (3.63 min vs. 4.90 min, p = 0.0002). As for the withdrawal time and total procedure time, those with polyp management were excluded owing to the great variability regarding the degree of difficulty and time of polyp management. Comparing the left 88 patients with patient education and 79 without, total procedure time was also significantly shorter (9.32 min vs. 10.53 min, p = 0.0072) but there was no significant difference of withdrawal time (5.72 min vs. 6.11 min, p = 0.10). Adenoma detection rate was calculated in those with positive fecal immunochemical test, while no significant difference was noted in the two groups (9 adenoma detection in 23 vs. 11 adenoma detection in 23, p = 0.552). Regarding the bowel preparation quality, more poor preparation was found in the non-patient education group (2 in 150 vs. 6 in 124) but the significance wasn’t achieved (p = 0.086). Conclusions: Dedicated Staff for Patient Education on Bowel Preparation could reduce the cecal intubation time and total procedure time of colonoscopy, with a trend of lowering the rate of poor colon preparation.

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發炎症性腸道疾病與闌尾黏液囊腫之關係：系統回顧和觀察性研究 THE RELATIONSHIPS BETWEEN INFLAMMATORY BOWEL DISEASE AND APPENDICEAL MUCOCELE: A SYSTEMIC REVIEW AND AN OBSERVATIONAL STUDY 1,2,3

1,2,3

李儀鳴章振旺林煒晟王鴻源 1 馬偕紀念醫院內科部肝膽腸胃科 2 馬偕醫護管理專科學校 3 馬偕醫學院

1,2,3

陳銘仁

Background: The role of Inflammatory Bowel Disease (IBD) plays in appendiceal mucocele remains unclear. In patients with IBD, chronic inflammation is an important risk factor for the development of gastrointestinal malignancies. Orta et al. observed a higher incidence rate of appendiceal mucocele, particularly cystadenoma, in patients with IBD with concurrent colorectal neoplasms. Aims: The aim of this systemic review was to identify the relationship between IBD and appendiceal mucocele. Methods: A comprehensive literature review identified the articles or case reports discussed with the relationship between IBD (including Crohn’s disease and ulcerative colitis) and appendiceal neoplasm. Two reviewers independently screened relevant articles, extracted data, and assessed the cases. The PubMed databases were searched without language restrictions, from their inceptions through Dec 2020. Additional records identified through reference lists checking and google search. Results: The flowchart of article selection is shown in Fig. 1. The search of PubMed identified 94 potentially relevant articles, and additional 6 articles identified through reference lists checking and google search (total n = 100). Eighty-one of which were duplicates. In all, 18 records were screened by title and abstract and assessed for eligibility. Records excluded (n = 5) with reasons: 1. One case study without detailed data; 2. Three cases with appendiceal tumors without presenting mucocele; 3. One article discussed the same patient. Finally, 14 articles (15 cases) were included in the study. The 14 articles last from the year 1998 to 2020. A total of 15 cases (10 male, 5 female, mean age 45.7 ± 13.5 years) were enrolled in the study with the majority of cases are ulcerative colitis (93.3%, 14/15). The disease duration was 11.8 ± 10.1 years, and one case had ruptured appendiceal mucocele (6.7%). The largest appendiceal mucocele was 3.5x11cm. Before

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P.149 the operation, 54.8% (7/13) of patients can be diagnosed from the endoscopy. Only 60% (9/15) had significant symptoms such as abdominal pain or bloody diarrhea. In the histopathological findings, 13.3% (2/15) had a malignancy change of appendiceal mucocele. Conclusions: In conclusion, from this systemic review, some experts had found some connection between IBD and appendiceal mucocele. In this observational study of appendiceal mucocele, the majority of cases are ulcerative colitis with only 60% cases had significant symptoms and 13.3% had a malignancy change.

IBD 患者停用 Vedolizumab 後之急性發作率：單一中心回朔性統計 THE RATE OF RELAPSE IN IBD PATIENTS AFTER CESSATION OF VEDOLIZUMAB: A RETROSPECTIVE STUDY IN A SINGLE MEDICAL CENTER 1,2

1,2

張峻愷馮意哲許銘仁郭行道 1 奇美醫療財團法人奇美醫院胃腸肝膽科 2 奇美醫療財團法人奇美醫院內科部 Background: Inflammatory bowel disease includes Crohn’s disease and ulcerative colitis, and has been rising in its incidence in Taiwan nowadays. Compared to traditional steroids, 5-ASA, DMARD treatments, several novel biologics has been emerged and been widely administrated clinically. Vedolizumab, as a humanized monoclonal antibody, which blocksα-4β7 integrin, decreasing gutselective inflammation were applied in those IBD patient with moderate to severe disease activity since 2017 in ChiMei Medical center. However, we found that some patients would suffered from relapse after few-month cessation of Vedolizumab for insurance or other personal reasons. Aims: Thus, we tried to determine: (1) The relapse rate of IBD after cessation of Vedolizumab. (2) The relationship between relapse group and patient’s basic disease characteristics. Methods: We included the IBD patients (ulcerative colitis and Crohn’s disease were both selected) underwent Vedolizumab since 2017 and had ceased Vedolizumab for 1 months at least. Meanwhile, those who experienced any other intestinal diseases or major comorbidities at the same time would be excluded. The definitions of relapse are set to be fulfill criteria below: (1) CD: an increase in CDAI score of ≥70 points (baseline), or a CDAI score of more than 220; (2) UC: endoscopic mayo score ≥ 2, or Stool Frequency ≥ 2 (> 3-4 /day), or rectal bleeding ≥ 2 (in 50% time). Several basic data were obtained such as: age, gender, biologic exposure history, surgical history, type of CD or UC, previous medications, reasons of discontinuation, follow-up. We evaluated the response of Vedolizumab during 12 months later and relapse status. Results: We included total 12 IBD (both UC and CD included) cases with mostly biologic naive patients without previous operation history. The types of UC and CD varied. The previous medication ranged from steroids, AZA, MTX 2-anti-TNF. There were 5 cases relapse after Vedolizumab cessation among total 12 cases in the average 2.2 months.

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P.150 In contrast, there were 7 cases did not experience relapse after Vedolizumab cessation with the average about 8.1 months to date. As the two groups comparison, we found that the IBD patients most likely to relapse after Vedolizumab cessation may related to previous steroid use than those with DMARD as treatment. Conclusions: In conclusion, the retrospective study implicates that though Vedolizumab is effective as monotherapy during course of treatment, somehow 42% of IBD patients relapse after cessation with the average of 2.2 months, and 80% among them have previous treatment with steroid.

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救援式胃鏡在不完整大腸鏡檢查時的臨床使用經驗 CLINICAL EXPERIENCE OF THE USEFULNESS OF IMMEDIATE RESCUE GASTROSCOPIC EXAMINATION AFTER INCOMPLETE COLONOSCOPY 辛政憲黃仁杰陳季宏李政祺澄清綜合醫院中港分院胃腸肝膽科 Background: Increasing colon diseases include adenomatous polyp, adenocarcinoma or inflammatory bowel disease in the past decades. Although the following non-invasive modalities for example of barium lower gastro-intestinal series, virtual CT or MRI colonoscopy have been developed to evaluate the colon lumen. Colonoscopy with minimally invasive character involves examination of the colon and terminal ileum by using a video-endoscope. With the both diagnostic and therapeutic technique, colonoscopy remains the most popular method to study the colo-rectal disease. Under progressive improvement of scope structure and single person operating technique, up to more than ninety-five percents of cecum intubation rate and less than 0.1 percent of both morbidity and mortality, in respect, has been published in the literature. Although intravenous anesthesia is rather safe in most people, a subgroup of cases with old age and co-morbidity may be not indicated and accepted by the anesthesiologist. The role of small caliber scope like gastroscope will be clarified in this study. Aims: To evaluate the complete rate, safety or total examination time of rescue gastroscopic examination immediately after incomplete colonoscopy in difficult case. Methods: From December, 2017 to December, 2020, incomplete colonoscopy with varying causes was reviewed from single colonoscopist who performs more than twelve hundred cases with 98% of cecum intubation rate per year in executive health management center of Cheng Ching General Hospital. Colonoscope (CF-H290L, Olympus, Co.Ltd, Japan) are used in all the cases by single handed method, underintravenous general anesthesia and CO2 inflation. Rescue gastroscope (GIF-H260, Olympus, Co. Ltd, Japan) was immediately applied to evaluate the colon after incomplete colonoscopy in the same course. Left lateral lying is the preferred position. The variables of age, sex, co-morbidity, safety, cecum intubation rate and its consuming time were reviewed. Results: A total of 12 cases (11 females, 91.6%) with

