2023消化系聯合學術演講年會摘要手冊

消化系聯合學術演講年會

論文摘要

台灣消化系醫學會 ( 第五十三屆 ) 學術演講年會

台灣消化系內視鏡醫學會 ( 第三十二次 ) 學術演講年會

會長演講（台灣消化系醫學會）

HCC IMMUNOTHERAPY: NEW HOPE AND NEW CHALLENGE

Yi-Hsiang Huang（黃怡翔）

Division of Gastroenterology & Hepatology, Taipei Veterans General Hospital, Taipei, Taiwan

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

The landscape of hepatocellular carcinoma (HCC) systemic therapy has been changed in recent years. Immuno-oncology (IO) based combination treatment either by atezolizumab plus bevacizumab, or tremelimumab plus durvalumab is now recommended as the front-line systemic therapy for unresectable HCC in international guidelines. IO is not only effective for advanced HCC, a recent Phase III clinical trial IMbrave 050 shows positive results in prolong recurrence-free survival for high risk HCC after curative treatment. In addition, for intermediate stage HCC, TACE is no longer the only treatment of choice after the concept of TACE unsuitable emerges in 2019, and curative treatment for intermediate stage HCC is not a dream by introducing systemic therapy including atezolizumab/bevacizumab or lenvatinib in this field. Even though IO provides new hope to cure HCC even in advanced stage, there are still several challenges on the road. Firstly, there is no clear guidance after atezo/beva or tremel/durva from current international

guidelines. Secondly, the response rate to IO is around 20-30% only. There is lack of clinically practical biomarker to select responder before IO treatment for HCC. One of our studies showed that early AFP reduction by 10-10 rule is a useful on-treatment predictor by IO monotherapy. Recently, we discover that gut microbiota and their metabolites could serve as biomarkers not only to predict objective response rate, but also progression-free survival and overall survival by prospective validation. But how to choose IO-IO combination or IO-anti-VEGF treatment based on a biomarker-driven strategy is still a way to go. Thirdly, the survival of HCC patients with poor liver function seems hard to be prolonged even responders to IO treatment. How to improve survival for ChildPugh B patients with HCC is still a challenge. Fourthly, the etiology of HCC is currently considered to affect the outcome of immunotherapy. Therefore how to choose systemic therapy for patients with nonviral etiology required further evidences.

會長演講（台灣消化系內視鏡醫學會）

‘BRAIN-GUT’ INTERACTION AND BEYOND: A JOURNEY FROM BEDSIDE TO BENCH

Ching-Liang Lu（盧俊良）

Endoscopy Center for Diagnosis and Treatment, Taipei Veterans General Hospital, Taipei, Taiwan

Institute of Brain Science, National Yang Ming Chiao Tung University, Taipei, Taiwan

Functional gastrointestinal disorders (FGIDs), currently known as disorders of gut–brain interaction, are common disorders worldwide. Despite of the fact, the awareness and related research in FGIDs is often overlooked among gastroenterologists in Taiwan in the past. With the success in the control of viral hepatitis by the application and vaccination and new antiviral drugs, it is expected that the disease burden of chronic liver disease will be decreasing. Therefore, we should start to recognize the impact of FGID in our society. In this talk, I will present our research works in FGID. Hopefully, this talk will inspire the new generation of physicians to join this interesting field.

‘Visceral pain’ is the predominant symptom for functional gastrointestinal disorder (FGID, such as irritable bowel syndrome (IBS), functional dyspepsia, and gastroesophageal reflux disorder). FGID patients suffered from chronic and recurrent upper or lower abdominal pain without identifiable organic lesions. The pathogenesis of the visceral pain in FGID remains unclear. In Taiwan, FGID bring a significant burden to society and individual patients due to its high prevalence (10-20% with female predominant), increased sick leave, increased physician visits, and more insomnia than the asymptomatic ones. We further noticed that the IBS patients is one of the main risk factors leading to unnecessary surgery (negative appendectomy). In clinical trials for the treating of visceral pain among IBS patients, the mean placebo response can be up to 50%. By using fMRI, we found the placebo manipulation

would reduce the cerebral blood signals in viscera pain matrix during esophageal pain. We further noticed that the brain circuits are quite different between IBS patients and healthy volunteer. During placebo visceral analgesia, IBS showed higher brain signal activities in the cognitive and affective regions than those of controls.

We also tried to explore the molecular mechanism in mediation of visceral pain. Through this approach, we may have the chance to identify the key to develop new drugs in treating visceral pain. By using animal models of visceral pain, we demonstrated that estrogen play an important role in mediating visceral hypersensitivity/ pain, which can go through GPR30 receptor. In addition, chronic intractable visceral pain is also a predominant presentation for the patients with chronic pancreatitis (CP). In a CP rodent model, we first demonstrated that the spinal microglia and its P2X7 receptor mediate the initiation and maintenance of the chronic visceral pain in CP. These findings may serve as the basis for novel drug for visceral pain treatment.

Recently, gut microbiota and related dysbiosis has been shown to be linked in the pathogenesis of FGID through the interaction of the newly identified ‘microbiota-gut-brain’ axis. Emerging evidences in human and animal models have highlighted microbiota influences on brain function though brain-gut axis. For example, anxiety-like behaviors have been found to be reduced in germ-free mice, indicating that anxiogenic pathways may be predicated on the presence of a healthy microbiota. We have demonstrated that probiotics/

psychobiotics may modulates the axis and attenuate the visceral pain in an IBS rodent model, in support of the effectiveness of probiotics in treating FGID. Proton pump inhibitor (PPI) is commonly prescribed drugs in our daily practice. However, PPIs would decrease gastric acid production and raise the pH of the stomach, which would facilitate intestinal bacterial overgrowth due to elimination of gastric acid barrier. This increases the risk of translocation of gut bacteria to the mesenteric lymph nodes and from there to the blood and lymph. We are among the first to demonstrate that PPI use increase the risk of hepatic encephalopathy development among patients with cirrhosis. Chronic H. pylori infections are common in the general population, and current guidelines suggest that all subjects with known H. pylori infection should be offered eradication treatment with multiple antibiotics and proton pump inhibitors, which will lead to gut dysbiosis. GI dysbiosis and disruption of the GI microbiota has been linked with a variety of psychiatric disorders, including major depressive disorder. We found that H. pylori eradication may lead to a short-term (<30 days) increased risk of depression, which data provide indirect evidence suggesting a potential interaction between antibiotic-induced gut dysbiosis and depressive disorder in human being. By the analysis of gut microbiota and fMRI, we found a significant difference in the gut microbial composition between patients with late-life depression and healthy controls. The genera Enterobacter and Burkholderia were positively correlated with depressive symptoms and negatively correlated with grey matter volumesin regions associated with memory, somatosensory integration, and emotional processing/ cognition/regulation. We further demonstrated a close correlation of brain functional connectivity within mood regulation related brain networks and the alteration of fecal microbiota composition. All these findings strengthen the role of microbiota-gut-brain axis in the pathophysiology of depressive disorder.

Understanding how gut microbes affect gutbrain axis communication is emerging as the subject of significant research. Growing efforts worldwide are engaged to dissect out the mechanisms of this communication at all levels of the axis. It is becoming believed that the gut microbiota is critically important

for the adequate development and maintenance of brain function. From our study and recent literature, accumulating evidences have already indicated that the microbiota mediates not only in gastrointestinal disorders, but also in a variety of psychiatric, neurological, and neurodegenerative diseases. However, it is still many unexplained answers in this field. In addition, diet play an important role in modulating the microbiota. Thus, a new ‘diet-microbiota-gut-brain’ axis can be the focus of our future research in this regard.

References:

1. Tsai CF, Chuang CH, Wang YP, Lin YB, Tu PC, Liu PY, Wu PS, Lin CY, Lu CL. Differences in gut microbiota correlate with symptoms and regional brain volumes in patients with late-life depression. Front. Aging Neurosci. 2022;14:885393.

2. Tsai CF, Chen MH, Wang YP, Liu PY, Hou MC, Lee FY, Lu CL. Increased risk of short-term depressive disorder after Helicobacter pylori eradication: a population-based nested cohort study. Helicobacter 2 2021;26:e12824.

3. Wang YP, Herndon CC, Lu CL. Nonpharmacological Approach in the Management of Funcioanl Dyspepsia. J Neurogastroenterol Motil. 2020;26:6–15.

4. Liu YW, W, Wang YP, Yen SF, Liu PY, Tzeng WJ, Tsai CF, Lin HC, Lee FY, Jeng JO, Lu CL. Lactobacillus plantarum PS128 Ameliorated Visceral Hypersensitivity in Rats Through the Gut–Brain Axis. Probiotics and Antimicrobial protein. 2020;12:980–93.

5. Tsai CF, Du PC, Wang YP, Chu CJ, Huang YH, Lin HC, Hou MC, Lee FY, Liu PY, Lu CL. Altered cognitive control network is related to psychometric and biochemical profiles in covert hepatic encephalopathy. Sci Rep. 2019;9:6580. https://doi. org/10.1038/s41598-019-42957-6

6. Lee HF, Liu PY, Wany YP, Tsai CF, Chang FY, Lu CL. Sexual abuse is associated with an abnormal psychological profile and sleep difficulty in patients with irritable bowel syndrome in Taiwan. J Neurogasroenterol Motil. 2018;24:79–8.

7. Lu CL, Hemdon C. New Roles for Neuronal

Estrogen Receptors. Neurogastroenterol Motil. 2017;29:e13121.

8. Chang FM, Wang YP, Lang HC, Tsai CF, Hou MC, Lee FY, Lu CL. Statins decrease the risk of decompensation in hepatitis B virus– and hepatitis C virus–related cirrhosis: A population-based study. Hepatology. 2017;66:896-907.

9. Xiong L, Gong, Siah KT, Pratap N, Uday Chand Ghoshal UC, Abdullah M, Syam AF, Bak YT, Choi MG, Lu CL, Gonlachanvit S, Chua ASB, Chong KM, Ricaforte-Campos JD, Shi Q, Hou XH, Whitehead WE, Gwee KA, Chen MH. Rome Foundation Asian Working Team Report: Real world treatment experience of Asian patients with Functional Bowel Disorders. J Gasrtoenterol Hepatol. 2017;32:1450–6.

10. Tasi CF, Chen MH, Wang YP, Chu CJ, Hwang YH, Lin HC, Hou MC, Lee FY, Su TP, Lu CL. Proton Pump Inhibitors Increase Risk for Hepatic Encephalopathy in Patients With Cirrhosis in Population Study. Gastroenterology. 2017;152:134–41.

11. Tasi CF, Chu CJ, Wang YP, Liu PY, Chu CJ, Hwang YH, Lin HC, Lee FY, Su TP, Lu CL. Increased serum interleukin-6, not minimal hepatic encephalopathy, predicts poor sleep quality in nonalcoholic cirrhotic patients. Aliment Pharcol Therap. 2016 44;836–45.

12. Liu PY, Lee IH, Tan PJ, Wang YP, Tsai CF, Lin HC, Lee FY, Lu CL. P2X7 Receptor Mediates Spinal Microglia Activation of Visceral Hyperalgesia in a Rat Model of Chronic Pancreatitis. Cell Mol Gastroenterol Hepatol. 2015;1:710–720.

13. Tasi CF, Chu CJ, Hwang YH, Wang YP, Liu PY, Lin HC, Lee FY, Lu CL. Detecting Minimal Hepatic Encephalopathy in an Endemic Country for Hepatitis B: The Role of Psychometrics and Serum IL-6. PLOS ONE. 2015. DOI:10.1371/journal. pone.0128437

14. Ghoshal UC, Gwee KA, Chen M, Gong XR, Pratap N, Hou X, Syam AF, Abdullah M, Bah YT, Choi MG, Gonlachavit S, Chua ASB, Chong MK, Siah ATH, Lu CL, Xiong L, Whitehead WE. Development, Translation and Validation of Enhanced Asian Rome III Questionnaires for

Diagnosis of Functional Bowel Diseases in Major Asian Languages: A Rome Foundation-Asian Neurogastroenterology and Motility Association Working Team Report. J Neurogastroenterol Motil. 2015;21:83–92.

15. Lu CL. Spinal microglia: A potential target in the treatment of chronic visceral pain. J Chin Med Assoc. 2014;77:3–9.

16. Wang YP, Chen YT, Tsai CF, Li YS, Luo JC, Wang SJ, Tang CH, Liu CJ, Lin HC, Lee FY, Lu CL. Short-term Use of Serotonin Reuptake Inhibitors is Associated with an Increased Risk of Upper Gastrointestinal Bleeding. Am J Psych. 2014;171:54–61.

17. Tsai CF, Liu JL, Chen TJ, Chu CJ, Lin HC, Lee FY, Su TP, Lu CL (corresponding author). Increased Incidence of Orthopedic Fractures in Cirrhotic Patients: A Nationwide Population-Based Study. J Hepatol. 2013:58:706–14.

18. Gwee KA, Ghoshal UC, Gonlachanvit S, Chua AS, Myung SJ, Rajindrajith S, Patcharatrakul T, Choi MG, Wu JCY, Chen MH, Gong XR, Lu CL, Chen CL, Pratap N, Abraham P, Hou XH, Ke MY, Ricaforte-Campos JD, Syam AF, Abdullah M. Primary care management of chronic constipation in Asia: the ANMA chronic constipation tool. J Neurogastroenterol Motil. 2013;19:149–60.

19. Lee HF, Hsieh JC, Lu CL (corresponding author), Yeh TC, Tu CH, Cheng CM, Niddam DM, Lin HC, Lee FY, Chang FY. Enhanced affect/cognitionrelated brain responses during visceral placebo analgesia in irritable bowel syndrome patients. Pain. 2012;153:1301–10.

20. Liu PY, Lu CL, Wang CC, Lee IH, Hsieh JC, Chen CC, Lee HF, Lin HC, Chang FY, Lee SD. Spinal Microglia Initiate and Maintain Hyperalgesia in a Rat Model of Chronic Pancreatitis. Gastroenteorlogy. 2012;142:165–73.

21. Miwa H. Ghoshal UC. Fock KM. Gonlachanvit S. Gwee KA. Ang TL. Chang FY. Hongo M. Hou X. Kachintorn U. Ke M. Lai KH. Lee KJ. Lu CL. Mahadeva S. Miura S. Park H. Rhee PL. Sugano K. Vilaichone RK. Wong BC. Bak YT. Asian consensus report on functional dyspepsia. J Gastroenterol

Hepatol. 2012;27:626–41.

22. Niddam DM, Tsai SY, Lu CL, Ko CW, Hsieh JC. Reduced hippocampal glutamate-glutamine levels in irritable bowel syndrome: preliminary findings using magnetic resonance spectroscopy. Am J Gastroenterology. 2011;106:1503–11.

23. Chang FY, Lu CL. The clinical significances of irritable bowel syndrome in Taiwan. J Gastroenterol Hepatol. 2011;26(supp 3):102–5.

24. Lu CL, Chang FY. Placebo effect in patients with irritable bowel syndrome. J Gastroenterol Hepatol. 2011;26(supp 3):116–8.

25. Lu HC, Hsieh JC, Lu CL, Niddam; DM, Wu YT, Yeh TC, Cheng CM, Chang FY, Lee SD. Neuronal Correlates in the Modulation of Placebo Analgesia in Experimentally-induced Esophageal Pain: a 3TfMRI study. Pain. 2010;148:75–83. (cover story)

26. Lu CL, Lang HC, Luo JC, Liu CC, Lin HC, Chang FY, Lee SD. Increasing trend of the Incidence of Esophageal Squamous Cell Carcinoma, but not Adenocarcinoma, in Taiwan. Cancer Cause Control. 2010;21:269–274.

27. Lu CL, Hsieh JC, Dun NJ, Oprea TI, Wang PS, Luo JC, Lin HC, Chang FY, Lee SD. Estrogen rapidly modulates 5-hydroxytrytophan-induced visceral hypersensitivity via GPR30 in rats. Gastroenterology. 2009;137:1040–50.

28. Gwee KA, Lu CL, Ghoshal UC. Epidemiology of IBS in Asia – Something Old, Something New, Something Borrowed. J Gastroenterol Hepatol. 2009;24:1601–7.

29. Lu CL, Liu CC, Fuh JL, Liu PY, Wu CW, Chang FY, Lee SD. Irritable Bowel Syndrome and Negative Appendectomy: A Prospective Multivariable Investigation. GUT. 2007;56;655–60.

30. Lu CL, Hsieh JC, Tsaur ML, Huang YH, Wang PS, Wu LL, Liu PY, Chang FY, Lee SD. Estrogen Rapidly Modulates Mustard Oil-induced Visceral Hypersensitivity in Conscious Female Rat: A Role of CREB Phosphorylation in Spinal Dorsal Horn Neurons. Am J Physiol. 2007;292:G438–446.

31. Lu CL, Chang FY, Chen CY, Luo JC, Lee SD. Significance of Rome II-defined functional constipation in Taiwan and comparison with

constipation-predominant irritable bowel syndrome. Aliment Pharmacol Therap. 2006;24:429–38.

32. Lu CL, Lang HC, Chang FY, Chen TJ, Chen CY, Luo JC, Lee SD. Social and medical impact, sleep quality, and pharmaceutical costs of heartburn in Taiwan. Aliment Pharmacol Ther. 2005;22:739–47.

33. Lu CL, Pasricha PJ, Hsieh JC, Lu RH, Lai CR, Wu LR, Chang FY, Lee SD. Changes of the neuropeptides content and gene expression in spinal cord and dorsal root ganglion after noxious colorectal distension. Reg Pep. 2005;131:66–73.

34. Lu CL, Chang FY, LangHC, Chen CY, Luo CJ, Lee SD. Gender difference on the symptoms, health seeking behavior, social impact and sleep quality in irritable bowel syndrome: a Rome-II based survey in an apparent healthy adult Chinese population in Taiwan. Aliment Pharmacol Ther. 2005;21:1497–1505.

35. Lu CL, Chang FY, Hsieh JC. Role of primary/ secondary somatosensory cortex and insula in functional brain image study during painful stimulation from proximal stomach. Gastroenteorlogy. 2005;127:1529–31.

36. Lu CL, Lang HC, Chang FY, Chen CY, Luo CC, Wang SS, Lee SD. Prevalence and health/social impacts of functional dyspepsia in Taiwan: a study based on Rome criteria questionnaire survey assisted with endoscopic exclusion among a physical checkup population. Scand J Gastroenterol. 2005;40:402–11.

37. Lu CL, Chen CY, Luo JC, Chang FY, Lee SD, Wu HC, Chen JD. Impaired Gastric Myoelectricity in Patients with Chronic Pancreatitis: Role of Maldigestion. World J Gastroenterology. 2005;11:372–6.

38. Lu CL, Chang SS, Wang SS, Chang FY, Lee SD. Silent Peptic Ulcer Disease: the Prevalence, Factors Leading to ‘Silence’ and the Implications to the Pathogenesis of Visceral Symptoms. Gastrointestinal Endoscopy. 2004;60:34–8.

39. Lu CL, WU YT, Yeh TC, Chen LF, Chang FY, Lee SD, Ho LT. Hsieh JC. Neuronal Correlates of Gastric Pain Induced by Fundus Distension: a 3T-Fmri Study. Neurogastroenterol Motil. 2004;16:575–88.

特別演講

從台灣癌症登月計畫展望癌症精準醫療

TAIWAN CANCER MOONSHOT: PATHWAY TO PRECISION ONCOLOGY

Yu-Ju Chen（陳玉如）

Institute of Chemistry, Academia Sinica, Taiwan

Combing proteomics with the long standing success of genomics, proteogenomics has been rapidly advanced as an emerging tool for full delineation of genomic-to-proteomic network associated with disease. Aiming for understanding cancer biology and speeding up progress in development of prevention, early detection and novel therapies, Taiwan was invited to join the “Cancer Moonshot” program initiated by US in 2016. In first part of this talk, I will present the first model study in the project, focusing on non-smoking lung cancer in East Asia. Integrated genomic, proteomic, and phosphoproteomic analysis delineated the demographically distinct molecular attributes and hallmarks of tumor progression, high prevalence of APOBEC mutational signature in younger females and over-representation of environmental carcinogen-like mutational signatures in older females. Most excitingly, the proteomicsinformed classification demonstrated differentiation of the diverse clinical trajectories of patients within early stages. Following this prospective study, this multiomic molecular architecture inspired development

a few strategies toward precision oncology for management of early stage non-smoking lung adenocarcinoma. In the second part, I will present the preliminary result of proteogenomics study for a perspective cohort of gastric cancer. Advancement in robust proteomics technology and their translational value as a next-generation clinical assay for early cancer detection will be introduced.

References:

1. “Proteogenomic Landscape of Early Stage Non-smoking Lung Adenocarcinoma in East Asia”, Cell, 182, 226-244, (2020), (Cover Story, highlighted by Nature Review Clinical Oncology (2020, 17, 519), Cancer Discovery)

2. “A Data-independent Acquisition-based Global Phosphoproteomics System Enables Deep Profiling”, Nat. Commun., 12, 2539 (2021)

3. “Exploring the expression bar code of SAA variants for gastric cancer detection”, Proteomics, 17, doi: 10.1002/pmic.201600356, (2017), (Cover Story)

外賓演講（一）

BARRETT’S ESOPHAGUS, DYSPLASIA AND CANCER: AN UPDATE

Prateek Sharma

University of Kansas School of Medicine, Kansas City, KS, USA

Esophageal adenocarcinoma (EAC) is on the rise worldwide with increased rates of disease despite efforts to improve screening and detection. Barrett’s esophagus (BE) remains the only known precursor to EAC, and its early detection, surveillance for dysplastic progression and endoscopic treatment dysplasia and early BE cancer are the best options currently for mitigating disease. The diagnosis of BE begins with accurate identification of the anatomic landmarks and meticulous inspection of the mucosa. Once the BE segment is identified, proper documentation of the extent of disease using the Prague C & M criteria. This classification system has been validated to show that those with short segment BE (M ≤ 3 cm) has significantly reduced risk of progression of non-dysplastic Barrett’s esophagus (NDBE) to high grade dysplasia (HGD) and EAC compared to those with long segment BE (M ≥ 3 cm). Length of the BE segment has also been shown to be an important risk factor for dysplastic progression and has been used in prediction modeling to estimate this risk and is a key factor in the Progression in Barrett’s Esophagus (PIB) score. Following a standard biopsy protocol, and avoidance of biopsy of the irregular Z line < 1 cm. Improved detection is also seen with the use of high-definition white light endoscopy increases detection (OR 3.27; 95% CI, 1.27-8.40) compared to standard definition endoscopy. The use of narrow band imaging (NBI) has also shown to increase the accuracy of dysplasia detection and using the BING criteria, which characterizes BE surface pending on mucosal and vascular pattern irregularities, and is currently recommended for use during BE diagnosis and surveillance.

Duration of endoscopic imaging has been directly correlated with improved identification of abnormal lesions. This is well documented in colonoscopy, and the 6-minute minimum withdrawal time is standard of care for improved quality in detection. Similar findings have been shown with the duration of exam and detection of HGD and/or EAC in BE. The Barrett’s inspection time (BIT) has been proposed as a quality indicator for BE surveillance. A post-hoc analysis from a multicenter trial at tertiary referral centers for BE identified a significant improvement in detection suspicious lesions and of improved HGD/EAC detection when the endoscopic time was longer than 1 min per cm detected BE. The main components of Barrett’s esophagus management include:

1. Surveillance: Regular endoscopic surveillance with biopsies is recommended to monitor the development of dysplasia or cancer. For non dysplastic BE, surveillance every 3-4 years is recommended.

2. Lifestyle modifications for GERD: Patients should make lifestyle changes to reduce reflux symptoms, such as avoiding large meals, eating slowly, avoiding trigger foods, and maintaining a healthy weight.

3. Medications to treat GERD: Proton pump inhibitors (PPIs) are the first-line treatment for acid reflux.

4. Endoscopic treatment: Endoscopic treatments, such as endoscopic mucosal resection (EMR) for visible HGD/EAC followed by mucosal ablation with, radiofrequency ablation (RFA), cryotherapy or hybrid-APC or may be used to treat dysplasia or early cancer.

外賓演講（二）

HBV REACTIVATION RELATED TO NEW CLASSES OF IMMUNOSUPPRESSANTS AND IMMUNOMODULATORS

Anna Lok

Division of Gastroenterology and Hepatology, University of Michigan, Ann Arbor, MI, USA

Hepatitis B reactivation (HBVr) can be associated with a wide spectrum of immunosuppressants and immunomodulators. Because HBsAg+ and often HBsAg-/anti-HBc+ patients are excluded from clinical trials of immunosuppressants and immunomodulators, the incidence of HBVr associated with these therapies is unknown. Yet, when new immunosuppressants and immunomodulators are approved, they are used in patients with chronic or past HBV infection. While universal use of NA prophylaxis might prevent most if not all cases of HBVr, its use may not be necessary if the risk of HBVr is low.

A recent systematic review and meta-analysis of recently approved immunosuppressants and immunomodulators categorized immune check point inhibitors, tyrosine kinase inhibitors, cytokine inhibitors, and chimeric antigen receptor (CAR) T-cell immunotherapies as high HBVr risk in HBsAg+ patients; cytokine inhibitors, CAR T-cell immunotherapies, and corticosteroids as intermediate risk in HBsAg-/anti-HBc+ patients; and immune check point inhibitors as low risk in HBsAg-/antiHBc+ patients; based on medium-high quality evidence (Figure).

Due to the paucity of high-quality studies, categorization of risk was supplemented by opinions of an expert panel. The expert panel concur with professional society guidelines that universal screening for HBsAg and anti-HBc should be performed in all patients prior to the start of immunosuppressants or

immunomodulators, and prophylactic nucleos(t)ide analogues (NA) should be administered to patients who will be receiving therapies associated with high risk of HBVr, while close monitoring and on-demand NA therapy at the first sign of HBVr is recommended for therapies with low risk of HBVr. The experts agreed that either NA prophylaxis or close monitoring and on-demand NA can be considered for therapies associated with intermediate risk of HBVr, though most leaned towards NA prophylaxis.

The expert panel also proposed nomenclature and definitions for HBVr and associated outcomes to harmonize the field and allow data from different studies to be integrated. They also urged future trials of new immunosuppressants and immunomodulators to include HBsAg+ and HBsAg-/anti-HBc+ patients with protocolized monitoring and use of prophylactic or on-demand NA therapy to generate meaningful data to inform the risk of HBVr and the need for NA prophylaxis after these drugs are approved and used clinically.

References:

1. Papatheodoridis G, Lekakis V, Voulgaris T, Lampertico P, Berg T, Chan HLY, Kao JH, Terrault N, Lok AS, Reddy KR. Hepatitis B virus reactivation associated with new classes of immunosuppressants and immunomodulators: A systematic review, meta-analysis, and expert opinion. J Hepatol. 2022;77:1670–1689.

外賓演講（三）

THE ROAD TO EXCELLENCE IN COLONIC ESD PRACTICE

Ken Ohata

Department of Gastrointestinal Endoscopy, NTT Medical Center Tokyo, Tokyo, Japan

ESD was developed more than 20 years ago. The technique was invented in Japan and has became popular as a treatment for gastric cancer due to the large number of gastric cancer patients in the Asian region. (Ono H, et al: Gut 2001) On the other hand, the technique did not spread to colorectal tumors due to its high technical difficulty and relatively small surgical invasion. During that time, many new tools and radiofrequency devices were developed, and colorectal ESD gradually became safer and more feasible. As ESD for colorectal tumors became more feasible, more institutions began to introduce ESD, even in Europe and the United States, where there was

little interest in ESD due to the lack of gastric cancer.

Last year, we reported the first multicenter prospective long-term outcomes of ESD for colorectal tumors. (Ohata K, et al: Gastroenterology 2022) We were able to show high Disease-Specific-Survival Rate and Intestinal Preservation Rates. Some have argued that these are results from advanced centers and that EMR and EPMR are sufficient for costeffectiveness and technical difficulty, and verification of these results is a future challenge.

In this lecture, I would like to share the history of colorectal ESD, the actual technique, and how to learn it.

外賓演講（四）

A DEEP DIVE INTO IMMUNOTHERAPY FOR UHCC FROM PHASE 3 CLINICAL TRIALS

Richard S. Finn

Division

of

Hematology/Oncology, Department of Medicine, David Geffen School

of

Medicine, University of California, Los Angeles, CA, USA

Drug development in advanced liver cancer has evolved dramatically in the past few years. After a decade of only sorafenib, we now have numerous active agents in the front-line and secondline and beyond. Arguably, the greatest impact in overall survival has come with the introduction of immunotherapy into the management of our patients. At this time, there are numerous Phase 3 studies that have evaluated single agent PD-1/PDL1 therapies as well as combinations with anti-

VEGF monoclonal antibodies, multi-kinase TKIs, and CTLA-4 antibodies. Some of these have met their endpoints, others have not. In the lecture, we will look into the details of these results in the context of scientific rationale, study design, study end-points, and toxicity. At the end of the lecture, participants with have a better understanding of the state-of-the-art for systemic therapy in HCC and directions for future research.

外賓演講（五）

PERSONALIZED APPROACH FOR GERD

Feinberg School

of

John Pandolfino

Medicine, Northwestern University, Chicago, IL, USA

Gastroesophageal reflux disease (GERD) is a heterogeneous disease with varying presentations and a broad range of pathologic abnormalities that can lead to abnormal reflux burden or impaired defense mechanisms. It is becoming clear that many presentations of GERD represent distinct phenotypes with unique predisposing co-factors and pathophysiology that can be defined using careful selection of diagnostic tests. Given this heterogeneity, it is reasonable that clinical management should target the unique pathophysiological features of each syndrome as one size does not fit all. Not every patient benefits from increased potency of acid inhibition and

many are potentially harmed by surgical intervention. It is from that perspective that we attempt to apply “personalized medicine” to the management of GERD. The current discussion will focus on using important clinical biomarkers and physiomarkers to phenotype GERD and target the appropriate mechanism. The delicate interplay between psychological distress in the form of hypervigilance and visceral anxiety will be discussed in the context of the overlying mechanisms of increased reflux burden and heightened perception. In the end, the goal will be to develop a more precise phenotype with targeted therapies.

外賓演講（六）

MANAGEMENT OF CONSTIPATION: AN UPDATE

Lin Chang

Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, USA

Chronic constipation is a common, gastrointestinal condition that affects individuals of all ages and significantly impacts health related quality of life. Constipation can be occasional or chronic in frequency and duration of symptoms. Primary chronic constipation has been subtyped into normal-transit constipation, slow transit constipation and rectal evacuation disorders (latter overlaps with the prior two). The diagnosis of chronic constipation involves symptom assessment using diagnostic criteria and alarm symptoms (e.g., unintentional weight loss, rectal bleeding, family history of colon cancer) that might indicate “organic” diseases, limited diagnostic testing. Treatments include first-line treatments such

dietary or supplemental fiber, lifestyle modifications and over-the-counter laxatives. If symptoms do not improve, investigations to diagnose rectal evacuation disorders such as dyssynergic defecation and slow transit constipation are performed, such as digital rectal examination, balloon expulsion test, anorectal manometry or defecography, and colonic transit tests (such as radiopaque marker test, wireless motility capsule test, or scintigraphy). Pharmacologic treatments include secretagogues (linaclotide, plecanatide, lubiprostone) and prokinetic agent (prucalopride). New emerging therapy for chronic constipation includes a vibrating colon capsule.

醫療與性別課程

醫療場域的性騷擾議題與防治 王志嘉

Department of Family and Community Health, Tri-Service General Hospital, Taipei, Taiwan

醫療場域的性騷擾具有多樣性，涵蓋員工、 學生及病人等面向，性別平等三法的實施與通過， 適足以處理性騷擾的各類種類型，了解性別平等 三法的適用場域與對象，是身為醫療人員基本的 專業素養。其次，依據性騷擾的定義，性與性別 有關以及違反當事人的意願，是性騷擾成立的要 件，法條與實務均針對事實採取綜合判斷說，同 時也會將被害人的主觀認知感受、事後反應、周 圍親友觀察等證據推斷。最後，在處理醫病間發 生的性騷擾事件，太過強勢或過度退讓，可能適 得其反，應該以折衷協商型為主，透過釐清問題、 建立流程以及醫病協商的方式，讓性騷擾事件妥

適解決。

本次演講預定的大綱如下：

1. 性平三法與醫療場域之適用

2. 性騷擾定義與調查

性騷擾的認定

我國實務相關見解

3. 醫療場域的性騷擾議題與防治 醫事人員間的性騷擾議題

醫病之間的性騷擾議題

性霸凌、性騷擾、猥褻與性交

4. 結論

專題討論（一）

Facing Grey Zone Chronic Hepatitis B

DEFINITION AND NATURAL COURSE

Wen-Juei Jeng（鄭文睿）

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

Recently, whether to expand treatment indication to chronic hepatitis B patients in grey zone has raised much attention. Several studies have proposed evidence of significant fibrosis and even cirrhosis among these patients while antiviral therapy may halt or reduce risk of HCC. However, it is important to define the grey zone in the right way that those not belong to current treatment indication and those

without significant inflammation nor fibrosis were defined as grey zone CHB patients. In this session, we’ll review how important the definition of grey zone is that misclassification may lead to misinterpretation of the results. It is also important to review the natural history of the true grey zone CHB population and understanding the dynamic course of CHB as phase transition.

專題討論（一）

Facing Grey Zone Chronic Hepatitis B

HCC RISK AND BIOMARKER

Pin-Nan Cheng（鄭斌男）

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

Hepatitis B virus (HBV) infection is an important etiology of hepatocellular carcinoma (HCC) development and is also a global heathy issue. Risk factors, including host, virus, and metabolic, have been characterized to associate with HBV related HCC. Based on these factors, many prediction scoring models have been established and may determine the program of regular surveillance. Earlier detection of HCC is one of the goals of surveillance in HBV infected patients, however, current tools, including

AFP and sonography, are less sensitive and not satisfactory. Biomarkers with high sensitivity and specificity are crucial for early diagnosis of HCC and improving patients’ outcomes. Virus and host related biomarkers that are associated with pathogenesis of HCC development are investigated and may have potential role of further clinical application. Such surrogate markers may lead to a better understanding of early detection of HCC in HBV-infected patients, thereby improving prognosis.

專題討論（一）

Facing Grey Zone Chronic Hepatitis B

TO TREAT?

Tung-Hung Su（蘇東弘）

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

The grey zone for chronic hepatitis B refers to conditions between inactive carrier (HBV DNA < 2000 IU/mL and ALT < 1x ULN) and active hepatitis (HBV DNA ≥ 2000 IU/mL and ALT ≥ 2x ULN). It includes mildly elevated ALT level (ALT 1-2x ULN) with low, intermediate (HBV DNA 2000-20000 IU/ mL) to high viral load (HBV DNA ≥ 20000 IU/ mL). This grey zone may be associated with varying degrees of liver inflammation, some risk of HCC and may require close monitoring and potentially medical intervention, depending on individual circumstances such as age, fibrosis status, family history of HCC, and other risk factors including high quantitative HBsAg or HBcrAg levels. The definition and management

of the grey zone may differ among different clinical practice guidelines.