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P.151 a mean age of 52.7 (30-68) years were included in the analysis. Indications for index colonoscopy included health screening and co-morbidity for 1/12 (8.4%). The failure site were at splenic flexture (4/12, 33.3%) and recto-sigmoid 8/12 (66.7%). 1/12 (acute angle, 8.4%), 8/12 (acute angle and twisted lumen, 66.6%) and 3/12 (pelvic adhesion, 25%) were the causes of incomplete study, in respect. Cecum intubation rate by resuce gastroscope was 7/12 (58.3%, 60-110 cm site) and the remnant A-colon, T-colon and D-colon intubation were 1/12 (8.4%), 3/12 (25%) and 1/12 (8.4%) after total insertion of 110 cm of scope. 8/12 (66.6%) showed normal study and 4/12 (33.4%) had colon polyp. No complication or post-procedure suffering were traced. The mean time for cecum intubation of 7/12 was 398 seconds (6 minutes and 38 seconds). Conclusions: (1) Female is predomint in incomplete colonoscopy. (2) Rescue gastroscope is a helpful diagnostic instrument in incomplete colonoscopy. (3) It is safe and easy to perform rescue gastroscopic examination of colon without time-consuming in failed traditional colonoscopy. (4) Rescue gastroscope can save cost and time when incomplete study of colon. (5) It is time to develop a small caliber colonoscope with 130 cm in length and 3.2 mm working channel for rescue examination or nonsedation and its role of diagnosis and therapy needs to be clarified including cecum intubation rate and safety in mass screening for colonic neoplasm both in healthy, high morbidity and mortality and impropriate case for intravenous general anesthesia.

與大腸直腸癌癌症演進相關的微生物相變化 THE EFFECT ON CANCER CELLS OF BACTERIA ASSOCIATED WITH COLORECTAL CANCER DEVELOPMENT 1,2

1,2

2,3

余方榮吳登強王照元羅嘉慧林仲彥李玲慧 1 高雄醫學大學附設中和紀念醫院胃腸內科 2 高雄醫學大學臨床醫學研究所 3 高雄醫學大學附設中和紀念醫院大腸直腸外科 4 中央研究院生物醫學科學研究所 5 中央研究院資訊科學研究所

Background: Gut microbiota dysbiosis is strongly associated with colorectal cancer (CRC) development. Fusobacteria nucleatum and endotoxin Bacteroides fragilis have been proven to contribute to CRC development. Considering the composition of gut microbiota varies among populations, it is necessary to identify bacteria that contribute to CRC development in Taiwanese population. Aims: We aimed to identify bacteria associated with progression of colorectal adenoma to CRC in Taiwanese population and investigate the effects of these bacteria on biological functions of CRC cells. Methods: Microbiota composition was determined by 16S rRNA amplicon sequencing of adenocarcinomas, paired adenomatous polyps, and paired non-neoplastic colon tissues (referred as tri-part samples) from individual patients. Taxonomic analysis was performed using a merging database including Greengenes, Silva, RDP, HOMD, and Ezbiocloud. Difference of taxa between paired samples was determined by a novel scoring system. The abundance of candidate bacteria was verified by genomic qPCR. Effect of candidate bacteria on cell proliferation, migration, and invasion of CRC cells were evaluated by co-culture system. Results: Fusobacteria nucleatum and Bacteroides fragilis were overrepresented in adenocarcinomas compared to paired adenomatous polyps and non-neoplastic colon tissues. In addition, Bacteria X was also more abundant in carcinomas compared to paired adenomatous polyps. All the three bacteria significantly increased migration and invasion ability of CRC cells while showed minor effect on cell growth. Conclusions: In addition to F. nucleatum and B. fragilis, Bacteria X may contribute to CRC development in Taiwanese population. The increase of these three bacteria in human gut may induce malignant transformation of colorectal adenomas.

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P.152

P.153

安潰悠使用於中重度潰瘍性結腸炎病患之某醫學中心臨床經驗 ULCERATIVE COLITIS TREATED WITH VEDOLIZUMAB: REAL-WORLD EXPERIENCE OF ONE SINGLE MEDICAL CENTER

安潰悠使用於中重度克隆氏症病患之某醫學中心臨床經驗 CROHN’S DISEASE TREATED WITH VEDOLIZUMAB: REAL-WORLD EXPERIENCE OF ONE SINGLE MEDICAL CENTER

吳家慶黃儀倢陳家昌廖思嘉張崇信柯忠旺臺中榮民總醫院胃腸肝膽科

陳義鵬張崇信黃儀倢廖思嘉葉宏仁楊勝舜 1 臺中榮民總醫院胃腸肝膽科 2 中山醫學大學醫學系

Background: The prevalence of ulcerative colitis (UC) in Taiwan is increasing. Biological agents are recommended in patients with moderate to severe UC. Aims: We conduct the study to evaluate the efficacy and safety of anti-integrin Vedolizumab during one-year therapy. Methods: From November 2017 to January 2021, 18 patients of UC who received Vedolizumab in Taichung Veterans General Hospital were enrolled for analysis. We evaluate the clinical response (defined by reduction in MAYO score ≥ 3 and ≥ 30% from baseline) and clinical remission rate (defined by MAYO score ≦ 2 and MAYO endoscopic subscore ≦ 1). The safety profiles including adverse events, infection, and malignancy were also evaluated. Results: Excluding two patients who received vedolizumab less than 14 weeks, we analyse 16 patients of UC for the clinical response and remission rate. The average age at Vedolizumab administration is 49.6 ± 10.1 year-old, and the average duration of UC is 7.24 ± 5.9 years, with a male gender predominant (75%). Eleven patients (68.8%) received steroids and seven patients (43.8%) received azathioprine concomittently. Seven patients were exposed to anti-TNF-alpha biological agents previously. The baseline MAYO score is 11 ± 0.85. One patient discontinued vedolizumab during therapy due to spine surgery. One patient suffered from Vedolizumab secondary failure. The clinical response rate is 87.5% (N = 14), and clinical remission rate is 56.3% (N = 9). One patient suffered from one episode of urticaria during the fourth vedolizumab infusion. No serious adverse events or malignancy were noted during the treatment. Conclusions: Vedolizumab provided effective clinical response and clinical remission in patients with moderate to severe UC during one-year therapy. The safety profile is excellent, without serious adverse events, infection, and malignancy.

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1,2

Background: The prevalence of Crohn’s disease (CD) in Taiwan is increasing. Biological agents are recommended in patients with moderate to severe CD. Aims: We conduct the study to evaluate the efficacy and safety of anti-integrin Vedolizumab during one-year therapy. Methods: From December 2017 to January 2021, totally 22 patients of CD who received Vedolizumab in Taichung Veterans General Hospital were enrolled for analysis. We evaluate the clinical response (defined by CDAI-100) and endoscopic response (defined by SES-CD) during oneyear of Vedolizumab therapy. The safety profiles including adverse events, infection, and malignancy were also evaluated. Results: Excluding 5 patients who received Vedolizumab less than 38 weeks, a total of 17 patients were enrolled for analysis. The average age at Vedolizumab administration is 30.7 ± 11.5 year-old, and the average duration of CD is 3.78 ± 5.0 years, with a male gender predominant (N=81%). Eleven patients (N=64.7%) received steroids use and eleven patients (N=64.7%) received azathioprine use concomitantly. Thirteen patients (N=61.9%) were exposed to anti-TNF-alpha biological agents previously. The baseline CDAI score is 355.2 ± 59.0, and the SES-CD score is 13.0 ± 9.1. One patient suffered from Vedolizumab primary failure, and four patients suffered from deteriorated SES-CD score (>15). The clinical response (CDAI-100) rate is 70.6% (N=12) and the endoscopic remission rate is 29.4% (N=5). One patient had one episode of urinary tract infection during therapy. No serious adverse events or malignancy were noted during the treatment. Conclusions: Vedolizumab provided effective clinical and endoscopic response in patients with moderate to severe CD. The safety profiles are good. However, the clinical remission rate (defined by CDAI < 150) is not high.

2021 消化系聯合學術演講年會

P.154 腸道糞便菌群植入在原位直腸癌小鼠模型之建立 GUT FECAL MICROBIOTA TRANSPLANT IN A MOUSE MODEL OF ORTHOTOPIC RECTAL CANCER 1

2,3

3,4

model of orthotopic rectal cancer and transplant of target bacteria, we can further explore the relationship between gut microbiota and CRC. The role of fecal microbiota transplant in the treatment and alleviation of adverse events of chemotherapy in CRC could be clarified in subsequent studies.

3,4

陳韋志陳彥成謬志豐王照元吳登強盧建宇 1 高雄巿立旗津醫院內科 2 高雄醫學大學附設中和紀念醫院大腸直腸外科 3 高雄醫學大學醫學系 4 高雄醫學大學附設中和紀念醫院胃腸內科

Background: The gut microbiota is reported to play an important role in carcinogenesis and the treatment of colorectal cancer (CRC). Orthotopic CRC model has some advantages such as use of human cancer cells, metastatic potential and with lymphovascular invasion. Compared with other available models, orthotopic CRC can better investigate the tumor microenvironment. With this study, we present our preliminary data of target bacteria transplant in an orthotopic rectal cancer mouse model. Two-part experiments were performed. The first part was the establishment of orthotopic rectal cancer in nude mice. The second part was transanal infusion of two target bacterial solution, demonstrating the application of FMT. Aims: By using these animal models, we may further investigate the pathogenic or protective effects of specific bacterial species on CRC tumors in mice. Methods: SW480 and SW620 colon cancer cells integrated with infrared fluorescent proteins were injected into the rectal submucosa of nude mice. In the subsequent 30 days, we observed tumor growth weekly using an in vivo imaging system. The bacterial solution was infused anally into the mice to perform bacterial transplant. Phosphatebuffered saline, Acinetobacter lwoffii, and Bifidobacterium longum solutions were infused individually. The 16S ribosomal DNA (rDNA) and polymerase chain reaction of murine feces were investigated to confirm the colonization of target bacteria. Results: In the SW620 orthotopic xenograft rectal cancer model, 4 of 5 mice developed rectal cancer by 30 days after submucosal injection. In the SW480 orthotopic xenograft rectal cancer model, 2 of 6 mice developed rectal cancer by 30 days after submucosal injection. For the 16S rDNA analysis, the mice receiving the bacterial solution infusion demonstrated positive findings for A. lwoffii and B. longum. Conclusions: With the successful establishment of a mouse

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P.155 以低劑量阿斯匹林及營養介入大腸腺性息肉之患者，探討預防大腸直腸癌之前瞻性研究 A PROSPECTIVE STUDY OF PREVENTION OF COLORECTAL CANCER USING LOW DOSE ASPIRIN AND NUTRITIONAL INTERVENTION IN SUBJECTS WITH ADENOMATOUS POLYPS IN COLON 1

張安迪黃柏儒林俊哲林肇堂 1 中國醫藥大學附設醫院消化內科 2 中國醫藥大學附設醫院消化醫學中心 Background: According to cancer registration statistics of the National Health Administration, the incidence of colorectal cancer in Taiwan is increasing year by year. After 2006, the number of colorectal cancers surpassed liver cancer for the first time, becoming the cancer with the largest number of cancers in Taiwan. According to the statistics of the cause of death of the Ministry of Health and Welfare, Taiwan’s colorectal cancer mortality ranks third among all cancer death causes, second only to lung cancer and liver cancer. Aims: According to the “Adenoma to carcinoma” formation theory (Adenoma carcinoma sequence) is the basic model of colorectal cancer; colorectal cancer mostly evolves from polyps slowly, from abnormal lesions to cancer tissues. This study is to use colorectal polyps as the intermediate factor for colorectal cancer to find out the possible influencing factors. After dietary adjustment (more fiber, less red meat) and aspirin for chemopreventive interventional treatment, follow the colonoscopy to see incidence of polyps reduced or not, and analyze the difference between the fecal microflora before and after to estimate whether it can effectively reduce the incidence of colorectal cancer. Methods: The acceptance, screening, and execution of this research case will be based on the medical institution attached to the China Medical University Hospital. It is expected to recruit 200 volunteer subjects. The trial is expected to run from 2020.07.01 to 2023.06.31. Participants fill out questionnaires to assess gastrointestinal symptoms, eating habits, measure height, weight, waist and hip circumference, blood pressure, etc. Draw 20ml of whole blood, detecting blood sugar, blood lipids (lipid profiles: triglycerol (TG), total cholesterol, low density lipoprotein (LDL) and high density lipoprotein (HDL), uric acid and

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determining serum carcinoembryonic antigen (CEA); retention of stool samples, storage for future microflora analysis. Participants participating in the research project were randomly assigned to two groups using the random number table: the group receiving chemoprevention and the group not receiving chemoprevention. The group receiving chemoprevention will take 100 mg of low dose aspirin (low dose aspirin) daily, and the group not receiving the chemoprophylaxis will not give any medicine. All the subjects participating in the research project are subject to individual nutrition evaluations by professional dietitians in this hospital. Those who are willing to participate in nutritional intervention are arranged to receive nutritional health education and interventional therapy in the nutrition consultation clinic of our hospital. Participants will reduce the total amount of red meat taken in the daily diet, increase the total amount of fiber, and moderately lose weight; participants in nutritional interventions will receive nutritional assessment, blood test and retention of stool at the time of receipt, 3, 6, 9, 12, 18, 24, 30 and 36 months; those who do not participate in nutrition interventions, only take blood tests, retain stool and perform nutritional assessments at the time of receipt, at the 12th month, the 24th month and at the end of three years. All subjects participating in the research project will undergo colonoscopy at the following time (at the time of receipt, 12, 24 and 36 months) in order to find out new colorectal polyps or precancerous lesions or colorectal cancer. Results: After three to six months follow up, body weight decreased accompanied with laboratory examination improvement in the subjects participating in nutrition intervention by reducing the total amount of red meat taken in the daily diet and increasing the total amount of fiber. We analysis the stool microbiota of all participants, and showed the difference of the composition of bacteria (including bacteroidia, clostridia, actinobacteria, fusobacteria etc.) between before and after nutrition intervention with or without chemoprevention. Conclusions: Based on the result, thee nutrition intervention by reducing the total amount of red meat taken in the daily diet and increasing the total amount of fiber decreased the patient’s body weight and make blood lipid improved. Nutrition intervention with or without aspirin chemoprevention both make the difference of the stool microbiota.

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P.156

P.157

急性膽石性胰臟炎經壺腹切開術後，膽囊切除術可下降各種膽石性醫療事件 SERIES CHOLECYSTECTOMY DECREASE RECURRENT BILIARY EVENTS IN ACUTE BILIARY PANCREATITIS PATIENTS UNDERWENT THERAPEUTIC ENDOSCOPIC RETROGRADE CHOLANGIOPANCREATOGRAPHY

接續性膽囊切除術在高手術風險的急性膽囊炎病人，接受膽囊引流術後的臨床角色 ─ 全人口資料庫研究 THE ROLE OF SERIES CHOLECYSTECTOMY IN HIGH RISK ACUTE CHOLECYSTITIS PATIENTS WHO UNDERWENT GALLBLADDER DRAINAGE ‒ A POPULATION DATABASE STUDY

1,2,4

2,4

5,6

汪奇志楊子緯陳宣怡宋文緯陳威良林俊哲 3 1,2,4 曾明性蔡明璋 1 中山醫學大學醫學研究所 2 中山醫學大學醫學系 3 中山醫學大學醫資系 4 中山醫學大學附設醫院肝膽腸胃科 5 中國醫藥大學附設醫院內科 6 中國醫藥大學醫學系

Background: There is few benefit analysis for the role of cholecystectomy (CCY) after therapeutic endoscopic retrograde cholangiopancreatography (ERCP) in gallstone pancreatitis patients. Aims: We analyze the current clinical practice patterns and the subsequent recurrent biliary events (RBEs) between series CCY and no CCY groups in Taiwan. Methods: 317 acute biliary pancreatitis patients underwent therapeutic ERCP were selected from the nationwide population databases of two million random samples. These patients were further divided into series CCY (early CCY & delayed CCY) and no CCY performed. RBEfree survival in the following year, the method of surgical intervention, and types of RBEs were evaluated. Results: In our analysis, only 47 (14.83%) of the 317 patients underwent CCY within 60 days of therapeutic ERCP and 15 (4.73%) patients underwent CCY during index admission. The proportion of laparoscopic CCY in early and delayed CCY group were 80% and 90.6% respectively. RBEs free survival rates are significantly different (p < 0.0001) in the early CCY (93.33%), delayed CCY (96.88%), and no CCY (64.04%) groups in the following year. The hazard rates of acute pancreatitis, cholecystitis and cholangitis are lower in series CCY group. Conclusions: Series CCY in acute biliary pancreatitis who underwent therapeutic ERCP improve RBE-free survival in the following year. The risks of acute pancreatitis, acute cholecystitis and cholangitis are decreased in series CCY group.