The rationale to treat patients with in the grey zone is because of increased risk of HCC compared with inactive carriers. Accumulating evidences demonstrate treating patients within the grey zones may reduce the risk of fibrosis progression, and HBV DNA integration to host genomes. The overall effects might reduce the risk of HCC development. While the compliance of antiviral therapy, economic burden, and low rate of functional cure (seroclearance of HBsAg) are major concerns in early antiviral treatment of grey zone patients.

專題討論（一）

Facing Grey Zone Chronic Hepatitis B

TO OBSERVE?

Chien-Hung Chen（陳建宏）

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

With the wide use of potent and safe nucloes(t-) ide analogues (NAs) treatment, patient-centered care is getting important. Intensive care for comorbidity has gain utmost importance in care of aging chronic hepatitis B (CHB) patients with life-long antiviral treatment. Linkage to care of patients with CHB is essential for the goal of hepatitis B virus (HBV) eradication. As long-term suppression of HBV DNA replication does not prevent hepatocellular carcinoma (HCC), prevention of HCC is another challenge for NAs treatment.

There is a possibility of hepatocarcinogenesis in the immune-tolerant phase and risk of loss of patients during active monitoring seeking the time point for antiviral treatment initiation. Initiation of NAs treatment from the immune-tolerant phase would improve the linkage to care. However, universal recommendation is premature and evidence for costeffectiveness needs to be accumulated. Previous studies showed that early initiation of NAs in the evidence of significant disease progression, either HBV associated or comorbidity associated, would be a better strategy to reduce the risk of HCC in

patients located in the gray zone (GZ). However, many studies also showed that CHB patients who did not meet treatment criteria at presentation, outcome was favorable when patients are closely monitored and antiviral treatment initiated when patients transitioned to a more active phase. One study showed that prospective follow-up study shows that the persistent low-viraemia (≤20000-IU/mL) is associated with a benign outcome in HBeAg-negative/ anti-HBe- positive carriers: in almost half of cases the low viraemia active carrier profile beckons transition to Inactive-Infection and Inactive-Infection in 20% of cases preludes to HBsAg clearance within a 5 years time frame. One study also showed that most Caucasian GZ patients present excellent long-term outcomes in the absence of treatment, with a high rate of HBsAg loss and low rate of progression to HBeAgnegative CHB. HBV-genotyping and HBsAg levels could help to predict outcomes and better classify GZ patients. Thus, we suggested observation and require monitoring of ALT and HBV DNA in these GZ patients.

專題討論（二）

大腸激躁症的整合治療

Multi-discipline Approach in IBS Patients

PRACTICAL APPROACH OF DIET TREATMENT FOR IBS PATIENTS

Jane Muir

Department of Gastroenterology, Central Clinical School, Faculty of Medicine, Nursing and Health Sciences, Monash University, Melbourne, Australia

Irritable bowel syndrome (IBS) is one of the most common gastrointestinal conditions seen by gastroenterologists affecting between 4 and 9% of the population worldwide. IBS is a disorder of the gutbrain interaction and is characterized by abdominal pain and associated altered stool form or frequency. While a range of therapies are used by healthcare professionals to manage IBS symptoms, over the last decade diet has become popular as a first-line therapy for this condition. The focus on diet has been driven by the strong association of many patients between diet and symptoms and also the uptake by the medical and dietetic professions of the FODMAP diet.

FODMAP is an acronym (Fermentable OligoDi- and Mono-saccharides And Polyols). FODMAPs are slowly absorbed or indigestible short-chain carbohydrates and are found in a wide variety of foods. The low FODMAP diet has now been evaluated in patients with IBS in multiple centres, generally with efficacy in 50-80% of people. The FODMAP diet is a 3-step diet strategy. In Step 1 (low FODMAP diet) intake of all FODMAP groups is reduced to pre-

defined cut-off levels in an effort to induce symptom control in FODMAP sensitive individuals. In Step 2 (FODMAP reintroduction) staged food challenges using foods rich in only 1 FODMAP subgroup at a time to determine which FODMAP groups are tolerated and which are not. In Step 3 (FODMAP personalisation) the diet is liberalised - well tolerated FODMAPs subgroups are included in the diet, while poorly tolerated FODMAP subgroups are restricted, but only to a level that provides adequate symptom relief.

This strong evidence supporting the efficacy of a low FODMAP diet is now reflected in clinical guidelines worldwide and in clinical practice and the diet is now considered part of standard dietetic practice. Dietitians with training in this area have a key role to play as part of a multi-disciplinary team approach to manage IBS patients. The dietitian will guide patients through the 3-steps of the FODMAP diet protocol and importantly ‘adapt’ the diet to suit their culture, country, cuisine and patient needs.

專題討論（二）

大腸激躁症的整合治療

Multi-discipline Approach in IBS Patients

FODMAP DIET TREATMENT FOR IBS PATIENTS IN EASTERN COUNTRIES

Po-Shan Wu（吳柏姍）

Department of Dietetics and Nutrition, Taipei Veterans General Hospital, Taipei, Taiwan

There is growing evidenced in dietary restricted with fermentable oligo-, di-, mono-saccharides, and polyols (FODMAPs) 4-8 weeks, influence clinical outcomes in patients with irritable bowel syndrome

(IBS). This presentation will discuss the low FODMAPs dietary approach for treating in Eastern Asian countries and the efficacy.

專題討論（二）

大腸激躁症的整合治療

Multi-discipline Approach in IBS Patients

PSYCHIATRIC APPROACH FOR THE IBS TREATMENT

Chia-Fen

Tsai（蔡佳芬）

Department of Psychiatry, Taipei Veterans General Hospital, Taipei, Taiwan

Irritable bowel syndrome (IBS) is an important and common functional gastrointestinal disorder. Patients complain of various symptoms, including changes in bowel habits, constipation or diarrhea, abdominal pain, meteorism, anxiety, and depression, leading to a significant reduction in their quality of life. The pathophysiology is complex and best explained using the biopsychosocial model, which encompasses biological, psychological, and psychosocial factors. The recommended treatment often consists of a multitude of components. In general, patients begin with lifestyle changes and dietary advice, followed by

medical interventions that include pharmacological and non-pharmacological treatments. Notably, psychiatric approaches are important treatment options for patients with IBS and should not be restricted to those with psychiatric comorbidities. Several evidence-based psychotherapeutic treatment options exist, such as cognitive-behavioral therapy, relaxation therapy, multi-component psychological therapy, hypnotherapy, dynamic psychotherapy, and antidepressant treatments, which will be presented and discussed in this talk.

專題討論（二）

大腸激躁症的整合治療

Multi-discipline Approach in IBS Patients

HOW TO APPROACH WITH DIFFICULT-TO-TREAT IBS PATIENTS

Lin Chang

Division of Digestive Diseases, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, USA

Irritable bowel syndrome (IBS) is a common gastrointestinal (GI) disorder characterized by recurrent or chronic abdominal pain associated with diarrhea and/or constipation. IBS has been redefined as a disorder of gut-brain interaction (DGBI), which is classified by GI symptoms related to any combination of the following: motility disturbance, visceral hypersensitivity, altered mucosal and immune function, altered gut microbiota, and altered central nervous system (CNS) processing. IBS is considered a multifactorial disorder where there are various factors associated with an increased vulnerability to develop IBS, including infectious gastroenteritis, stressful life events, and genetic or familial predisposition. There are also factors associated with triggering symptom flares, such as food and stress. Guidelines

for diagnostic testing and treatment efficacy and safety in IBS can help guide management, however, a patient-centered approach that considers multiple factors that affect treatment response is recommended. The biopsychosocial conceptual model and multidimensional clinical profile (MDCP) provide interconnected frameworks that integrate biomedical and psychosocial factors which explain the patient’s illness experience and guide a personalized treatment plan to enhance clinical care. Integrating scientific evidence and clinical experience to provide individualized, patient-centered care, or what some refer to as the art of medicine, is recommended to improve patient satisfaction and health-related quality of life and reduce cost.

專題討論（三）

門脈高壓新進展

UPDATE OF BAVENO VII CONSENSUS Tsung-Chieh Yang（楊宗杰）

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

The virtual Baveno VII workshop was organized for October 2021 aiming at expanding on the work of previous meetings. Among patients with compensated cirrhosis or compensated advanced chronic liver disease (cACLD), the presence or absence of clinically significant portal hypertension (CSPH) is associated with differing outcomes, including risk of death, and different diagnostic and therapeutic needs. Accordingly, the Baveno VII workshop was entitled “Personalized Care for Portal Hypertension”.

The main fields of this workshop were the relevance and indications for measuring the hepatic venous pressure gradient as a gold standard, the use

of non-invasive tools for the diagnosis of cACLD and CSPH, the impact of etiological and non-etiological therapies on the course of cirrhosis, the prevention of the first episode of decompensation, the management of an acute bleeding episode, the prevention of further decompensation, as well as the diagnosis and management of splanchnic vein thrombosis and other vascular disorders of the liver.

In this topic, I will organize and introduce the most important new or changed conclusions/ recommendations derived from the workshop compared with previous Baveno VI consensus.

專題討論（三）

門脈高壓新進展

MICROBIOTA IN LIVER CIRRHOSIS: FROM BENCH TO BEDSIDE

Pei-Chang Lee（李沛璋）

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

Liver cirrhosis is an increasing cause of morbidity and mortality in more developed countries, being the 14 th most common cause of death and causing 1.03 million deaths per year worldwide. In Taiwan, an endemic area of chronic viral hepatitis, liver cirrhosis is the 10th cause of death which caused 4,315 deaths (standardized death rate as 11.6%) in 2018.

Several studies have evaluated the taxonomic composition of the fecal microbiota in cirrhotic patients. A common feature of cirrhosis is an increase of potentially pathogenic bacteria, including Enterobacteriaceae and Streptococcaceae , with the reduction of commensal bacteria, such as Ruminococcaceae, and Lachnospiraceae, etc. Besides,

small bowel bacterial overgrowth in combination with translocation of these bacteria and their endotoxins will expose the liver to substantial amount of immunogens and ultimately culminate in hepatic injury and systemic inflammation. This alteration of microbial composition and function has been reported to worsen and contribute to hepatic encephalopathy (HE), spontaneous bacterial peritonitis (SBP) and ACLF. It also can be a predictor of readmissions and mortality in cirrhotic patients. In this topic, we will summarize the role of gut microbiota in liver cirrhosis and cirrhotic complications from the basic pathophysiology to the potential therapeutic application in clinical practice.

專題討論（三）

門脈高壓新進展

DIABETES IN PATIENTS WITH LIVER CIRRHOSIS Fu-Shun Yen（顏福順）

Yen’s Clinic, Taoyuan, Taiwan

The global prevalence and mortality of chronic liver disease and diabetes mellitus (DM) has gradually increased conceivably due to changes in diet and lifestyle. According to the Institute for Health Metrics and Evaluation, ~1,690 million patients had chronic liver disease including cirrhosis in 2019 (prevalence rate 22.7%), and about 1.47 million people globally died of chronic liver disease (2.6% of global all-cause mortality). Moreover, according to the ninth edition of the International Diabetes Federation Diabetes Atlas in 2019, among the global adult population in the age range of 20–79 years, ~463 million patients had DM (prevalence rate 9.3%), and ~4.2 million people have died of DM (11.3% of global all-cause mortality). Chronic liver disease has long been known to be closely related to DM. Non-alcoholic fatty liver disease (NAFLD) is characterized by excessive triglyceride and fatty acid accumulation of liver (fat accounts for more than 5% of the liver’s weight) not caused by alcohol. Nonalcoholic steatohepatitis (NASH) is a form of NAFLD with inflammation and damage of the liver, which can lead to hepatic fibrosis, scarring, or even cirrhosis. Cirrhosis is characterized by diffuse nodular regeneration surrounding by a dense fibrotic septum, accompanied by the loss of liver parenchyma with collapse of the liver structure, and caused significant distortion of the hepatic vascular structure. It is the ultimate stage of chronic liver disease. Clinically, cirrhosis can be divided into compensated and decompensated cirrhosis. Patients with decompensated cirrhosis may have variceal hemorrhage, ascites, hepatic encephalopathy, jaundice, or hepatorenal syndrome. Cirrhotic patients without these complications are defined as having compensated cirrhosis. Patients with liver cirrhosis usually have portosystemic and intrahepatic shunt with resulting peripheral hyperinsulinemia, which can downregulate

the number of insulin receptors in muscle tissues and result in insulin resistance. Patients with cirrhosis may be associated with beta cell dysfunction and decreased insulin secretion. Therefore, 60–80% patients with liver cirrhosis have glucose intolerance and 10–30% have overt type 2 diabetes (T2D). Similarly, approximately 50–70% of patients with T2D have NAFLD. T2D can accelerate the progression of chronic liver disease to liver cirrhosis and cirrhosis to subacute bacterial peritonitis, hepatic encephalopathy, and death. People with T2D also have about four times higher risk of hepatocellular carcinoma (HCC) than those without T2D.

For patients with coexisting T2D and liver cirrhosis, the choice of antidiabetic medication is complicated. As liver is the primary site of drug metabolism, most antidiabetic medications will be metabolized in the liver and then be released to the systemic circulation. Patients with liver cirrhosis may have widespread extinction and collapse of hepatic parenchyma, which can decrease the metabolism of antidiabetic medications. Moreover, the portosystemic and intrahepatic shunts of cirrhosis may prevent the antidiabetic medications from entering the liver and directly go to the systemic circulation. Both these aforementioned phenomena may increase the systemic concentration of antidiabetic medications, leading to adverse effects.

The use of antidiabetic medications in patients with chronic liver disease has not been extensively studied. Recently, the long-term outcomes of using antidiabetic medications in patients with chronic liver disease have been uncovered. Herein, we reported the recent studies about the use of antidiabetic medications and the risks of cirrhosis development, decompensated cirrhosis, hepatocellular carcinoma, hypoglycemia, cardiovascular events and mortality in patients with type 2 diabetes.

專題討論（三）

門脈高壓新進展

ROLE OF NON-SELECTIVE BETA-BLOCKERS IN CIRRHOTIC PATIENTS WITH DIFFERENT SCENARIOS

Cheng-Kun Wu（吳鎮琨）

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

Non-selective beta-blockers (NSBBs) are considered the primary treatment for managing portal hypertension in patients with cirrhosis. In comparison to esophageal variceal ligation (EVL), which is a localized therapy that has no effect on portal pressure, NSBBs lower portal pressure and offer the additional benefit of reducing the risk of decompensation events, death, or liver transplantation.

In compensated cirrhotic patients, a new paradigm has emerged based on the results of a large randomized controlled trial known as the PREDESCI trial. This paradigm focuses on treating clinically significant portal hypertension (CSPH) rather than just high-risk varices, and aims to prevent all forms of

decompensation, including variceal bleeding, ascites, and hepatic encephalopathy, rather than just variceal bleeding.

In patients with decompensated cirrhosis, all patients have CSPH. The survival benefits of NSBBs in these patients depend on maintaining mean arterial pressure (MAP) above 65mmHg. Despite concerns, three independent meta-analyses suggest that NSBBs are not an absolute contraindication in patients with ascites, refractory ascites, spontaneous bacterial peritonitis (SBP), and acute-on-chronic liver failure (ACLF). However, it is crucial to titrate the doses carefully and re-evaluate all patients after they recover from acute decompensation events.

專題討論（三）

門脈高壓新進展

NUTRITION IN CRITICALLY ILL CIRRHOTIC PATIENTS

Ming-Hung Tsai（蔡銘鴻）

Division of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkuo, Taiwan

Malnutrition is a common complication of liver cirrhosis, occurring in 20-50 percent of cirrhotic patients. Malnutrition is associated with the progression of liver failure and other complications of liver cirrhosis such as bacterial infection, hepatic encephalopathy and ascites.

Sarcopenia has been shown to be a robust predictor of poor clinical outcomes. Currently, skeletal muscle index assessed by CT is the most reproducible tool to evaluate muscle mass in patients with liver cirrhosis. Despite the prognostic significance of sarcopenia in liver cirrhosis, its clinical application has been limited by a lack of safe, consistent and inexpensive assessment tools.

Patients with liver cirrhosis frequently develop complications that necessitate ICU admissions. Nutrition assessment using traditional tools for ambulatory patients may be inaccurate or impossible because of fluid retention and difficulties in obtaining nutrition history. Nutrition Risk in Critically Ill (NUTRIC) score, which is specifically designed for ICU patients and endorsed by ASPEN, has been shown to be a useful assessment tool for critically ill

cirrhotic patients.

Prediction equations do not provide useful estimates of resting energy expenditure (REE). When available, REE should be measured by indirect calorimetry to provide a personalized energy prescription. In critically ill cirrhotic patients who can not achieve the nutrition target through oral diet, enteral nutrition feeding should be performed. The presence esophageal varices is not an absolute contraindication to placement of enteral feeding tube.

Protein intake should not be restricted in cirrhotic patients with acute decompensation. 1.2-2.0 g/Kg/ day is a recommendation from AASLD and Society of Critical Care Medicine for critically ill cirrhotic patients. EASL and ESPEN guidelines recommend BCAA (0.25 g/kg/d) in patients who can not achieve protein goals or are unable to tolerate protein, although further validation is needed.

Until further data specific for liver cirrhosis with septic shock are available, nutrition intervention should be implemented in this clinical setting according to current guidelines for non-cirrhotic patients.

專題討論（四）

Advances in Small Intestinal Disease and Inflammatory Bowel Disease: From Diagnosis to Treatment

THE DIFFERENTIAL DIAGNOSIS OF ENTERITIS AND COLITIS

Jen-Wei Chou（周仁偉）

Division of Gastroenterology and Hepatology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan

Enteritis and colitis mean the inflammation of small intestinal and colon. They common causes of digestive disease. The small intestine accounts for about 75% of the gastrointestinal (GI) tract length and nearly 90% of the GI mucosa, it is the most difficult evaluation part of the GI tract due to its length and complex loops. Thus, enteritis is usually difficult approach than colitis in clinical practice.

Although a few erosions and small ulcers are frequently found in the small bowel and colon of healthy volunteers, the differential diagnosis of enteritis and colitis is broad and well known. They include inflammatory bowel disease (including Crohn’s disease and ulcerative colitis), drugs (including non-steroidal anti-inflammatory drugs, anticoagulation and others) (NSAIDs), alcohol, allergy, radiation enteritis and colitis, diverticulitis (congenital or acquired), vasculitis, intestinal infections (including bacteria, virus, TB, ameba, etc.) and certain

neoplasms. History taking, physical examination, imaging studies, and endoscopic examination can provide us to make a differential diagnosis of enteritis and colitis.

The clinical symptoms of patients with enteritis and colitis are very complex, including abdominal pain/bloating, bleeding, fever, vomiting/nausea, loss of weight, poor appetite or diarrhea, etc. Colonoscopy is the major diagnostic modality for colitis. However, the diagnostic yield of conventional radiological images, angiography, nuclear medicine, ultrasound, manometry, computed tomography, and surgery is not very high for enteritis. The newly developed diagnostic modalities, including deep enteroscopy and wireless capsule endoscopy, have been shown the higher diagnostic yields of enteritis.

The treatment of colitis and enteritis depends on the histopathological type and causes, including medicines, chemotherapy, radiotherapy, or surgery.

專題討論（四）

Advances in Small Intestinal Disease and Inflammatory Bowel Disease: From Diagnosis to Treatment

DEEP ENTERSCOPE: CLINICAL APPLICATION AND FURTHER ADVANCE

Chi-Ming Tai（戴啟明）

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

The introduction of double-balloon enteroscopy in 2001 enabled endoscopic scrutiny of the entire small bowel with intervention capabilities. Additional methods were later introduced such as single-balloon enteroscopy in 2007 and spiral enteroscopy in 2008. A novel motorized spiral enteroscope was described in 2015 allowing faster and easier progression into the small bowel. These techniques are known as device-assisted enteroscopy (DAE). The field of DAE continues to evolve with the development of new enteroscopes taking therapeutic endoscopy in the small bowel to another level. Endoscopic retrograde cholangiopancreatography is nowadays feasible with

the help of DAE in patients with altered anatomy

DAE has played an important role in the diagnosis and management of Crohn’s disease, and the main advantage of DAE is that it enables endotherapy. DAE facilitates the retrieval of foreign bodies and endoscopic balloon dilation, with high success rates and a low frequency of intra- and postprocedural complications. Endoscopic balloon dilation can be repeated, depending on the clinical presentation, and may postpone or obviate the need for intestinal resection, improving the patient’s overall quality of life

專題討論（四）

Advances in Small Intestinal Disease and Inflammatory Bowel Disease: From Diagnosis to Treatment

OPTIMAL USE OF CONVENTIONAL TREATMENT FOR IBD

Chia-Jung Kuo（郭家榮）

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

IBD is a lifelong illness for which there is currently no medical cure. Several agents are available for the medical treatment of IBD, which including conventional therapies. and biologic therapies.

The majority of patients with IBD use conventional therapies. (namely, aminosalicylates, corticosteroids and immunomodulatory agents) for both induction and maintain remission.

Treatment paradigms in IBD have evolved

towards a rapid escalation of therapy to achieve stringent goals, including mucosal healing and a reduction in the need for hospital admission and surgery. Doctors should fully grasp the indications, contraindications, as well as evidence-based medicine of various drugs and treatments, so as to develop individualized treatment plans based on the comprehensive assessment of the patient.

專題討論（四）

Advances in Small Intestinal Disease and Inflammatory Bowel Disease: From Diagnosis to Treatment

THE ROLE OF BIOLOGIC AGENT IN TREATMENT FOR IBD

Tien-Yu Huang（黃天祐）

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

Inflammatory bowel disease (IBD), such as Crohn’s disease (CD) and ulcerative colitis (UC), is a chronic and relapsing disease of gut inflammation. Since the report in 1997 about Infliximab treatment in patients with CD, biologics are the main therapeutic agents for patients with moderate to severe IBD. Among the current biologics for IBD treatment, there are different mechanisms of action of biologics in blocking the associated pathways of gut inflammation. In clinical practice, there are different concerns in the

efficacy and safety issues using these biologics for subgroups patients with IBD. In addition, the newly developed concepts of treatment goals also highlight the importance of biologic or small molecule therapy in the medical treatment of IBD patients. Therefore, my talk will focus on the update of different biologics in treatment of IBD patients, the dual use of biologics, and the biologic use in different subgroups of IBD patients.

專題討論（五）

NAFLD/MAFLD新進展

DYNAMIC OF DISEASE SPECTRUM IN NAFLD/NASH

Ming-Lung Yu（余明隆）

National Sun Yat-Sen University, Kaohsiung, Taiwan Kaohsiung Medical University, Kaohsiung, Taiwan

Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide.

NAFLD has a broad disease spectrum, from nonalcoholic fatty liver (NAFL) or simple steatosis to nonalcoholic steatohepatitis (NASH), which is associated with liver fibrosis and can progress to cirrhosis, hepatocellular carcinoma (HCC), and endstage liver diseases. Almost one-fifth of with NAFLD and advanced fibrosis develop cirrhosis; of which, one-fifth progress to decompensated liver diseases. Although patients with cirrhosis or fibrosis continue to have a high risk for HCC progression, growing evidence shows that NAFLD-HCC can develop even in the absence of cirrhosis.

However, NAFLD is a dynamic condition that exhibits bidirectional evolution among NAFL, NASH,

NASH with advanced fibrosis, and NASH cirrhosis. Studies that investigated the change between paired liver biopsies have observed that 30% to 40% of NAFLD patients had fibrosis progression, whereas a substantial group of up to 25% of patients had fibrosis regression during 2-16 years of follow-up. Even among the patients with NASH cirrhosis, regression of fibrosis occurred in 16% of patients during a 48week follow-up in two large placebo‐controlled trials. Since obesity, metabolic syndrome, age, ethnicity, and higher NAS score are at high risk of rapid progression to end-stage liver disease, lifestyle interventions such as diet and physical exercise, the current cornerstone of treatment, are highly recommended to reduce the risk of cirrhosis and HCC.

專題討論（五）

NAFLD/MAFLD新進展

CLINICAL IMPLICATION OF LEAN MAFLD

Mohammed Eslam

Storr Liver Centre, Westmead Institute for Medical Research and Westmead Hospital, University of Sydney, Australia

Excessive calorie consumption relative to expenditure, intake of unhealthy diets, and lack of physical activity are globally fuelling an increase in the prevalence of poor metabolic health, even in individuals of normal weight. Consequently, this trend entails increased risk of various metabolic disorders, including metabolic associated fatty liver disease (MAFLD), which affects up to a third of the global population.

MAFLD burden has grown in parallel with rising rates of type 2 diabetes and obesity and increases the risk of end-stage liver disease, hepatocellular carcinoma, death, and liver transplantation, and has extrahepatic consequences including cardiometabolic disease and cancers. Although classically is associated with obesity, there is accumulating evidence that not all overweight or obese develop fatty liver disease. On the other hand, a considerable proportion of patients with MAFLD are lean, indicating the importance of metabolic health in disease pathogenesis regardless of body mass index. A complex and dynamic interaction between a multitude of factors, including genetic,

epigenetic, dietary, and lifestyle factors, enterohepatic circulation, and gut microbiota is likely to shape individual metabolic health status.

The clinical profile, natural history and pathophysiology of lean patients with MAFLD is not well characterised. In this talk, I am going to provide the recent epidemiological data on this group of patients. The talk will illustrate the novel concept considering the overall metabolic health and metabolic adaptation as a framework to best explain the pathogenesis of MAFLD and its heterogeneity, both in lean and non-lean individuals. This framework provides a conceptual schema for interrogating the MAFLD phenotype in lean individuals that can translate to novel approaches for diagnosis and patient care. I will also touch briefly on the prospective aspects including the initiatives bringing together diverse stakeholders across the metabolic disease spectrum that are pivotal in our efforts to firstly understand and then to provide personalized, timely, equitable and affordable health interventions for lean patients with MAFLD.

專題討論（五）

NAFLD/MAFLD新進展

ANTIDIABETIC AGENTS, LIPID-LOWERING AGENTS AND MALFD/NASH

Horng-Yih Ou（歐弘毅）

Division of Endocrinology and Metabolism, Department of Internal Medicine, National Cheng-Kung University Hospital, Tainan, Taiwan

Metabolic associated fatty liver disease (MAFLD) is the most common form of chronic liver disease worldwide. Currently, there were no Food and Drug Administration-approved medications for MAFLD. However, as MAFLD is closely associated with metabolic disorders such as obesity, type 2 diabetes, and dyslipidemia, various clinically pharmacological approaches using existing drugs such as antidiabetic, anti-obesity, antioxidants, and cytoprotective agents

have been considered in the management of MAFLD and nonalcoholic steatohepatitis (NASH). Emerging data from clinical studies with drugs targeting diverse molecular mechanisms show promising outcomes. This section will summarize the current understanding of the pathogenic mechanisms of MAFLD and then focus on the use and effects of anti-diabetic agents on MAFLD/NASH in the clinical setting.

專題討論（五）

NAFLD/MAFLD新進展

CROSS TALK OF NAFLD/MAFLD BETWEEN CARDIOLOGISTS AND GASTROENTEROLOGISTS

Yen-Wen Wu（吳彥雯）

Cardiovascular Medical Center, Far Eastern Memorial Hospital, New Taipei City, Taiwan

School of Medicine, National Yang Mind Chao Tung University, Taipei, Taiwan

Non-alcoholic fatty liver disease (NAFLD) or metabolic associated fatty liver disease (MAFLD) is closely related to cardiovascular diseases, and there is an close bi-directional relationship between them. It is not only a simple comorbidity, but also inextricably linked. Several large-scale meta-analyses show that the incidence of cardiovascular diseases in these patients increases, and the pathophysiological mechanisms may be through metabolic abnormalities, systemic inflammation, or directly related to hemodynamics. On the other hand, the hemodynamic changes after liver inflammation or cirrhosis are more likely to exacerbation of pre-existing cardiovascular diseases, including atrial fibrillation and heart failure. Fatty liver has become an important topic of global concern, including the Asian Pacific Association for the Study of the Liver (APASL), the American College of Cardiology/American Heart Association (ACC/AHA), the American College

of Endocrinology (ACE)/American Association of Clinical Endocrinologists (AACE), have published their consensus or guidelines, including the definitions, diagnosis, risk Factors, disease course, extrahepatic manifestations, noninvasive tests, liver biopsy, treatment, and management of patients with cirrhosis. In theory, patients with NAFLD/ MAFLD should screen the cardiovascular risks and diseases, and then primary or secondary prevention and appropriate treatments of cardiovascular disease according to their risk profiles and disease status. For patients with different cardiovascular risks/diseases, personalized screening or treatment strategies for their liver conditions is also encouraged. The present lack of a targeted pharmacological approach makes the identification of patients with liver disease at higher CVD risk of major clinical interest. The strategies for protecting the liver and heart at the same time warrant in the future.

專題討論（六）

Trans-papillary or Non Trans-papillary Biliopancreatic Drainage: An Update Issue

經由乳突或不經由乳突的膽胰道引流術的內視鏡治療

TRANS-PAPILLARY BILIARY DRAINAGE FOR OBSTRUCTIVE HILAR LESION

Ming-Chang Tsai（蔡明璋）

Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan

Patients with malignant hilar obstruction (MHO) are challenging to manage. Only 20-30% patients are amenable for surgical resection. Most patients are unresectable and present with clinical sign and symptoms of biliary obstruction. Non-surgical management includes endoscopic or percutaneous drainage, chemo or radiotherapy. At present, transpapillary route biliary drainage (endoscopic retrograde cholangiopancreatography, ERCP) with stent placement remains the standard treatment for biliary drainage in MHO. The primary goal is to resolve bile duct obstruction, to achieve long-term ductal patency and to maintain liver function. ERCP provides internal drainage by insertion of multiple plastic stents or metal stents with better quality of life compared to percutaneous routes. Before procedure, we should

review cross-session imagine with emphasis on volumetric liver assessment. Limit injection of contrast to bile duct is needed to avoid post-ERCP cholangitis. The aim is to drain >50% of liver volume. Bilateral stents provide better drainage function than unilateral stent and endoscopist may use stent-in-stent or stent-by-stent approach for bilateral metallic stent insertion. Although the stent patency rate is higher in patients undergoing self-expanding metallic stent (SEMS) than plastic stent, re-intervention in SEMS group is challenging and plastic stent replacement is much easier. In this session, I will present how to manage MHO in trans-papillary route. Update data, guideline, tips and stent selections will also be addressed.

專題討論（六）

Trans-papillary or Non Trans-papillary Biliopancreatic Drainage: An Update Issue

經由乳突或不經由乳突的膽胰道引流術的內視鏡治療

ENDOSCOPIC ULTRASOUND-GUIDED BILIARY DRAINAGE FOR HILAR OBSTRUCTION

Yu-Ting Kuo（郭雨庭）

Division of Endoscopy, Department of Integrated Diagnostics & Therapeutics, National Taiwan University College of Medicine, Taipei, Taiwan

Endoscopic management of hilar strictures is challenging and should be performed in tertiary referral centers. It requires a thorough understanding of the anatomy, including anatomical variants, the extent of the disease, surgical resectability of the tumor, and the primary objective of biliary drainage (in preparation for surgery or as palliation). These complex situations require upfront discussions during multidisciplinary meetings involving interventional endoscopists, hepatopancreaticobiliary surgeons, digestive oncologists, and interventional radiologists to decide the optimal endoscopic biliary drainage strategy.

In complex Bismuth type III and IV strictures, the European Society of Gastrointestinal Endoscopy (ESGE) guidelines in 2017 recommended the use of percutaneous transhepatic biliary drainage (PTBD) over endoscopic retrograde cholangiopancreatography (ERCP) or a combination of PTBD and ERCP.

Furthermore, in Bismuth type III and IV, drainage of more than 50% of the liver volume should be attempted, which often requires bilateral stenting or stenting of both right-sided anterior and posterior ducts to achieve this goal. However, ERCP remains frequently used for malignant hilar strictures and may have fewer complications and achieve more complete biliary drainage in expert hands.

Endoscopic ultrasound-guided biliary drainage (EUS-BD) has emerged as a safe and effective means of biliary decompression following failed ERCP. In unresectable malignant hilar strictures, EUS-BD may be considered in addition to ERCP to optimize biliary drainage. One prospective, multicenter study compared a combination of ERCP and EUS-BD to bilateral PTBD in 36 patients. The combined ERCP/ EUS-BD approach provided a lower rate of recurrent biliary obstruction at 3 and 6 months, with similar AE and mortality rates.

專題討論（六）

Trans-papillary or Non Trans-papillary Biliopancreatic Drainage: An Update Issue

經由乳突或不經由乳突的膽胰道引流術的內視鏡治療

TRANS-PAPILLARY PANCREATIC DRAINAGE

Yi-Chun Chiu（邱逸群）

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

Transpapillary pancreatic drainage has been increasingly used for treating pancreatic disorders such as pancreatic duct obstruction (often related to pancreatic stricture and/or stones) and pancreatic duct leakage. It involves the placement of an endoprosthesis through the major or minor papilla into the pancreatic duct, forming a route for the outflow of pancreatic secretions. Transpapillary drainage has been also found to be effective in treating fluid

collections such as pseudocysts with successful resolution. This method is different from transmural drainage as it uses the normal anatomical route of drainage and does not involve creating an alternative route.

This topic will review the recent applications transpapillary pancreatic drainage in pancreatic disease.

專題討論（六）

Trans-papillary or Non Trans-papillary Biliopancreatic Drainage: An Update Issue

經由乳突或不經由乳突的膽胰道引流術的內視鏡治療

ENDOSCOPIC ULTRASOUND GUIDED PANCREATIC DRAINAGE (EUS-PD)

Cheuk-Kay Sun（孫灼基）

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

Although endoscopic or surgical drainage is available for the management of symptomatic pancreatic duct obstruction or leakage, endoscopic transpapillary (or trans-anastomotic) drainage is often preferred as a first-line treatment option due to its less invasive nature. Nonetheless, it should be noted that endoscopic drainage may present technical or anatomical challenges in certain situations, such as complete pancreatic duct obstruction in chronic pancreatitis, disconnected duct syndrome following severe acute pancreatitis or pancreatic trauma, duodenal stricture, and surgically altered anatomy. In those difficult cases, surgical, or rarely percutaneous, pancreatic duct drainage (PD) is performed as an alternative method. The recent advances in interventional endoscopic ultrasound (EUS) have enabled access to a range of areas, including the biliary tract, pancreatic fluid collections, abdominal abscesses, and the pancreatic duct, even in cases where endoscopic retrograde cholangiopancreatography (ERCP) is difficult.

In 1995, Harada et al. reported EUS-guided pancreatography as a means of accessing the pancreatic duct following unsuccessful ERCP. EUS-guided PD (EUS-PD) was first reported as

rendezvous and transmural drainage in 2002. Since then, numerous studies have been published on EUSPD, although the majority of these have been in the form of case reports or case series. EUS-PD is widely considered to be one of the most challenging interventional EUS procedures from a technical standpoint.

EUS-PD is indicated for the management of various conditions, including pancreatic duct obstruction, pancreatic leakage, and disconnected pancreatic duct syndrome. EUS-PD is frequently attempted following unsuccessful ERCP, for a variety of reasons. When normal anatomy is present, EUS-PD is typically attempted after failed ERCP. However, in cases where anatomical challenges such as duodenal obstruction or surgically altered anatomy are present, EUS-PD may be considered as a first-line treatment option. Contraindications to EUS-PD include the inability to visualize the pancreatic duct under EUS, the presence of intervening vessels, severe coagulopathy, and an unstable general condition that precludes endoscopic procedures. EUS-PD carries a risk of pancreatic fistula and peritonitis in cases of massive ascites, and thus, the indications for EUS-PD should be carefully evaluated in patients with ascites.

專題討論（六）

Trans-papillary or Non Trans-papillary Biliopancreatic Drainage: An Update Issue

經由乳突或不經由乳突的膽胰道引流術的內視鏡治療

TRANS-PAPILLARY BILIARY DRAINAGE IN PATIENTS WITH SURGICALLY ALTERED ANATOMY

Yao-Sheng Wang（王堯生）

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

Endoscopic retrograde cholangiopancreatography (ERCP) in surgical-altered anatomy (SAA) is technically challenging. Surgical-altered anatomy includes gastrojejunostomy (GJ) bypass surgery, subtotal gastrectomy with Billroth II(B-II) reconstruction, pancreatoduodenectomy (PD) with or without Braun’s procedure, and any types of rouxen-y reconstruction (RY). Contrary to naive anatomy, only limited cases with SAA could be performed by conventional duodenoscope, mostly in subtotal gastrectomy with Billroth II reconstruction. For long limbs of afferent loop in GJ or Y limb in Roux-en-y cases, a short-type enteroscope is developed for ERCP procedure. Short-type enteroscope may be used with balloon overtube for bowel shortening. Single balloon or double balloon overtube, and even spiral system is now available. For all those types of enteroscope, the

technical and clinical success rate is around 70~100% according to different studies. A transparent hood may increase the 5-10% technical success rate. The skill of short-type enteroscope is similar to a conventional enteroscope like abdominal manual compression, bowel loop shortening, water immersion, and avoiding much air inflation for getting into the target site. Cannulation through naïve papilla by end viewing enteroscope without elevator is challenging. Combing contrast and wire technique is sometimes necessary. Retroflex or reverse endoscope method for a better approaching position is also an option. For those newly designed enteroscopes, endoscopic length is around 150-152cm with a 3.2mm instrument channel that can be loaded with any accessories less than 9Fr. Bile duct stones and benign or malignant biliary stricture thus can be treated as for naïve anatomy.

專題討論（六）

Trans-papillary or Non Trans-papillary Biliopancreatic Drainage: An Update Issue

經由乳突或不經由乳突的膽胰道引流術的內視鏡治療

ENDOSCOPIC ULTRASOUND GUIDED BILIARY DRAINAGE (EUS-BD) IN PATIENTS WITH SURGICALLY ALTERED ANATOMY

Chia-Hsien Wu（吳佳憲）

Division of Gastroenterology, Taitung Mackay Memorial Hospital, Taitung, Taiwan

ERCP is the first-line treatment option for malignant or benign biliary obstruction. In cases of surgically altered anatomy (SAA), such as after a Whipple procedure or Roux-en-Y gastric bypass, enteroscopy-assisted ERCP should be considered as the first-line therapy.

Since its introduction in 2001, EUS-BD has become an alternative option to PTBD in cases when ERCP has failed or in SAA cases. As more studies are conducted, the efficacy and safety of EUS-BD are accumulating more and more evidence.

Yuki et al. conducted a systematic review of PubMed through December 2021 to identify studies performing EUS-BD in patients with SAA.

[1] Finally, 18 studies meeting the study criteria for analysis reported data for 409 patients with SAA who underwent EUS-BD. The pooled technical success, clinical success, and adverse event proportions in patients with SAA were 97.8% (95% confidence interval [CI], 95.8–99.7%), 94.9% (95% CI, 91.8–98.1%), and 12.8% (95% CI, 7.4–18.1%), respectively. The high technical success rate of EUSBD was thought to be better than that of singleballoon enteroscopy-assisted ERCP (75.8%) in a previous systematic review and meta-analysis[2] and also proved the efficacy of EUS-BD for patients with SAA.

The pooled adverse event rate of EUS-BD was high at 12.8%. Although the majority of these adverse

events are mild-to-moderate, it was still higher than the pooled adverse event rate in the previous systematic review and meta-analysis of single-balloon enteroscopy-assisted ERCP (6.6%).[2]

Therefore, further prospective comparative studies are needed to evaluate the efficacy and safety of EUS-BD in patients with SAA to determine whether EUS-BD could be considered as the first treatment choice for patients with SAA.

EUS-BD includes various EUS-guided techniques. In scenarios of SAA with benign anastomosis stricture or malignant bile duct obstruction (hilar or distal bile duct), the most often used techniques were EUS-HGS, EUS-HGS + bridging to right IHD or antegrade stenting (EUSAG). The EUS rendezvous technique was less frequently used because of the necessity of time and labor-consuming enteroscopy-assisted ERCP. There are no studies to date to demonstrate which EUS-BD techniques is more beneficial and safe to the patient. At present, the choice depends on the postoperative reconstruction method, the obstruction level, the patient’s condition, the expertise of the endoscopist, and the availability of resources.

Most studies used a metal stent for EUS-BD, but there were few studies reporting on the usefulness of plastic stent placement with similar technical and clinical success rates.[3,4]

Increased standardization of the technical

procedure, proposed algorithms for standardization of the choice of management techniques, and further development of dedicated devices were practical approaches to lower the adverse event rate. Besides, proficiency of the endosonographer who was familiar with all EUS-BD techniques and multidisciplinary cooperation also played an important role in achieving the technical success and lowering the adverse event rate.

Conclusions

EUS-BD is effective for patients with SAA. However, the possibility of adverse events must be considered when performing EUS-BD in these patients.

The role of EUS-BD as the first-line treatment of bile duct obstruction in altered surgical anatomy remains a topic of ongoing research and needs further prospective studies to prove.

References:

1. Tanisaka Y, Mizuide M, Fujita A, et al.

Endoscopic ultrasound-guided biliary drainage in patients with surgically altered anatomy: a systematic review and Meta-analysis. Scand J Gastroentero. 2023;58(2):107–115.

2. Tanisaka Y, Ryozawa S, Mizuide M, et al. Status of single-balloon enteroscopy-assisted endoscopic retrograde cholangiopancreato-graphy in patients with surgically altered anatomy: systematic review and meta-analysis on biliary interventions. Dig Endosc. 2021;33(7):1034–1044.

3. Kanno Y, Koshita S, Ogawa T, et al. EUS-Guided biliary drainage for unresectable malignant biliary obstruction: 10-year experience of 99 cases at a single center. J Gastrointest Cancer. 2019;50(3):469–477.

4. Matsunami Y, Itoi T, Sofuni A, et al. EUS-guided hepaticoenterostomy with using a dedicated plastic stent for the benign pancreaticobiliary diseases: a single-center study of a large case series. Endosc Ultrasound. 2021;10(4):294–304.

專題討論（七）

抗栓塞藥物與內視鏡檢查與治療：高齡社會的新挑戰 抗栓塞藥物與內視鏡檢查與治療最新實證與國際最新指引介紹 Tsung-Hsing Chen（陳聰興）

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

Taiwan’s society has entered the aging population, and the prevalence of cardiovascular disease is also increasing with age. Therefore, the probability of using anticoagulant drugs will also increase. The incidence of gastrointestinal cancer also increases with age, and the two have a high degree of overlap. Various interventional therapies of endoscopy have been developed maturely, so it is necessary to explore in depth the issues of elderly patients taking anticoagulant drugs in this regard.

In the past, to avoid bleeding complications caused by endoscopic treatment, most doctors would recommend that patients stop using anticoagulant drugs. However, this will unknowingly increase the risk of other important complications of cardiovascular disease, putting the patient at a high risk. Previous

studies have shown that patients who have had a stroke after receiving a heart stent, if they suddenly stop taking antiplatelet or anticoagulant drugs, the risk of other cardiovascular or cerebrovascular diseases will increase threefold, and this is within a few days after stopping the medication, so clinical doctors need to be more cautious.

Currently, many surgical diseases in Taiwan can be replaced by endoscopy, such as endoscopic submucosal dissection (ESD) for early gastrointestinal cancer, POEM for achalasia, and cold or hot cutting of colon polyps. For patients taking anticoagulant drugs in these situations, we need to explore in depth to avoid unnecessary complications caused by endoscopic treatment.

專題討論（七）

抗栓塞藥物與內視鏡檢查與治療：高齡社會的新挑戰 抗栓塞藥物與進階內視鏡治療考量：大腸鏡息肉切除術與冷革命 Li-Chun Chang（張立群）

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

Colorectal cancer (CRC) is the third most common cancer worldwide and is a leading cause of cancer-related death. It is assumed that CRC arises from colorectal polyps, and removal of these polyps can significantly reduce the risk of developing CRC. Cold snare polypectomy (CSP) is a widely used technique for removing small colorectal polyps. The use of anti-thrombotic agents in patients undergoing CSP has been debated. This talk will discuss the current evidence on using anti-thrombotic agents in patients undergoing CSP.

Anti-thrombotic agents are drugs that prevent or reduce the risk of blood clots. They are commonly used in patients with cardiovascular diseases such as atrial fibrillation, deep vein thrombosis, and pulmonary embolism. Anti-thrombotic agents can be broadly classified into two categories: antiplatelet agents and anticoagulants. Antiplatelet agents include drugs such as aspirin, clopidogrel, and ticagrelor,

while anticoagulants include drugs such as warfarin, heparin, and direct oral anticoagulants (DOACs).

CSP is a technique for removing small colorectal polyps (less than 10mm in size) without using electrocautery. CSP has several advantages over conventional hot snare polypectomy, including a lower risk of bleeding and perforation and a higher rate of complete polyp resection. The current evidence suggests that using anti-thrombotic agents does not significantly increase the risk of bleeding or adverse events following CSP. However, the quality of the evidence is low to moderate, and further highquality studies are needed to confirm these findings. In the absence of high-quality evidence, the decision to continue or withhold anti-thrombotic agents in patients undergoing CSP should be made on a caseby-case basis, taking into account the individual patient’s risk of thrombotic events and the risk of bleeding associated with CSP.

專題討論（七）

抗栓塞藥物與內視鏡檢查與治療：高齡社會的新挑戰

抗栓塞藥物與進階內視鏡治療考量：內視鏡下粘膜剝離術

Chu-Kuang Chou（周莒光）

Division of Gastroenterology and Hepatology, Department of Internal Medicine, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi, Taiwan

Anticoagulants and anti-platelet medications are commonly used medications to prevent conditions such as coronary artery disease (CAD), deep vein thrombosis (DVT) and pulmonary embolism (PE), and are also used to prevent stroke in people with atrial fibrillation (AF). However, the use of anticoagulants poses certain challenges when it comes to invasive endoscopic procedures.

As the popularity of endoscopic submucosal dissection (ESD) as a treatment for gastrointestinal

tract neoplasms and tumors continues to increase, the challenge of balancing the benefits and risks of using anticoagulants and anti-platelet medications becomes increasingly crucial. In this section, we will examine the most recent research and guidelines to assist therapeutic endoscopists in making informed decisions regarding the use of anticoagulants and antiplatelet medications, taking into account both their benefits and potential risks.

專題討論（七）

抗栓塞藥物與內視鏡檢查與治療：高齡社會的新挑戰 抗栓塞藥物與進階內視鏡治療考量：介入性內視鏡超音波與膽胰內視鏡 Szu-Chia Liao（廖思嘉）

Division of Gastroenterology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan

There is more and more therapeutic endoscopy for pancreaticobiliary diseases. In recent years, the population of aging people are increasing. Therefore, more and more patients need antiplatelet or anticoagulant therapy for cardiovascular diseases. It is important to understand that the patients are advised of the thrombotic risks of discontinuing antiplatelets or anticoagulants, as well as the hemorrhagic risks of continuing therapy.

In meta-analysis, the overall hemorrhagic rate following ERCP was 1.3%. Post-ERCP bleeding is most frequently seen after endoscopic biliary sphincterotomy (EPT). There are a lot of methods which can reduce the risk of hemorrhage at ERCP including avoidance of EPT before biliary stenting and use of blended current rather than pure-cutting current.

The incidence of hemorrhage following EUSFNA for the pancreatic solid tumors has been analysed in several systemic reviews; the incidence is less than 1%. But the risk of hemorrhage become higher (5.5%) when EUS-FNA is focusing on the pancreatic cystic lesions. The study showed no significant difference in patients with or without discontinued antithrombotic therapy. EUS-guided drainage, an alternative to ERCP-guided biliary drainage stenting, has been to be safely feasible in patients with use of antiplatelet and/ or anticoagulants. The safety of EUS-guided biliary drainage should be confirmed in prospective studies before a recommendation can be made.

References:

1. Andrew M Vieitch, Franco Radaelli, Raza Alikhan, et al. Endoscopy in patients on antiplatelet or anticoagulant therapy: British Society of Gastroenterology (BSG) and European Society of Gastrointestinal Endoscopy (ESGE) guideline update. Gut. 2021;70:1611–1628.

2. Tsou YK, Lin CH, Liu NJ, et al. Treating delayed endoscopic sphincterotomy-induced bleeding: epinephrine injection with or without thermotherapy. World J Gastroenterol. 2009;15:4823–8.

3. Liao WC, Tu YK, Wu MS, et al. Balloon Dilation With Adequate Duration Is Safer Than Sphincterotomy for Extracting Bile Duct Stones: A Systematic Review and Meta-analyses. Clin Gastroenterol Hepatol. 2012;10:1101–9.

4. Bournet B, Migueres I, Delacroix M, et al. Early morbidity of endoscopic ultrasound: 13 years’ experience at a referral center. Endoscopy. 2006;38:349–54.

5. Al-Haddad M, Wallace MB, Woodward TA, et al. The safety of fine-needle aspiration guided by endoscopic ultrasound: a prospective study. Endoscopy. 2008;40:204–8.

6. Kien-Fong Vu C, Chang F, Doig L, et al. A prospective control study of the safety and cellular yield of EUS-guided FNA or Trucut biopsy in patients taking aspirin, nonsteroidal anti-inflammatory drugs, or prophylactic low molecular weight heparin. Gastrointest Endosc. 2006;63:808–13.

專題討論（七）

抗栓塞藥物與內視鏡檢查與治療：高齡社會的新挑戰 停藥或續用？ ─ 心臟科觀點 Ting-Tse Lin（林廷澤）

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

Patients underwent PCI, CIEDs implantation and other cardiac or vessel intervention are indicated to use of antithrombotic agents, including antiplatelet agents and anticoagulants. The management of patients using antithrombotic agents and requiring gastrointestinal endoscopy is an important clinical challenge. Gastrointestinal endoscopy is related to bleeding risk – there is bleeding risk stratification according to endoscopic procedures (high- and low-risk ones). Treatment with antithrombotic drugs in the periprocedural endoscopic period is based on balancing the bleeding risk against the

thromboembolic risk. Antithrombotic agents in endoscopic procedures with lower bleeding risk are not needed to be withheld. It is recommended temporary discontinuation of antithrombotic treatment in high-risk endoscopic procedures and to consider the use of “bridging” therapy with LWMH for patients on Vitamin K antagonists who are at high thrombotic risk. Evaluating cardiovascular risk and management of antithrombotic therapy could be a challenge for gastrointestinal endoscopists, therefore, collaboration with a cardiologist is of great importance, at least for some patients.

專題討論（八）

Controversy in GERD and Motility Symposium: Novel Concepts and the Debate

TO TEST LPR SYMPTOMS BEFORE TREATMENT – PRO Han-Chung Lien（連漢仲）

Division of Gastroenterology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan

LPR symptoms do not equate LPR. Unlike typical GERD, LPR is just one of the etiologies or an aggravating factor that contribute to the LPR symptoms. Most patients with LPR symptoms or LPR have non-erosive esophagus and non-specific laryngoscopic signs. Moreover, the presence of concomitant typical reflux symptoms is unlikely to predict the presence of pathological reflux. Given the lack of diagnostic gold standard, biomarkers that predict the response to anti-reflux therapy is desirable in clinical practice. In Lyon consensus for the diagnosis of GERD, impedance-pH which detects both liquid and gas refluxate with bolus transit directionality irrespective acidity along the entire esophagus is considered the gold standard to diagnose reflux episodes. Despite the uncertain role in the management of LPR symptoms, hypopharyngeal multichannel intraluminal impedance-pH potentially

enable to simultaneously detect pathological reflux in both hypopharynx and esophagus. Composite pH parameter incorporating both pathological pharyngeal acid reflux and pathological esophageal acid exposure has been shown to predict the response to PPI therapy in patients with isolated LPR symptoms but not in those with concomitant typical reflux symptoms. Thus, given the high specificity nature of pH-metry, pre-treatment test should be considered in patients with isolated LPR symptoms after excluding common non-reflux etiologies of chronic laryngitis. On the other hand, in patients with LPR symptoms and concomitant typical reflux, reflux itself may be the inducer, cofactor, or bystander of LPR symptoms. Reflux monitoring may also be valuable in those who are refractory to PPI therapy to determine whether inadequate acid suppression is the cause of refractory LPR symptoms.

專題討論（八）

Controversy in GERD and Motility Symposium: Novel Concepts and the Debate

TO TEST LPR SYMPTOMS BEFORE TREATMENT – CON Ming-Wun Wong（翁銘彣）

Department of Medicine, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Hualien, Taiwan

Laryngopharyngeal reflux (LPR) is a condition with symptoms including throat clearing, hoarseness, pain, globus sensation, cough, excess mucus production, and dysphonia, considered as extraesophageal manifestations of GERD, however, objective evidence of GERD is not consistently found. No gold standard for diagnosis and treatment of LPR exists, making it a challenge for healthcare systems.

Empiric proton pump inhibitor (PPI) therapy focused on response of LPR symptoms can help assess the association between reflux and these symptoms. Ambulatory reflux monitoring can provide objective evidence of GERD, however, in this talk we will discuss the difficulties of performing such testing before first-line PPI treatment in real-world settings.

專題討論（八）

Controversy in GERD and Motility Symposium: Novel Concepts and the Debate

ENDOLUMINAL TREATMENTS FOR GERD IS READY NOW – PRO Chen-Shuan Chung（鍾承軒）

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

Gastroesophageal reflux disease (GERD) is a common disorder worldwide and is notable for its high disease burden on healthcare system and increasing both incidence and prevalence. Proton pump inhibitors (PPIs) are the mainstay of therapy, however, there is a substantial proportion of patients with GERD may fail to medical treatment, either partially or completely, or become dependent on PPI use. Traditionally, these patients are referred to laparoscopic fundoplication to re-establish gastroesophageal barrier. However, concerning the adverse effects from both long-term PPI use and surgical intervention, the majority of

patients with GERD are hesitant to receive invasive surgery. In the past two decades, trans-natural orifice endoscopic anti-reflux procedures fill the treatment gap between medical therapy and surgical intervention. These procedures take advantages of less invasiveness, less blood loss, faster recovery to daily activity, less post-operative bloating, shorter procedure time and hospital stay with satisfactory efficacy in GERD-related symptoms control. Herein, I will be briefing the performance of endoscopic antireflux procedures on the management of GERD.

專題討論（八）

Controversy in GERD and Motility Symposium: Novel Concepts and the Debate

CONSIDER GASTRIC EMPTYING TEST FOR GASTROPARESIS AND FUNCTIONAL DYSPEPSIA – PRO

Ping-Huei Tseng（曾屏輝）

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

Normal gastric emptying is the result of coordinated activity in the proximal and distal regions of the stomach, and may be affected by several factors, such as the volume, composition and total calories of the ingested food, various neurohormonal factors and personal factors, such as pregnancy, anxiety and aging. Delayed or rapid gastric emptying has been associated with a number of gastrointestinal disorders, such as gastroparesis, functional dyspepsia, gastroesophageal reflux disease and dumping syndrome. Among them, gastroparesis is characterized by the remarkably delayed gastric emptying, accompanied by severe nausea, vomiting and abdominal fullness, in the absence of mechanical obstruction of the stomach. Gastroparesis may occur in association with diabetes, gastric surgery (consequence of peptic ulcer surgery and vagotomy) or for unknown reasons (idiopathic gastroparesis). Among them, idiopathic gastroparesis may represent the most common form. Currently, gastric emptying scintigraphy (GES) with solid test meals remains the gold standard to assess delayed gastric emptying. Nevertheless, methodologies related to test meal and imaging protocols in determining gastric emptying time differ between institutions and regions. At present, a low-fat egg-white test meal has been standardized by both the American Neurogastroenterology and Motility Society and

the Society of Nuclear Medicine based on a large multicenter study of 123 healthy volunteers. Other novel tests, including 13C-octanoate breath testing and wireless motility capsule, have been applied in several recent studies to determine gastric emptying, and each has its own advantages and limitations.

Since delayed and rapid gastric emptying may cause similar gastrointestinal symptoms, such as nausea, vomiting and bloating, the importance of determining the rate of gastric emptying to guide the treatment choice could not be overemphasized. Similarly, there is a great overlap of clinical symptoms between gastroparesis and functional dyspepsia, including postprandial fullness, early satiety, bloating. The pathogenesis of gastroparesis and functional dyspepsia is also complex and poorly understood. A number of factors, including autonomic neuropathy, poor glycemic control, duration of diabetes and comorbidity with psychiatric diseases, have been implicated. Compared with functional dyspepsia, gastroparesis has severe impact on the nutritional status and dramatically affect the quality of life of suffering patients. Therefore, it is also important to measure gastric emptying rates to confirm the diagnosis and severity, clarify the pathogenesis of dyspeptic symptoms, and determine the treatment strategy.

專題討論（八）

Controversy in GERD and Motility Symposium: Novel Concepts and the Debate

CONSIDER GASTRIC EMPTYING TEST FOR GASTROPARESIS AND FUNCTIONAL DYSPEPSIA – CON

Yen-Po Wang（王彥博）

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

Functional dyspepsia is a common functional gastrointestinal disorder that affects approximately 10% of the general population. It is characterized by persistent symptoms of postprandial fullness, early satiation, epigastric pain or burning, without any evidence of structural disease. Gastroparesis, on the other hand, is a condition of chronic nausea and vomiting that is associated with delayed gastric emptying and no obvious structural obstruction. Some studies have considered gastroparesis to be a more severe form of functional dyspepsia, with interchangeable symptoms of nausea and vomiting. Delayed gastric emptying is known to play a role in the development of both functional dyspepsia and gastroparesis, however, its value in establishing a diagnosis and guiding treatment is limited. The relationship between gastric emptying time and gastrointestinal symptoms is inconsistent across

studies, and other overlapping functional disorders, such as constipation or irritable bowel syndrome, are more closely linked to poor gastrointestinal symptoms. Additionally, gastric emptying test results do not accurately predict treatment response. It is currently unclear who would be the best candidate for a gastric emptying test, such as those with poor response to conventional treatment, those with nausea symptoms, or those considering interventional treatment.

For these reasons, gastric emptying tests are not recommended for routine use in patients with typical symptoms of functional dyspepsia according to guidelines from Asia, America, Europe, and the United Kingdom. In a clinical practice setting, gastric emptying tests are not suggested for routine use in patients with either gastroparesis or functional dyspepsia.

專題討論（九）

Unmet Needs of Immunotherapy for HCC

UNMET NEEDS OF SYSTEMIC THERAPY FOR UHCC FROM CURRENT PHASE 3 CLINICAL TRIALS

Richard S. Finn

Division of Hematology/Oncology, Department of Medicine, David Geffen School of Medicine, University of California, Los Angeles, CA, USA

The results of pivotal studies of immunotherapy combinations have dramatically changed the natural history of advanced HCC. They are significantly improving overall survival, delaying progression, and inducing durable double-digit responses with acceptable toxicity while maintain quality of life. However, these studies have highlighted various unmet needs in the HCC space. These include how do we manage patients with de novo resistance to these regimens and similarly, what is our best choice for patients that progress after an initial benefit (acquired

resistance). In addition, we know that patients with main portal vein invasion, while they do benefit from atezolizumab and bevacizumab, we know that their progress is still poor and new approaches are needed. All phase 3 studies to date have concentrated on patients with CP A liver disease, clearly highlighting a need for data in patients with less compensated liver disease. In the lecture, we will address these unmet needs as well as others and discuss how to address these in the future.

專題討論（九）

Unmet Needs of Immunotherapy for HCC

APPLICATION OF SYSTEMIC THERAPY FOR INTERMEDIATE-STAGE HCC AND HIGH RISK PATIENTS

I-Cheng Lee（李懿宬）

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

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

Intermediate-stage hepatocellular carcinoma (HCC) is composed of a very heterogeneous disease with a wide range of tumor burden, and not all patients could benefit from transarterial chemoembolization (TACE). New treatment strategies, such as early initiation of systemic therapies, have been proposed for patients who might be unsuitable or refractory to TACE treatment, especially in patients with high tumor burden. The updated 2022 BCLC treatment strategy recommended that curative therapy could be considered in intermediate-stage HCC patients with low tumor burden, while systemic therapy should be considered in patients with high tumor burden. We recently proposed the seven-eleven criteria, which evenly stratified HCC patients into low, intermediate and high tumor burden, and had good discriminative power in predicting radiologic

response and survival after TACE. The seven-eleven criteria could guide novel treatment strategies in patients with intermediate-stage HCC. For patients with advanced stage HCC, whether combination therapy with immune-checkpoint inhibitor (ICI) plus tyrosine kinase inhibitor (TKI) could provide survival benefit remains controversial. A recent randomized trial showed comparable survival outcomes in patients receiving lenvatinib monotherapy versus lenvatinib plus pembrolizumab therapy, while subgroup analysis showed a trend of survival benefit for combination therapy in patients with higher disease burden. Our real-world experience also showed a favorable role of ICI plus TKI in subgroup patients with metastatic HCC or extremely high AFP levels. Further studies are warranted to define the high risk population who may benefit from ICI plus TKI.

專題討論（九）

Unmet Needs of Immunotherapy for HCC

REAL-WORLD EVIDENCE OF IMMUNOTHERAPY IN HCC PATIENTS WITH IMPAIRED LIVER FUNCTION AND BEYOND CLINICAL TRIAL CRITERIA

Teng-Yu Lee（李騰裕）

Division of Gastroenterology& Hepatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan

Immunotherapy, i.e. immune checkpoint inhibitor (ICI), has been the standard of treatment for advanced hepatocellular carcinoma (HCC); however, the evidence from clinical trials only come from patients in good conditions, such as compensated liver function, no organ transplant, or low HBV viral loads. However, in the real-world practice, we often encounter HCC patients who are beyond the inclusion criteria of clinical trials, but they still eager for a more durable therapy than tyrosine kinase inhibitor (TKI), i.e. immunotherapy. For resolving this problem, we can obtain some implications from studies of the real-world experience. Liver function impairment itself is an independent risk factor of poor prognosis, therefore almost all clinical trials excluded patients beyond Child-Pugh class A. Only few trials included patients with Child-Pugh score B7. Unfortunately, a substantial proportion of patients with advanced HCC has suffered from impaired liver function, e.g.

beyond Child-Pugh class A or B7. In the real-world experience, we can see some patients obtained good responses to the immunotherapy, and immunotherapy might be beneficial to patient survival. In addition, severe acute rejection has been observed in organ transplant patients after ICI therapy, and ICI therapy may increase the risk of acute rejection. However, some case studies reported that no acute rejection after organ transplantation took place after 3 months of ICI therapy. One of the issue is underlying HBV infection during ICI therapy. The prevalence of HBV carriers is common in Taiwan, and patients with high HBV viral load are excluded from clinical trials. However, in real-word experience, HCC patients under ICI therapy is not subject to hepatitis B flare, and HBV prophylaxis with antivirals should be safe for high viral-load patients who plan to receive ICI therapy. In this talk, the above-mentioned issues will be discussed.

專題討論（九）

Unmet Needs of Immunotherapy for HCC

UNMET NEEDS OF BIOMARKERS INCLUDING GUT MICROBIOTA FOR IMMUNOTHERAPY OF HCC

Pei-Chang Lee（李沛璋）

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

Hepatocellular carcinoma (HCC) is the sixth most common cancer and the third leading cause of cancer-related death worldwide, which constitutes a major global health problem. Despite implementation of universal hepatitis B vaccination, direct-acting antiviral agents for hepatitis C, and active surveillance for high-risk populations, a significant portion of patients still presented with or progressed to unresectable, advanced-stage diseases that require systemic therapy. Immunotherapies with immune checkpoint inhibitors (ICIs) are promising therapeutic agents for unresectable HCC. In general, the response rate of HCC to ICIs treatment is around 16-20% for ICI monotherapy, and 30-36% for ICI combinations. The PD-L1 expression level is not recommended as a

selection marker for ICI treatment for HCC. CTNNB1 mutation represents an immune-exclusive subclass of HCC and may be resistant to immunotherapy, but further validation is required. On-treatment decline of alpha fetoprotein (AFP) has been reported to predict tumor response to immunotherapy. So far, pretreatment tumor or host-related biomarkers which are associated with the outcomes of HCC to ICI treatment are in unmet needs. On the other hand, emerging studies indicate that the gut microbiome has a role in response to cancer therapy across cancer types. Recently, the potential role of fecal microbiota in ICItreated HCC has also been reported. In this topic, we will discuss the unmet need of biomarkers for immunotherapy-treated HCC.

專題討論（十）

COVID-19感染在胃腸道及肝臟疾病之表徵

Clinical Manifestation of GI and Liver Disease in the COVID-19 Era

GI MANIFESTATION DURING/POST COVID-19 INFECTION

新冠病毒感染在胃腸道之臨床表現

Yu-Jen Chen（陳宥任）

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

Severe acute respiratory syndrome coronavirus 2 (SARS- CoV-2) and the associated coronavirus disease 2019 (COVID-19) have been spreading all around the world for past 3 years. Some of these convalescent individuals experienced longterm sequelae termed ‘long COVID’, or ‘postacute COVID-19 syndrome’(PACS). Common manifestations are systemic, neuropsychiatric, cardiorespiratory and gastrointestinal.

The prevalence of gastrointestinal PACS was 2-5% in different literatures. The risk factors of gastrointestinal PACS include anosmia, ageusia, and presence of chronic bowel disease, dyspeptic symptoms and the psychological comorbidity. Previous articles have discussed pathogenesis of PACS, which was associated with increasing serum cytokine level and persisted inflammatory status.

Whereas, the influence of chronic inflammation to target organ has not been well studied. Liu et al explored the gut microbiota dynamics in patients with PACS, which revealed higher levels of Ruminococcus gnavus, Bacteroides vulgatus and lower levels of Faecalibacterium prausnitzii. Another article established the association between multisystem inflammatory syndrome in children (MIS-C) and zonulin-dependent loss of gut mucosal barrier. According to previous studies, infectious enteritis may cause subsequent post infectious irritable bowel syndrome, which was associated with increased gut permeability, T-lymphocyte, Mast cell and proinflammatory cytokine. It is reasonable that gastrointestinal PACS might be also associated with dysfunction of gut mucosal barrier.

專題討論（十）

COVID-19感染在胃腸道及肝臟疾病之表徵

Clinical Manifestation of GI and Liver Disease in the COVID-19 Era

FMT IN POST COVID PANDEMIC ERA

新冠疫情後對微菌叢植入之影響

Tien-En Chang（張天恩）

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

Fecal microbiota transplantation (FMT) is used to treat recurrent or refractory Clostridioides difficile infection (CDI). Screening of fecal donors required surveillance of personal behavior, medical history, and diseases that could be transmitted by the blood or fecal–oral route in the past. However, this task has become more difficult in the time of the coronavirus disease-2019 (COVID-19) pandemic. Screening for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) among stool donors was recommended by US FDA.

To prevent transmission of SARS-CoV-2 through fecal product, screening for SARS-CoV-2 is

required. To properly exclude individuals with higher risk of SARS-CoV-2 infection, clinical symptoms, personal history of travelling or contact infected patients must be checked during donor screening. To detect asymptomatic patients, serologic tests for SARS-CoV-2 antibodies, polymerase chain reaction (PCR) quantification for nasopharyngeal swab or stool samples may considered. These tests should be obtained serially during the stool donation. The collected stool products should also be put into quarantine and the donor’s health condition should be checked respectively after donation.

專題討論（十）

COVID-19感染在胃腸道及肝臟疾病之表徵

Clinical Manifestation of GI and Liver Disease in the COVID-19 Era

COVID-19 IN CHRONIC LIVER DISEASE

新冠病毒感染在慢性肝病之臨床表現

Tung-Hung Su（蘇東弘）

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

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been found to be associated with dysfunction or damage of liver tissue, and about 14% - 53% of COVID-19 cases showed abnormal levels of aspartate aminotransferase (AST) and alanine aminotransferase (ALT). The liver injury may be due to a direct effect of SARS-CoV-2, or an indirect effect following septic shock, multiorgan dysfunction, drug-related toxicity, immune-related hepatitis, or systemic inflammatory responses (cytokine release or storm) of the COVID-19 syndrome. The prevalence of chronic liver disease in COVID-19 patients ranges from 2%-11%. COVID-19 patients with HBV co-infection were more prone to develop liver damage with more adverse outcomes and mortality.

We conducted a retrospective cohort study of COVID-19 patients at National Taiwan University Hospital, stratified according to hepatitis B surface antigen (HBsAg) serostatus, with demographics, laboratory data, and hospitalization course reviewed, and clinical outcomes compared through multivariable analyses. We enrolled 109 COVID-19 patients

unvaccinated against SARS-CoV-2 by August 2021. The HBsAg-positive group (n = 34) had significantly higher alanine aminotransferase (ALT) (26 vs. 16 U/L, P = 0.034), platelet (224 vs. 183 k/µL, P = 0.010) and longer hospitalizations (17 vs. 13 days, P = 0.012) compared with HBsAg-negative group (n = 75), while percentages of hepatitis (2-fold ALT elevation), oxygen supplementation, ventilators usage, COVID-specific treatment, intensive care unit (ICU) admission and mortality were comparable. Older age (odds ratio [OR]: 1.04, 95% confidence interval [CI]: 1.00–1.08, P = 0.032) and higher aspartate aminotransferase (AST) (OR: 1.08, 95% CI: 1.004–1.16, P = 0.038) were associated with oxygen supplementation according to multivariable analyses. Higher AST predicted ICU admission (OR: 1.11, 95% CI: 1.03–1.19, P = 0.008). Oxygen usage (OR: 5.64, 95% CI: 1.67–19.09, P = 0.005) and shock (OR: 5.12, 95% CI: 1.14–22.91, P = 0.033) were associated with liver dysfunction. We concluded that patients with chronic hepatitis B had higher ALT levels and longer hospitalizations during COVID-19. Higher AST levels predict severe COVID-19 and ICU admission.