1,2,4

2,4

汪奇志曾明性楊子緯宋文緯陳宣怡 1,2,5 1,2,5 6,7 1,2,4 李祥麟許倍豪林俊哲蔡明璋 1 中山醫學大學醫學研究所 2 中山醫學大學醫學系 3 中山醫學大學醫資系 4 中山醫學大學附設醫院肝膽腸胃科 5 中山醫學大學附設醫院外科部 6 中國醫藥大學附設醫院內科 7 中國醫藥大學醫學系

Background: Cholecystectomy (CCY) is the only definitive therapy for acute cholecystitis. We conducted this study to evaluate which patients may not benefit from further CCY after percutaneous transhepatic gallbladder drainage (PTGBD) has been performed in acute cholecystitis patients. Aims: To evaluate which patients may not benefit from further CCY after percutaneous transhepatic gallbladder drainage (PTGBD) has been performed in acute cholecystitis patients. Methods: Acute cholecystitis patients with PTGBD treatment were selected from one million random samples from the National Health Insurance Research Database obtained between January 2004 and December 2010. Recurrent biliary events (RBEs), RBE-related medical costs, RBE-related mortality rate and an RBE-free survival curve were compared in patients who accepted CCY within 2 months and patients without CCY within 2 months after the index admission. Results: 365 acute cholecystitis patients underwent PTGBD at the index admission. A total of 190 patients underwent further CCY within 2 months after the index admission. The other 175 patients did not accept further CCY within 2 months after the index admission. RBEfree survival was significantly better in the CCY within 2 months group (60% vs. 42%, p < 0.001). The RBE-free survival of the CCY within 2 months group was similar to that of the no CCY within 2 months group in patients ≥ 80

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P.158 years old and patients with a Charlson Comorbidity Index (CCI) score ≥ 9. Conclusions: CCY after PTGBD reduced RBEs, RBErelated medical expenses, and the RBE-related mortality rate in patients with acute cholecystitis. In patients who accepted PTGBD, the RBE and survival benefits of subsequent CCY within 2 months became insignificant in patients ≥ 80 years old or with a CCI score ≥ 9.

高風險急性膽囊炎患者，膽囊引流後接受膽囊切除手術，可有效降低反覆膽道系統就醫事件 SUBSEQUENT CHOLECYSTECTOMY IS THE KEY FOR RECURRENT BILIARY EVENT-FREE SURVIVAL AFTER GALLBLADDER DRAINAGE 1,3

1,2,3

4,5

謝秉勳汪奇志蔡明璋黃彥斌黃文信 4,5 8 1,2,3 4,5 4,5 蔡宗佑曾明性楊子緯林肇堂林俊哲 2,6,7 顏旭亨 1 中山醫學大學醫學研究所 2 中山醫學大學醫學系 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消化醫學中心 5 中國醫藥大學醫學系 6 彰化基督教醫院肝膽腸胃科 7 建國科技大學通識教育中心 8 中山醫學大學醫資系

Background: In previous data, early or delayed cholecystectomy leads to less recurrent biliary events comparing to using a wait-and-see strategy. We wondered if the subsequent cholecystectomy strategy is the most important factor to improve recurrent biliary event-free survival after gallbladder drainage. Aims: The present study aimed to explore the most important factor to improve the clinical outcome after percutaneous transhepatic gallbladder drainage. Methods: We studied 211 adult acute cholecystitis patients who received percutaneous transhepatic gallbladder drainage during index admission between July 2017 and December 2018 in Chung Shan Medical University Hospital and Changhua Christian Hospital. Patients who died during the index admission or lost follow-up within 30 days were excluded. We further divided these patients into those who received subsequent cholecystectomy within 2 months and those who received no cholecystectomy within 2 months. Recurrent biliary events, mortality and biliary event-related mortality were compared. Multivariate analysis was applied to find the most important factors of recurrent biliary event-free survival. Results: There were 8 cases (13.6%) in the subsequent cholecystectomy group that experienced recurrent biliary events, while 39 cases (32.2%) experienced recurrent biliary events in the no cholecystectomy within 2 months group. The proportion and average recurrent biliary events per person were all significantly lower in the subsequent

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P.159 cholecystectomy group. The recurrent biliary event-related mortality difference is insignificant. The most decisive factor to determine recurrent biliary event-free survival is whether a subsequent cholecystectomy performed or not (HR: 0.485, 95% CI: 0.250-0.941, p=0.032). Conclusions: Subsequent cholecystectomy can decrease further recurrent biliary events and improve recurrent biliary event-free survival in high risk patients with acute cholecystitis that accepted percutaneous transhepatic gallbladder drainage initially.

洗腎病患接受膽道內視鏡導致胰臟炎與出血的危險因子探討 RISK FACTOR OF PANCREATITIS AND HEMORRHAGE IN HEMODIALYSIS PATIENTS UNDERGOING ENDOSCOPIC RETROGRADE CHOLANGIOPANCREATOGRAPHY 1,2

1,2

李沅融陳文誌蔡維倫孫煒智李昀達蔡騌圳 1 高雄榮民總醫院胃腸肝膽科 2 陽明交通大學

Background: The cause of pancreatitis and hemorrhage in hemodialysis (HD) patients undergoing endoscopic retrograde cholangiopancreatography (ERCP) is not yet clearly understood. Aims: To investigate the incidence of pancreatitis, hemorrhage and mortality in hemodialysis patients receiving ERCP and to search the risk factors predicting pancreatitis and hemorrhage. Methods: This retrospective cohort study reviewed the clinical data of the hemodialysis patients receiving ERCP in our institute from July 2010 to June 2020. Incidences of pancreatitis, hemorrhage and mortality were assessed, and risk factors were analyzed. Results: The incidence of pancreatitis in hemodialysis p a t i e n t s u n d e rg o i n g E R C P w a s 1 0 . 9 % ( 1 0 / 9 2 ) . The hemorrhage rate is 28.6% (2/7) in endoscopic sphincterotomy (EST), 2.0% (1/50) in endoscopic papillary balloon dilation (EPBD). The mortality rate was 2.2% (2/92). The procedure time of HD patient was significantly longer in the patients with pancreatitis and hemorrhage after ERCP procedure than without (P=0.008, P<0.001). Pancreatitis risk in HD patient received EPBD with balloon less than 8mm was higher than HD patient received EPBD with balloon largest than 8mm (P=0.036). HD patient who received EST had high bleeding rate (P=0.003). Conclusions: Hemodialysis patients to undergo ERCP is still relatively safe. If the procedure time is longer, or if a smaller balloon less than 8mm is used for EPBD, postERCP pancreatitis can be easily occurred. Long procedure time or the use of EST can also easily lead to hemorrhage. Therefore, patients with hemodialysis need to be dilated the biliary tract, EPBD should be considered.

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P.160

P.161

論膽囊息肉形成與脂肪肝疾病的相關性 IS GALLBLADDER POLYP AN INCIDENTAL PHENOMENON IN PATIENT WITH FATTY LIVER DISEASE?

單核苷酸多態性 rs1347093 影響 microRNA216A 的表達並且可能與胰腺癌風險相關 SINGLE NUCLEOTIDE POLYMORPHISM RS1347093 AFFECTS MICRORNA-216A EXPRESSION AND IS ASSOCIATED WITH PANCREATIC CANCER RISK

2,3

林淑賢吳坤達邱逸群王植熙趙景華 1 高雄長庚紀念醫院胃腸肝膽科系 2 高雄長庚紀念醫院一般外科 3 高雄長庚紀念醫院肝臟移植中心

Background: Gallbladder polyps (GBP) are increasingly detected due to widespread use and high image quality of abdominal sonography. In the previous literatures, the association between fatty liver disease (FLD) and gallbladder polyp is still controversial. Furthermore, the risk factors for presentation of GBP such as male sex, obesity and insulin resistance have ever been reported. Aims: To investigate the possible risk factors related to the polyp formation in the gallbladder. Methods: This retrospective study randomized enrolled 270 patients who underwent abdominal sonography for a health evaluation in Kaohsiung CGMH General Health Evaluation Center from September 2019 to July 2020. We excluded patients with history of cholecystectomy, hepatectomy, polycystic liver disease, malignant liver tumor and children with age less than 20-year-old. Baseline characteristics of the study subjects were recorded. Risk factors which were probably related to GBPs were analyzed. Results: Among 270 study subjects, 200 cases (74.07%) with clinically evident FLD were documented by abdominal sonography in our study. GBP was found in 42 (21%) patients, while 158 of them did not associate with GBP. The presence of fatty liver is significantly associated with GBP (GBP patients 42:0 vs non-GBP patients 70:157, p = 0.0002; OR: 189.9, 95% CI: 11.52-3129.69) However, the degree of fatty liver is not dose-dependently associated with GBP (p = 0.376). GBP formation is significantly correlated with BMI (p = 0.013), HbA1c (p = 0.0019), systolic hypertension (p = 0.0002). At the meanwhile, GBP are more frequent found in male (male 30:122 vs female 12:105, p = 0.04; OR: 2.15, 95% CI: 1.054.41), alcohol consumption (alcohol user 5:37 vs non-alcohol user 9:218, p = 0.049; OR: 3.27, 95% CI: 1.04-10.31). Conclusions: GBP formation is associated with male gender, higher BMI, higher HbA1c, systolic hypertension, and alcohol consumption. Furthermore, FLD is an independent-risk factor for GBP formation. Thus, more attention should be paid to figure out GBP in patient with FLD received abdominal sonography.