專題討論（十）

COVID-19感染在胃腸道及肝臟疾病之表徵

Clinical Manifestation of GI and Liver Disease in the COVID-19 Era

COVID-19 VACCINES IN CHRONIC LIVER DISEASE

慢性肝病患者之新冠疫苗注射

Chung-Feng Huang（黃釧峰）

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

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection has caused millions of subjects being infected, hospitalization and death since 2019. Vaccination is the key strategy to fight the global coronavirus disease 2019 (COVID-19) pandemic. Patients with chronic liver disease in particular those with liver cirrhosis are at a great risk of COVID-19 associated hospitalization and mortality. In addition, post-liver transplantation patients were less responsive to 2 doses of COVID-19 vacations. Compared to patients who received 2-dose COVID-19 vaccines, a 3rd dose booster has been to decrease severe COVID-19 and mortality in cirrhotic patients. As a consequence, the international liver association advocates that all the patients with chronic liver disease should receive least 3 doses of vaccines or equivalent spike protein exposures. On the other hand, while eliciting neutralizing antibody and virialspecific T cell response against spike protein, the triggering innate and adaptive responses may cause autoimmunity to self-antigen by the COVID-19

vaccines. In view of liver injuries, albeit that drug induced liver injury due to vaccine per se or the adjuvant has been postulated, emerging evidence has given the hint that immune-mediated hepatitis is the mainstream driver for hepatitis. The pathological feature has been pointed to be associated with SARSCoV-2-specific CD8 T-cell activation. Other forms of hepatic events including portal vein thrombosis, splanchnic vein thrombosis, acute cellular rejection of the liver, hepatomegaly and hepatic porphyria have also been presented. From the current literature review and evidence, the chance of vaccine related immunemediated hepatitis is rare and is often self-limited or manageable. A recent population-based study has indicated that there was a minimal risk of acute liver injury following mRNA and inactivated COVID-19 vaccine, which was even much lower than SARSCoV-2 associated hepatitis. Taken collectively, It should not refrain people from vaccination inoculation while facing this worldwide pandemic.

專題討論（十一）

Obesity: Pathogenesis and Management

OBESITY: PATHOGENESIS, PREVALENCE, AND COMPLICATIONS 慢性肝病患者之新冠疫苗注射

Chih-Yen

Chen（陳志彥）

Faculty of Medicine and Institute of Emergency and Critical Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan

Obesity is a complex, chronic disease and global public health challenge. The pathogenesis of obesity has been extensively investigated over the past decades, and an increasing number of signal transduction pathways have been implicated in obesity, making it possible to fight obesity in a more effective and precise way. For instance, MAPK, PI3K/ AKT, JAK/STAT, TGF-β signaling, and AMPK Wnt/ β-catenin signaling pathways have been targeted. On the other hand, ER stress factors and the involved pathways, as well as immune-related pathways, are implicated.

More than 1.9 billion adults are overweight and

650 million are obese. According to ICMR-INDIAB study 2015, prevalence rate of obesity and central obesity are varies from 11.8% to 31.3% and 16.9% to 36.3% respectively. Obesity sharply increases the risk of several diseases, such as type 2 diabetes, cardiovascular disease, and nonalcoholic fatty liver disease. Interestingly, obesity increases the prevalence of atrial fibrillation, partly related to electroanatomic remodeling in obese patients. Finally, obesity is linked to lower life expectancy. Therefore, obesity should be regarded as a disease and seriously treated (JASSO, APMBSS 2018).

專題討論（十一）

Obesity: Pathogenesis and Management

LIFESTYLE MODIFICATION AND MEDICAL TREATMENT FOR OBESITY 肥胖症的生活型態改變及內科治療

Tun-Jen Hsiao（蕭敦仁）

Charity Clinic, Taoyuan, Taiwan

Obesity is a major public health issue in the world, and the prevalence of it is increasing gradually including Taiwan. Diabetes, hypertension, hyperlipidemia, gout, infertility, degenerative arthritis, etc. are obesity-related abnormalities. Recently metabolic syndrome (MetS), focus on insulin resistance (IR), makes it easier for clinicians to explain their risks and make patients understand the health hazards caused by obesity. Obesity also has significant health hazards to the digestive system, from gastroesophageal reflux, Barret's esophagus, esophageal cancer, gastric cancer, colorectal polyps, colorectal cancer, non-alcoholic fatty liver, liver cancer, gallstones, gallbladder cancer, acute pancreas Inflammation and pancreatic cancer are all related to obesity; although obesity was mostly dealt with by doctors of metabolism and family medicine in the past, when diagnosing and treating these related diseases, specialists in gastroenterology should also give considerable weight management advice and treatment for our patients to avoid obesity. The disease recurs because the cause cannot be eradicated.

The treatment of obesity is mainly based on "dietary education, exercise guidance, and adjustment of living habits". However, in order to achieve better results, various treatments have been introduced for decades years. Among them, weight

loss drugs are the most popular treatments, but many drugs after listing, they were taken off the market due to adverse reactions, such as Sibutramine and Lorcaserin. Currently, only Orlistat, Liraglutide, and Contrave® (Bupropion/Naltrexone) are the weight loss drugs approved by the Taiwan Food and Drug Administration. Meal replacement meal is an available therapy between dietary education and drug therapy. Bariatric surgery is a proven treatment for longterm weight loss, but because of its invasiveness, the proportion of patients who meet surgical indications are willing to undergo surgical treatment is not high. Bariatric endoscopy is a therapy between drug therapy and surgery. The current mainstream bariatric endoscopic methods are intragastric balloon and endoscopy sleeve gastrectomy. In the future, the role of GI specialist physicians in obesity treatment will become increasingly important.

This speech will start with the health hazards of obesity, and then talk about the current mainstream methods of obesity treatment and future prospects, and will emphasize therapeutic life style change and medical treatment. I believe that the quality and quantity of the GI specialist physicians in the prevention and treatment of obesity will gradually become more important, and I look forward to everyone joining in this future challenge.

專題討論（十一）

Obesity: Pathogenesis and Management

BARIATRIC SURGERY: CURRENT STATUS AND FUTURE PERSPECTIVE

Chih-Kun Huang（黃致錕）

Department of Metabolic & Bariatric Surgery / International Center / Body science & Metabolic Disorders International (B.M.I) Medical Center, China Medical University Hospital, Taichung, Taiwan

Bariatric surgery has been recognized as the most efficient and effective treatment for for severe obesity. It could lead more than 50 % excess weigh loss and remission of associated co-morbidities and shows longterm and durable results. Type II diabetes mellitus (T2DM) have been known as one of the most difficulttreated progressive metabolic diseases in this century. Since 1980, surgeons observed that many patients with type 2 diabetes who had undergone bariatric surgery experienced a durable weight loss and also diabetes remission. Since then, there have been many studies confirming the efficacy of surgery in treating type 2 diabetes; so called “Metabolic Surgery”. Mostly commonly performed bariatric and metabolic operations int the world is Roux-en-Y gastric bypass (RYGB) and sleeve gastrectomy (SG). However, when comparing with RYGB that can maintain better weight loss and achieve higher remission rates of obesity related co-morbidities

especially type 2 diabetes mellitus, SG still shows inferior results.

Bowel bypass causing stronger gastro-intestinal hormonal modulation has been proved to be the the key points involved in longterm weight maintenance and remission of diabetes mellitus when comparing these two procedures. Otherwise adopting RYGB has been declined since these 5 years because of more anatomic and nutritional complications, such as marginal ulcer, dumping syndrome and vitamin deficiency.

Sleeve plus is defined as adding bowel bypass in SG to improve the weight loss and remission of comorbidites. It has great potentials in replacing RYGB and SG in many aspects and has been developed to more than 10 procedure in the world till now.

In this presentation, we will review the studies of present status, indications and future perspectives.

專題討論（十一）

Obesity: Pathogenesis and Management

THERAPEUTIC ENDOSCOPY IN THE TREATMENT OF OBESITY 慢性肝病患者之新冠疫苗注射

Chu-Kuang Chou（周莒光）

Division of Gastroenterology and Hepatology, Department of Internal Medicine, Ditmanson Medical Foundation Chia-Yi Christian Hospital, Chiayi, Taiwan

Obesity has become a widespread global health concern for related morbidity and mortality. Advancements in weight control medications, bariatric endoscopy, and metabolic and bariatric surgery have improved the options for managing obesity. Bariatric endoscopy may fit in the gap between medical treatment and surgical treatment. Due to the

growing obesity epidemic, there is a growing need for specialized endoscopists with expertise in both therapeutic endoscopy and obesity management. In this section, we will conduct an evidence-based review of bariatric endoscopy options in Taiwan and share our experience.

專題討論（十二）

Microbiota and Systematic Diseases

GUT-BRAIN AXIS

Yen-Po Wang（王彥博）

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

The gut-brain axis plays a crucial role in the communication between the gastrointestinal system and the central nervous system. Communication occurs through neuronal, immune, endocrine, and metabolic pathways, affecting the central nervous system, enteric nervous system, autonomic system, and hypothalamic pituitary adrenal pathway. This bilateral communication can lead to changes in both neuropsychiatric and neurodegenerative diseases, such as mood disorders, schizophrenia, Parkinson’s disease, Alzheimer’s disease, and intestinal disorders

such as irritable bowel syndrome and inflammatory bowel disorders. The gut’s homeostasis is influenced by the intestinal microbiota. Altered intestinal microbiota, gut infections, or dysbiosis can result in changes in cytokines, neurotransmitters, and bile acids, leading to visceral hypersensitivity and neurocognitive dysfunction. A better understanding of the mechanisms by which microbiota impact the gutbrain axis could lead to new treatment pathways and targets for both gut and brain diseases.

專題討論（十二）

Microbiota and Systematic Diseases

GUT-HEART AXIS

Ming-Shiang Wu（吳明賢）

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

The work of Robert Koch in the nineteenth century has established the “Germ Theory” (Koch’s Postulates) for infectious disease. With the application of microscope and advance of microbiology, more and more bacterial pathogens were found. Indeed, the human gut is a bioreactor with a microbiota that encompasses hundreds or thousands of bacteria taxa. Through metabolites, immune and inflammatory reaction and Gut-Systemic axis, gut microbiota can play an important role in host’s health. Dysbiosis can

not only result in common gastrointestinal disease but also non-GI or non-communicable disease such as obesity, diabetes mellitus, atherosclerosis, cancer and even degenerative diseases of brain. In addition to changing our viewpoints in pathogenesis, therapeutic interventions, especially stool bank and fecal microbiota transplantation, has become a hot topic and may revolutionize diagnosis and treatment of diseases. In this speech, I will use atherosclerosis to illustrate the viewpoint of Gut-Heart Axis.

專題討論（十二）

Microbiota and Systematic Diseases

GUT-LIVER AXIS

Chun-Ying Wu（吳俊穎）

Institute of Biomedical Informatics, National Yang-Ming University, Taipei, Taiwan

Division of Translational Research, Taipei Veterans General Hospital, Taipei, Taiwan

微菌叢透過 Gut-liver axis，與許多肝臟疾病 的發生及進展，有非常密切的關係，譬如：脂肪 肝、酒精肝、肝硬化、肝癌、等疾病。透過瞭解

Microbiota 在 gut-liver axis 所扮演的角色，可以對 於許多肝臟疾病的致病機轉以及治療方式，有更 多的瞭解。

本演講會回顧近幾年在 Microbiota, gut-liver

axis 的最新觀念以及重要的研究進展，將會聚焦 於討論動物試驗以及臨床研究的有趣發現，同時 會討論其臨床上之可能應用。本演講適合對於微 菌叢與肝臟疾病研究有興趣的學者，以及對於微 菌叢在相關肝臟疾病之將來可能應用性有興趣的 臨床醫師參加。

專題討論（十二）

Microbiota and Systematic Diseases

THE ROLE OF URINE MICROBIOTA IN PATIENTS WITH UROLITHIASIS

Hsiang-Ying Lee（李香瑩）

Department of Urology, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan

Department of Urology, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan

Urolithiasis is a disease with high prevalence and recurrence rate. There are various risk factors impacting on stone formation including intestinal micorbiome. This study aims to investigate the relationship between urine microbiota with urolithiasis.

We collected mid-stream voided urine samples from urolithiasis 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. 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.

We enrolled 28 urolithiasis patients and 59 control participants who reported no recent antibiotic usage. In the beta diversity analysis, there was a significant difference between the microbiota in the samples of the urolithiasis and control groups according to ANOSIM statistical analysis. (P = 0.004). On comparing the groups, it showed Alcaligenes, Bacteroides, Blautia, Ruminococcaceae_UCG, Cutibacterium, Alistipes, Lachnoclostridium present more significant in urolihtiasis patient than control group.

Our current study shows that dysbiosis of urine microbiota may be related to the development of urolithiasis. 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.

一般演講

主題：C 型肝炎（一） ①

醫學中心的經驗

C 肝患者使用全

BY USING ELECTRONIC ALERT SYSTEM EFFECTIVELY PROMOTE HCV SCREENING IN PREVENTIVE HEALTH CARE SERVICES: EXPERIENCE FROM A MEDICAL CENTER

REFERRALS

Background: As the major cause of liver cancer is Hepatitis B and C in Taiwan, the screening of Hepatitis B and C become the first important step for early diagnosis and appropriate treatment. To achieve the goal of eliminating hepatitis in 2025, people aged from 45 to 79 could receive screening of hepatitis B and C in terms of preventive health care services for adults since September 28, 2020.

Aims: The purpose of the study is to analyze the efficacy of referrals by using electronic alert system into HCV screening in preventive health care services.

Methods: The target population is outpatients who are aged from 45 to 79, have not received screening of hepatitis B and C through blood testing. Screening resources are funded by government general budget of Health Promotion Administration in Taiwan and screening program has begun from Sep.28, 2020. We set up a referral process since February 2021 by using electronic alert system to see the efficacy of this screening program. The target population would receive a referral sheet from outpatient nurse and complete the screening of Hepatitis B and C at family medicine department or health check center. The screening period was divided into three phases that phase 1 means before referral (Oct 2020 to Jan 2021); phase 2 means after referral but before covid pandemic (Feb 2021 to May 2021); phase 3 means after covid pandemic (Jun 2021 to Oct 2022).

Results: The average screen numbers per month were 372 in phase 1, 538 in phase2 and 379 in phase 3 respectively. The growth rate was 45% before and after referral system. The total accumulative screen number was 8596 in phases 2 and 3. 1.5% (127/8596) of these screening population were seropositive of anti-HCV antibody, in which 17.3% (22/127) were detected HCV RNA. 86.4% (19/22) of patients with viremia had received DAA treatment.

Conclusions: Integrating electronic alert system into preventive health care services is an effective tool to improve HCV screening in hospital-based practice.

RISK FACTORS OF TUMOR RECURRENCE FOR CHRONIC HEPATITIS C PATIENTS WITH EARLY

STAGE HEPATOCELLULAR CARCINOMA AFTER THERAPY WITH ALL ORAL DIRECT-ACTING ANTIVIRALS

Background: The therapeutic landscape of chronic hepatitis C (CHC) evolved dramatically after the invention of all-oral direct-acting antivirals (DAAs). DAAs-induced sustained virological response (SVR) resulted in reduced future hepatocellular carcinoma (HCC) development, risk of liver-related and all-cause mortality. However, for patients with CHC-related HCC after anti-cancer therapy, the clinical benefits of DAAs treatment in preventing HCC recurrence and risk factors responsible for tumor recurrence after DAAs remained to be clarified.

Aims: At present, real-world data evaluating the independent variables associated with tumor recurrence for CHC-HCC patients after treatment with all-oral DAAs are scarce in Taiwan. Therefore, we conducted this study to address the above important issues.

Methods: From January 2017 to August 2021, all consecutive patients with CHC-HCC who were treated by all-oral DAAs at Taipei Veterans General Hospital were eligible candidates. We included patients with early BCLC stage (0 and A), who had been successfully treated without evidence of residual tumor before initiation of DAAs treatment for analyses. History of liver transplantation or active HCC before DAAs treatment, short follow-up period (<0.5 year) after DAAs initiation and patients with intermediate or advanced HCC (BCLC stage B, C, D) were excluded. The primary outcome was recurrence of HCC after initiation of DAAs. Variables independently associated with the primary outcome were evaluated using multivariate Cox proportional hazards models.

Results: A total of 94 patients were enrolled. The mean age of study population was 75.9 ± 8.9 years; 44.7% of

運用 E 化轉介系統有效促進院內 C 肝篩檢：

楊芳琦1 劉怡伶1 蘇培元2 曾雅慧1 顏旭亨2 1 彰化基督教醫院消化系中心 2 彰化基督教醫院胃腸肝膽科

them were male; and 94.7% of them belonged to ChildPugh class A. Staging of HCC were as follows: 17.0% belonged to BCLC stage 0; 46.8% belonged to BCLC stage A with a single tumor <5 cm in diameter; 13.8% belonged to BCLC stage A with a single tumor ≥5 cm in diameter; 11.7% belonged to BCLC stage A with two or three nodules; and the remaining 10.7% of patients could not be analyzed due to insufficient data. Before the initiation of DAAs, 31.9% of study population had documented HCC recurrence after successful treatment. The median followup period after DAAs initiation was 2.08 years (interquartile range, 0.72–2.99 years). After DAAs, a total of 95.7% CHC-HCC patients achieved SVR and phenomenon of HCC recurrence was found in 54.3% of study population. The cumulative incidence of recurrent HCC after DAAs initiation was 31.1% at 1 year, 42.5% at 2 years, 57.3% at 3 years, 60.6% at 4 years, and 68.5% until 5.69 years, respectively. Multivariate analyses demonstrated variables independently associated with HCC recurrence were: prior HCC recurrence before DAAs (hazard ratio [HR] = 3.15; 95% CI, 1.63–6.11, P = 0.001), no SVR after DAAs (HR = 6.829; 95% CI, 1.42-32.83, P = 0.016), post-DAAs 12 weeks AFP > 10 ng/mL (HR = 2.34; 95% CI, 1.06–5.17, P = 0.036), and BCLC stage A with two or three nodules compared to BCLC stage 0 and A with single nodule (HR = 2.31; 95% CI, 1.05–5.09, P = 0.039).

Conclusions: Our real-world data strongly supported that achievement of SVR post DAAs significantly reduced tumor recurrence in CHC patients with early-stage HCC. Even with high SVR rate, tumor recurrence of CHCHCC patients after DAAs are quite common. Prior HCC recurrence before DAAs, post-DAAs 12 weeks AFP > 10 ng/mL, and BCLC stage A with two or three nodules were independent risk factors associated with HCC recurrence.

③

TACR 資料庫分析治療慢性 C 型肝炎患者

肝功能異常的相關因素 FACTORS ASSOCIATED WITH LIVER FUNCTION ABNORMALITIES IN CHRONIC HEPATITIS C PATIENTS TREATED WITH SOFOSBUVIR/ VELPATASVIR OR GLECAPREVIR/ PIBRENTASVIR: REAL- WORLD RESULTS FROM A NATIONWIDE REGISTRY IN TAIWAN

余明隆

1 國立中山大學

2 台南市立醫院

9

8

10

Background: Both European Association for the Study of the Liver (EASL) and American Association for the Study of Liver Diseases and the Infectious Diseases Society of America (AASLDIDSA) guidelines have recommended simplified hepatitis C virus (HCV) treatment with pangenotypic sofosbuvir/velpatasvir (SOF/VEL) or glecaprevir/pibrentasvir (GLE/PIB) for eligible patients.

Aims: This study aimed to use real-world data to assess the safety of these regimens in patients eligible for simplified treatment by the EASL or AASLD-IDSA criteria and to identify risk factors associated with liver function abnormalities in these patients.

Methods: In this retrospective-prospective analysis, 10,641 HCV-infected patients registered in the Taiwan HCV Registry between August 2019 to August 2021 were screened, and were included if they received ≥1 dose of SOF/VEL or GLE/PIB and fulfilled the EASL or AASLD-IDSA criteria for simplified treatment. Efficacy data and incidence of laboratory abnormalities in alanine aminotransferase (ALT), aspartate aminotransferase (AST), and total bilirubin (BIL[T]) during treatment and the threemonth post-treatment follow-up period were analyzed.

Results: A total of 7,677 patients were included.

Overall, 92.8% (7,128/7,677) of patients achieved sustained virological response and only 1.9% (146/7,677) experienced Grades 2–4 laboratory abnormalities in ALT/ AST/BIL(T). Eighteen patients (0.23%) experienced Grades 3–4 abnormalities, among whom two discontinued treatment (one treated with SOF/VEL and one with GLE/ PIB). Multivariate analyses identified the following patient characteristics associated with higher risks of Grades 2–4 abnormalities: age >70 years old, presence of hepatocellular carcinoma, BIL(T) >1.2mg/dL, estimated glomerular filtration rate (by the Modification of Diet in Renal Disease equation) <60 mL/min/1.73m2, and Fibrosis-4 >3.25.

Conclusions: Real-world data confirmed that pangenotypic SOF/VEL and GLE/PIB are generally effective and well-tolerated in patients meeting the EASL or AASLD-IDSA criteria for simplified treatment. However, special attention may be needed for some patients who are at higher risks of developing liver function abnormalities.

ASSOCIATION OF INTERFERONBASED THERAPY WITH RISK OF AUTOIMMUNE DISEASES IN PATIENTS WITH CHRONIC HEPATITIS C VIRUS INFECTION: A NATIONWIDE POPULATION-BASED COHORT STUDY

Background: Interferon in combination with ribavirin has been the standard of care for chronic hepatitis C virus infection (HCV) for the past few decades. However, its effect on the risk of autoimmune diseases (ADs) among patients with HCV infection remains unclear. We assessed the potential association between interferon-based therapy (IBT) and AD risk in patients with HCV infection.

Aims: Extrahepatic manifestations are common in chronic hepatitis C virus (HCV) infection, some of which are mediated by antiviral immune response. As the standard treatment for HCV patients from 1980s to 2011, interferonbased therapy (IBT) includes dual therapy with pegylated interferon plus Ribavirin (RBV), both of which have possible impact on numerous immune responses. This study aims to investigate the association between interferonbased therapy (IBT) and the risk of autoimmune disease in patients infected with hepatitis C virus (HCV).

Methods: This retrospective cohort study identified patients diagnosed with HCV infection between January 1, 2006, and December 31, 2015, from Taiwan’s National Health Insurance Research Database. In total, 16,029 patients with HCV infection who received IBT and 141,214 patients with HCV infection who did not receive IBT were included. Both cohorts were followed up to assess the development of ADs. Hazard ratios (HRs) were calculated using the Cox proportional hazards regression model, whichwas adjusted for potential confounders.

Results: The median follow-up period for IBT and non-IBT users was 4.53 and 3.34 years, respectively. No significant difference in the risk of overall ADs (adjusted HR [aHR]: 0.96, 95% confidence interval [CI]: 0.81–1.14) or systemic ADs (aHR: 0.88, 95% CI: 0.71–1.10) was noted during the study period. However, a slight increase in the risk of organ-specific ADs was noted among IBT users (incidence

④

C 肝患者接受干擾素治療後之自體免疫疾病 風險：利用台灣健保資料庫之回溯性研究

rate ratio: 1.33, 95% CI: 1.02–1.72). Furthermore, analysis of AD subgroups revealed a significant increase in the risks of Graves’ disease (aHR: 6.06, 95% CI: 1.27–28.8) and Hashimoto’s thyroiditis (aHR: 1.49, 95% CI: 1.01–2.21) among IBT users.

Conclusions: IBT use increases the risk of autoimmune thyroid diseases (Graves’ disease and Hashimoto’s thyroiditis) in patients with HCV infection to a greater extent than non-IBT use.

代謝功能障礙而非超音波診斷肝脂肪變性增 加 C 型肝炎治癒患者發生肝臟相關事件的 風險 METABOLIC DYSFUNCTION BUT NOT ULTRASONOGRAPHIC HEPATIC STEATOSIS INCREASES THE RISK OF LIVER-RELATED EVENTS IN PATIENTS WITH CURED HEPATITIS C

許偉帆

Background: Chronic hepatitis C (CHC) is known for its extrahepatic manifestations, including diabetes mellitus (DM). Previous studies have shown that DM is a risk factor for liver fibrosis progression and liver-related events (LREs). Hepatitis C virus (HCV) and DM have a complex bi-directional relationship. However, the impact of metabolic dysfunction-associated fatty liver disease (MAFLD) or metabolic dysfunction in LREs in CHC patients with a sustained virologic response (SVR) to direct-acting antiviral agents (DAAs) is still unknown.

Aims: To analyze predictors of LREs, according to MAFLD or metabolic dysfunction, in CHC patients with SVR after DAA therapy.

Methods: From September 2012 to April 2022, 924 patients with cured CHC and documented body mass index (BMI) were included in the analysis. Exclusion criteria included hepatitis B or human immunodeficiency virus infection, non-SVR, preexisting LREs (including esophageal or gastric variceal bleeding, ascites, hepatic encephalopathy, and hepatocellular carcinoma [HCC]), and end-stage renal disease. Hepatic steatosis was defined as follows: Model 1, ultrasonographic fatty liver (uFL); Model 2, either uFL or hepatic steatosis index > 36 (eFL) at 12 weeks after DAA therapy (PW12). MAFLD (both models) was defined as hepatic steatosis in addition to one of the following three criteria: overweight or obesity (BMI > 23 kg/m2), DM, and non-DM metabolic dysfunction. Factors associated with LREs at baseline and PW12 were collected. Results: Of 924 patients, 418 (45.2%) patients were male, and 174 (18.8%) and 156 (16.9%) patients had DM and liver cirrhosis, respectively. There were 404 (43.7%) and 573 (62.0%) patients with Model 1 and 2 MAFLD,

respectively. The median age was 58 (49–65) years (first–third quartile). The median follow-up duration after the end of DAA therapy was 34.09 (17.31–50.20) months. Because of the collinearity between MAFLD definition and FL, we used hepatic steatosis (uFL or eFL) and metabolic dysfunction instead of MAFLD in the multivariable Cox regression analysis. The Model 1 multivariable Cox regression analysis identified age, male, albumin at PW12, total bilirubin at PW12, α-fetoprotein (AFP) at PW12, uFL (hazard ratio [HR]: 0.347, 95% confidence interval [CI]: 0.176–0.683, P = 0.002), and per metabolic dysfunction (HR: 1.737, 95% CI: 1.241–2.432, P = 0.001) as the independent predictors of LREs in CHC patients with SVR to DAA therapy. The Model 2 multivariable Cox regression analysis identified age, albumin at PW12, total bilirubin at PW12, AFP at PW12, and per metabolic dysfunction (HR: 1.676, 95% CI: 1.137–2.469, P = 0.009) as the independent predictors of LREs. MAFLD (p = 0.246 in Model 1 and p = 0.256 in Model 2) and FIB-4 were not predictors of HCC by the multivariable Cox regression analysis.

Conclusions: Metabolic dysfunction increased the risk of LREs, but ultrasonographic hepatic steatosis reduced the risk in CHC patients with SVR to DAA therapy. The mechanisms by which ultrasonographic hepatic steatosis reduced the risk of LREs warrant further study.

C 型肝 炎病人之療效與安全性：單一醫學中心報告 PANGENOTYPIC DIRECT-ACTING ANTIVIRALS FOR CHRONIC HEPATITIS C VIRUS-INFECTED PATIENTS: EFFECTIVENESS AND SAFETY REPORT IN ONE HOSPITAL

曾敬棠

Background: Hepatitis C virus (HCV) can be eliminated by all-oral direct-acting antivirals (DAA) nowadays.

Aims: We report real-world data on the effectiveness and safety of pangenotypic DAAs namely sofosbuvir/ velpatasvir (SOF/VEL) and glecaprevir/pibrentasvir (G/ P) in a hospital applying ‘call-back’ strategy during SARSCoV-2 global pandemic era.

Methods: A total of 832 chronic HCV-infected patients with different liver disease severity completed 8 or 12 weeks DAAs treatment are retrospectively enrolled. The effectiveness was determined by a sustained virologic response at off-treatment 12 weeks (SVR12). Baseline patient characteristics, laboratory data, and adverse events were analyzed and compared between two antiviral regimens and ‘call-back’ vs. ‘non-call-back’ populations.

Results: By per-protocol analyses, the overall SVR12 rate was 98.0% with SOF/VEL 98.9% vs. G/P 97.2%, ‘callback’ 98.6% vs. ‘non-call-back’ 97.8% respectively. Twenty patients died and 14 patients discontinued treatment due to non-virologic causes throughout the antiviral therapy course, none with SVR12 data available. The median age was 64.0 (vs. 59.0, p < 0.001), >65 y/o 45.9% (vs. 32.4%, p < 0.001), fewer male patients (48.5% vs. 56.2%, p = 0.044), more treatment-experienced (9.5% vs 5.2%, p = 0.021), less FIB-4 <1.45 and more FIB-4 >3.25 (26.2% vs. 36.6%, and 31.9% vs. 24.0%; p = 0.008) in ‘call-back’ compared to ‘non-call-back’ subjects. Aged, history of HCC, more genotype 1b and less genotype 2, higher FIB4 scores, poorer laboratory data (AST, ALT, T. bil., INR, and albumin), while less CKD subjects noted in patients receiving SOF/VEL compared to G/P. A total of 332 (40.4%) experienced any adverse event, of them fatigue (19.6%) and pruritus (15.4%) were the most common AEs in SOF/VEL and G/P respectively. Elevated ALT or T. bil. level during the treatment course was mild and did not lead to treatment discontinuation.

全基因型口服抗病毒藥物治療慢性

呂宜達 李少武 李騰裕 張崇信 林宛姿 蔡炘儒 楊勝舜 臺中榮民總醫院胃腸肝膽科

Conclusions: Real-world data in HCV management were heterogeneous and we found several baseline patient characteristics which might lead to different pangenotypic DAA choices by the physicians. While in our ‘call-back’ cohort, age, female, prior antiviral treatment failure, and FIB-4 score were significantly more than the ‘non-call-back’ cohort, and both with the same favorable SVR12 rate and tolerable AEs to the two pangenotypic DAA regimens.

主題：

B 型肝炎（一）

GGT 預測服用口服抗病毒用藥的 B 肝病人 死亡率

PRE-TREATMENT GAMMA-GLUTAMYL TRANSFERASE PREDICTS MORTALITY IN PATIENTS WITH CHRONIC HEPATITIS B TREATED WITH NUCLEOTIDE/NUCLEOSIDE ANALOGS

張庭遠1 黃釧峰1 戴嘉言1 黃志富1 莊萬龍1

Background: Elevated serum gamma-glutamyl transferase (GGT) levels are associated with chronic hepatitis B (CHB)related hepatocellular carcinoma.

Aims: Their role in predicting mortality in patients with CHB treated with nucleotide/nucleoside analogs (NAs) remains elusive.

Methods: Altogether, 2,843 patients with CHB treated with NAs were recruited from a multinational cohort. Serum GGT levels before and 6 months (Month-6) after initiating NAs were measured to explore their association with all-cause, liverrelated, and non-liver-related mortality.

Results: The annual incidence of all-cause mortality was 0.9/100 person-years over a follow-up period of 17,436.3 personyears. Compared with patients who survived, those who died had a significantly higher pre-treatment (89.3 U/L vs. 67.4 U/ L, P = 0.002) and Month-6-GGT levels (62.1 U/L vs. 38.4 U/ L, P < 0.001). The factors associated with all-cause mortality included cirrhosis (hazard ratio [HR]/95% confidence interval [CI]: 2.66/1.92–3.70, P < 0.001), pre-treatment GGT levels (HR/ CI: 1.004/1.003–1.006, P < 0.001), alanine aminotransferase level (HR/CI: 0.996/0.994–0.998, P = 0.001), and age (HR/ CI: 1.06/1.04–1.07, P < 0.001). Regarding liver-related mortality, the independent factors included cirrhosis (HR/CI: 4.36/2.79–6.89, P < 0.001), pre-treatment GGT levels (HR/CI: 1.006/1.004–1.008, P < 0.001), alanine aminotransferase level (HR/CI: 0.993/0.990–0.997, P = 0.001), age (HR/CI: 1.03/1.01–1.05, P < 0.001), and fatty liver disease (HR/CI: 0.30/0.15–0.59, P = 0.001). Pre-treatment GGT levels were also independently predictive of non-liver-related mortality (HR/CI: 1.003/1.000–1.005, P = 0.03). The results remained consistent after excluding the patients with a history of alcohol use. A dose-dependent manner of <25, 25–75, and >75 percentile of pre-treatment GGT levels was observed with respect to the all-cause mortality (trend P < 0.001).

Conclusions: Pre-treatment serum GGT levels strongly predicted all-cause, liver-related, and non-liver-related mortality in patients with CHB treated with NAs.

B

Background: The kinetics of serum hepatitis B surface antigen (HBsAg) levels during long-term nucleos(t)ide analogue (NA) therapy remains unclear.

Aims: We aimed to delineate the kinetics of HBsAg and analyze its association with long-term treatment outcomes.

Methods: We enrolled 912 treatment-naive chronic hepatitis B (CHB) patients who had received NA therapy for >12 months from January 2003 to August 2018 to analyze the kinetic patterns by using group-based trajectory models (GBTMs).

Results: Of 912 patients, 312 had HBeAg-positive CHB and 600 had HBeAg-negative CHB, and 290 (31.80%) patients had liver cirrhosis. Their median age was 49 (40–57) years. The median treatment duration for the entire cohort was 61.6 (35.9–96.2) months. The GBTMs revealed four groups of patients for both achieving HBsAg loss (Groups 1–4) among all patients and achieving an HBsAg level of <100 IU/mL in HBeAg-negative patients with baseline HBsAg ≥100 IU/mL (Groups A–D). Group 1 patients had the highest rate of HBsAg loss (23.1%, 6/26), and Group A patients had the highest rate of achieving a final HBsAg level of <100 IU/mL (48.3%, 56/116).

Absolute HBsAg levels at 12 months of NA treatment best predicted the probability of being categorized into Group 1 (AUC = 0.9976) or Group A (AUC = 0.9698). An HBsAg level of <40 IU/mL and <400 IU/mL at 12 months of treatment predicted Group 1 (sensitivity = 100%, specificity = 97.97%, positive predictive value [PPV] = 60%, and NPV = 100%) and Group A (sensitivity = 90.68%, PPV

= 78.68%, specificity = 92.70%, and NPV = 97.1%) among all and HBeAg-negative patients, respectively. Multivariable Cox regression analysis showed that HBeAgpositive, HBsAg trajectory group (Group 1 vs. Group 3 & 4, hazard ratio [HR]: 179.46, 95% confidence interval [CI]: 14.26–2258.61; Group 2 vs. Group 3 & 4, HR: 24.34, 95% CI: 4.80–123.39) and the magnitude of HBsAg decline (HR: 82.14, 95% CI: 12.12–556.76) were the independent predictors of HBsAg loss. Another multivariable Cox regression analysis showed that younger age, male, liver cirrhosis, HBsAg trajectory group (Group A vs. Group C & D, HR: 54.44, 95% CI: 21.72–136.45; Group B vs. Group C & D, HR: 5.76, 95% CI: 2.28–14.55) and the magnitude of HBsAg decline (HR: 2.91, 95% CI: 2.06–4.10) were the independent predictors of achieving a final HBsAg level of <100 IU/mL.

Conclusions: The trajectory of serum HBsAg levels and HBsAg decline predict HBsAg loss and the achievement of <100 IU/mL HBeAg level in CHB patients receiving longterm NA therapy.