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徐祖岳黃信閎詹德全林煊淮施宇隆張維國 1 謝財源 1 三軍總醫院內科部胃腸科 2 振興醫療財團法人振興醫院內科部胃腸科 3 三軍總醫院外科部一般外科

Background: Pancreatic cancer is a highly fatal disease and is associated with genetic variations. Aberrant expressions of microRNAs (miRNAs) are associated with pancreatic cancer development and progression. Downregulated expression of miR-216 has been commonly observed in pancreatic cancer. Aims: The aim of this study is to investigate the effect of a single nucleotide polymorphism rs1347093 on miR-216a expression. Methods: Genetic variation rs1347093 was determined from tissues or blood using DNA sequencing method. Quantitative real-time PCR using constructs containing the wild-type or mutant-type rs1347093 (G>T) was performed in two different pancreatic cancer cell lines. Results: The genotyping results indicated that the individuals who carry the genetic variation rs1347093 (G/ T) have a high proportion of pancreatic cancer. Further, genetic variation rs1347093 was demonstrated to inhibit the expression of miR-216a. Conclusions: This study indicated that genetic variation rs1347093 can affect miR-216a expression and may be relevant to pancreatic cancer risk.

2021 消化系聯合學術演講年會

P.162

P.163

胃食道靜脈曲張在晚期胰臟癌病人上的臨床特徵 THE CLINICAL SIGNIFICANCE OF ESOPHAGOGASTRIC VARICES IN PATIENTS WITH ADVANCED PANCREATIC CANCER

在經內視鏡逆行性膽胰管攝影術取得膽汁細菌培養的臨床意義 CLINICAL SIGNIFICANCE OF BILE CULTURE DURING ENDOSCOPIC RETROGRADE CHOLANGIOPANCREATOGRAPHY

1,2

陳宥任侯明志 1 臺北榮民總醫院胃腸肝膽科 2 國立陽明大學醫學院內科學部

陳柏翰陳彥仰黃仲岐彭彥鈞 1 臺中榮民總醫院嘉義分院胃腸肝膽科 2 臺中榮民總醫院胃腸肝膽科

Background: The prevalence of esophagogastric varices in patients with advanced pancreatic cancer is high. However, its clinical significance has never been investigated. Aims: This study was aimed to explore the clinical implication and outcomes of these patients. Methods: A retrospective analysis comprising 257 patients with advanced pancreatic cancer managed from October 2012 to December 2019 identified 35 patients who had presented with esophagogastric varices (EGVs). Clinical characteristics and outcomes were analyzed with special emphasis and comparison between patients with earlyonset or late-onset EGVs. Results: Patients with EGVs had lower platelet count, and higher proportion of splenomegaly, but no difference on overall survival in comparison to those without EGVs. Patients with early-onset EGVs had higher variceal bleeding rate (hazard ratio 11.171, CI: 1.320-94.549, P=0.027) and poorer survival (median: 169 days VS. 288 days, P<0.001) in comparison to those with late-onset EGVs. On multivariate analysis, the response to cancer treatment determine patient’s survival. Patients with tumor invasion to superior mesenteric and portal vein tend to have esophageal varices; those with splenic vein invasion tend to have gastric varices. Conclusions: Patients with advanced pancreatic cancer and early-onset EGVs indicated worse outcomes in terms of bleeding and survival. Further studies are needed to clarify the benefits of prophylactic intervention.

Background: Bile culture is usually performed during during the endoscopic retrograde cholangiopancreatography (ERCP) procedure. The results may indicate antibiotics treatment, but the clinical significance is still not well known. Aims: to evaluate the clinical significance of the bile culture results during ERCP procedure. Methods: During Dec 2019 to Sep 2020, a total 101 bile culture via ERCP procedure were performed at our hospital. The clinical characteristics, bile culture, blood culture and clinical results were collected and analysis. Results: There were 42 patients with positive bile culture results were determined, and total 55 bacteria species were determined. Enterococcus spp., E. coli and Klebsiella pneumoniae were the most common species. There were no significance of the association of bile culture with blood culture, urine culture, and sputum culture. Conclusions: Enterococcus spp., E. coli and Klebsiella were the most common growth in bile culture. The clinical significance needs further investigation.

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P.164 內視鏡超波細針抽吸及細針切片術在胰臟實質病灶診斷的比較 ─ 單一中心的經驗 COMPARE THE ENDOSCOPIC ULTRASOUND WITH FINE NEEDLE ASPIRATION AND FINE NEEDLE BIOPSY FOR DIAGNOSIS OF SOLID PANCREATIC LESIONS ‒ A SINGLE CENTER EXPERIENCE 1

楊其穎黃文信溤俊龍陳政國鄭幸弘 1 中國醫藥大學附設醫院消化內科 2 中國醫藥大學附設醫院新竹分院胃腸肝膽科 3 亞洲大學附設醫院胃腸肝膽科 Background: The diagnosis of pancreatic solid lesion is difficult and challenge by imaging techniques. The endoscopic ultrasound guided fine needle aspiration (EUSFNA) is the important method for tissue acquisition of pancreatic solid lesion. The fine needle biopsy (FNB) needle was developed and obtain more core tissue. There is no optimal needle gauge, number of needles passes, and presence of an on-site pathologist for EUS guided tissue sampling. Some meta-analysis revealed there was no significant difference in the diagnostic accuracy of tissue acquisition rate between EUS-FNA and EUS-FNB. Aims: Compare the specificity and accuracy of EUS-FNA and EUS-FNB in the diagnosis of pancreatic solid lesions. Whether it is different in different parts of the pancreas. Methods: A retrospective review of all EUS-guided sampling with fine needle aspiration or fine needle biopsy was performed from January 2014 to November 2020. The 19-gauge or 22-gauge aspiration needle (EZ Shot 2®, EZ Shot 3 Plus®, Olympus; Expect Slimline®, Boston Scientific) and 22-gauge biopsy needle (Acquire®, Boston Scientific) were used. There was no rapid on-site evaluation cytopathologist during the procedure. The designation of nondiagnostic, atypical gland, atypia, and suspicious are considered negative for malignancy by histology or cytopathology. The malignant or high-grade dysplasia are considered a true positive. The technical success, the cytological diagnostic accuracy, histological diagnostic accuracy, and complications were reviewed and compared. Results: One hundred twenty-one patients (75 men and 46 women) with solid pancreatic lesion were indicated. The median age was 63.6 years (range, 26-89 years). Eighty patients with solid pancreatic lesion received EUS-FNA (19-guage, n=6; 22-guage, n=74) and 41 patients received EUS-FNB. In 72 patients with pancreatic head lesion, 49

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patients received EUS-FNA and 23 patients received EUSFNB; in 38 patients with pancreatic body lesion, 23 patients received EUS-FNA and 14 patients received EUS-FNB; in 11 patients with pancreatic tail lesions, 8 patients received EUS-FNA and 4 patients received EUS-FNB. Ninety-three patients were malignancy and 28 patients were benign lesions, including inflammation change and abscess. The technical success rate was 100%. The specificity of pancreatic tumors was 84.9% (79/93) in all patients, 82% (50/61) in EUS-FNA group, and 90.6% (29/32) in EUSFNB group. The accuracy of pancreatic tumor was 88.4% in all patients, 86.2% in EUS-FNA group, and 92.7% in EUS-FNB group. According to the location, the specificity of the head, body and tail of the pancreas is 82% (41/50), 87.1% (27/31) and 91.7% (11/12), respectively. In EUSFNA group, the specificity of the head, body and tail of the pancreas is 80% (28/35), 83.3% (15/18), and 87.5% (7/8), respectively. In EUS-FNB group, the specificity of the head, body and tail of the pancreas is 86.7% (13/15), 92.3% (12/13), and 100% (4/4) respectively. The specificity of cytolopathology and histology were 62.2% (38/61) and 63.9% (39/61) in EUS-FNA group; 75% (24/32) and 78.1% (25/32) in EUS-FNB group, respectively. Two patient had symptomatic post-procedure acute pancreatitis. Only one patient had active bleeding and needed endoscopic hemostasis. Conclusions: EUS has good diagnostic accuracy and minimal invasive for sampling pancreatic solid lesion. The sensitivity and accuracy of EUS-FNB is better than EUSFNA. Whether it is EUS-FNA or FNB, the diagnosis rate of pancreatic head solid lesion is lower than other parts. The complication of EUS-FNA or EUS-FNB are rare.

2021 消化系聯合學術演講年會

P.165 內鏡括約肌切開術後延遲出血的內視鏡止血治療功效：一個醫療中心的經驗 THE EFFICACY OF ENDOSCOPIC HEMOSTASIS FOR DELAYED POSTENDOSCOPIC SPHINCTEROTOMY (EST) BLEEDING: ONE MEDICAL CENTER EXPERIENCE 1

温家昇莊世杰黃文信余承儒楊其穎鄭幸弘 1 中國醫藥大學附設醫院消化內科 2 長安醫院肝膽腸胃科

Background: Delayed bleeding is the most frequent complication of endoscopic retrograde cholangiopancreatography (ERCP) with endoscopic sphincterotomy. We identify the efficacy of endoscopic hemostasis for delayed post-endoscopic sphincterotomy (EST) bleeding and the risk factors of re-bleeding after hemostasis. Aims: To identify the efficacy of endoscopic hemostasis for delayed post-endoscopic sphincterotomy (EST) bleeding and the risk factors of re-bleeding after hemostasis. Methods: In a single medcal center, total 2632 times sphincterotomy was performed during April, 2015 to March, 2020. To predict the risk factors of repeat endoscopic hemostasis for delayed post-endoscopic sphincterotomy bleeding, we analyzed the characters of the patients before and during these procedures. The analyzation included gender, age, endoscopic retrograde cholangiopancreatography (ERCP) indication, platelet count, international normalized ratio (INR), total-bilirubin, cirrhosis, monotherapy or combined therapy, previous ERCP hemostasis, endoscope type and renal function. Results: Over a 5-year period in a sinle center, total 2632 times EST was perfromed. There were 52 patients (2.13%) had delay post-EST bleeding and dealed with endoscopic hemostasis. In these cases, 41 patients (78.8%) with one session of esophagogastroduodenoscopy (EGD), 9 patients (17.3%) with two sessions, and 2 patients (3.8%) with three sessions, total 65 sessions were noted. Overall success rate is 76.9%. The average days from ERCP to the endoscopic hemostasis is 5.5 days (0-21 days). Monotherapy (n=33) included: Epinephrine injection (n=15); Heater probe (n=12); Hot biopsy forceps (n=5); Argon plasma coagulation (APC) (n=1). Combined therapy (n=32): Epinephrine + thermal coagulation (n=31); Epinephrine injection + thermal coagulation + endoclip (n=1). The endoscope type included duodenoscope (n=32); forward-view (n=28); side-view (n=5). After analyzation,

we found the risk factor of EGD hemostasis failed is CKD stage IV and V (OR: 12.33, p=0.003). No statistically significant in gender, age, ERCP indication, PLT count, INR, T-bilirubin, cirrhosis, mono or combined therapy, previous ERCP hemostasis, endoscope type. In our study, the blood transfusion for post-EST bleeding was 0U (n=26); 1-2U (n=21); 3-4U (n=9); 5-6U (n=2); 7-8U (n=5); 9-10U (n=2). One patient received angiographic embolization/ transarterial embolization (TAE) but no active bleeder identified. One patient expired due to decompsated cirrhosis. Conclusions: The risk factor of EGD hemostass failure after delayed post-EST bleeding is CKD stage IV and V (OR: 12.33, p=0.003).

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P.166 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臨床表現 THE CLINICAL PRESENTATIONS OF LIVER ABSCESS AFTER ENDOSCOPIC RETROGRADE CHOLANGIOPANCREATICOGRAPHY WITH CHOLEDOCHOLITHIASIS 1

劉安哲吳鎭琨邱逸群郭仲謀郭仲煌盧龍生 2 2 3 梁志明蔡成枝許茜甯 1 長庚醫療財團法人高雄長庚紀念醫院內科部長庚醫療財團法人高雄長庚紀念醫院胃腸肝膽科系暨 2 長庚大學醫學系 3 長庚醫療財團法人高雄長庚紀念醫院藥劑部 Background: Pyogenic liver abscesses (PLA) are the most common type of human visceral abscess. Endoscopic retrograde cholangiopancreaticography (ERCP) with sphincterotomy (ES) 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 retrospective study to analyze the clinical presentations of PLA among patients receiving ERCP with choledocholithiasis to figure out the difference of pattern of liver abscess between the patients with ES or not. Methods: We performed a retrospective, descriptive case series at multiple centers assessing demographic characteristics, presentation patterns, etiological factors, microbiological etiology, and management for patients treated for PLA after ERCP with choledocholithiasis. The data retracted 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 patients were enrolled as a cohort and 220 (1.88%) cases developed PLA in the following period for 17 years. We further divided the liver abscess cases into the endoscopic sphincterotomy (ES) group (n = 195) and other ERCP group (n = 25) for analysis. Results: The gender, age, prevelance of malignancy developing, aspirin ( ≧ 28 cDDD), statin ( ≧ 28 cDDD), and proton pump inhibitos ( ≧ 28 cDDD) usage were similar between the two groups. The laborary data, such as glycated hemoglobin, white blood count, liver function, creatinin, and C-eractive protein were also similar, but the

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lower bilirubin level in ES groups than non-ES groups (1.9 ± 2.0 vs. 4.3 ± 5.8, p < 0.001) at the admission date of liver abscess. More patients received endoscopic retrspective biliary drainage in previous ERCP before liver abscess formation in ES than non-ES groups (75.4% vs.36.0%, p < 0.001). The prevelence of complications, such as lung abscess, and meningitis were similar between two groups. The size, location, single or multiple distributions of abscess were also similar. The interval time from previous ERCP to PLA developed was 835.6 ± 1121.9 days vs. 948.3 ± 968.6 days (p = 0.674) in ES and non-ES groups, respectively. We observed blood or pus culture study in 213 cases of which only 67.1% (143) came with positive microbial reports. The most common organism identified was Klebsiella pneumonia (33.3%~40.0%), followed by Escherichia coli (20.0%~25.6%). There were significantly less prevalence infection of Pseudomona in ES than nonES groups (3.6% vs.16.7%, p = 0.007). The choices of treatment for liver abscess (antibiotics only/aspiration/ pigtail/operation) were similar between ES and non-ES groups (36.9/27.7/24.1/9.2% vs. 40/40/12/8%, p = 0.529). More patients were retreated with ERCP in trend in ES than non-ES groups (22.8% vs. 8.3%, p = 0.102). The hospital stay (18.5 ± 13.2 days vs. 22.2 ± 10.4, p = 0.182) and inhospital mortality (12.8% vs. 12.0%, p = 0.908) did not show significant difference between ES and non-ES groups. Conclusions: Although the PLA was the late and relatively minor complication of ERCP after CBD stone removal, it was noteworthy that non-ES group showed the higher Pseudomona infection rate and higher level jaundice than ES groups after damaging the biliary defence system. It should be paid more attention to check the patency of hepatobiliary system in treating this kind of PLA.

2021 消化系聯合學術演講年會

P.167 胰臟癌患者的間質性肺病：盛行率、成因、嚴重度、風險因子與預後的探討 INTERSTITIAL LUNG DISEASE IN PANCREATIC CANCER: PREVALENCE, ETIOLOGY, SEVERITY, RISK FACTOR, AND PROGNOSIS 1,2

1,2

2,3

2,4

于洪元李君陽林俐君趙毅李重賓 1 臺北榮民總醫院胃腸肝膽科 2 國立陽明大學醫學系 3 臺北榮民總醫院護理部 4 臺北榮民總醫院腫瘤醫學部

1,2

Background: Pancreatic cancer is a life-threatening cancer in the world. In recent decades, new anti-neoplastic therapy developed. However, interstitial lung disease (ILD) during anti-neoplastic therapy with gemcitabine, nanoparticle albumin-bounded (nab) paclitaxel and erlotinib, is still unsettled. Aims: To evaluate the prevalence, etiology, risk factor, and prognosis of patients with advanced pancreatic cancer who suffered from ILD. Methods: We retrospectively reviewed all patients with pancreatic cancer who were treated in Taipei Veteran General Hospital in June, 2012 to June, 2020. Baseline characteristics, cancer status, treatment regimens, treatment response, the onset day of interstitial lung disease, the severity, progression-free survival and overall survival were collected. The statistical analysis was performed by R software. Results: Total 1185 patients were diagnosed of pancreatic cancer. Within 940 patients receiving cancer-related therapy, 786 patients ever treated with gemcitabine, 283 patients with nab-paclitaxel, and 407 patients with erlotinib. There were 62 patients suffered from ILD. The prevalence of ILD was 7.3% during gemcitabine therapy, 10.6% during nab-paclitaxel therapy and 7.9% during erlotinib treatment. Among these patients, 57 patients were admitted to hospital for further management. During admission, 15 patients (24%) died due to respiratory failure and 17 patients (27%) developed severe hypoxia and acute respiratory distress syndrome and recovered after intensive care, including intubation and ventilator support. In patients who died after ILD and respiratory failure, 10 patients identified the pathogen that could cause ILD (5 patients with CMV, 1 patient with CMV and PJP, 2 patients with fungal infection, 1 patient with MTB and 1 patient with NTM) and 1 patient had lung metastases with

lymphatic spreading. In 47 patients that survived after the episode, the chemotherapy was re-challenged in 33 patients after the ILD subsided and pancreatic cancer progression. Only 3 patients (9%) developed another ILD episode, and 2 patients identified the pathogen that could cause ILD (one with CMV infection and another with Chlamydophila pneumonia). Only one patient could not identify specific etiology other than medication in both episodes of ILD. Re-challenging chemotherapy again was performed after the ILD subsided and pancreatic cancer progression to the patient who suffered from ILD twice without specific etiology, and no more ILD was noted. Survival analysis was done and the median overall survival was 8.9 months in all patients diagnosed with pancreatic cancer and 13.2 months in patients with ILD history during pancreatic cancer treatment (p < 0.001). Conclusions: ILD happened in patients who underwent treatment for advanced pancreatic cancer. However, in most patients (91%) ILD didn’t happened again after rechallenge of anti-neoplastic agents. Therefore, the ILD was more likely to be drug-related, but not drug-induced and re-challenge after the ILD subsided may be a reasonable option because there was few treatment choice for pancreatic cancer patients and the ILD recurrence was rare.