代謝異常相關脂肪肝病促進 B 型肝炎表面 抗原清除及血清轉化 CONCURRENT METABOLIC DYSFUNCTION-ASSOCIATED FATTY LIVER DISEASE FACILITATES HEPATITIS B SURFACE ANTIGEN SEROCLEARANCE AND SEROCONVERSION

≥ 100 IU/mL (adjusted hazard ratio [aHR]: 3.13, 95% confidence interval [CI]: 1.70 – 5.74, p < 0.001) and baseline HBsAg < 100 IU/mL (aHR: 1.48, 95% CI: 1.16 – 1.89, p = 0.002); in addition, a higher rate of HBsAg seroconversion was also found in patients with MAFLD versus those without MAFLD (aHR: 1.64, 95% CI: 1.15 –2.33, p = 0.006). Furthermore, the presence of overweight/ obesity had an additive effect on HBsAg seroclearance. In the sensitivity analysis, patients with intermittent fatty liver by sonography (intermittent MAFLD group) had an intermediate probability of HBsAg seroclearance between those with persistent MAFLD and those without MAFLD after adjustment. The results remained consistent after multiple imputation for the missing data.

3 國立臺灣大學醫學院附設醫院肝炎研究中心

4 國立臺灣大學醫學院臨床醫學研究所

5 國立臺灣大學醫學院附設醫院醫學研究部

6 國立臺灣大學醫學院附設醫院癌醫中心分院

7 國立臺灣大學醫學院附設醫院整合醫學科

8 國立臺灣大學醫學院附設醫院新竹分院風濕免疫科

Background: Hepatitis B surface antigen (HBsAg) seroclearance is the goal of functional cure of hepatitis B virus (HBV) infection. However, the impact of concurrent metabolic dysfunction-associated fatty liver disease (MAFLD) on this favorable outcome is unclear.

Aims: This study aimed to investigate the impact of concurrent MAFLD on HBsAg seroclearance and seroconversion.

Methods: Patients with HBeAg-negative chronic hepatitis B (CHB) without antiviral therapy were consecutively recruited from National Taiwan University Hospital. MAFLD was defined by concurrent steatosis and either obesity, diabetes mellitus, or other metabolic risk abnormalities according to the diagnostic criteria. Cumulative incidences of HBsAg seroclearance, seroconversion, and associated factors were compared between the MAFLD and non-MAFLD groups. Patients without serial HBsAg measurements were excluded.

Results: From 2006 to 2021, a total of 3,257 treatmentnaïve HBeAg-negative CHB patients were included with a median follow-up of 4.5 years. CHB patients with concurrent MAFLD (n = 780) had significantly lower baseline quantitative HBsAg titers, HBV DNA levels, and Fibrosis-4 index compared with the non-MAFLD group (n = 2477). After adjustment for confounding factors, concurrent MAFLD was associated with a higher rate of HBsAg seroclearance for both baseline HBsAg

Conclusions: In untreated HBeAg-negative CHB patients, concurrent MAFLD is independently associated with higher rates of HBsAg seroclearance and seroconversion.

有無代謝相關脂肪性肝病的慢性 B 型肝炎 患者之盛行率與特性：大型社區型研究 PREVALENCE AND CHARACTERISTICS OF CHRONIC HEPATITIS B PATIENTS WITH OR WITHOUT METABOLIC DYSFUNCTION-ASSOCIATED FATTY LIVER DISEASE IN A LARGE COMMUNITY SURVEY

non-lean ones (OR/CI: 0.46/0.26-0.83, p = 0.01), whereas diabetes patients were more likely to have metabolic syndrome (OR/CI: 6.33/2.32-17.3, p < 0.001). Albeit there is a substantially higher proportion of hepatic steatosis with the progression liver fibrosis, the liver fibrotic stages did not differ between patients with or without MAFLD. Logistic regression analysis revealed that factors associated with significant fibrosis included diabetes (OR/CI: 3.32/1.18-9.33, p = 0.023), BMI (OR/CI: 1.17/1.03-1.31, p = 0.012) and HBV DNA > 2000 IU/mL (OR/CI: 3.98/1.4111.3, p = 0.009). Among the subpopulations, DM MAFLD patients had the highest prevalence of significant fibrosis (23.1%) in contrast to the lean MAFLD group (0%).

Background: The nomenclature of metabolic dysfunctionassociated fatty liver disease (MAFLD) has been adopted for patients with hepatic steatosis in addition to metabolic disarrangement irrespective of concurrent liver disease. The clinical characteristics and the association with liver disease severity of the novel term in patients with chronic hepatitis B (CHB) was elusive.

Aims: This study aimed to elucidate the clinical characteristics of CHB patients with or without MAFLD and its association with hepatic fibrosis in a community basis survey.

Methods: A community surveillance of viral hepatitis was carried out in southern Taiwan from 2019 to 2021. Basic demography and metabolic profiles were collected. Meanwhile, transient elastography (Fibroscan®) was performed to address hepatic steatosis and liver fibrosis in CHB patients. Patients with anti-hepatitis C virus (HCV) seropositivity were excluded. Hepatic steatosis grades were categorized to S0 (<248 dB/m), S1 (248-268 dB/m), S2 (268-280 dB/m), and S3 (a>280 dB/m) by CAP score. Hepatic steatosis was defined as a CAP value greater than 248 dB/m. Fibrotic stages were categorized as F01 (<7 kPa), F2 (7-9.5 kPa), F3 (9.5-12.5 kPa), and F4 (>12.5 kPa). Significant liver fibrosis was defined as patients whose fibrotic stage were equal or greater than F2.

Results: A total of 197 CHB patients were included in the study, The mean age was 54.1±11.3 year-old. 48.7% (96/197) patients had both hepatic steatosis and MAFLD. Compared to CHB patients without MAFLD, those with MAFLD had a significantly higher body mass index (BMI) (Odds ratio [OR]/95% confidence intervals (CI): 1.28/1.151.43, p < 0.001) and higher triglyceride (OR/CI: 1.01/1.011.02, p < 0.001). Among the 96 MAFLD patients, lean ones had a significantly lower uric acid level compared to

Conclusions: Half of the CHB patients possessed MAFLD in the community survey. CHB MAFLD patients were more likely to have metabolic disarrangement than their counterpart patients. Its impact on liver disease severity awaited further exploration.

慢性 B 型肝炎非肝硬化病人停藥後 B 型肝 炎病毒復發的形式沒有增加發生肝癌的風險

SIMILAR RISK OF HCC IN NONCIRRHOTIC CHRONIC HEPATITIS

B PATIENTS OF DIFFERENT HBV RELAPSE PATTERNS AFTER TREATMENT CESSATION AND PATIENTS CONTINUING TREATMENT

independent predictor of HCC and all-cause mortality in all patients. In 1550 propensity score-matched patients (775 in Group A and 775 in Group B), there were no significant differences in the risk of HCC (p = 0.792) or all-cause mortality (p = 0.446) between patients of different relapse patterns in Group A and Group B.

Conclusions: HBV relapse patterns after treatment cessation were not associated with an increased risk of HCC or all-cause mortality compared with patients who received long-term NA treatment in CHB patients without cirrhosis.

Background: It remains unclear whether HBV relapse patterns in non-cirrhotic patients who discontinued nucleos(t)ide analogue (NA) therapy affect the risk of hepatocellular carcinoma (HCC) and mortality.

Aims: To compare the incidences of HCC and mortality between patients who discontinued and continued entecavir or tenofovir disoproxil fumarate (TDF) treatment in CHB patients without cirrhosis.

Methods: This study included patients who had received entecavir or TDF treatment for at least 3 years and discontinued treatment for at least 12 months (Group A: discontinuing group; n = 837) and patients who had received continuous entecavir or TDF treatment for at least 4 years (Group B, continuing group; n=988). Patients who developed HCC within the first 12 months after entecavir or TDF cessation (Group A) or 4 years of treatment (Group B) were excluded.

Results: Among the 837 patients in Group A, 235 were sustained responder (Pattern I), 215 had virological and/ or clinical relapse without retreatment (Pattern II) and 387 received retreatment (Pattern III). The cumulative incidences of HCC and all-cause mortality at 10 years after treatment cessation in patients with Patterns I, II and III in Group A and Group B were 3.9% and 0%, 2.5% and 0.5%, 3.6% and 1.1%, respectively. The cumulative incidences of HCC and all-cause mortality at 10 years after 3 years of treatment in Group B were 4.9% and 2%, respectively. There were no significant differences in the risk of HCC (p = 0.723) or all-cause mortality (p = 0.461) between patients of different relapse patterns in the discontinuing group and the continuing group, regardless of HBeAg-positive (HCC: p = 0.583, morality p = 0.790) or HBeAg-negative (HCC: p = 0.419, morality p = 0.663) status at treatment initiation. Multivariable analysis showed that only old age was an

曾子寧1 陳建宏1 彭成元2 胡琮輝1 賴學洲2 王景弘1 洪肇宏1 盧勝男1

1 高雄長庚紀念醫院胃腸肝膽科系

2 中國醫藥大學附設醫院消化系內科

主題：B

型肝炎（二） ⑫

B 型肝炎吸煙患者戒菸後對肝硬化與肝癌長 期相關性比較：一項回顧性世代研究 COMPARISON BETWEEN THE LONGTERM ASSOCIATION OF SMOKING CESSATION WITH LIVER CIRRHOSIS AND HEPATOCELLULAR CARCINOMA AMONG SMOKING PATIENTS WITH HEPATITIS B VIRUS INFECTION: A RETROSPECTIVE COHORT STUDY

Background: In several epidemiologic studies, it has been shown that tobacco smoke contains various carcinogens, which along with hepatitis B virus (HBV) infection increases the risk of liver cirrhosis and hepatocellular carcinoma (HCC).

Aims: In the current study, we sought to compare the association of liver cirrhosis and hepatocellular carcinoma with three kinds of common treatments for smoking cessation.

Methods: We conducted a retrospective cohort study using the National Health Insurance Research Database in Taiwan from 2007 to 2018. The cohort study was conducted on the patients receiving smoking cessation prescriptions (exposed cohort) and nontreated smokers who had not tried smoking cessation (unexposed cohort). The clinical diagnosis was defined following the International Classification of Disease, Ninth and Tenth Revision, and Clinical Modification. We treated the patients with varenicline, nicotine replacement therapy (NRT), and a combination of both prescriptions from the sample size of 2,000,000 at the National Health Insurance program. We followed up with all individuals from each group from the date of the first prescription to the end of 2018, and we recorded the symptoms including different stages of disease progression or death whichever occurred first. The primary symptoms were the incidence of liver cirrhosis and HCC. The hazard ratios (HRs) and 95% confidence intervals (CIs) derived from multiple cox regression models were adjusted with the comorbidity, and the medication history of the patients was used to compare the risk of target outcomes.

Results: During the 10-year follow-up experiment, a total of 2869 patients with HBV infection were enrolled in this study. The smoking cessation groups were comprised of smokers using varenicline (n = 413), NRT (n = 1716),

a combination of varenicline with NRT (n = 299), and the nontreatment group (n = 441). The mean followup duration was 8.1 ± 4.4 years (median 8.2 years). The cumulative incidence, such as the prevalence of liver cirrhosis and HCC, was lower in the treated group than in the nontreated group. The prevalence of liver cirrhosis between varenicline, NRT, combined varenicline with NRT, and nontreated groups was 2.9%, 7.9%, 2.3%, and 10.7%, respectively, while the prevalence of HCC was 10.2%, 13.6%, 10.4%, and 22.4%, respectively. The HR of liver cirrhosis between varenicline, NRT, combined varenicline with NRT, and nontreated groups were 0.51 [95% CI 0.16–1.56], 0.80 [95% CI 0.38–1.7], and 0.33 [95% CI 0.12–0.9], respectively. The HR of HCC between varenicline, NRT, combined varenicline with NRT, and nontreated groups were 0.83 [95% CI 0.38–1.8], 0.69 [95% CI 0.37–1.28], and 0.40 [95% CI 0.18–0.88], respectively.

Conclusions: This study provides a piece of longitudinal evidence that smoking cessation prescriptions are associated with a reduced risk of liver cirrhosis and HCC in patients with HBV infection. Despite the relatively small number of epidemiological studies on HBV patients that have assessed smoking cessation and have developed cancer, the methodological limitations lead to a lack of understanding of how smoking cessation might associate with HCC in HBV smokers. Therefore, we speculate that the findings of our study would provide contribution to understanding the health behavior of HBV patients.

毛元治 王俊雄 牟聯瑞 台南市立醫院（委託秀傳醫療社團法人經營）肝膽腸 胃內科

B 型肝炎藥物停用後之 B 型肝炎復發之研究

A STUDY OF HBV RELAPSE AFTER DISCONTINUATION OF TENOFOVIR ALAFENAMIDE AND ENTECAVIR THERAPY

治療第 5 年血清 Mac-2 結合蛋白糖基化異

構體濃度預測慢性 B 型肝炎肝硬化病人接 受貝樂克或惠立妥治療 5 年後發生肝癌和死 亡之風險

SERUM MAC-2 BINDING PROTEIN

GLYCOSYLATION ISOMER LEVEL AT 5 YEARS OF TREATMENT PREDICTS

HEPATOCELLULAR CARCINOMA

DEVELOPMENT AND MORALITY

Background: According to the National Health Insurance reimbursement guidelines in Taiwan, the patients in positive HBeAg could take nucleos(t)ide analogues only more one year after HBeAg loss. The patients in negative HBeAg should discontinue nucleos(t)ide analogues after an undetectable serum HBV DNA level for three times every 6 months. However, the likelihood of HBV relapse may presence due to no sustained viral suppression after discontinuation of nucleos(t)ide analogues. Hence, we investigated the relapse rate of HBV between tenofovir alafenamide (TAF) and Entecavir after antivirus therapy discontinuation.

Aims: Incidence of HBV relapse after discontinuation of tenofovir alafenamide and Entecavir Therapy.

Methods: We enrolled patients with chronic hepatitis B who finished TAF and Entecavir therapy at Changhua Christian Hospital during January 2015 to September 2021. The end point of TAF and entecavir therapy was based on the National Health Insurance reimbursement guidelines in Taiwan. The patients in positive HBeAg would be terminated the therapy after HBeAg loss for 1 year. And patients in negative HBeAg, the therapy would be discontinued after undetectable serum HBV DNA level for three times every 6 months. After discontinuation of anti-virus therapy, we followed alanine aminotransferase (ALT) at 12 weeks, 24 weeks and 48 weeks. The serum HBV DNA level would be checked if the patients had 2-fold elevation of ALT level from the upper limit of normal (<41 IU/mL). The clinical relapse was defined as 2-fold elevation of ALT level and HBV DNA level more than 2000 IU/mL. Then we compared the relapse rate of HBV between TAF and entecavir at 12 weeks, 24 weeks and 48 weeks.

Results: Overall, 117 patients were enrolled. 78 patients were in Entecavir group, and 39 patients in TAF group. The HBV clinical relapse rate in Entecavir group and TAF group was 1.3%, and 13.2% (P < 0.05) at 24 weeks, and 9.2%, and 24.2% at 48 weeks (P = 0.055). No clinical relapse was noted at 12 weeks in Entecavir group, but 4 patients in TAF group had clinical relapse was observed.

Conclusions: Discontinuation of TAF therapy had earlier, and higher clinical relapse rate than Entecavir therapy. Continued monitoring was necessary after discontinuation of anti-virus therapy.

BEYOND YEAR 5 OF ENTECAVIR OR TDF THERAPY IN CHRONIC HEPATITIS B PATIENTS WITH CIRRHOSIS

陳建宏

Background: Our previous study showed that the FIB-4 index at year 5 of treatment was predictive of hepatocellular carcinoma (HCC) development beyond year 5 of entecavir therapy in patients with chronic hepatitis B (CHB).

Aims: To determine whether serum Mac-2 binding protein glycosylation isomer (M2BPGi) level at year 5 of treatment could predict HCC development beyond year 5 of entecavir or tenofovir disoproxil fumarate (TDF) treatment in CHB patients with cirrhosis.

Methods: A total of 852 CHB patients with cirrhosis under entecavir or TDF for >5 years were enrolled in this study. None of the patients developed HCC within the first 5 years of treatment.

Results: Out of 852 patients, 98 and 22 developed HCC and died, respectively, during the median follow-up period of 67 months. The cumulative incidences of HCC and liver-related mortality at year 1, 5 and 8 years after 5 years of treatment were 1.3% and 0.4%, 13.4% and 2.8% and 23.9% and 4.1%, respectively. The M2BPGi level of 1.6 and 1.1 COI at 5 years of treatment was optimal for predicting HCC development and liver-related mortality beyond year 5. Multivariable analysis showed that old age, HBeAg-negative status, higher AFP and FIB-4 levels and M2BPGi >1.6 COI at 5 years of treatment were the independent predictors of HCC beyond year 5. Higher M2BPGi and FIB-4 levels at 5 years of treatment were the independent predictors of liver-related mortality beyond year 5. The cumulative rates of HCC at year 8 after 5 years of treatment in patients with M2BPGi level >1.6 versus

黃稚雯 顏旭亨 蘇培元 彰化基督教醫院肝膽腸胃科

≤1.6 COI at year 5 were 47.8% versus 19.8% (p < 0.001). The cumulative rates of liver-related mortality at year 8 after 5 years of treatment in patients with M2BPGi level >1.1 versus ≤1.1 at year 5 were 10.4% versus 1.5% (p < 0.001).

Conclusions: M2BPGi level at year 5 of treatment is a useful marker for predicting HCC development and liverrelated mortality beyond year 5 of entecavir or TDF therapy.

B 型肝炎低病毒量病患接受口服抗病毒藥物 可改善肝功能

IMPROVED ALANINE AMINOTRANSFERASE LEVEL IN NONCIRRHOTIC AND LOW-VIRAL-LOAD CHRONIC HEPATITIS B PATIENTS TREATED WITH NUCLEOTIDE/ NUCLEOSIDE ANALOGUES

張庭遠 戴嘉言 高雄醫學大學附設中和紀念醫院肝膽胰內科

Background: The biochemical response is an important indicator of prognosis in chronic hepatitis B (CHB) patients receiving nucleotide/nucleoside analogues (NAs).

Aims: Among low viral load (HBV DNA of were <2,000 IU/mL) and non-cirrhotic CHB patients, the efficacy of NAs in alanine aminotransferase (ALT) normalization and hepatitis B virus (HBV) DNA suppression of and is elusive.

Methods: The longitudinal study recruited 31 non-cirrhotic CHB patients with hepatitis B e-antigen (HBeAg) negative who received NAs. ALT levels were examined at the first year of anti-HBV therapy. Normal ALT was defined as <19 U/L for females and <30 U/L for males, and the risk factors associated with ALT abnormality were analysed.

Results: Seven patients (22.6%) with baseline ALT >40 U/ L and sixteen patients (51.6%) were ALT abnormal (>19 U/L for females and >30 U/L for males). After 1-year NAs therapy, thirty patients (91.7%) had undetectable HBV DNA. Post-treatment ALT levels significantly decreased, compared to the pre-treatment levels (23.3 U/L vs 33.5 U/ L, respectively; P = 0.002). The proportion of patients with normal ALT was also significantly higher after treatment, compared to the pre-treatment status of patients (61.3% vs 48.4%, respectively; P = 0.003). The strongest factor associated with ALT abnormality after first year treatment with NAs was body mass index (BMI) (odds ratio [OR]/95% confidence interval [CI], 1.80/1.07-3.01, P = 0.003).

Conclusions: Among non-cirrhotic CHB patients with HBeAg negative and low viral load, NAs could improve the ALT level by adjusting the confounding factors. It could also increase the proportion of ALT normality after 1-year NAs treatment.

EFFECT OF ANTIVIRAL THERAPY IN CHRONIC HEPATITIS B PATIENTS WITH UNRESECTABLE HEPATOCELLULAR CARCINOMA TREATED WITH 1ST LINE SYSTEMIC THERAPY WITH LENVATINIB: ONE SINGLE CENTER REAL-WORLD EXPERIENCE

Background: Lenvatinib is approved as the first-line treatment for patients with advanced hepatocellular carcinoma (HCC) per the REFLECT study. Hepatitis B virus (HBV)-related advanced HCC (HBV–HCC) seemed to have a better response than hepatitis C virus (HCV)-related HCC (HCV–HCC) to lenvatinib treatment, but it is undetermined. Aims: This study aimed to investigate the effect of lenvatinib between HBV–HCC, HCV–HCC and non-HBV/non-HCV (NBNC)–HCC patients.

Methods: We retrospectively evaluated 53 patients with HCC who received 1st line systemic therapy with lenvatinib from January 2020 to August 2022 at China Medical University Hospital. Baseline patient characteristics, treatment response and survival outcomes were reviewed and analyzed. Kaplan–Meier analysis was used to compare the survival outcomes among subgroups. Results: In this cohort, patients who belonged to BCLC stage B and C were 39.6% and 60.4%, respectively. There were 31 (58.5%) HBV–HCC patients, 14 (26.4%) HCV–HCC patients and 8 (15.1%) NBNC-HCC patients. Before lenvatinib initiation, 26 (83.9%) HBV–HCC patients had received nucleoside analogs (NAs) for HBV management. The median overall survival (mOS) of HBV–HCC patients, HCV–HCC patients and NBNC-HCC patients was not reached, not reached, and 20 months, respectively. The OS of HBV–HCC patients were noninferior to HCV–HCC patients and NBNC-HCC patients (p = 0.424). The median OS of HBV–HCC patients without NA treatment was significantly inferior to the other subgroups, including HBV–HCC patients with NA treatment, HCV–HCC patients, and NBNC-HCC patients (8 months vs not reached, p = 0.003).

Conclusions: Antiviral therapy might improve survival of advanced HBV–HCC patients receiving lenvatinib therapy and confer comparable OS to patients with HCV–HCC or NBNC–HCC.

腫瘤壞死是肝細胞癌病患接受手術切除的預

後因子

TUMOR NECROSIS IS AN INDICATOR OF POOR PROGNOSIS AMONG HEPATOMA PATIENTS UNDERGOING RESECTION

顏毅豪1 郭芳穎2 王植熙3

1 高雄長庚紀念醫院胃腸肝膽科

2 高雄長庚紀念醫院病理科

3 高雄長庚紀念醫院一般外科

Background: Tumor necrosis has been associated with poor prognosis in hepatocellular carcinoma (HCC) patients undergoing liver resection (LR).

Aims: However, more evidence is needed to clarify this issue.

Methods: Patients who underwent upfront LR between 2010 and 2018 for newly diagnosed HCC without undergoing neoadjuvant therapy were enrolled in this retrospective study. Tumor necrosis was classified as present or absent according to retrospective examinations. The association between tumor necrosis, pathologic characteristics, overall survival (OS), and recurrence-free survival (RFS) were analyzed.

Results: Among 756 patients who underwent LR for HCC, tumor necrosis was present in 279 (36.9%) patients. Compared with patients without tumor necrosis, patients with tumor necrosis had higher proportions of tumors sized >5.0 cm (p < 0.001), multiple tumors (p < 0.001), micro- or macrovascular invasion (p<0.001), poorly differentiated or undifferentiated tumors (p < 0.001), and T stage 3 or 4 (p < 0.001) on pathological examination. The presence of tumor necrosis was associated with worse OS and RFS compared with the absence of tumor necrosis: 5-year OS was 56% vs. 78% (p < 0.001); 5-year RFS was 42% vs. 55% (p < 0.001). In multivariate analysis, the presence of tumor necrosis was an independent factor associated with worse OS (hazard ratio [HR]: 1.956; 95% confidence interval [CI]: 1.409–2.716; p < 0.001) and RFS (HR: 1.422; 95% CI: 1.085–1.865; p = 0.011).

Conclusions: Tumor necrosis was associated with worse OS and RFS among patients who underwent LR for HCC.

針對無法切除之慢性 B 型肝炎肝癌患者接 受樂衛瑪為第一線全身性治療之抗病毒藥物 的影響：單一中心的真實世界經驗

邱逸民 王鴻偉 賴學洲 許偉帆 彭成元 中國醫藥大學附設醫院消化醫學中心

主題：肝腫瘤（一） ⑰

Child-Pugh B 的肝細胞癌患者之預後以及影 響因子

THE OUTCOMES OF PATIENTS WITH HEPATOCELLULAR CARCINOMA AND WITH CHILD-TURCOTTE-PUGH CLASS B

and therefore provided more accurate mortality prediction than MELD score, ALBI grade, modified ALBI grade and CTP score.

Conclusions: Tumor factors, presence of ascites, and treatment modalities determined the outcomes of HCC patients with CTP class B. Patients in the CTP-B7 group and CTP-B8 group had comparable OS, both of them were better than those in the CTP-B9 group. Moreover, MELD 3.0 provided the best accurate mortality prediction in HCC patients with CTP class B.

Background: Child-Turcotte-Pugh (CTP) score is a widely applied tool for assessing the liver functional reserve for patients with advanced chronic liver disease (ACLD) and hepatocellular carcinoma (HCC). However, little studies have been conducted to explore the prognostic factors and the performance of the mortality prediction models in patients with HCC and with CTP class B.

Aims: To explore the outcomes of patients with HCC and with CTP class B and to investigate the prognostic accuracy of the prediction models for ACLD in these patients.

Methods: We retrospectively enrolled 1,143 patients with HCC, CTP class B from 2007 to 2022 in a tertiary medical center. Patients were divided into 3 subgroups, CTP-B7, CTP-B8 and, CTP-B9, respectively, by the CTP score. We also compared the corrected Akaike information criterion (AICc) between each mortality prediction model, including the CTP score, albumin-bilirubin (ALBI) score, modified ALBI score, the model for end-stage liver disease (MELD) and MELD 3.0.

Results: Among the enrolled patients, 576 (50.3%) patients were in the CTP-B7 group, 363 (31.8%) patients were in the CTP-B8 group, and 204 (17.9%) patients were in the CTP-B9 group, respectively. After a median follow-up of 4.6 months (interquartile range IQR 1.8-17.2 months), 963 patients expired, and the 5-year overall survival (OS) rate was 11.4%. The 5-year OS rates were 11.6%, 13.6% and 8.3% in the CTP-B7, CTP-B8, and CTP-B9 groups, respectively. Patients in the CTP-B7 group and CTP-B8 group had comparable OS (p = 0.089), and both of them were better than those in the CTP-B9 group (p < 0.001). A multivariate analysis revealed tumor size ≥5 cm, the presence of vascular invasion, presence of extra-hepatic metastasis, presence of ascites and receiving non-curative treatment were the independent predictors of poor OS. Moreover, the MELD 3.0 score had the lowest AICc value

ALBI 及 EZ-ALBI Grade 對合併腹水之肝 癌的預後評估能力

PROGNOSTIC ROLE OF ALBUMINBILIRUBIN (ALBI) GRADE AND EASY (EZ)-ALBI GRADE IN HEPATOCELLULAR CARCINOMA PATIENTS WITH ASCITES

廖家毅1 何樹仁2 黃怡翔1 侯明志1 霍德義3 1 臺北榮民總醫院胃腸肝膽科 2 敏盛綜合醫院胃腸肝膽科 3 臺北榮民總醫院醫學研究部

Background: Patients with hepatocellular carcinoma (HCC) often have co-existing ascites which is a hallmark of liver decompensation. The albumin-bilirubin (ALBI) grade and EZ (easy)‐ALBI grade are used to assess liver functional reserve in HCC, but the predictive accuracy of these two models in HCC patients with ascites is unclear.

Aims: We aimed to determine the prognostic role of ALBI and EZ-ALBI grade in these patients.

Methods: A total of 4,431 HCC patients were prospectively enrolled and retrospectively analyzed. Independent prognostic predictors were identified by the multivariate Cox proportional hazards model.

Results: Of all patients, 995 (22.5%) patients had ascites. Grade 1, 2, and 3 ascites were found in 16%, 4%, and 3% of them, respectively. A higher ascites grade was associated with higher ALBI and EZ-ALBI score and linked with decreased overall survival. In the Cox multivariate analysis, serum bilirubin level > 1.1 mg/dL, creatinine level ≥ 1.2 mg/dL, α‐fetoprotein ≥ 20 ng/mL, total tumor volume > 100 cm3, vascular invasion or distant metastasis, poor performance status, ALBI grade 3, EZ‐ALBI grade 2 and 3, and non-curative treatments were independently associated with increased mortality (all p < 0.05) among HCC patients with ascites. The ALBI and EZ-ALBI grade can adequately stratify overall survival in both the entire cohort and specifically in patients with ascites.

Conclusions: Ascites is highly prevalent and independently predicts patient survival in HCC. The ALBI and EZ-ALBI grade are feasible markers of liver dysfunction and can stratify long-term survival in HCC patients with ascites.

⑳

中期肝癌患者利用「7-11 準則」優化手術切 除的最佳利益

OPTIMIZING SURVIVAL BENEFIT BY SURGICAL RESECTION IN INTERMEDIATE STAGE

HEPATOCELLULAR CARCINOMA BY THE SEVEN-ELEVEN CRITERIA

廖思涵8 洪俊銘9 劉振驊3 楊宏志3 劉俊人3,4 陳培哲3,4,6,7 高嘉宏3,4,6,7

1 國立臺灣大學醫學院醫學系

2 好心肝診所

3 國立臺灣大學醫學院附設醫院胃腸肝膽科

4 國立臺灣大學醫學院附設醫院肝炎研究中心

5 國立臺灣大學醫學院附設醫院北護分院內科部

6 國立臺灣大學醫學院臨床醫學研究所

7 國立臺灣大學醫學院附設醫院醫學研究部

8 國立臺灣大學醫學院附設醫院癌醫中心分院消化道科

9 國立臺灣大學醫學院附設醫院整合醫學科

Background: Hepatocellular carcinoma (HCC) is the sixth most commonly diagnosed cancer and the third leading cause of cancer-related death worldwide in 2020. According to the Barcelona Clinic Liver Cancer (BCLC) classification, transarterial chemoembolization (TACE) is recommended as the standard therapy for patients with intermediate stage (BCLC-B) HCC. However, patients with intermediate stage HCC comprise a heterogeneous population with various tumor burden, therefore, not all patients could benefit from TACE. Several BCLC subclassification systems have been proposed using tumor burden and liver reserve with the aim to allocate personalized treatments to improve the outcome of intermediate stage HCC. Recently, the seven–eleven criteria had been introduced, which is simply calculated by the sum of the total number of tumors and the diameter of the largest tumor. The seven–eleven criteria were shown to be most discriminative in predicting radiologic response and overall survival (OS) in patients with intermediate stage HCC undergoing TACE than the up-to-7 criteria and the up-to-11 criteria. Several studies have demonstrated that surgical resection (SR) can have better survival than TACE in selected patients with intermediate stage HCC. Besides, according to National Comprehensive Cancer Network (NCCN) guideline, SR is a potentially curative therapy for carefully selected patient, based on patient characteristics including performance status, comorbidity, as well as liver reserve and the tumor location. Moreover,

according to Asian Pacific Association for the Study of the Liver (APASL) guideline, SR should be considered in the intermediate stage patients in a multidisciplinary setting as a potentially curative therapy, regardless of tumor burden or liver function status. However, the guidance for optimal candidates to receive SR or TACE in BCLC-B HCC remains inconclusive.

Aims: Transarterial chemoembolization (TACE) is a standard therapy for intermediate stage (Barcelona Clinic Liver Cancer [BCLC] -B) hepatocellular carcinoma (HCC). We aimed to identify candidates for surgical resection (SR) in BCLC-B HCC with survival benefit.

Methods: Patients with BCLC-B HCC at the National Taiwan University Hospital during 2005 and 2019 were screened and those who received TACE or SR were consecutively included. The tumor burden was classified by the seven-eleven criteria into low (≤7), intermediate (711) or high (>11). Multivariable cox proportional hazard regression analysis was used for outcome prediction.

Results: Overall, 474 patients who received SR (n = 247), and TACE (n = 227) were enrolled. Patients underwent SR were significantly younger with better liver reserve. There were 76 (31%), and 129 (57%) deaths in the SR and TACE groups after a median follow-up of 3.9 and 2.1 years, respectively. The 7-11 criteria could distinguish median overall survival (OS) among low (n=149), intermediate (n = 203), and high (n = 122) tumor burden groups (7.7 vs. 6.9 vs. 2.8 years, respectively, P < 0.001). Patients receiving SR had a significantly higher median OS compared with TACE in those with intermediate (8.2 vs. 2.6 years, P < 0.001) and high (5.6 vs. 1.5 years, P = 0.001) tumor burden. After adjustment for age, sex, and liver reserve, SR was predictive for better OS in intermediate (adjusted hazard ratio [aHR]: 0.45, 95% CI: 0.27-0.75) and high tumor burden (aHR: 0.54, 95% CI: 0.32-0.92), but not in those with low tumor burden (aHR: 0.82, 95% CI: 0.43-1.55). The survival benefit of SR especially confines to patients within 3 tumors.

Conclusions: In patients with BCLC-B HCC with tumor burden beyond the up-to-7 criteria but within 3 tumors, SR has better OS than TACE and should be considered in resectable patients.

肝癌手術切除後輔助性免疫治療臨床試驗篩 選條件未達需求

UNSATISFACTORY CRITERIA OF CLINICAL TRIALS TO SELECT

PATIENTS FOR ADJUVANT

IMMUNOTHERAPY

Background: Clinical trials of adjuvant immunotherapies for patient with hepatocellular carcinoma (HCC) after surgical resection are ongoing. However, the actual outcomes in patients defined as high risk in the clinical trials remain unclear.

Aims: The aim of this study was to evaluate the risk of recurrence, survival and post-recurrence outcomes in patients defined as high risk by IMbrave 050 criteria.

Methods: Consecutive 1522 HCC patients receiving curative resection were retrospectively enrolled, including 1057 (69.4%) patients fulfilled with high risk criteria by IMbrave 050. In the high risk group, patients were classified as group 1 (up to three tumors, with largest tumor >5, n = 583), 2 (four or more tumors, with largest tumor ≤5 cm, n = 17) and 3 (up to three tumors, with largest tumor ≤5 cm with vascular invasion and/or poor tumor differentiation, n = 457) by IMbrave 050 definition. Longterm outcomes including recurrence-free survival (RFS), overall survival (OS) and post-recurrence treatment in high risk patients were evaluated.

Results: The median RFS and OS in high risk patients were 35.8 and 99.2 months, respectively. The median RFS in patients with group 1, 2 and 3 were 23.4, 16.2 and 48.3 months, respectively (p < 0.001), while the corresponding OS were 76.6, 60.4 and 168.6 months, respectively (p < 0.001). By multivariate analysis, group 3 patients (hazard ratio (HR) = 0.827, p = 0.021), AFP > 20 ng/mL (HR = 1.296, p = 0.001), ALBI grade 2-3 (HR = 1.331, p = 0.001), presence of cirrhosis (HR = 1.391, p < 0.001) and tumor size >10 cm (HR = 1.620, p < 0.001) were independent predictors of RFS. In 424 patients with recurrence, 128 (20.2%), 164 (25.8%), 197 (31%) and 85 (13.4%) patients received subsequent resection, local ablation, transarterial

chemoenzolization and systemic therapy, respectively, and the corresponding post-recurrence survival by each treatment was not reached, 76, 30.3 and 8.9 months, respectively (p < 0.001).

Conclusions: The high risk patients defined by the IMbrave 050 criteria were heterogeneous and outcomes varied widely. The survival remains good in about 45% of patients who could receive a second curative treatment after recurrence. A more stringent criteria should be defined to select patients suitable for adjuvant immunotherapy.

在無法切除肝癌病人一線樂衛瑪失敗後續治 療效果

POST-TREATMENT EFFICACY AFTER FIRST LINE LENVATINIB FAILURE IN PATIENTS WITH UNRESECTABLE HEPATOCELLULAR CARCINOMA

Background: Lenvatinib has been approved as a firstline treatment option for patients with unresectable hepatocellular carcinoma (HCC); however, adequate treatments following lenvatinib remains undetermined. Aims: This study was to evaluate the outcome of postlenvatinib treatment in clinical real-world practice.

Methods: We retrospectively evaluated patients with unresectable HCC who had undergone lenvatinib treatment between January 2018 and Dec 2021. Patients were excluded if they had previously received other systemic therapy or had become lost to follow-up during treatment. Treatment response was assessed by radiologic imaging according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST).

Results: A total of 181 patients (Male/Female: 131/50, mean age: 65.9 years) were recruited including 92 (50.8%) patients with hepatitis B virus (HBV) infection, 45 (24.9%) hepatitis C virus (HCV) patients, 2 (1.1%) B+C patients and 42 (23.2%) non-B, non-C (NBNC) patients. The Kaplan-Meier estimate of overall survival (OS) and progression free survival (PFS) was 18.2 months and 6.5 months, respectively. The overall objective response rate (ORR) and disease control rate (DCR) was 18.4% and 70.7%, respectively. A total of 158 (87.3%) patients have terminated lenvatinib during the follow-up, and 74 of them received sequential treatments, including 24 with immunotherapy, 5 with tyrosine kinase inhibitor (TKI), 27 with locoregional treatment, and 18 with systemic chemotherapy. From first-line therapy, the longest median OS was obtained with the sequence lenvatinib and immunotherapy / TKI (25.9 months), followed by locoregional treatment (25.9 months), chemotherapy (18.6 months), and best supportive care (6.1 months) (p < 0.001). The most five frequently used second line treatment options after lenvatinib were chemotherapy (n = 18), atezolizumab plus bevacizumab (n = 11), radiotherapy / proton beam therapy (n = 9), nivolumab (n = 9) and transarterial

郭垣宏 王景弘 洪肇宏 盧勝男 胡琮輝 陳建宏 蔡明釗 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

chemoembolization (n = 8).

Conclusions: As the first-line therapy, lenvatinib therapy showed a favorable efficacy for unresectable HCC in a realworld practice. After lenvatinib failure, patients who could afford post-treatment had a better prognosis, especially for those who with sequential immunotherapy, TKI or locoregional treatment.

A NOVEL MODEL TO PREDICT OUTCOME IN CRITICALLY ILL PATIENTS WITH ACLF ADMITTED TO

Background: Patients with liver cirrhosis are more inclined to suffer from acute decompensation complicated with organ failure, which is defined as having acuteon-chronic liver failure (ACLF). The syndrome usually requires admission to an intensive care unit (ICU) due to high mortality. Many scores were created to predicted the mortality. In clinical practice, which score is superior to others at predicting overall mortality in ACLF patients remains controversial. In addition, it is also intriguing whether a new model could be created to outperform than the pre-existing prognostic scores.

Aims: We first aimed to compare the five APACHEII, CLIF-ACLF, CLIF-ACLF lactate, MELD, MELDlactate scores in predicting short-term mortality (1-month mortality, and 3-month mortality). Second, a novel predicting score system was created and being tested whether it was superior to the other five prognostic scoring systems in predicting the short-term mortality of patient with ACLF who was admitted to the ICU.

Methods: Patients who met the inclusion criteria comprise recurrent cirrhosis patients with ACLF admitted to our hospital’s hepato-gastroenterology ICU for intensive and specialized care from November 2012 to December 2021. Data were collected from medical record which in the hepato-gastroenterology ICU in Chang-Gung Memorial Hospital (CGMH), Linkou. All scores and data were calculated according to their own formula, and data were acquired at or within the 24 hours of the first ICU admittance were utilized. The primary outcome were 1-month mortality and 3-month mortality rate. The area under the receiver operating characteristic (AUROC) curve was calculated to assess the accuracy of the new predicting model and other prognostic score in predicting survival.

Results: 265 patients with ACLF admitted into intensive

主題：肝硬化及其他肝病（一）

以新模型更好的去預測慢性肝衰竭急性發作 的加護病房重症患者的預後

care unit between November 2012 and December 2021 were enrolled and were tracked until February 2022. We used AUROC analysis of new model and the five prognostic score predicting one-month and three-month mortality. The AUROC (95% confidence intervals) of the new model at one-month (0.863 [0.818-0.907]), threemonth (0.829 [0.780-0.879]) were both significant superior to MELD, MELD-lactate, CLIF ACLF and CLIF ACLF lactate. Besides, the predicting strength of new model at in-hospital, six-month and one-year mortality were also significant superior to the other five prognostic scores.

Conclusions: In our study, the new model was significant superior to other models, included CLIF-C ACLF score, MELD score, MELD-lactate and APACHE-II. It shows better predictors than others of in-hospital, one-month, three-month, six-month and one-year mortality rate among critically ill patients with liver cirrhosis and ACLF admitted to our ICU.

以及發生感染性併發症相關

VITAMIN D DEFICIENCY ASSOCIATES WITH GUT DYSBIOSIS AND THE RISK OF INFECTIOUS COMPLICATIONS IN PATIENTS WITH LIVER CIRRHOSIS

Background: Vitamin D deficiency and gut dysbiosis are common problems in patients with liver cirrhosis and both would be associated with poor clinical outcomes. Vitamin D was suggested to have impacts on gut barrier and microbiota in cirrhotic rats, but few clinical studies have reported these findings.

Aims: In recent study, we aimed to investigate the association between vitamin D deficiency and gut microbiota, and their impacts on development of infectious complications in patients with liver cirrhosis.

Methods: From September 2018 to December 2020, 80 cirrhotic patients were prospectively enrolled in Taipei Veterans General Hospital. Serum level of 25 hydroxyvitamin D [25(OH)D], cytokines, fecal microbiota and clinical characteristics were measured and analyzed. The associations between vitamin D deficiency and gut microbiota as well as the development of 1-year cirrhotic infectious complications were investigated.

Results: During the follow-up period of one year, total 41 infectious events and 91 hospitalizations were observed among these patients. Vitamin D deficiency, with the serum 25(OH)D cut-off value less than 15 ng/ml, acceptably predicted the development of infectious complications in these patients (AUROC: 0.818, 95% CI: 0.716 – 0.895, p = 0.001). More incidences of ascites, higher Child-Pugh scores, neutrophil-to-lymphocyte ratio and prothrombin time, as well as lower platelet count and serum albumin level were noted in patients with vitamin D deficiency. The serum levels of lipopolysaccharides and TNF-alpha were significantly higher in patients with lower serum vitamin D. Besides, the richness and evenness of fecal microbiota were significantly decreased in vitamin D-deficient cirrhotic patients, and a significant microbial dissimilarity was identified by un-weighted UniFrac analysis according to the presence of vitamin D deficiency. In addition, a prominence of Streptococcus and Ruminococcus gnavus were observed in the feces of vitamin D deficient cirrhotics. In contrast,

維他命 D 缺乏與肝硬化病患腸道菌叢失衡

李沛璋 李癸汌 陳宥任 鄭琮譯 呂學聖 楊宗杰 黃怡翔 侯明志

臺北榮民總醫院胃腸肝膽科

Bacteroides was more prominent in patients with higher serum vitamin D.

Conclusions: Vitamin D deficiency was associated with significant gut dysbiosis and significant increased risks to infectious complications in patients with liver cirrhosis. These findings potentiate to improve the outcomes of these patients by vitamin D supplementation and also gut microbial modification.

FECAL CARRIAGE OF MULTIDRUGRESISTANT ORGANISMS IS ASSOCIATED WITH INCREASED RISKS OF HEPATIC ENCEPHALOPATHY IN CIRRHOTIC PATIENTS

Background: Multidrug-resistant bacterial infections negatively impact the prognosis of cirrhotic patients.

Aims: We aimed to investigate the role of fecal carriage of multidrug-resistant organisms (MDROs) on cirrhosisassociated clinical outcomes.

Methods: A total of 88 cirrhotic patients and 22 healthy volunteers were prospectively enrolled in Taipei Veterans general hospital. Blood and fecal samples were collected at enrollment. Patients were followed for at least one year and the cirrhosis related clinical outcomes were recorded. Cox proportional hazards regression models were used to identify predictors for clinical outcomes.

Results: Cirrhotic patients had higher rates of fecal MDRO colonization than healthy population (33% vs. 9.1%, p = 0.026) and ESBL-producing Escherichia coli was the most predominant pathogen (58.6%) for cirrhotics. Baseline characteristics were similar between cirrhotic patients with and without MDRO carriage. However, MDRO carriers had higher serum levels of lipopolysaccharide (LPS) (16.51 ± 7.80 vs. 12.19 ± 5.58 ng/ml, p = 0.006) and higher proportion of admission within 30 days (34.5% vs 13.6%, p = 0.002) than non-carriers. Thirty-six patients (40.1%) developed cirrhosis related complications within one year. Of the complications, MDRO carriers to have rates of hepatic encephalopathy than non-carriers (20.7 vs. 3.4%, p = 0.008). Cox-regression analysis lower serum levels of sodium (<139 mmol/L), high levels of LPS (>13.6 ng/mL) and fecal carriage of MDROs are potential predictors for hepatic encephalopathy.

Conclusions: Cirrhotic patients had high prevalence of fecal carriage of MDROs, which was associated with increased risk of hepatic encephalopathy within one year. The results provide novel information for clinical physicians to identify patients who are benefit from aggressive surveillance of fecal MDROs.

解連蛋白及脂多醣結合蛋白可做為預測肝硬 化患者急性腎損傷、肝腎症候群、感染、敗 血症及敗血性休克之標記 ZONULIN AND LBP CAN BE PRACTICAL MARKERS FOR PREDICTION OF AKI, HRS, INFECTION, SEPSIS, AND SEPTIC SHOCK IN CIRRHOTIC PATIENTS

2 國立陽明交通大學醫學系

Background: Acute kidney injury (AKI) and infection are common and severe complications of cirrhosis, representing considerable health and economic burden. AKI occurs in 29% of cirrhotic patients, causing a six-fold increased risk of in-hospital mortality. Among different AKI etiologies, hepatorenal syndrome (HRS) has the highest mortality rate of 83%, followed by infection-related AKI. Improved outcomes and reduced healthcare expenditure may be achieved by early detection of AKI and infection in cirrhosis and prompt intervention. Higher zonulin (marker of intestinal mucosal integrity) correlates with poor renal function in patients with type 2 diabetes mellitus. In an animal model, Lipopolysaccharide binding protein (LBP), an endotoxemia biomarker, played an important role in renal fibrosis, an important mechanism of sepsisinduced AKI, and the removal of LBP was associated with protective effects on renal function.

Aims: This study aimed to investigate the probability of serum zonulin and LBP as applicable predictive markers for infection, sepsis/septic shock, and impaired renal function in cirrhotic patients.

Methods: This prospective longitudinal tertiary-center cohort study enrolled patients with cirrhosis between 2013 and 2020. Basic demographic data on age, sex, and the etiology of cirrhosis were retrieved. Child–Pugh scores, MELD scores, Aspartate Aminotransferase to Platelet Ratio Index (APRI) score, Aspartate Aminotransferase/ Alanine Aminotransferase ratio (AAR), Fibrosis-4 (FIB4) score, Acute Physiology and Chronic Health Evaluation (APACHE) II scores, and the Asian Pacific Association for the Study of the Liver (APASL) ACLF Research Consortium (AARC) scores were calculated at the time

of enrollment. In addition, white blood cell count (WBC), CRP, and serum creatinine were also retrieved at the time of enrollment.

Results: The mean levels of zonulin and LBP in cirrhotic patients were significantly higher than in the healthy control group. The etiology of cirrhosis in this study was mostly caused by viral hepatitis (82.9%), followed by alcoholism (35.7%). The mean APRI score of our cirrhotic patients was 3.93. The severity of liver cirrhosis was mild to moderate with the mean Child-Pugh score of 7.30 and MELD score of 10.11. The highest odds ratio was observed in the risk of development of AKI and infection. Patients with a zonulin level higher than the third quartile (6.95) are at significantly higher risk to develop the events mentioned above in the following six-month period after enrollment, compared to those with a zonulin level lower than the first quartile (3.60). Similarly, patients with an LBP level higher than the third quartile (91.25) are at significantly higher risk to develop the events mentioned above in the following sixmonth period after enrollment, compared to those with an LBP level lower than the first quartile (55.75). The results revealed that the levels of zonulin and LBP were positively correlated with the occurrence of complications. Both markers can predict the occurrence of these complications including AKI, HRS, infection, sepsis, and septic shock. Conclusions: In conclusion, our study proved that zonulin and LBP could be practical markers for the prediction of AKI, HRS, infection, sepsis, and septic shock in cirrhotic patients. Thus, we recommend that zonulin and LBP levels could be used to follow up on cirrhosis and for anticipating its common complications.

南臺灣肝硬化病人感染新冠肺炎後死亡影響 因素之探討

COVID-19 SEVERITY AND MORTALITY AMONG CIRRHOSIS PATIENTS IN A SINGLE CENTER OF SOUTHERN TAIWAN

3 奇美醫療財團法人奇美醫院胸腔內科

Background: COVID-19 caused by SARS-CoV-2 infection has emerged as a major international public health crisis. Previous research has stated that the risk factors of poor prognosis are cardiovascular disease, chronic lung disease and cirrhosis. Previous study (Thomas Marjot, et al. 2020) had demonstrated that cirrhosis and ALD were risk factors for death in patients with COVID-19 (cirrhosis OR: 1.90~9.32; ALD OR: 1.79). As regional difference and different variants of virus spread in Taiwan, we retrospectively analyzed risk factors for mortality in patients with history of cirrhosis.

Aims: This study aimed to assess the risk factors associated with mortality among COVID-19 cases with cirrhosis in south Taiwan.

Methods: This was a cross sectional study that included laboratory-confirmed COVID-19 patients with cirrhosis hospitalized at a single tertiary-care hospital in south Taiwan. Demographic, clinical history, comorbidity and outcomes data were retrieved from January 2022 to September 2022. Data was collected using Excel (Version 2017, Microsoft, Redmond, WA) and statistical analysis was performed in SPSS (Version 26.0, IBM, Armonk, NY). Results: We included 92 COVID-19-positive patients in database of Chi Mei hospital, with a median age of 67.9 years. Of these, 10.87% were in the mortality group. Risk factors associated with mortality included shock (p < 0.01), endotracheal intubation (p = 0.03) and hemodialysis (p = 0.01); no significant risk factors were found in baseline characteristics.

Conclusions: The mortality rate of patients with COVID-19 pneumonia and cirrhosis was 10.87%. Shock, endotracheal intubation and hemodialysis were found as significant factors associated with mortality.

抑制腎素原受體改善脂性肝炎小鼠之肝脂肪 堆積、發炎與纖維化 (PRO)RENIN RECEPTOR INHIBITION ATTENUATED LIVER STEATOSIS, INFLAMMATION AND FIBROSIS IN MICE WITH STEATOHEPATITIS

Background: The (Pro)renin receptor (PRR) is reportedly involved in hepatic lipid metabolism and hepatocyte PRR knockdown protects mice against hepatosteatosis. However, the impact of PRR inhibition on liver inflammation and fibrosis in nonalcoholic steatohepatitis (NASH) remains unclear.

Aims: To investigate the effect of PRR inhibition on NASH.

Methods: C57BL/6 mice were fed a normal chow diet or fast food diet (FFD) for 24 weeks. Lentivirus-mediated PRR short hairpin RNA (shRNA) or handle region peptide (HRP), a PRR blocker, was administered for PRR inhibition. Mouse primary hepatocytes were cultured with palmitic acid, prorenin, siRNA-targeted PRR and HRP.

Results: In FFD-fed mice, PRR inhibition via lentivirusmediated PRR knockdown or HRP significantly attenuated liver steatosis, inflammation and fibrosis. Mechanistically, PRR knockdown or HRP decreased hepatic acetylCoA carboxylase (ACC) abundance and upregulated peroxisome proliferator-activated receptor-alpha (PPARα). HRP treatment also decreased hepatic PRR expression. In addition, intrahepatic oxidative stress, apoptosis and inflammatory cell recruitment were ameliorated by PRR knockdown or HRP treatment, along with suppression of proinflammatory cytokine expression. PRR inhibition downregulated the hepatic expression of profibrotic factors, as well as TGF-β1/SMAD3 pathway. In primary mouse hepatocytes, PRR knockdown with siRNA or HRP downregulated cellular ACC and increased PPARα expression.

Conclusions: In conclusion, our findings revealed that PRR inhibition attenuated hepatic steatosis, inflammation and fibrosis in mice with NASH. Accordingly, targeting PRR signaling may serve as a potential treatment for NASH.

2 奇美醫療財團法人奇美醫院腎臟科

主題：脂肪肝相關疾病 ㉘

謝昀蓁 吳佩珊 黃怡翔 侯明志 李癸汌 林漢傑 臺北榮民總醫院胃腸肝膽科

病態性肥胖病人非酒精性脂肪肝炎與肝纖維 化的肝臟脂質組學特徵

LIVER LIPIDOMIC PROFILES OF NONALCOHOLIC STEATOHEPATITIS AND FIBROSIS IN PATIENTS WITH MORBID OBESITY

吳華倩1 王偉2 張宜崴3 陳志榮4 張君照1,5 張嘉軒6 謝茵如6 高偉育1,5 黃士懿6

1 臺北醫學大學醫學院內科學科

2 臺北醫學大學附設醫院消化外科

3 臺北醫學大學萬芳醫院病理實驗部

Background: The prevalence rate of nonalcoholic steatohepatitis (NASH) has been reported in 50% to 70% of morbidly obese patients.

Aims: This study aims to investigate lipidomic profile features between NASH with mild fibrosis and NASH with significant liver fibrosis in morbidly obese patients.

Methods: Lipidomics was performed using ultrahigh performance liquid chromatography-tandem mass spectrometer on liver samples from a prospective cohort study involved morbidly obese patients who underwent sleeve gastrectomy at Taipei Medical University Hospital. Wedge liver biopsy was performed during surgery, and significant liver fibrosis was defined as a fibrosis score > 2. We selected NASH with fibrosis stage 0-1 (n = 30) and NASH with fibrosis stage 2-4 (n = 30) patients. Lipid components of triglyceride (TG), cholesterol ester (CE), phosphatidylcholine (PC), sphingomyelin (SM) were selected for further investigation.

Results: The results revealed that the fold changes of triglyceride (TG) (52:6) and (43:0); cholesterol ester (CE) (20:1); phosphatidylcholine (PC) (38:0), (39:0), and (50:8); phosphatidic acid (PA) (40:4), phosphatidylinositol (PI) (49:4), phosphatidylethanolamines (PE) (41:6), phosphatidylglycerol (PG) (40:2); and sphingomyelin (SM) (35:0) and (37:0) were significantly lower in patients with NASH with significant liver fibrosis than those with NASH with mild fibrosis (p < 0.05). However, the fold changes of PC (42:4) were relatively lower in patients with NASH with stage 0–1 fibrosis (p < 0.05). Moreover, predictive models incorporating serum markers levels, ultrasonographic studies, and levels of specific lipid components [PC (42:4) and PG (40:2)] yielded the highest area under receiver

operating curve (0.941), suggesting a potential correlation between NASH fibrosis stages and liver lipid accumulation among specific lipid species subclasses.

Conclusions: The present study demonstrated that the concentration of particular lipid species of TG, CE, SM, PC in the liver correlate with NASH fibrosis stages and may indicate hepatic steatosis regression or progression in patients with morbid obesity.

4 臺北醫學大學附設醫院病理部

5 臺北醫學大學附設醫院消化內科

6 臺北醫學大學營養學院

機器學習模型預測顯著肝纖維化於非酒精性 脂肪肝疾病之病態肥胖性患者

MACHINE LEARNING MODEL TO PREDICT SIGNIFICANT LIVER FIBROSIS IN MORBIDLY OBESE PATIENTS WITH NONALCOHOLIC FATTY LIVER DISEASE RUNNING

TITLE: MACHINE LEARNING MODEL AND LIVER FIBROSIS

1 臺北醫學大學附設醫院消化內科

2 臺北醫學大學醫學科技學院醫學資訊研究所

3 臺北醫學大學健康資訊科技國際研究中心

4 臺北市立萬芳醫院皮膚科

5 臺北醫學大學附設醫院消化系外科

6 臺北醫學大學醫學院醫學系外科學科

7 臺北醫學大學附設醫院病理科

8 臺北醫學大學醫學院醫學系病理學科

9 臺北醫學大學醫學院醫學系內科學科

10 臺北醫學大學消化醫學研究中心

11 臺北醫學大學臺北癌症中心

Background: Non-alcoholic fatty liver disease (NAFLD) is common in the general population and more prevalent in obese patient, ranging from 74% to 90%. Liver fibrosis is a severe form of NAFLD, and advanced stage is associated with higher morbidity and mortality. Liver biopsy is the gold standard but is costly and invasive. Combination of non-invasive serum biomarkers, including the Fibrosis-4 index (FIB-4), aspartate aminotransferase/platelet ratio index (APRI), nonalcoholic fatty liver disease fibrosis score (NFS), and BARD score, as well as ultrasonography, and transient elastography had been utilized to assess the severity of liver fibrosis. However, they have limited prediction accuracy. Also, machine learning models for advanced liver fibrosis in morbidly obese patients have not been validated.

Aims: We aimed to predict significant liver fibrosis using machine learning models in morbidly obese patients using serum biomarkers, ultrasonography fibrosis score, and liver stiffness measurement.

Methods: This prospective study involved 130 morbidly obese patients with liver biopsy who underwent laparoscopic sleeve gastrectomy at Taipei Medical University Hospital between October 2016 and October 2018. Wedge liver biopsy was performed during surgery,

and significant liver fibrosis was defined as a fibrosis score > 2. Considering data availability and clinical relevance, the input variables included age, diabetes mellitus status, HbA1c, creatinine, total cholesterol, aspartate aminotransferase (AST), platelet count, prothrombin time international normalized ratio (PTINR), ultrasound fibrosis score, and liver stiffness measurement (LSM). Machine learning models of Support Vector Machine (SVM), Random Forest (RF), K-Nearest Neighbor algorithm (KNN), XGBoost, and Artificial Neural Network (ANN) were trained to predict significant liver fibrosis. Training and validation cohort were split to 60% and 40% respectively by random. 5-fold cross validation and average performance of 10 times were adopted for preventing overfitting and achieving more stable prediction performance.

Results: In all cohort (n = 130), 46 (35.4%) had significant liver fibrosis (≥F2); the mean age was 35.2 years; 25 (19.2%) had diabetes mellitus; the mean HbA1c was 6.2%; the mean creatinine was 0.7 mg/dl; the mean total cholesterol was 191.9 mg/dl; the mean AST was 36.6 U/ L; the mean platelet count was 284.1 x 103/mm3; the mean PT INR was 1.1; the mean ultrasound fibrosis score was 5.1, and the mean LSM was 8.5 kPa. The Support Vector Machine and XGBoost models achieved best prediction performance. The training/validation average sensitivity, specificity, accuracy and area under receiver operating curve achieved 74.7/71.4%, 68.1/67.9%, 71.3/68.1%, 0.81/0.80 in SVM, 73.4/77.0%, 78.2/74.6%, 76.8/74.8%, 0.82/0.78 in XGBoost, 84.9/69.2%, 81.9/70.8%, 83.3/69.2%, 0.92/0.75 in RF, 59.4/44.7%, 92.0/82.4%, 80.1/69.2%, 0.89/0.68 in KNN, and 61.3/55.1%, 90.8/83.1%, 80.5/72.9%, 0.83/0.76 in ANN, respectively.

Conclusions: Machine learning models were accurate for predicting significant liver fibrosis in morbidly obese patients using serum biomarkers, ultrasound fibrosis score and liver stiffness measurement. A larger-scale population of the morbidly obese is warranted for a more accurate and reliable prediction model using machine learning algorithm. The presented machine learning prediction models may serve as a tool to screen significant liver fibrosis in these patients.

預測瘦脂肪肝的機器學習工具的開發和比較 DEVELOPMENT AND COMPARISON OF MACHINE LEARNING TOOLS TO PREDICT LEAN FATTY LIVER

Background: The clinical and biochemical presentations of lean fatty liver are milder than obesity fatty liver. However, the lean fatty liver is also risk for cirrhosis and hepatocellular carcinoma. There is limit tool to predict fatty liver in lean patients.

Aims: We try to develop a tool to predictive lean fatty liver by using machine learning algorithm and fatty liver index (FLI).

Methods: 12191 patients with BMI < 23 kg/m2 received health checkup in our hospital since was retrospective collected into the study from January 2009 to January 2019. The patients were divided into two groups including training group (8533/12191 (70%)) and validation group (3658/12192 (30%)). Fatty liver was defined as moderateto-severe fatty liver by ultrasound finding. Twice patients without fatty liver were random selected as control in each two groups. 27 different features were analyzed including age, gender, weight, height, waist, complete blood count and other biochemistry. We compared the nine different machine learning algorithms using the Azure ML platform and FLI.

Results: The ratio of fatty liver in patients with BMI < 23 kg/m2 of training group and validation group was 6% (508/8533) and 6.4% (233/3658). The patients with fatty liver were older and heavier than patients without fatty liver. The higher scores of ten features included waist, TG, BMI, HDL, glucose, SBP, ALT, DBP, weight and age were selected using Pearson correlation. The algorithm of twoclass neural network had the highest AUROC value (0.877) than the other eight machine learning algorithms and the accuracy rate, Recall, F1 score, and Precision values were 0.793, 0.624, 0.683 and 0.756, respectively. After implementing the algorithm and FLI into validation group, The AUROC of FLI (cut-off point as 0.895) was the highest (0.786, 0.750-0.823) than two-class neural network (0.751, 0.710-0.793) and FLI (cut-off point as 15) (0.722, 0.6790.765).

Conclusions: The algorithm of two-class neural network and FLI are two reliable tools to predict lean-fatty liver. The optimal cut off point of FLI might be 0.895.

床意義的肝臟脂肪量減少的效用 USEFULNESS OF CONTROLLED ATTENUATION PARAMETER IN MONITORING CLINICALLY RELEVANT DECLINE OF HEPATIC STEATOSIS FOR NON-ALCOHOLIC FATTY LIVER DISEASE PATIENT

Background: Magnetic resonance imaging-derived proton density fat fraction (MRI-PDFF) is the non-invasive standard reference of hepatic steatosis assessment. Decline of ≥ 30% relative to baseline by MRI-PDFF is defined as clinical relevant outcome associated with histology response and fibrosis regression.

Aims: This study aimed to evaluate the usefulness of controlled attenuation parameter (CAP) in monitoring the clinically relevant decline by MRI-PDFF in non-alcoholic fatty liver disease (NAFLD) patients.

Methods: Patients with NAFLD diagnosis were enrolled prospectively. Lifestyle modification with exercise and control of metabolic factors were instructed at enrollment. MRI-PDFF and CAP (M or XL probe, Echosens, Paris, France) were performed at enrollment and follow-up. Those patients with liver stiffness ≥10 KPa were excluded. With the changes of MRI-PDFF as standard reference, we analyzed the performance, cutoff and validity of CAP in monitoring clinically relevant decline.

Results: A total of 75 patients (M/F: 49/26, mean age: 53.2) were enrolled. Baseline hepatic steatosis, CAP and liver stiffness is 14.4%, 300.2 dB/m and 6.5 kPa, respectively. In a median interval of 369 days, there are 13 (17.3%) patients achieving clinically relevant outcome with mean decline of 46.7 dB/m in CAP, compared with 5.1 dB/ m increase in the other patients. In multivariate analysis, the clinically relevant decline by MRI-PDFF is associated with ΔCAP and Δ fasting glucose. Assessed by area under receiver operating curve, the performances of ΔCAP in predicting clinically relevant decline are 0.815 and 0.808. With the specificity set >90%, the ΔCAP cutoff is -46dB/ m and -15% relative to baseline. The sensitivity was 53.8% and 46.2% with negative predictive value of 90.3% and

蘇培元 蘇維文 陳洋源 黃秀萍 顏旭亨 彰化基督教醫院胃腸肝膽科

可控衰減參數監測非酒精脂肪肝病患達具臨

王景弘1 歐信佑2 顏毅豪1 洪肇宏1 盧勝男1

1 長庚醫療財團法人高雄長庚紀念醫院胃腸肝膽科系暨 長庚大學醫學系

2 長庚醫療財團法人高雄長庚紀念醫院放射診斷科系暨 長庚大學醫學系

88.9%.

Conclusions: There is good performance for CAP in predicting clinically relevant outcome for NAFLD. With the cutoffs of -46dB/m or -15%, ΔCAP is useful in excluding ≥30% decline relative to baseline by MRI-PDFF.

主題：上消化道疾病（一） ㉝

創新的雙鏡牽引技術在內視鏡黏膜下剝離術 的運用

NOVEL COLORECTAL ENDOSCOPIC SUBMUCOSAL DISSECTION WITH DOUBLE-ENDOSCOPE AND SNAREBASED TRACTION

袁名璟

Background: Colorectal endoscope submucosal dissection is technically demanding. Conventional endoscopic submucosal dissection offered traction by gravity, cap, or clip-with line remains unsatisfactory. In addition, robotic systems are still under development and are expensive. Therefore, we proposed double-scope endoscopic submucosal dissection with strong and adjustable traction offered by snaring the lesion with additional scope.

Aims: This study aimed to test the efficacy and safety of the novel double-scope endoscopic submucosal dissection with snare-based traction.

Methods: We matched fifteen patients who underwent novel double-scope endoscopic submucosal dissection for the large-size lateral spreading tumor with the control group who underwent ESD with similar size, location, morphology, and pathology. All procedures were performed by the same endoscopist who had completed more than 400 ESD procedures and more than 5000 colonoscopy insertions in 1 hospital. We compared DS-ESD/c-ESD and statistically analyzed participant’s lesion characteristics, procedure time, completeness, and complications.

Results: Compared with the controls group that underwent conventional ESD, the novel double-scope traction ESD provided a shorter pure ESD time of 28.23 versus 54.61 minutes (p-value: 0.005), shorter total procedure time of 54.61 versus 32.45 minutes (p-value: 0.021), and the same comparison of completeness and complications. The preESD baseline characteristics had no difference between the two groups.

Conclusions: The novel DS-ESD offers traction in efficacy and safety, with approximately a 40% reduction in procedure time. However, DS-ESD is a novel technique, and we suggest DS-ESD be performed only by endoscopists who master colonoscopy insertion and have adequate ESD experience.

內視鏡口咽吞嚥障礙檢查：腦神經患者長期 管灌肺炎風險評估 ENDOSCOPIC EVALUATION OF OROPHARYNGEAL DYSPHAGIA: NEUROLOGICAL DISORDER PATIENTS ON LONG-TERM ENTERAL FEEDING FOR RISK STRATIFICATION OF PNEUMONIA

Background: Nasogastric tube (NGT) and percutaneous endoscopic gastrostomy (PEG) are widely used techniques to feed patients with neurological disorders with oropharyngeal dysphagia. Aspiration pneumonia is the leading cause of death in tube-fed patients.

Aims: This study aimed to evaluate the role of oropharyngeal dysphagia in patients with neurological disorders on longterm enteral feeding for risk stratification of pneumonia requiring hospitalization.

Methods: Flexible endoscopic evaluation of swallowing was performed to evaluate oropharyngeal dysphagia in patients with neurological disorders and conducted a prospective follow-up for pneumonia requiring hospitalization. A total of 209 and 148 orally-fed and tube-fed patients were enrolled. Multivariate Cox analysis was performed to identify risk factors of pneumonia requiring hospitalization and mortality.

Results: Multivariate analyses showed that the risk of pneumonia requiring hospitalization significantly increased in patients with a history of pneumonia and tube feeding. A higher body mass index was associated with a lower risk of mortality, whereas multivariate analyses revealed that older ages and a higher incidence of pneumonia were associated with an increased risk of mortality. Subgroup analysis revealed that the risk of pneumonia requiring hospitalization was significantly lower in patients with PEG than in those with NGT among patients with oropharyngeal dysphagia (adjusted hazard ratio, 0.21; 95% confidence interval, 0.10–0.44; P < 0.001). All patients receiving tube feeding had a significantly lower mortality risk in the PEG group than in the NGT group in all tube-fed patients (adjusted hazard ratio 0.09, 95% confidence interval: 0.03–0.30, P < 0.001).

Conclusions: Oropharyngeal dysphagia should be crucially evaluated in patients with neurological disorders on longterm enteral feeding. For patients with neurological disorders with oropharyngeal dysphagia requiring long-term enteral tube feeding, PEG is a better choice than NGT.

切除後的存活預後

POST-OPERATIVE PROGNOSTIC NUTRITIONAL INDEX PREDICTS

SURVIVAL BENEFITS OF PATIENTS WITH SMALL BOWEL ADENOCARCINOMA AFTER SURGICAL RESECTION

李佳儒

Background: Nutritional status is an important prognostic factor to all cancer patients. Patients who underwent surgical resection for small bowel cancer often suffered from disturbance of digestion and absorption.

Aims: In this study, we aimed to investigate the clinical significance of post post-operative nutrition marker, prognosis prognostic nutritional index (PNI), on clinical in the outcomes of patients with resectable small intestine bowel adenocarcinoma.

Methods: From June 2014 to March 2022, 44 patients with small bowel adenocarcinoma and received surgical resection in Taipei Veterans General Hospital were retrospectively enrolled. Baseline characteristics, tumor status, post-operative PNI were analyzed. Overall survival (OS) and progression-free survival (PFS) were calculated by the Kaplan Meier method. Predictors to survivals were investigated by COX-regression analysis.

Results: At the date end of data-cut on October 31, 2022, the median follow-up time of these patients was 24 months (interquartile: 9.5 – 40.1). 13 deaths developed and the median OS was not yet reached. The median change of PNI after surgical resection was -1.821. Post-operative PNI (less than 45) acceptably predicted OS in these patients (AUROC: 0.826, 95% CI. 0.686 – 0.967, p = 0.001). More patients with lower post-operative PNI had experienced Whipple operation rather than intestinal segmentectomy compared to the counterpart. Besides, patients who underwent Whipple operation encountered significant reduction of PNI after surgery in comparison with patients who received segmentectomy of intestine (-2.000 vs. 6.204, p = 0.015). In addition, patients with lower post-operative

張維國 林泰瀚 楊志偉 黃天祐 陳鵬仁 施宇隆 謝財源 三軍總醫院胃腸科

術後的預後營養指標可預測小腸癌患者腫瘤

PNI had significantly poorer OS compared to the others (OS: 19.3 vs. not reached, p < 0.001). According to the multivariate analyses, male gender (hazard ratio [HR]: 13.0, p = 0.022), presence of lymphovascular invasion of tumor (HR: 12.7, p = 0.003), administration of adjuvant chemotherapy (HR: 0.03, p = 0.001) and lower postoperative PNI (HR: 9.5, p = 0.007) were independent predictors to OS.