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P.168

P.169

膽囊切除術後，非預期之總膽管結石，一個醫學中心之十年經驗 UNEXPECTED COMMON BILE DUCT STONE AFTER CHOLECYSTECTOMY: TEN YEAR EXPERIENCE OF A SINGLE MEDICAL CENTER

內視鏡超音波指引下肝臟切片：病例系列報告 ENDOSCOPIC ULTRASOUND-GUIDED LIVER BIOPSY: A CASE SERIES STUDY

鄭幸弘黃文信楊其穎彭成元林俊哲林肇堂中國醫藥大學附設醫院消化醫學中心 Background: Unexpected common bile duct (CBD) stones detected after cholecystectomy in patients without preoperative evidence of CBD stones is a significant clinical issue. Aims: The aim of this study was to assess the prevalence and clinical features of these cases. Methods: A retrospective analysis was performed between 2011 and 2020 at our hospital. Of 1646 patients who underwent cholecystectomy, seven patients received postoperative endoscopic retrograde cholangiopancreatography (ERCP) for clinically significant CBD stones. We reviewed the clinical data of these patients. Results: Overall, seven (4 women, 3 men, age range 2277) of 1646 patients (0.4%) underwent postoperative ERCP after cholecystectomy because of clinical evidence of retained CBD stones. The median time from cholecystectomy to ERCP was 35 days (range, 1 to 113 days). The median size of CBD stones was 6.2 mm. Four of 7 patient had impacted cystic duct stone or cystic duct wall thickening noted during operation. Indications of performing ERCP was jaundice, fever and abdominal pain in most cases. CBD stones were confirmed by image such as computed tomography, abdominal sonography or T tube cholangiogram in five patients before ERCP. There was no post-ERCP complications in these seven patients. Conclusions: The prevalence of clinically significant CBD stones after cholecystectomy was 0.4% and the median time from cholecystectomy to ERCP was 35 days. If impacted cystic duct stone or cystic duct wall thickening observed during operation, the risk of CBD stones after cholecystectomy might be increased.

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1,2

詹崴宇陳建華蕭宗賢徐榮源趙有誠 1 台北慈濟醫院胃腸肝膽科 2 慈濟大學醫學系

1,2

Background: Ultrasonography (US) or computed tomography (CT)-guided liver biopsy is typically used for the diagnosis of hepatic lesion. Acquisition of a pathological tissue remains challenging, especially the hilum and left lobe, due to difficulty in percutaneous access. The presence of ascites is also a contraindication for percutaneous biopsy. Endoscopic ultrasound-guided fine needle biopsy (EUS-FNB) is a well-designed tool for obtaining histology tissue. However, there have been few studies about EUS-FNB using a core needle for liver biopsy. Aims: To evaluate the efficacy of EUS-FNB using core needle for hepatic lesion. Methods: In our case series, EUS-FNB was conducted for hilar lesion, left lobe or other contraindication for percutaneous access, such as ascites between April and September 2020. EUS-FNB was performed using linear scanning echoendoscope (GF-UCT260) with either a 20G (n=2), 21G (n=1) or 22G (n=3). Transduodenal puncture route was done for hilar lesions (n=2) and transgastric puncture route for left lobe lesions (n=4). Assessment included tumor size, puncture route, needle size, number of needle passes, procedure time and pain score after EUSFNB. Results: Six patients underwent EUS-FNB for liver tumor. The range of tumor size was 15-65 mm. The accuracy was 100%. Both sensitivity and specificity were 100%. Two patients had moderate to large amount of ascites. There was no complication. Post EUS-FNB pain score was 0 (n=5). The range of procedure time was 32-53 minutes. The pathology revealed either hepatocellular carcinoma (n=2), cholangiocarcinoma (n=1), abscess (n=2), or gallbladder adenocarcinoma (n=1). Conclusions: EUS-FNB for liver tumor had accurate diagnostic value and safety.

2021 消化系聯合學術演講年會

P.170

P.171

Kayexalate 或 Kalimate 引起的腸胃道副作用：最新資料審查研究 ADVERSE GASTROINTESTINAL EFFECTS CAUSED BY KAYEXALATE OR KALIMATE: A STATE OF THE ART REVIEW

內視鏡手工清洗後之內窺鏡檢視有助於評估手工清洗成效 BORESCOPE CHECK-UP AFTER MANUAL CLEANING OF ENDOSCOPE REPROCESSING CAN HELP TO ASSESS THE EFFECTIVENESS OF ENDOSCOPE MANUAL CLEANING

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吳宜樺周仁偉鄭庚申舒敬軒陳宗偉 1 中國醫藥大學附設醫院肝膽胰腸胃科 2 中國醫藥大學附設醫院內科部 3 中國醫藥大學附設醫院病理科

Background: Patients with chronic kidney disease often suffer from hyperkalemia, an electrolyte adverse event (AE). It is commonly treated by cation-exchange resins such as sodium polystyrene sulfonate (Kayexalate) and calcium polystyrene sulfonate (Kalimate). However, both drugs are associated with some fatal AEs of the gastrointestinal tract. Aims: Our study aimed to assess the clinical characteristics and outcomes of gastrointestinal AEs induced by Kayexalate or Kalimate from published case reports. Methods: We conducted a systematic review of eligible case reports of Kayexalate or Kalimate induced gastrointestinal AEs, from PubMed, Medline, Cochrane Library, Clinical Key, and Google Scholar databases (1948 to March 31, 2020). Then, we analyzed the symptoms, sex, age, gastrointestinal injury locations, and risk factors of enrolled patients. We identified 41 articles describing 135 cases of gastrointestinal AEs induced by Kayexalate (103 cases) or Kalimate (32 cases). Results: The mean age of all patients was 55.54 years (± 20.196 standard deviation). Most patients were male (54.8%). Furthermore, 75 preparations of Kayexalate or Kalimate were administered with sorbitol (75/135, 55.6%), whereas 60 preparations had no sorbitol (60/135, 44.4%). The average treatment period of Kayexalate or Kalimate causing gastrointestinal AEs was 19.84 days (0.5 days to 1 year). The most frequently affected site of gastrointestinal tract was colon (103/135, 76.3%). Histopathological proof for Kayexalate or Kalimate crystals was seen in 95.5% (n = 129) of the patients. Meanwhile, mortality was reported in 20.7% (n = 28). Conclusions: Usage of Kayexalate or Kalimate, without or with sorbitol combination, may be related to fatal gastrointestinal damage. Uremia, hypertension, and transplantation are predisposing factors. Therefore, careful assessment of patient’s history of medications, surgery, intestinal motility, and comorbidity before prescribing Kayexalate or Kalimate for hyperkalemia management is necessary, particularly in end-stage renal disease patients.

倪靜儀王堯生莊喬雄陳炯瑜陳啟益 1 嘉義基督教醫院 2 成大醫院

Background: Endoscope reprocessing including precleaning, manual cleaning, high level disinfection, air drying, and storage. Quality of manual processing is highly emphasized because disinfection of endoscopes would be failed without adequate cleaning. Successful manual cleaning depends on not only human issue but also lots of factors. Many guidelines recommended steps of manual cleaning, and its quality control is through surveillance by ATP (Adenosine Triphosphate Bioluminescence) testing. Utility of borescope for endoscopic channel inspection is for checking surface defects undoubtedly, and borescope may be also a good tool for quality of control of manual cleaning by luminal debris check-up. Aims: We aimed at using ATP test to evaluate the factors relating to successful manual cleaning. Methods: Twelve gastroscopes bear 100 daily endoscopies practicing in the Chia-Yi Christian hospital were enrolled in this study. Factors that may influence the effectiveness of manual cleaning were recorded. Prototypes of borescopes made by National Cheng Kung University were applied to check the working channel for presence of debris before and after manual cleaning. Two kinds of endoscope brushes, the HedgeHog™ brush and the PULL THRU™ brush, were randomly used for manual cleaning. The method and times of brushing were followed according to the instruction of each brush. Besides, the age of the endoscope, the length of manual cleaning time, and the specific procedure of endoscopy were all recorded. The steps of manual cleaning have conformed to the guideline of “The digestive endoscopy society of Taiwan”, and total manual cleaning time was around 5-10 minutes. The ATP test was done with a value lower than 200 RLU to indicate effective manual cleaning. Results: Both HedgeHog™ brush and PULL THRU™ brush were effective for manual cleaning with a respective effective rate of 91.4% (53/58) and 78.6% (n= 33/42) (p =