Conclusions: Patient underwent surgical resection for small bowel cancer frequently encountered nutritional impairment. Post-operative PNI could independently predict OS in these patients.

A RANDOMIZED, CONTROLLED TRIAL OF ARGON PLASMA COAGULATION PLUS DILUTED ADRENALIN INJECTION VERSUS HEMOCLIPPING PLUS DILUTED ADRENALIN INJECTION FOR TREATMENT OF HIGH–RISK PEPTIC ULCER BLEEDING: AN INTERIM REPORT

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 adrenalin injection (APC group) with clipping plus diluted adrenalin injection (Clip group) in treating high-risk peptic ulcer bleeding.

Methods: From Jan. 2019 to Nov. 2022, 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 adrenalin injection or hemoclipping plus diluted adrenalin 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 or arterial embolization. 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. All hypothesis tests were performed against a two-sided alternative, where appropriate. A p < 0.05 was viewed as statistically significant. Analyses were undertaken using SPSS software (SAS, SPSS Inc., Chicago, Ill., USA).

在腎上腺素注射術後，比較併用氬氣電漿凝 固術或併用止血夾兩者對於消化性潰瘍出血 的止血療效之隨機控制試驗

顏廷宇 王惠民 高崧碩 蔡峯偉 蔡維倫 蔡騌圳 陳文誌 高雄榮民總醫院胃腸肝膽內科

Results: In all, 138 eligible patients were analyzed. Hemostatic efficacy in 68 patients treated with APC plus diluted adrenalin injection (APC group) was prospectively compared with 70 patients treated with hemoclipping plus diluted adrenalin injection (Hemoclip group). The two treatment groups were similar with respect to all baseline characteristics. Initial hemostasis was accomplished in 67 patients treated with APC combined with diluted adrenalin injection therapy, and 69 patients with hemoclipping plus diluted adrenalin injection therapy (98.5% vs. 98.6%, P = 1.000). Bleeding recurred in 5 patients in the APC group, and in 6 patients in the Clip group (7.4% vs. 8.6%, P = 1.000). No significant differences were observed between the 2 groups in surgery (1.5% vs. 1.4%, P = 1.000) and mortality (1.5% vs. 1.4%, P = 1.000). No significant differences were observed between the 2 groups in hospital stay and transfusion requirement.

Conclusions: Endoscopic therapy with APC plus diluted adrenalin injection is similarly effective as hemoclipping plus diluted adrenalin injection for preventing rebleeding in the treatment of high-risk bleeding ulcers. Both treatment methods also have similar safety during therapeutic endoscopy.

醫學中心的 10 年世代研究

CLINICAL OUTCOMES OF T4B

ESOPHAGEAL SQUAMOUS CELL CARCINOMA: A 10-YEARS COHORT STUDY IN SINGLE MEDICAL CENTER

陳以勳1 王耀廣1 方本慈2 吳宜珍1

1 高雄醫學大學附設中和紀念醫院胃腸內科

2 高雄醫學大學附設中和紀念醫院放射腫瘤部

Background: T4b esophageal squamous cell carcinoma (ESCC) indicates tumor invaded adjacent major organs such as air way, aorta, or vertebral body and has dismal survival outcome.

Aims: We presented with our ESCC 10-years cohort in our hospital about the risk factors and clinical outcomes of T4b ESCC.

Methods: Our prospective cohort study recruited from October 2011 to May 2022 at a single medical center in Taiwan. Inclusion criteria were all ESCC patients, and exclusion criteria were non-ESCC patients or double cancers. All patients received lab data survey, chest/abdomen computed tomography, esophagogastroduodenoscopy, bronchoscopy for tumors within upper- or middle-third of the esophagus, and positron emission tomography. The treatment options were divided by definite chemoradiotherapy (dCRT), chemotherapy alone (CT), radiation therapy alone (RT), immunological trials and best supportive care according to the clinical condition and Eastern Cooperative Oncology Group (ECOG).

Results: Total 471 ESCC patients were screened, and 130 (27%) patients were stage T4b and then enrolled in our final analysis. About the first line treatment, 83 patients with dCRT, 15 patients with CT only, 5 patients with RT only, 7 patients with immunological trials, and 20 patients with best supportive care. dCRT group had better median overall survival (OS) than CT or RT only group (OS, dCRT vs CT or RT only: 23.94 months vs 5.29 months, p < 0.01). There were 22 (16.9%) ESCC patients with tracheal-esophageal (TE) fistula. CT or RT only group had higher risk to develop T-E fistula compared to dCRT group (95% CI: 1.14-18.96, adjusted HR: 4.66, p = 0.032).

Conclusions: The median overall survival for T4b ESCC patients was about two years. Trachea-esophageal fistula was a major complication with high prevalence rate in T4b ESCC patients, especially those with poor initial condition or ECOG and only received chemotherapy or radiotherapy.

T4b 食道鱗狀上皮細胞癌的臨床結果：一家

經皮冠狀動脈介入術後雙聯抗血小板藥物治 療的冠心病加護病房患者其上消化道出血的 危險因子及抑制潰瘍藥物預防作用的研究 THE RISK FACTORS FOR UPPER GASTROINTESTINAL HEMORRHAGE AFTER DUAL ANTIPLATELET TREATMENT OF PERCUTANEOUS CORONARY INTERVENTION PATIENTS IN A CORONARY CARE UNIT AND PREVENTIVE EFFECT OF ANTI-ULCER MEDICATIONS

劉安哲1,2 施竣庭1,3 梁志明1,2 戴維震1,2 蔡成枝1,2 陳永隆1,3 陳煌中1,3 鍾昇穎1,3

1 高雄長庚紀念醫院內科部

Background: Gastrointestinal bleeding may occur in critically ill patients diagnosed with coronary artery diseases in the coronary care unit (CCU), many of whom receive dual antiplatelet treatment (DAPT) after percutaneous coronary intervention (PCI). Given the potential adverse effects associated with dual antiplatelet therapy, such as hematemesis and melena. Histamine-2 receptor antagonists (H2RA), or proton pump inhibitors (PPIs) are often administered in CCUs. Nevertheless, whether the anti-ulcer mentioned medications above may bring any benefits has still yet to be confirmed.

Aims: To determine the benefits of prophylactic anti-ulcer medications for patients diagnosed with coronary artery diseases in the CCU after DAPT and PCI.

Methods: We retrospectively recruited 288 eligible patients with DAPT (most with aspirin 100 mg QD, ticagrelor 90 mg bid) after PCI in a CCU. Incidence of upper gastrointestinal bleeding (UGIB) was correlated with clinical hematemesis and melena. Investigations on the issue were carried out with categorizations based on (1) their past histories before the hospitalization, (2) the findings of PCI of drug-eluting stents or bare metal stents, and thrombectomy, (3) UGIB ≤ 72 hours after catheterization and (4) UGIB > 72 hours after catheterization.

Results: Twenty-four patients (8.3%) suffered from acute UGIB ≤ 72 hours after catheterization. The independent risks factors of UGIB ≤ 72 hours in the CCU were female patients (95% confidence interval [CI]: 0.275 [0.0980.770], P = 0.014), history of cerebrovascular accident (95% CI: 6.483 [1.234-34.061], P = 0.027), and Killip

grade (95% CI: 0.377 [0.237-0.600], P < 0.001). With the aforementioned acute UGIB cases excluded initially, there were 41 cases prescribed prophylactic PPIs and 57 cases with H2RA, and the remaining 166 cases without any preventive medications for UGIB. The UGIB rates were 9.3% in the PPIs group, 5.3% in the H2RA group, and 3.6% in the non-prophylactic group. There was no significantly lower rate of UGIB in the prophylactic group than in the non-prophylactic group (P = 0.264). Thirteen patients (4.9%) had delayed UGIB > 72 hours after catheterization. The independent risks factors of UGIB > 72 hours in the CCU were patients with chronic kidney disease (95% CI: 9.264 [2.516-34.111], P = 0.001), and Killip grade (95% CI: 0.534 [0.316-0.902], P = 0.019).

Conclusions: Although there was no significant difference in the incidence of UGIB after PCI among patients with or without prophylactic anti-ulcer medicines, the use of prophylactic medication and close monitoring may be still necessary when it comes to high-risk groups for gastrointestinal bleeding.

主題：其他消化道疾病 ㊴

新型冠狀病毒（COVID-19）大流行對消化

道內視鏡的執行和癌症診斷的衝擊和影響 ─

一個南台灣區域教學醫院的回溯性研究 THE IMPACT OF GLOBAL PANDEMIC COVID-19 INFECTION ON GASTROINTESTINAL ENDOSCOPIC PROCEDURE AND CANCER DIAGNOSIS

‒ A RETROSPECTIVE STUDY OF A REGIONAL TEACHING HOSPITAL IN SOUTHERN TAIWAN

蔡雨潔

Background: There were an estimated 4.8 million new cases of gastrointestinal cancers and 3.4 million related deaths, worldwide, in 2018. Gastrointestinal cancers account for 26% of the global cancer incidence and 35% of all cancer-related deaths. Of which, Colorectal cancer, Gastric cancer and Esophageal cancer are the third, fifth and seventh most commonly occuring cancers in terms of global incidence. Furthermore, They have high mortality rates and are deadly diseases that continue to plague our world today. Endoscopy has been widely used as a screening, surveillance and diagnostic tool in gastrointestinal neoplasms due to high sensitive and costeffective characters. However, hesitation, rejection or cancelling of procedures due to positive PCR, policy of quarantine and concerning of being infected has been observed in the past 2 years. In short, the COVID-19 pandemic disrupted both routine screening, indicated diagnostic procedures and subsequent treatment of gastrointestinal cancers.

Aims: In this article, we retrospectively reviewed the changes in number of endoscopic procedures, diagnosis of Colorectal, Gastric and Esophageal cancers and staging at diagnosis before and during the pandemic.

Methods: In this study, we retrospectively reviewed the number of endoscopic procedures and identified patients with pathological carcinoma diagnosis of esophageal, gastric and colorectal origin resulting from biopsy or surgical resected specimens in our institution between the period of Jan 2018 ~ Dec 2019 (preCOVID-19) and Jan 2020 ~ Dec 2021 (COVID-19). And 1st Jan 2020 was used as a cut-point to delineate the preCOVID-19 and COVID-19 period. The AJCC staging at diagnosis was reviewed and the numbers of early stage (0~l) and intermidiate~late stage (ll~lV) at diagnosis were compared.

The Chi-square test was used to compare the significant differences in number of cancer diagnosis and staging at the time of diagnosis between two periods.

Results: There was a reduction in number of overall endoscopic procedures (-16%) during the COVID-19 period. A total of 1038 patient with pathological carcinoma diagnosis of esophagus, stomach and colorectum were reviewed and identified during the study period. A reduction in number of overall gastrointestinal cancer (-19%) as well as esophageal (-30%) gastric (-28%) and colorectal (-17%) cancer diagnosis during COVID-19 period was observed. The diagnostic yield of overall gastrointestinal cancers between preCOVID-19 (1.3%) and COVID-19 period (1.2%) was insignificant (p = 0.182). The diagnostic yield of two periods in both esophageal (0.2%, 0.1%), gastric (0.2%, 0.2%) and colorectal cancers (3.1%, 2.8%) were insignificant (p = 0.377, p = 0.368, p = 0.144). A minor raise in proportion of intermediate~late stage (AJCC ll~lV) at diagnosis was observed in esophageal (97%, 94%, p = 0.467) and colorectal (61%, 60%, p = 0.553) cancers during COVID-19 period. A slim reduction in proportion of intermediate~late stage (AJCC ll~lV) at diagnosis was observed in gastric CA (74%, 81%, p = 0.215) during COVID-19 period.

Conclusions: A reduction in number of overall endoscopic procedures (-16%) as well as number of gastrointestinal cancer diagnosis (-19%) was observed during COVID-19 period (Jan 2020 ~ DEC 2021) when compared with preCOVID-19 period (Jan 2018 ~ Dec 2019). However, the diagnostic yield rate showed a consistency in both overall, esophageal, Gastric and colorectal cancer in our institution in between 2 periods. In short, the reduction of cancer diagnosis during COVID-19 period is irrelevant to lower incidence rate, instead, it was an unfavorable consequences resulting from fewer endoscopic procedures due to the pandemic. The difference of AJCC staging at diagnosis between 2 periods in this study was insignificant. However, increasing emergency visits due to obstruction, bleeding or perforation in advanced stages of gastrointestinal cancer was observed during COVID-19 period. Delayed or interuption of diagnostic or screening endoscopic procedures due to the pandemic resulting in serious consequences such as increased emergency conditions, worsening cancer-related complications, medical cost raising, and at worst, the reduction of patient life quality and survivals. In pace with the retardation of Covid-19 pandemic, serious efforts and intervention should be carried out for preventing this declining trend.

林成業 陳君豪 王嗣仁 陳錫榮 孫盟舜 蔡青陽 阮綜合醫療社團法人阮綜合醫院消化內科

枸杞多醣和辣椒素對葡聚醣硫酸鈉誘導的結 腸炎大鼠的氧化壓力、炎症反應及疼痛信號 的抑制 LYCIUM BARBARUM

POLYSACCHARIDES AND CAPSAICIN

INHIBIT OXIDATIVE STRESS, INFLAMMATORY RESPONSES, AND PAIN SIGNALING IN RATS WITH DEXTRAN SULFATE SODIUM-INDUCED COLITIS

陳文昭

1 臺北醫學大學附設醫院消化內科

2 臺北醫學大學消化醫學研究中心

Background: Ulcerative colitis (UC) is an inflammatory bowel disease sub-type, commonly occurring in the sigmoid colon, characterized by relapsing and remitting inflammatory mucosa. From 2001 to 2015, the incidence and prevalence of UC in Taiwan were found to be raised from 0.54 to 0.95 per 100,000 and from 2.10 to 2.18 per 100,000, respectively.

Aims: Lycium barbarum polysaccharides (LBP) had the most biological activity in goji berry. LBP mainly contained nine monosaccharides, namely: xylose, rhamnose, glucose, mannose, galactose, arabinose, fructose, fucose, and ribose, and various activities such as antioxidation, immunomodulation, antitumor, and neuroprotection. Capsaicin (CAP), is a naturally occurring alkaloid and the primary capsaicinoid in chili pepper. CAP was known for its analgesic effect via binding to transient receptor potential cation channel V1 (TRPV1), and had antioxidative, anti-inflammatory, antitumor, and gastroprotective effects.

Methods: This study investigated the effects of Lycium barbarum polysaccharides (LBP) and capsaicin (CAP) in dextran sulfate sodium (DSS)-induced UC rats. Rats were divided into normal, DSS-induced UC, and UC treated with 100 mg LBP/kg bw, 12 mg CAP/kg bw, or 50 mg LBP/kg bw and 6 mg CAP/kg bw. Rats were fed LBP or CAP orally by gavage for 4 weeks, and UC model was established by feeding 5% DSS in drinking water for 6 days during week 3.

Results: [1] The disease activity index (DAI) score of the U group was dramatically increased to the peak on the last day (day 6) of DSS induction (Figure 1). The CAP and

mixture-treated groups showed significant decreases in DAI scores compared to the U group on day 6; however, the LBP treated group had no apparent changes in DAI score compared to the U group. [2] The ulcerative colitis group had significantly shrunken colon length compared to the control group (Figure 2A), indicating a induction of colitis symptoms by providing 5% DSS in drinking water to rats. The treatment with LBP or mixture of both recovered colon length compared to the U group (p < 0.05), but a similar result was not found in the CAP treated group. Rats with DSS-induced colitis had a significant increase in colon weight compared to those in the control group (p < 0.05) (Figure 2B). Unlike the results of the colon length, a significant reduction in colon weight was only observed in the mixed LBP and CAP group (p < 0.05). The colon weight/length ratio was correlated to the severity of colitis, and a significant increase was found in the U group compared to the control group (p < 0.05) (Figure 2C). Only the treatment with a mixture of both showed a significant decrease in colon weight/length ratio compared to the U group (p < 0.05). [3] Histological analysis for colonic damage in rats was examined and scored by H&E stain. The control group did not have inflammation and necrosis and had normal morphology in the gross structure, goblet cells, crypts, and mucosa (Figure 3A). Necrosis, mucosal edema, destruction of crypts, and infiltration of inflammatory cells were observed in UC rats induced by 5% DSS, leading to a significant increase in histological score. Although rats supplemented with LBP and/or CAP had lesser histological damage, but the results demonstrated that such intervention did not achieve significant differences compared to the U group (Figure 3B). [4] The UC rats significantly elevated the proinflammatory cytokines tumor necrosis factor-α (TNF-α) levels in the colon (Figure 5A) and interleukin-6 (IL-6) levels in serum (Figure 5B) compared to the control rats (p < 0.05). A significant reduction in colonic TNF-α levels was found in rats treated with LBP or mixture. All treatment groups significantly decreased serum IL-6 levels (p < 0.05). Although colonic anti-inflammatory cytokine IL-10 levels were not significantly different between the colitis and the control rats, the CAP treated group significantly increased colonic IL-10 levels compared to the U group (p < 0.05) (Figure 5C).

Conclusions: Colitis rats induced by 5% DSS and supplemented with 100 mg LBP/kg bw for 4 weeks reduces serum lipid peroxidation substance MDA levels, colonic TNF-α, serum IL-6 levels, and the expression of pain signaling proteins TRPV1 and TRPA1 in the colon,

3 臺北醫學大學保健營養學系

4 臺北醫學全球衛生暨發展碩士學位學程

5 臺北醫學大學附設醫院營養研究中心

and enhance serum antioxidative CAT activity. Colitis rats supplemented with 12 mg CAP/kg bw for 4 weeks decrease serum IL-6 levels and protein expression of TRPV1 and TRPA1 in the colon, and increase serum SOD and CAT activities and colonic IL-10 levels. Combined LBP (50 mg/kg bw) and CAP (12 mg/kg bw) for 4 weeks attenuate colonic TNF-α, serum IL-6 levels, and colonic protein expression of TRPA1. These results demonstrate that LBP and/or CAP can be used as a therapeutic agent against colitis by antioxidation, anti-inflammation, and the modulation of pain signaling proteins.

CHARACTERISTICS AND LONG-TERM OUTCOME OF FIT INTERVAL CANCERS IN RELATION TO DIFFERENT SCREENING ROUNDS

Background: Colorectal cancers (CRC) diagnosed after negative fecal immunochemical tests (FIT) [FIT interval cancers (ICs)] largely affect the effectiveness of screening. The characteristics and the long-term outcome of FIT ICs diagnosed after different screening rounds remain elusive. Aims: The aim of this study was to assess the characteristics, and the long-term outcome of FIT ICs diagnosed after different screening rounds.

Methods: Screening detected CRCs and FIT ICs in the Taiwan Colorectal Cancer Screening Program during 2004 to 2014 comprised the study cohort and were followed up till 2019. The FIT ICs were stratified into two groups according to screening rounds [first round (fFIT IC) and second or afterward rounds (sFIT IC)]. Their characteristics and survival status were compared each other and with screening-detected CRCs.

Results: Totally 1,810,162 subjects participated in FIT screening at least once, with 7,118 CRCs being diagnosed at the first screening round and 3,167 at the subsequent rounds. Totally 1,945 FIT ICs developed during the study period, with 1,382 fFIT ICs and 563 sFIT ICs. fFIT ICs presented at a more advanced stage (53.3% were stage ≥2) compared with sFIT ICs (39.9%) and FIT ICs at subsequent rounds (45.3%) (P < 0.0001). fFIT ICs are more likely located at the distal colon or rectum (72.8%) compared with sFIT ICs (67.1%) (P = 0.007). fFIT ICs had worse survival than sFIT ICs. (Log-rank test, p ≤ 0.0001). In the multivariable analysis, fFIT ICs were associated with a higher risk of CRC death compared with screeningdetected CRCs (aHR = 1.79, 95% CI, 1.62-1.97) and sFIT ICs (aHR = 1.41, 95% CI, 1.19-1.66).

Conclusions: FIT ICs diagnosed after the subsequent screening rounds presented at more early stages and had more favorable survival. The screening program should elaborate on improving the detection of CRC in the first round.

腸道擬桿菌與梭桿菌相關代謝組學及免疫組 學引起結直腸癌變過程之生存分析 SURVIVAL ANALYSES OF COLORECTAL CARCINOGENESIS RESULTING FROM INTESTINAL BACTEROIDES AND FUSOBACTERIUM RELEVANT METABOLOMICS AND IMMUNOMICS

楊光祖1,2,3,4,5 康水成1 李明義6 顏家祺7 謝博軒2 許郡倫2

葉彥秀8 葉耀宗9 稅皓靄2 林雅雯2 戴嘉言10 余明隆11

吳登強10 蔡成枝12 洪志勳13 董乃昀3 鄭文隆3 胡翔崴3

許秉毅14 司徒惠康15 許惠恒15

1 高雄市立民生醫院肝膽腸胃內科；2 國防醫學院醫學 科學研究所；3 國際創新生醫技術研究院；4 美國西南

大學；5 國際學士院；6 高雄市立民生醫院內科部心臟

內科；7 高雄市立民生醫院骨科；8 台大醫學院微生物 學科暨研究所；9 輔英科技大學；10 高雄醫學大學附設

中和紀念醫院；11 中山大學；12 高雄長庚紀念醫院；13 義守大學；

Background: Intestinal microbiota play important roles in colorectal carcinoma (CRC) development. Short chain fatty acids (SCFAs), especially butyric acid/propionic acid/ acetic acid were also investigated in CRC signaling pathways. However, the interplay between CRC-related microbiome and SCFA in metabolomics viewpoints was less discussed and undetermined.

Aims: Using biomedical informatics to explore the interlink between CRC, SCFAs, and intestinal microbiota.

Methods: We used GMrepo website tool to analyze the microbiota abundance. HMDB for metabolomics evaluation and GEPIA2 was deployed for CRC overall survival analyses. GeneMania for relevant genomics were studied. TIMER website was applied for immunomics and cancer patient survival analyses.

Results: After data identification and search, we found that bacteroides and fusobacterium were both strongly associated with CRC carcinogenesis. Table 1 showed intestinal microbiota samples and relative abundance in CRC/normal populations. Fig. 1 showed prevalence (X-axis) and abundance (Y-axis) in CRC. Fig 2. revealed species or genera networkings. We mined HMDB the detailed relevant enzymes and transporters for SCFAs (Table 2). GEPIA2 revealed SCFAs-associated gene markers for CRC overall survival analyses (Fig. 3). As genomic networks and functions, the detailed content were involved in Fig 4. Fig. 5 revealed fusobacterium related

immunocytes and HDAC gene family relevant CRC 5-year survivals.

Conclusions: Through biomedical informatics, we discovered that the potentially relevant gene markers adjusting CRC survival. HDAC family, especially HDAC4, seemed to be the most important key role in CRC.

BOWEL SOUND RECORDER TO MONITOR THE SEVERITY OF INFLAMMATION BOWEL DISEASE

Background: Inflammatory bowel diseases, including Crohn’s disease (CD) and ulcerative colitis (UC), are chronic idiopathic disorders causing relapsing inflammation of the gastrointestinal tract. The gold standard diagnostic tool to evaluate the severity of IBD is colonoscopy. But colonoscopy is an invasive procedure with clinical risk and inconvenient.

Aims: The aim of this study was to assess the findings of transabdominal bowel ultrasound and the automatic bowel sound recorder in IBD patients and determine its usefulness for the evaluation of IBD disease activity.

Methods: We enrolled 40 IBD patients who had regular clinic follow and 20 healthy volunteers as controls from Sep 2020 to September 2022 at Chang Gung Memorial Hospital, Kaohsiung, Taiwan. We evaluated the level of inflammation and disease activity by inflammatory markers like C-reactive protein (CRP) and IBD activity score (CD patient by Crohn’s disease activity index [CDAI] and in UC patient by Mayo score). Transabdominal Doppler sonographic findings were assessed in different parts of colon (cecum, ascending, descending and sigmoid colon) following an eight-hour fasting. The thickness of colon wall in involved site was measured. Bowel sound recorded using an electric automatic machine which could assess six parameters as below: (1) Time Duration of event (2) Maximum peak of each even; (3) Central frequency of each event; (4) Sound-index; (5) Event frequency; (6) Sound cluster and try to find the possible correlation to IBD severity (CD severity) were.

Results: Sixteen CD patients, 22 UC patients and 21 healthy controls were recruited for further analysis in the present study. The median thickness of colon wall 6.1mm in inactive phase of CD (CDAI <150) and 7.4mm in active phase if CD (CDAI >150). The similar result was also seen in active UC patients (Mayo score > 2). The median thickness of colon wall 4.5mm in inactive UC and 5.4 mm in active phase of UC. About the bowel sound analysis, we found that the duration of each event was more longer in

inactive UC than active UC (p = 0.045). The maximum of peak of each events was increase in inactive CD than active CD (p = 0.063). The sound index of bowel sound were more prominent in both inactive CD and UC than patients of active phase (p = 0.0068 and 0.0011 in CD and UC, respectively.) Otherwise, the bowel events of frequency were decrease in active UC, compare to inactive phase (p = 0.026).

Conclusions: In conclusion, this study reveals that transabdominal ultrasound might be applied as an adjunctive tool for the evaluation of IBD disease activity. Besides, different parameters of bowel sound were analyzed in present report. Whether these certain features of bowel sounds characteristic could correlated to disease activity of IBD need further large cohort studies.

使用腸音監測器評估發炎性腸道疾病嚴重度

盧威廷 葛振瑜 邱紹銘 林俊宇 李育騏 蘇輝明 梁志明 周業彬 蔡成枝 戴維震 姚志謙 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

主題：下消化道疾病（一） ㊹

IMPROVING THE QUALITY OF COLONOSCOPY WITH AN INTELLIGENT VOICE ASSISTANT VOICE RECOGNITION SYSTEM (EVAS): ONE TAIWAN REGIONAL HOSPITAL STUDY

2

Background: According to literature, a colonoscopy and report without any special finding takes an average about 11 minutes for a skilled endoscopist. However, endoscopist often need more time if there are colon polyps or even performing polypectomy. If the reporting time decreased, the endoscopist would complete the examination more efficiently. The Endoscopic Voice Assistant System (EVAS), designed with artificial intelligence computer-aided systems, is a powerful tool that can speed up reporting while doing colonoscopy. Our goal was to assess whether this tool can really increase the efficiency of colonoscopy study.

Aims: Our aim is to demonstrate that an artificial intelligence Endoscopic Voice Assistant System (EVAS) can help endoscopist. With the help of EVAS, endoscopists are more efficient when performing colonoscopy. It would not only save time for completing reports, but also accurately grasp the time of entering and withdrawing the colonoscopy.

Methods: Between 1 August 2022 and 31 August 2022, 43 patients underwent colonoscopy were enrolled in the study. All patients’ colonoscopic study were performed by GF290 colonoscope (Olympus Corporation, Tokyo, Japan). While performing colonoscopy, the endoscopist use voice commands to record the findings and colorectal markers by EVAS help. After performing colonoscopy in these patients, we collected time of original way to input report and time of using EVAS to assist. We also recorded the differences in the time of reporting lesions and interventional procedures. Finally, we compared the time gap between use of EVAS or not.

Results: According to our records, the average time for an endoscopist to complete a colonoscopy report is two

minutes and three seconds in traditional way. With the help of EVAS and the voice recording file, the average time to complete a colonoscopy report is 41 seconds. In contrast, EVAS can save about mean 67% time. Overall, in these 43 cases, EVAS could save up to 12 minutes and 21 seconds! Conclusions: The endoscopic voice assistant system (EVAS) can indeed greatly reduce the time for the endoscopist to make a report. It can make colonoscopy more efficient.

3 臺北醫學大學消化醫學研究中心

治療中至重度克隆氏症患者在生物製劑時代 MANAGEMENT OF MODERATE-TOSEVERE CROHN’S DISEASE IN THE ERA OF BIOLOGICS

Endocuff

年輕的內視鏡醫師

ENDOCUFF VISION-ASSISTED COLONOSCOPY MAY IMPROVE

ADENOMA DETECTION RATE AND SHORTEN CECAL INTUBATION TIME ESPECIALLY IN YOUNG ENDOSCOPISTS

Background: Over the last decade, biologics have gained an important place for the treatment of moderate-tosevere Crohn’s disease (CD). Because of a limited budget, the National Health Insurance program of Taiwan only reimburses biologics for 54 weeks in CD patients after adequate conventional therapy or biologic withdrawal.

Aims: To assess the efficacy of conventional therapy to maintain the disease activity in the biologic drug holiday.

Methods: We performed a retrospective review of collected records of CD patients with biologic withdrawal in Mackay memorial hospital, Taiwan. Demographic data, use of concomitant drug, withdrawal duration, treatment regimens and outcome for stopping biologic treatment were recorded.

Results: In total, thirty-six CD patients had biologic withdrawal between Jan 2015 and Dec 2021 were enrolled. Among the clinical courses, 75 times of intermittent biologic therapy were recorded. The average [standard deviation] age (year) was 35.0 [15.0] and the median disease duration to biologic use was 4.1 years. The most common prescribed biologics were Adalimumab, followed by the Vedolizumab and Infliximab (72.2%, 19.4%, 8.3% respectively). The average period of biologic treatment was 13.7 ± 5.9 months and 70.7% patients had clinical remission. During the biologic-free interval, steroid and immunosuppressants were commonly used for acute exacerbation of CD (22.7% and 21.3%, respectively). 20% patients had hospitalization, 6.7% patients required surgical intervention, and 2.7% patients suffered from infection. After the biologic withdrawal of 6.9 ± 5.1 months, 88% patients received a new cycle of treatment. 8% (6/75) CD patients had switching of biologics after re-applying.

Conclusions: The use of biologic agents in CD is changing and intermittent treatment may provide a well tolerated option for certain patients. Additional large study is needed to evaluate the efficacy of re-initiation of biological therapy.

Background: Adenoma detection rate (ADR) is considered the single most important quality measure in colonoscopy. Endocuff Vision is a new generation of single-use, plastic device, mounted on the distal tip of the colonoscope and may potentially improve the visualization of the polyps located behind folds and flexures. However, the performance of Endocuff Vision-assisted colonoscopy in Asian endoscopists had never been evaluated.

Aims: To evaluate the performance and ADR of Endocuff Vision-assisted colonoscopy in Asian endoscopists.

Methods: Patients underwent sedative colonoscopy performed by 13 endoscopists (7 young and 6 seniors [>10 years experiences]) for either symptoms or screening or surveillance were consecutively enrolled between December 2019 and June 2020 and allocated to receive endocuff-assisted or standard colonoscopy in block randomization. Patients who took antiplatelet, anticoagulants; having history of colectomy or inflammatory bowel disease; poor colon preparation or scheduled for endoscopic treatment were excluded. Primary outcome of study was ADR; Secondary outcomes included polyp detection rate (PDR), advanced ADR, adenomas per colonoscopy (APC), sessile serrated lesion detection rate (SDR), cecal intubation time, withdrawal time and adverse events.

Results: A total of 1,212 patients were screened for eligibility and finally 1,016 patients (median age of 56 years, 47.3% male) were included for analysis. (Figure 1). Among them, a total of 553 patients (54.4%) received endocuff-assisted and 463 standard colonoscopies (Table 1). The ADR (39.2% vs. 32.2%; P = 0.02), PDR (55.5% vs. 47.1%; P = 0.007) and APC (0.8 ± 1.3 vs. 0.6 ± 1.1; P

林煒晟1 章振旺1 陳銘仁1 許自齊2 王鴻源1

1 台北馬偕紀念醫院肝膽腸胃科

2 台北馬偕紀念醫院大腸直腸外科

Vision 輔助大腸鏡檢查可以提高腺 瘤偵測率，且縮短盲腸到達時間，特別是在

= 0.029) were significantly higher in the endocuff group than those in the standard group (Table 2). Endocoff was associated with a shorter cecal intubation time (4.2 ± 3.8 vs. 4.9 ± 4.0 minutes; P = 0.004, Table 1). The differences in ADR (37.3% vs. 27.5%; P = 0.036) and cecal intubation time (5.0 ± 3.3 vs. 6.5 ± 4.6 minutes; P < 0.001) were larger, when performed by young endoscopists (Table 3). Minor mucosal laceration was found in 3 patients, and no serious adverse events reported.

Conclusions: New-generation Endocuff Vision-assisted colonoscopy may not only improve the ADR, PDR and APC, but also shorten the cecal intubation time, especially in young endoscopists. Endocuff Vision can be routinely used to improve the quality and performance of colonoscopy.

DIET

BEFORE

THE QUALITY OF BOWEL PREPARATION IN PATIENTS WITH SCHIZOPHRENIA

Background: Quality of bowel preparation plays an important role in colonoscopy. However, Patients with schizophrenia take antipsychotic medicines, which may reduce gastrointestinal motility, and influence the effect of bowel preparation of colonoscopy. Poor quality of bowel preparation can reduce the benefit of colonoscopy, and increase the risk of ignoring possible colorectal cancers.

Aims: To apply diet adjustment before colonoscopy to improve the quality of bowel preparation.

Methods: Patients with schizophrenia in our institute who needed colonoscopy examination were divided into a standard group and a diet-modified group since January 2022. The standard group started a low-residue diet two days before the colonoscopy examination and a clean liquid diet the day before the examination. The diet-modified group started a lowresidue diet four days before the colonoscopy examination and a clean liquid diet two days before the examination. Both of the groups took bowel cleansing medicines the day before the examination and on the morning of the examination. We used Aronchick bowel preparation scale to evaluate the quality of bowel preparation. In this retrospective cohort study, we reviewed the data of patients receiving colonoscopy in our hospital from January 2021 to September 30, 2022, including non-schizophrenia patients and patients with schizophrenia.

Results: During the period of study, 668 non-schizophrenia patients and 344 patients with schizophrenia received colonoscopy examinations. The quality of bowel preparation was poor in 36/343 (10.50%) non-schizophrenia patients and 72/209 (34.45%) patients with schizophrenia in 2021 (p < 0.001). From January 2022 to September 30, 2022, the quality of bowel preparation was poor in 25/325 (7.69%) nonschizophrenia patients and 32/135 (23.70%) patients with schizophrenia (p < 0.001). Comparing the standard group and the diet-modified group, the quality of bowel preparation was poor in 20/59 (33.90%) patients of the standard group and 12/76 (15.79%) patients of the diet-modified group (p = 0.014).

Conclusions: Diet adjustment before colonoscopy can be used to improve the quality of bowel preparation in patients with schizophrenia.

大腸鏡檢查前的飲食調整可以改善思覺失調 症患者腸道準備品質

ADJUSTMENT

COLONOSCOPY CAN IMPROVE

之風險因子：回溯式世代研究 RISK FACTORS ASSOCIATED WITH THE SEVERITY OF A DELAYED POLYPECTOMY BLEEDING: A RETROSPECTIVE COHORT STUDY

Background: Colonoscopy is the gold standard for the detection of colon polyps for cancer prevention. Colonoscopic polypectomy with the snare is an effective and safe procedure. However, polypectomy bleeding has about 0.4 – 1.2 % event rate. Polypectomy bleeding can be divided into immediate or delayed polypectomy bleeding. Immediate polypectomy bleeding occurs right after the polyp excision, which can be detected right away with endoscopic hemostasis treatment. In contrast, delayed polypectomy bleeding occurs hours or days after the polypectomy. Polyp size > 1 cm, antiplatelet or anticoagulant agents use, the occurrence of immediate polypectomy bleeding, and polyps at the right colon are known risk factors for delayed polypectomy bleeding. Patients who encountered delayed polypectomy bleeding usually presented to the hospital for hematochezia, symptoms of anemia, and even hemodynamic instability and end-organ damage. Therefore, identifying the population with a higher risk of more severe complications after bleeding is an important issue.