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P.172 0.08). A time for working channel brushing more than 100 seconds had a higher effective rate than those less than 100 seconds (93.1% [54/58] vs. 11.9% [5/42], p < 0.01). Both which endoscopes and ages of endoscopes were not the factors (p > 0.05). Borescopes were used for evaluation of achievement of debris removal. The proportion of effective manual cleaning by inspection with borescope was as follows: successful debris cleaning after manual cleaning: 93.9% [1/33]; with debris after manual cleaning: 70.6% [24/34]; without debris before and after manual cleaning: 93.9% [31/33] (p = 0.006). The multivariate analysis indicates the only factor relating to effective manual cleaning to be successful debris removal (p = 0.013), rather than the type of brush used (p = 0.69), the procedure of endoscopy (p = 0.26), or the time length of manual cleaning (p = 0.06). Conclusions: In addition to the ATP test, absence of luminal debris at the end of manual cleaning is an indicator of effective manual cleaning. Both HedgeHog™ brushes and PULL THRU™ brush were equal to effectiveness in manual cleaning.

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不明原因腸系膜靜脈硬化疾病：中台灣一醫學中心之經驗 IDIOPATHIC MESENTERIC PHLEBOSCLEROSIS: A SINGLE INSTITUTE EXPERIENCE IN TAIWAN 1

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黃柏儒吳宜樺鄭庚申周仁偉 1 中國醫藥大學附設醫院內科部消化醫學中心 2 中國醫藥大學醫學院 3 台灣小腸醫學會 Background: Idiopathic mesenteric phlebosclerosis (IMP), originally described in 1989 by the Iwashita el al., is a rare type of ischemic bowel disease. It is characterized by thickening of the colonic wall with associated fibrosis, hyalinization, and calcification of the affected veins and submucosa. Initially, Yao et al. named this disease as the term “phlebosclerotic colitis” in 2000. But Iwashita et al. coined the term “idiopathic mesenteric phlebosclerosis” for this disease in 2003. In review of the literature, most reported patients with IMP were from Asian countries or regions, including Japan, Taiwan, Hong Kang, and Korea. In contrast, this disease was rarely reported in the Western countries. Aims: The aim of this study was to investigate the clinical features, diagnostic modalities, treatments, and outcomes of IMP in a teaching hospital in middle Taiwan. Methods: From January 1992 to December 2020, we retrospectively reviewed the medical records of patients diagnosed as IMP at our hospital. The diagnosis criteria were based on the radiographic characteristic of tree-like venous calcifications in the pictures of plain abdominal plain radiography or abdominal computed tomography scan. Clinical characteristic, diagnostic modality, endoscopic features, and treatment outcomes of all patients were analyzed. Results: A total of 35 patients with IMP were enrolled into this study. There were 18 females and 17 males, with a female-to-male ratio of 1.05:1. The mean age was 61.62 years (range, 43-85 years). In our present study, 29 patients (82.8%, 29/35) had at least one risk factor; however, only 6 patients (17.1%, 6/35) had no any risk factors. Twenty-five patients (71.4%, 25/35) were symptomatic and 10 patients (28.5%, 10/35) were asymptomatic. Abdominal pain (84.0%, 21/25) accounted for the major symptom of these patients. The other symptoms were fever, diarrhea, and bloody stools. All patients presented typical characteristics of linear calcifications in the colonic mesenteric veins, 33

2021 消化系聯合學術演講年會

P.173 patients (94%) were confirmed by computed tomography scan and plain abdominal radiography 2 patients (6%) were only confirmed by plain abdominal radiography. In the comorbidity of patients with IMP, our study showed 16 patients had cardiovascular disease (45.7%, 16/35), including hypertension, coronary artery disease, stroke and valvular heart disease; 15 patients had renal disease (42.8%, 15/35), including chronic kidney disease and end stage renal disease, 18 patients had cancer history (51.4%, 18/35), including hepatocellular cell carcinoma, hepatic angiosarcoma, transitional cell carcinoma, renal cell carcinoma and gastric cancer; 14 patients had chronic liver disease, including liver cirrhosis, chronic hepatitis B and chronic hepatitis C; 3 patients had diabetes mellitus (8.5%, 3/35). Our study showed 32 of 35 patients (91.4%, 32/35) received conservative treatment with a good recovery except for 10 patients died of sepsis several years later. In contrast, 3 of 35 patients (8.5%, 3/35) underwent surgical colectomy. Almost patients had good prognosis and the average time of follow-up was 64.2 months. Conclusions: Although IMP is a rare disease, it should be considered by clinicians when treating elderly patients with acute abdomen. Plain abdominal radiography and computed tomography scan are characteristic for definite diagnosis. In our study, conservative treatment is usually adequate for most patients and surgical treatment is only indicated for severe cases.

膽管結紮模式大鼠的腸道菌叢改變 MICROBIOTA DIVERSITY IN COMMON BILE DUCT LIGATION RAT MODEL 1

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彭啟益楊怡津何素鵬彭彥鈞 1 中興大學獸醫系 2 臺中榮民總醫院神經外科 3 臺中榮民總醫院嘉義分院胃腸科 4 臺中榮民總醫院胃腸科

Background: The gut microbiota has been implicated as a role in liver diseases. Recent evidence suggests that microbiota-mediated changes in bile acid profiles and signaling through the liver pathological contribute to impaired host metabolism. Aims: To investigated if the gut microbiota abundance changes in l common bile duct ligation (CBDL) rats. Methods: We fed SD rats for 10 weeks. CBDL were performed in six rats, and the other sham rats were for comparison. CBDL and sham rats were sacrificed 2 weeks after CBDL. We monitored weight, biological data and analysed the gut microbiota from faecal materials. Total DNA was isolated from faecal samples and the V4 region of the 16S rDNA gene was amplified using barcoded primers, and sequencing was performed. Results: The gut microbiota diversity has been demonstrated in Firmicutes abundance relative percentage of sham and CBDL rats (45.6% vs 70.7%, p < 005). At class level, Bacteroidia abundance relative percentage of sham and CBDL rats (44% vs 22%, p < 0.05) The diversity of species changed by species distribution heatmap. Conclusions: Our results indicate abundance percentage changes and the gut microbiota diversity in CBDL rat model.

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P.174 幽門螺旋桿菌與巴金森病的動作波動的研究 HELICOBACTER PYLORI OFTER THE MOTOR FLUCTUARTION IN PARKINSON’S DISEASE 1

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謝孟書張揚沛郭富珍楊淵韓吳登強吳政毅 1 高雄巿立小港醫院內科 2 高雄醫學大學附設中和紀念醫院神經部 3 高雄市立大同醫院神經內科 4 高雄醫學大學醫學系 5 義守大學學士後醫學系 6 高雄醫學大學附設中和紀念醫院胃腸內科

Background: Motor fluctuations can cause remarkable disability and reduced quality of life for patients with Parkinson disease (PD). Aims: To evaluate factors associated with the development of motor fluctuations in patients with PD. Methods: Patients with PD were enrolled in this study between August 01, 2019, and December 31, 2019, and were observed through August 31, 2020. Method: We performed a cross-sectional analysis of data from a hospital-based cohort. Patients who had regular followed up for PD were evaluated for the presence of motor fluctuations. The demographic data, age of onset, motor sub-type, levodopa equivalent daily dose and the stool antigen of Helicobacter pylori (H. pylori) were collected. The occurrence of motor fluctuations was confirmed with structured questionnaire. Results: Twenty-six out of eighty (32.5%) patients with PD developed motor fluctuations. Factor associated with the occurrence of motor fluctuations was Hoehn and Yahr stage ≥ 3 (OR: 4.25, 95% CI: 1.21-14.91, p = 0.024) after adjusting age of onset (>69 year-old), female gender, levodopa equivalent dose (>600 mg/day), and positive stool antigen of H. pylori. Female gender might be associated with higher risk of motor fluctuations without statistical significance (OR: 2.06, 95% CI: 0.66-6.46, p = 0.216). Conclusions: Advanced PD stage was associated with the occurrence of motor fluctuations. The effect of female gender and Helicobacter pylori on the motor fluctuations might warrant future longitudinal study.

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2021消化系聯合學術演講年會摘要手冊

Articles inside

三 ) Recent Advances in Diagnosis and Therapy of IBD

一 ) Cutting-edge of Digestive Endoscopy in Japan

四 ) Antiviral Therapy and Fibrosis Regression in Chronic Hepatitis C

六 ) Treatment Options in GERD: Medical, Endoscopic and Surgical

Carcinoma

五 ) State of the Art Update on the Microbiome in 2021