Aims: This study aimed to investigate the risk factors of a severe polypectomy bleeding complication. In such highrisk patients, prophylactic clipping may be beneficial.

Methods: From 2010/01/01 to 2022/07/30, the patients with delayed polypectomy bleeding were included in National Cheng-Kung University Hospital. We assessed the patients’ baseline characteristics, medication use, comorbidities, platelet counts, coagulation profiles, renal function, colon polyp size, type, and location. Their associations with severe blood loss (Hb loss over 2 g/dL) and the length of hospitalization were analyzed.

Results: From 2010/01/01 to 2022/07/30, 20681 patients accepted colon polypectomy, and 71 patients (0.34%) encountered delayed polypectomy bleeding. Among the 71 patients, 37 patients (52%) had severe blood loss, and 34 patients (48%) had minor blood loss. The median length of hospitalization was 4 days (IQR: 3 – 6 days). The mean polyp size of bleeding was 1.4 ± 0.6 cm. Patients with age

> 65 (relative risk: 3 (1.03 – 8.77), p-value: 0.036) and antiplatelet use (relative risk: 4.08 (1.01 – 16.67), p-value: 0.040) were related to severe delayed polypectomy bleeding. Polyp size, platelet count, ESRD, and cirrhosis were not related to severe delayed bleeding. However, patients with ESRD (relative risk: 7.71 (1.78 – 33.50), p-value: 0.010) and cirrhosis (relative risk: 9.33 (1.37 –68.83), p-value: 0.032) were related to long hospital stay > 7days. There was no bleeding-related mortality in the study. Conclusions: Patients with age > 65 or antiplatelet use have a higher risk of severe delayed polypectomy major bleeding. Although ESRD and cirrhosis were not related to major bleeding, they were related to more comorbidity and extended hospitalization.

探討影響延遲性大腸息肉切除後出血嚴重度

曾勗桓 姜學謙 林錫璋 陳柏潤 國立成功大學醫學院附設醫院胃腸肝膽科

Vedolizumab 對於老年潰瘍性結腸炎的治療 效果 TREATMENT EFFECT OF VEDOLIZUMAB IN ELDERLY-ONSET ULCERATIVE COLITIS PATIENTS

Conclusions: Vedolizumab is suitable for EOUC patients and can enable patients to achieve steroid-free remission during induction phase. However, the adverse effects such as opportunistic infections should be aware.

Background: Elderly-onset ulcerative colitis (EOUC) is defined as late onset of UC and accounts for 17.3% of total UC patients with rising incidence and prevalence rate. EOUC patients are at higher risks of opportunistic infections, hospitalizations, colorectal cancers, and mortality than non-elderly-onset patients. Challenges exist in the diagnosis and treatment of EOUC, complicated by atypical presentations, comorbidities, and polypharmacy. Vedolizumab was noted to have better treatment effect and less complications in EOUC patients, however there was no real-world data in Taiwan.

Aims: We aim to investigate the treatment effect and complications in EOUC patients under vedolizuamb.

Methods: We retrospectively collected EOUC patient from 2018-2022 under vedolizumab therapy. EOUC was defined as patients diagnosed with UC after 60 years old. We analyzed the clinical conditions, laboratory data, medications, and disease courses.

Results: We collected 3 EOUC patients who were under vedolizumab therapy. The average age of these cases were 69 years old, with 2 men and 1 woman. They all experienced symptoms of bloody stool 3-4 times a day. In addition, their extent of disease was at left colon and rectum rather than pan-colon. Initially, all of them received mesalazine therapy with concomitant steroid or azathioprine and then received Vedolizumab therapy after 6 months of prior oral medication control. After receiving vedolizumab for 6 weeks, all patients experienced improvements in symptoms and laboratory data (increased hemoglobin and albumin levels and decreased ESR level). Besides, two patients achieved steroid-free remission at week 6 of vedolizumab therapy, while one was still receiving budesonide due to occasional bloody stool. However, one patient encountered GNB bacteremia with urinary tract infection at week 9 of vedolizumab prescription. This episode was subsequently controlled.

許品文1 羅元鈞1,2 蔡宗佑1,3,4 1 中國醫藥大學醫學系

2 林口長庚紀念醫院教學部

3 中國醫藥大學附設醫院內科部

4 中國醫藥大學附設醫院消化系中心

主題：幽門螺旋桿菌

比較 10 天反轉式混合療法與 10 天三合療法 合併鉍劑對於胃幽門桿菌之除菌效益

10-DAY REVERSE HYBRID THERAPY

VERSUSs 10-DAY STANDARD TRIPLE THERAPY PLUS BISMUTH FOR HELICOBACTER PYLORI INFECTION

胡恭翊1 蔡峯偉1,4 許秉毅2 吳登強3 陳文誌1,4

1 高雄榮民總醫院胃腸肝膽科

2 臺南市立安南醫院消化內科

3 高雄醫學大學附設中和紀念醫院胃腸內科

Background: The 14-day reverse hybrid therapy and the 10 to 14-day bismuth quadruple therapy are both recommended as first-line regimens for Helicobacter pylori eradication in Taiwan. The 14-day reverse hybrid therapy was effective and shortening the duration to 12day regimen showed similar eradication rate (95.7%) with better drug compliance (96.8%). On the other hand, the eradication rate of 10-day bismuth quadruple therapy (PPI + bismuth + metronidazole + tetracycline, PBTM) could achieve 91.6%. With regard to the 2 kinds of bismuth quadruple therapy, standard triple therapy plus bismuth (PPI + bismuth + amoxicillin + clarithromycin, PBCA) showed similar eradication rate (95.3%) with fewer adverse effects and higher compliance than traditional PBTM under 14day regimen according to previous study. So far, the effect of 10-day reverse hybrid therapy and 10-day standard triple therapy plus bismuth was uncertain.

Aims: Because the effect of 10-day regimen therapy was uncertain, this study aimed to compare the eradication rate, adverse events, and drug compliance of 10-day reverse hybrid therapy and 10-day standard triple therapy plus bismuth.

Methods: The H. pylori -infected patients (≥ 20-yearold) were randomly assigned to receive either a 10-day reverse hybrid therapy (a 7-day quadruple regimen with pantoprazole 40 mg twice daily, amoxicillin 1 g twice daily, clarithromycin 500 mg twice daily, and metronidazole 500 mg twice daily, followed by a 3-day dual regimen with pantoprazole 40 mg twice daily, amoxicillin 1 g twice daily) or a 10-day triple therapy plus bismuth (pantoprazole 40 mg twice daily, amoxicillin 1 g twice daily, clarithromycin 500 mg twice daily, and tripotassium dicitrato bismuthate 600 mg twice daily for 10 days). Adverse events were evaluated on the 14th day after therapy initiated. The H. pylori status was examined by urea breath test after 6

weeks.

Results: A total of 250 H. pylori-infected participants were randomized to either reverse hybrid group (n = 125) or triple plus bismuth group (n = 125). The eradication rate of 10-day reverse hybrid therapy was 91.2% compared to 88.0% in triple plus bismuth group by intention-to-treat analysis (P = 0.407). Per-protocol analysis also showed similar results (90.8% vs 89.0%, P = 0.651). More adverse events were noted in 10-day reverse hybrid therapy but no significant difference was noted (25.6% vs 18.4%, P = 0.169). Both groups revealed high drug compliance (95.2% vs 94.4%, P = 0.776).

Conclusions: The 10-day reverse hybrid therapy and 10day triple therapy plus bismuth both showed acceptable eradication effect in southern Taiwan. No significant difference of adverse events was noted between the two groups.

4 國立陽明交通大學醫學院

標準三合療法與其他含 Clarithromycin 除 菌處方於第一線治療幽門螺旋桿菌感染時達 90% 除菌率的「Clarithromycin 抗藥率截 點」

BREAKPOINT OF CLARITHROMYCIN RESISTANCE OF STANDARD TRIPLE THERAPY AND OTHER CLARITHROMYCIN-CONTAINING REGIMENS FOR 90% ERADICATION RATE IN THE FIRST-LINE TREATMENT OF HELICOBACTER PYLORI INFECTION

石志安

1 安泰醫療社團法人安泰醫院胃腸肝膽科

In patients treated by 7-day triple standard therapy, the eradication rates of those harboring clarithromycinsusceptible strains and -resistant strains were 92.5% (223/241) and 42.9% (12/28), respectively. According to efficacy prediction model, the expected eradication rate is less than 90% when the frequency of clarithromycinresistant strains is higher than 5%. According to efficacy prediction model, the eradication rates of 14-day standard triple therapy, 14-day concomitant therapy, 14-day hybrid therapy and 7-day vonoprazan-based triple therapy were less than 90% if the frequency of clarithromycinresistant strains was higher than 4%, 90%, 58% and 23%, respectively.

Background: Current international consensuses on Helicobacter pylori ( H. pylori ) eradication therapy recommend that only regimens that reliably produce eradication rates of ≥90% should be used for empirical treatment. The real-world expectation survey of AsiaPacific patients for H. pylori eradication therapy (REAP-Hp survey) also showed 91% of accepted minimal eradication rate expected by H. pylori-infected patients.

Aims: To investigate the breakpoint of 90% eradication rate of standard triple therapy and other clarithromycincontaining regimens in the first-line treatment of H. pylori infection by efficacy prediction model.

Methods: A systemic review of randomized controlled trials reporting the efficacies of 7-day clarithromycinamoxicillin standard triple therapy, 14-day clarithromycinamoxicillin standard triple therapy, 14-day concomitant therapy, 14-day hybrid therapy, or 7-day vonoprazanclarithromycin-amoxicillin triple therapy for strains susceptible and resistant to clarithromycin in the first-line treatment of H. pylori infection in adults from 1 January 2011 to 1 January 2022 were systemically searched from PubMed. The eradication rate of clarithromycin-containing regimen in a region was predicted with clarithromycinresistance rate of p, eradication rates in strains susceptible (S) and resistant (R) to clarithromycin. The predicted eradication was “S x (1-p) + R x p”, and the breakpoint of 90% eradication rate was determined by normogram.

Results: Twelve literatures were eligible for the study.

Conclusions: In areas with low (<5%) clarithromycin resistance (e.g., Sweden, Philippine, Myanmar, and Bhutan), 7-day and 14-day standard triple therapies can be adopted for the first-line treatment of H. pylori infection with eradication rates of ≥90%. In areas with high (>5%) clarithromycin resistance (most other countries worldwide) or unknown clarithromycin resistance, 14-day hybrid, 14day concomitant and other effective therapies can be used to treat H. pylori infection with eradication rates of ≥90%.

5 台灣胃酸相關疾病暨微菌叢聯盟

「Tetracycline-Levofloxacin 四合療法」與

「標準鉍劑四合療法」在第二線幽門螺旋桿 菌除菌治療的療效與安全性之比較 一先 期報告

EFFICACY AND SAFETY OF TETRACYCLINE-LEVOFLOXACIN QUADRUPLE THERAPY AND STANDARD BISMUTH QUADRUPLE THERAPY IN THE SECOND-LINE TREATMENT OF HELICOBACTER PYLORI INFECTION ‒ A PRELIMINARY REPORT

rates were 92.5% (37/40; 95% confidence interval [CI]: 84.3 to 100.0%) for 14-TL quadruple therapy and 95.0% (38/40; 95% CI: 88.3 to 101.8%) for 14-day bismuth quadruple therapy. The two therapies had comparable eradication rate (P = 1.00). Per-protocol analysis yielded similar results (92.5% vs 97.4%). There were no differences in frequencies of adverse events (30.0% vs 27.5%) and drug adherence (92.5% vs 90.0%) between groups.

Conclusions: TL quadruple therapy and standard bismuth quadruple therapy have comparable efficacy and frequency of adverse events in the second-line treatment of H. pylori infection.

Background: Standard bismuth quadruple therapy and proton pump inhibitor (PPI)-amoxicillin-fluoroquinolone triple therapy are recommended second-line treatments for H. pylori infection by the Maastricht/Florence VI Consensus Report. A randomized controlled trial demonstrated that the tetracycline-levofloxacin (TL) quadruple therapy was superior to PPI-amoxicillinlevofloxacin triple therapy in the second-line treatment of H. pylori infection. However, whether TL quadruple therapy also can achieve a higher eradication rate than standard bismuth quadruple therapy remains unanswered.

Aims: To compare the efficacies of 14-day TL quadruple therapy and standard bismuth quadruple therapy in the second-line treatment of H. pylori infection.

Methods: Consecutive H. pylori -infected subjects after failure of first-line therapies were randomly allocated to receive either 14-day TL quadruple therapy (esomeprazole 40 mg b.i.d., tripotassium dicitrato bismuthate 300 mg q.i.d., tetracycline 500 mg q.i.d., and levofloxacin 500 mg q.d.), or 14-day bismuth quadruple therapy (esomeprazole 40 mg b.i.d., tripotassium dicitrato bismuthate 300 mg q.i.d., tetracycline 500 mg q.i.d., and metronidazole 250 mg q.i.d.). H. pylori status was assessed 6 weeks after the end of treatment.

Results: Eighty patients were randomly assigned in this study. The resistant rates of H. pylori strains for tetracycline, metronidazole and levofloxacin were 0%, 45% and 33%, respectively. The intention-to-treat eradication

病患對於一線幽門螺旋桿菌除菌之偏好配方 以及除菌率之期待 ─ 一個台灣多醫院的問

THE PREFERRED REGIMEN AND EXPECTATION FOR THE FIRST LINE HELICOBACTER PYLORI ERADICATION FROM PATIENTS ‒ A QUESTIONNAIREBASED STUDY FROM MULTIPLE HOSPITALS IN

屏東基督教醫院胃腸肝肝膽科；2 美和科技大學護理

3 臺北市立聯合醫院仁愛院區消化內科；4 高雄醫 學大學附設醫院胃腸內科；5 國立臺灣大學醫學院附設

醫院胃腸科；6 高雄長庚紀念醫院胃腸肝膽科；7 高雄

榮民總醫院胃腸肝膽科；8 新光吳火獅紀念醫院胃腸肝

膽科；9 花蓮慈濟醫院肝膽胃腸科；10 國泰綜合醫院腸

胃內科；11 台南市立安南醫院暨中國醫藥大學消化內

科；12 臺中榮民總醫院胃腸肝膽科；13 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 less than 80% in most other Asia-Pacific countries. Several novel first-line anti-H. pylori regimens including sequential therapy, concomitant quadruple therapy, hybrid therapy, high-dose dual therapy and bismuth-containing quadruple therapy have emerged to cure H. pylori infection recently. REAP-HP survey 2020 was the pioneer study investigating the expectation and preference of physicians in Taiwan for H. pylori eradication. However, there has been no relevant study involving patients. Therefore, this study emerged as questionnaire study focusing on the expectation of eradication rate and preferences of regimen in patients whom ever having been prescribed with anti-H. pylori regimens in multiple hospitals in Taiwan.

Aims: (1) To investigate the preferred regimens for the first-line anti- H. pylori therapy among patients in three hospitals (Ping Tung Christian Hospital, Kaohsiung Medical University Hospital and Tainan municipal An Nan hospital) with the information of eradication rate, side effect and medical cost provided to them. (2) To survey the minimal eradication rate for the first-line regimen accepted by patients in these hospitals, and (3) To investigate the factors with most concerned in patients receiving anti- H.

pylori regimens in clinical practice. Comparison was made between the two group of patients (group 1: 1-100 patients and group 2: 101 to 200 patients) to evaluate the consistency of the results.

Methods: A questionnaire for H. pylori eradication survey of patients was distributed to the patients who had ever received anti-H. pylori therapy before or being diagnosed of H. pylori infection was to be prescribed with relevant regimens in between January 2019 to December 2022. 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 200 patients from Ping Tung Christian Hospital, An Nan hospital and Kaohsiung Medical university hospital participated in the current survey. The top three most anticipated anti- H. pylori regimens in the group 1 were 14-day reverse hybrid therapy (87%; n = 87), 7-day standard triple therapy (10%; n = 10) and 14day Bismuth quadruple therapy (2%; n = 2) respectively. Similarly, the top three regimens in group 2 were 14 day reverse hybrid therapy (70%, n = 70), 7-day standard triple therapy (13%, n = 13) and 14-day hybrid therapy (9%, n = 9). The average minimal accepted eradication rate for first line regimen anticipated by patients in group 1 and group two were 83% versus 87% respectively. A total of 64% (n = 64) versus 70% (n = 70) of patients in group 1 and group 2 preferred eradication rate, side effect and medical costs in sequence as their top three most concerned factors when receiving anti-H. pylori therapy.

Conclusions: 14-day reverse hybrid therapy appeared to be the most popular regimen among patients. The expected minimal eradication for first line regimen should be at least 83% with eradication rate as their most concerned factor.

一線和三線幽門桿菌根除治療中分子檢測 引導治療與傳統藥敏試驗引導治療的比較 ─

兩項多中心、隨機對照、非劣效性試驗

MOLECULAR TESTING GUIDED

THERAPY VERSUS SUSCEPTIBILITY

TESTING GUIDED THERAPY IN FIRST-LINE AND THIRD-LINE

HELICOBACTER PYLORI ERADICATION

‒ TWO MULTICENTRE, OPEN-LABEL, RANDOMISED CONTROLLED, NONINFERIORITY TRIALS

陳美志1 陳柏岳2 方佑仁3 白明忠4 許耀峻5 吳明賢1

劉志銘6

1 國立臺灣大學醫學院附設醫院消化內科

2 嘉義基督教醫院內科部

3 國立臺灣大學醫學院附設醫院雲林分院內科部

4 台東馬偕紀念醫院內科部

5 義大醫院內科部

6 國立臺灣大學醫學院附設醫院癌醫中心分院內科部

Background: The point mutations of 23S rRNA and gyraseA correlate with clarithromycin and levofloxacin resistance, respectively. However, whether the efficacy of molecular testing guided therapy (MTGT) is non-inferior to that of susceptibilitytesting guided therapy (STGT) in H. pylori eradication remains uncertain.

Aims: We aimed to assess whether the eradication efficacy of MTGT was not inferior to traditional culture-based STGT in the first-line and third-line treatments of H. pylori infection.

Methods: We conducted two multi-center, open-label, randomized controlled trials in Taiwan. Treatment-naïve H. pylori -positive patients were included in Trial 1 and patients with refractory H. pylori infection were included in Trial 2. Eligible patients were allocated in a 1:1 ratio (permuted block sizes of four) to receive either MTGT or STGT. Clarithromycin and levofloxacin resistance were determined by agar dilution test for measuring of minimum inhibition concentrations in the STGT group, and by polymerase chain reaction and direct sequencing for detection of 23S rRNA and gyrase A mutations in the MTGT group. Study participants received clarithromycin sequential or levofloxacin sequential or bismuth quadruple therapy according to the resistance to clarithromycin and levofloxacin. The 13C-urea breath test was used to determine the status of H. pylori at least 6 weeks later after eradication therapy. Eradication rates were analyzed

according to intent-to-treat (ITT) and per protocol (PP) analyses. The frequency of adverse effects was analyzed in cases with available data. The pre-specified margins for non-inferiority analyses were 5% and 10% for Trial 1 and Trial 2, respectively.

Results: A total of 560 treatment-naïve patients were recruited in Trial 1, and another 320 patients with refractory H. pylori infection were recruited in Trial 2. In first-line therapy (Trial 1), the eradication rates in the MTGT group and the STGT group were 86·1% (95% CI: 82.0%-90.1%) versus 86·8% (95% CI: 82.8%-90.8%) in the ITT analysis (p-value=0.805), and were90.6% (95% CI: 87.1%-94.1%) versus 91.6% (95% CI: 88.2%-95.0%) in the PP analysis (p-value = 0.676), respectively. In third-line therapy (Trial 2), the eradication rates in the MTGT group and the STGT group were 88.1% (95% CI: 83.1%-93.1%) versus 86.9% (95% CI: 81.6%-92.1%) in the ITT analysis (p-value = 0.735), and were 90.3% (95% CI: 85.7%-95.0%) versus 89.1% (95% CI: 84.2%-94.0%) in the PP analysis (p-value = 0.723), respectively. The difference of eradication rate between the MTGT and STGT groups was -0.7% (95% CI: -6.4%-5.0%) in Trial 1 and was 1.3% (-6.0%-8.5%) in Trial 2 by ITT analysis; and was -1.0% (95% CI: -5.9%-3.8%) in Trial 1 and was 1.2% (-5.5%-8.0%) in Trial 2 by PP analysis. Meta-analysis of the two trials showed the pooled risk difference between the MTGT group and STGT group was -0.03% (95% CI: -4.4%-4.5%) in the ITT analysis and was -0.3% (95% CI: -4.2%-3.7%) in the PP analysis, respectively. Evidence showed no significant difference of side effects in both treatment groups in both Trial 1 and Trial 2.

Conclusions: Molecular testing guided therapy was not inferior to susceptibility testing guided therapy in firstline and third-line treatment of H. pylori infection, lending support to the use of molecular testing guided therapy for H. pylori eradication.

主題：膽胰疾病 55

特殊設計的組織細胞刷能增加不明原因膽道 阻塞的診斷率 THE UTILITY OF A NEWLY DESIGNED CYTOLOGY BRUSH WHICH COULD IMPROVE THE DIAGNOSTIC YIELD OF INDETERMINATE BILIARY STRICTURE

22G 穿刺切片與 經皮超音波引導下細針 22G 細胞穿刺在胰

ENDOSCOPIC ULTRASOUND-GUIDED FINE NEEDLE BIOPSY VERSUS PERCUTANEOUS ULTRASOUNDGUIDED FINE NEEDLE ASPIRATION IN DIAGNOSIS

OF SOILD PANCREATIC TUMOR

Background: Background: Indeterminate biliary stricture remains an important clinic problem regardless of emerging newly diagnostic modalities for the past ten years. Brushing cytology is a useful and easily available tool in the endoscopic retrograde cholangiopancreatography (ERCP) procedure when patients receiving concomitant biliary decompression.

Aims: AIM: To determine the utility of a newly designed brush which could improve the diagnostic yield of indeterminate biliary stricture.

Methods: METHODS: Retrospective chart review was performed in all ERCP procedures with indeterminate biliary stricture brushing between January 2014 and December 2022. A standard wire-guided cytology brush was used prior to protocol implementation in July 2019, after which, a new 7.5 French wire-guided cytology brush (Infinity® ERCP sampling Device, Steris Endoscopy Co., Mentor, OH) was used for all cases. All specimens were reviewed by two experienced cytopathologists who determined whether the sample was positive or negative for malignancy.

Results: RESULTS: Fourteen new brush cases were compared to 18 historical controls. Nine of 14 (64.3%) cases in the new brush group showed abnormal cellular findings consistent with malignancy as compared to 4 of 18 (22.2%) in the historical control group (P < 0.05). There are two true negative cases who proved to be benign strictures with the clinical course. There are three false negative patients who are two CBD and one pancreatic cancer cases after tissue proof by surgical intervention and endoscopic ultrasound guided fine needle aspiration, respectively. The overall accuracy value is 78.6%. The rate of whitish core tissue obtained is higher in the new design brush group in comparison with the historical controls.

Conclusions: CONCLUSION: The use of a new brush design for brush cytology of biliary strictures shows increased diagnostic accuracy, likely due to improved cellular yield, as evidenced by an increase in number of white tissue core obtained.

Background: Pancreatic cancer is a well-known cause of morbidity and mortality world-wide. Pancreatic cancer has one of the lowest at 5-year survival rates of all cancers. Therefore, early and precise diagnosis is very important for improving the results of surgery. The available literature comparing fine needle aspiration (FNA) and fine need biopsy (FNB) needles has not provided definitive results. A recent meta-analysis found no significant difference between one biopsy needle and standard FNA needles with regard to sample adequacy, diagnostic accuracy, or acquisition of a core specimen; however, the FNB needle established a diagnosis with fewer passes.

Aims: Our purpose of this study is to compare between the diagnostic accuracy of endoscopic ultrasound-guided (EUS)-FNB and percutaneous ultrasound-guided (US)-FNA in diagnosis of pancreatic solid tumor.

Methods: 358 cases of US-FNA or EUS-FNB for solid pancreatic mass between January 2011 and September 2022 in a single-centre university hospital were retrospectively reviewed, and we excluded non-pancreas lesions, cystic formation, and undetermined final diagnosis (n = 49).

US-FNA: Chiba needles, 22G were done under complete sonographic guidance with a biopsy attachment. EUSFNB: EUS was perfomed by Olympus EU-ME2 Premier. 19 G Echotip needles (Boston Scientific Acquire™ EUSFNB 22G Flexible Needle design) were administerred. A final diagnosis was based on definitive cytopathology, and surgical pathology. Specimens that contained inadequate material were not excluded from the primary analysis and were considered false negatives.

Results: A total of 309 patients (US-FNA, n = 162; EUSFNB, n = 147) with solid pancreatic mass detected by cross-sectional imaging of cumputed tomography. Age,

sex, mass location, were not significantly different between the two groups. There are similar percentage of benign and neoplasm beween FNA and FNB (14.2%/85.8% vs. 8.8%/91.2%, P = 0.143). The sensitivity was higher in EUS-FNB (91.97%, [95% CI: 86.1%-95.9%]) than in US-FNA (79.47%, [95% CI: 72.1%-85.6%]), P = 0.019. However, the US-FNA had higher specificity and accuracy than EUS FNB (100%, [95% CI:71.5%-100%] vs. 90%, [95% CI: 55.5%-99.8%], P < 0.001). As for solid neoplasm tumor ≥ 3 cm, the sensitivity of FNA was not inferior to FNB (86.1% vs. 93.4%, P = 0.095). The adverse event rate was not significantly different between two groups.

Conclusions: For solid pancreas tumor, the sensitivity was higher in EUS-FNB than in US-FNA in daignosis. For solid neoplasm tumor ≥ 3cm, the sensitivity of US-FNA was not inferior to EUS-FNB.

57

胰臟癌合併胃腸出口阻塞患者之臨床預後及 延長整體存活率

ENDOSCOPIC ENTERAL STENTING CAN IMPROVE THE CLINICAL OUTCOMES AND OVERALL SURVIVAL COMPARED WITH SURGICAL GASTROJEJUNOSTOMY IN ADVANCED PANCREATIC CANCER WITH SYMPTOMATIC GASTRIC OUTLET OBSTRUCTION: A RETROSPECTIVE COHORT STUDY

黃千睿1 王堯生1 莊喬雄1 陳炯瑜1

Background: About 10-25% pancreatic cancer patients have experience of gastric outlet obstruction (GOO). It is a major problem which caused patients suffered from symptoms such as weight loss, pain and jaundice. Surgical gastrojejunostomy (GJJ) has been the traditional treatment for patients with malignant GOO, but endoscopic duodenal stent placement (EDSP) was an alternative choice and had been performed increasing. Most of the previous studies compared GJJ with EDSP in all malignant tumors, but only few studies compared these two treatments focusing in pancreatic cancers, and the results showed no differences between surgical GJJ and EDSP groups.

Aims: In this domestic study, we compared the efficacy of surgical GJJ and EDSP in treating pancreatic cancer patients with GOO and the effects of clinical outcomes.

Methods: We retrospectively collected the patients with pancreatic cancers with symptomatic gastric outlet obstruction who has initial Gastric Outlet Obstruction Scoring System (GOOSS) 0-1 in a tertiary center in Southern Taiwan from July/2013 to Aug/2022. The patients all received surgical GJJ or EDSP to treat GOO. The primary outcomes was the overall survival after the intervention, and the secondary outcome median time to chemotherapy after the intervention. Other clinical outcomes were also analyzed.

Results: Total 73 patients were enrolled in this study and patients were divided to 2 groups (surgical GJJ and EDSP) based on the treatment choice for GOO. There were 52 patients in the EDSP group and 21 patients in the surgical GJJ group. The technical successful rate was 100% in both groups. The patients received EDSP had better nutrition

內視鏡腸道支架相較於胃腸繞道手術可改善

status (30- days albumin change after intervention surgical GJJ vs EDSP = -0.1 vs 0.8 g/dL, P = 0.032) compared to surgical GJJ group. Patients who could receive chemotherapy were also higher in EDSP group compared with surgical GJJ group (88.2% vs 57.1%, P = 0.009). Median time to chemotherapy after intervention was also shorter in EDSP group compared with surgical GJJ group (7 days vs 23 days, P = 0.003). The median overall survival was longer in the EDSP group (170 days, 95% CI = 106.67223.33) compared with surgical GJJ group (114 days, 95% CI = 44.7-183.3) (P = 0.006).

Conclusions: This is the first domestic study to compare these two ways in treating pancreatic cancers patients with symptomatic GOO. Endoscopic duodenal stent placement (EDSP) could prolong the overall survival after intervention comparing with surgical gastrojejunostomy. EDSP could also lead to higher rates of chemotherapy after intervention and shorter median time to chemotherapy.

LESIONS (PCLS)

曾敬棠1 廖思嘉1 葉宏仁1,2,3 廖苡君1 張惠郡1 楊勝舜1,2

Background: In current guidelines, EUS may provide superior image quality. In addition, EUS-FNA with cystic fluid analysis could examine mucin, biochemistry, tumor markers and cytology, which may provide guidance on cystic classification and provide a precise diagnosis of malignancy in some PCLs.

Aims: This study aims to investigate the diagnostic performance of EUS-FNA in pancreatic cystic lesions.

Methods: This retrospective study was conducted between September 2019 and December 2022. The patients with PCLs on CT or MRI scan undergoing EUSFNA procedures were enrolled. We collected baseline demographics, initial diagnosis based on CT/MRI image and the cystic characteristics under EUS and the results of cystic fluid analysis obtained from EUS-FNA.

Results: A total of 32 patients (mean age: 59.5 years; 18 females, 14 males) were analyzed with 81.3% of successful EUS-FNA procedures (6 failure, 26 success). The mean age of the two groups was 57.3 ± 11.1 and 60.0 ± 14.0 years, respectively. The failure group was male predominant (83 vs. 35%, p = 0.064). The serum CEA was higher in the failure group, but not statistically significant (median: 8.0 vs. 2.5 ng/ml, p = 0.194). The size of PCLs (2.7 vs. 3.1 cm, p = 0.769), diameter of main pancreatic duct (MPD) (2.5 vs.2.9 mm, p = 0.935), mural nodule, enhancing mural nodule, and history of pancreatitis showed no difference between the failure and success groups. Positive mucin string sign test was significantly higher in the failure group (83% vs 15%, p = 0.003). We also analyzed the difference between the cystic CEA > 192 ng/ml and ≤ 192 ng/ml groups for analysis of malignant potential in PCLs. Aged (65.2 ± 10.9 vs. 56.9 ± 15.5 years, p = 0.037), mucinous neoplasm based on EUS-FNA diagnosis (50 vs. 27%, p = 0.004), higher cystic CA 19-9 (median: 976 vs. 121.4 Unit/ ml, p = 0.023), and larger diameter of main pancreatic duct

內視鏡超音波併細針抽吸術在胰臟囊腫診斷 上之應用 THE DIAGNOSTIC ABILITY OF ENDOSCOPIC ULTRASOUND-GUIDED FINE-NEEDLE ASPIRATION (EUS-FNA) IN PANCREATIC CYSTIC

(median: 4.4 vs. 2.2mm, p < 0.001) showed a significant difference between these two groups. There was no significant difference in sex (male 60 vs.20%, p = 0.087), serum CA 19-9 (p = 0.005), size of PCLs (4.0 vs. 3.0 cm, p = 0.267), mural nodule, enhancing mural nodule, and history of pancreatitis in these two groups. The diagnostic consistency before and after EUS-FNA was only 68.8%. Conclusions: Mucin string sign test is the only factor that influences the success rate of EUS-FNA on PCLs. In our analysis, aged, mucinous neoplasm based on EUS-FNA diagnosis, high cystic CA 19-9 and larger main pancreatic duct are associated with higher risk of cystic CEA > 192 ng/ml which is considered as malignant potential in PCLs. How to check the malignant potential in PCLs is an emerging issue. We need more data to confirm our study.

WITH BILIARY PLASTIC STENT

Background: Biliary stent placement to prevent obstruction during endoscopic retrograde cholangiopancreatography (ERCP) is one of the most remarkable achievements in therapeutic endoscopy. Biliary stent opted an internal drainage instead of more invasive external drainage of surgery. However, stent occlusion is a major issue for the patients who require long-term plastic stent placement. Stent occlusion can lead to sepsis, which can be lifethreatening to the patient. So, scheduled ERCP for stent exchange is necessary. However, there are plenty of patients who did not come back to hospital for scheduled stent exchange. The reasons include forgetfulness, not knowing the stent needs to be exchanged, or others. There was no such mechanism that can remind physician and patient to receive scheduled stent exchange.

Aims: We invented a computer system called “Stent tracking and Reminder System”. The system can remind physician automatically that the certain patient who does not come back to hospital for stent exchange. Physician then can remind the patient to receive the procedure.

Methods: The stent tracking and reminder system was established in 2020. If the patient did not receive ERCP for stent exchange in 4 months, the system will remind the physician automatically. After the physician informed the patient, who needs to record the results that patient replies. A retrospective analysis was performed between 2018 and 2022 at our hospital. We reviewed the clinical condition of these patients.

Results: 288 and 254 patients received 2nd ERCP 4 months after the first ERCP before and after the establishment of the system, respectively. Before establishment of the system, 32 patients admitted due to cholangitis and received ERCP. After establishment of the system, 6 patients suffered from cholangitis which needed admission for antibiotics treatment and ERCP. Besides, there were 30 patients who received 2nd ERCP after the physician remind them according to the system.

Conclusions: Delayed stent exchange can be lifethreatening to the patient and increased potential cost of hospitalization. The stent tracking and reminder system

嶄新膽道塑膠支架更換提醒及追蹤系統 BRAND NEW TRACKING AND REMINDER SYSTEM FOR PATIENT

鄭幸弘 黃文信 楊其穎 莊世杰 謝宗霖 彭成元

中國醫藥大學附設醫院消化醫學中心

indeed provided an accurate and effective method to help the physician to solve the problem. In our experience, the system improves patient safety, minimize delayed procedure, and reduces potential cost of hospitalization. However, more statistical data is required to study the further impact of the system

主題：

C 型肝炎（二）

以 von Willebrand Factor/Platelet Ratio

THE

Background: The “left-over”, concurrent burden of liver fibrogenesis and portal hypertension cannot be completely abolished even after a sustained virological response (SVR). In the post-SVR status, which a post-SVR diagnosis of advanced chronic liver disease as well as the post-SVR correlation between concurrent clinically significant portal hypertension, portal hypertension-related events (PHREs), liver stiffness (LS) and spleen stiffness (SS) values remain unclear in cohorts worldwide, our previous study revealed that SS values at SVR can serve as an applicable pointof-care alternative biomarker to indicate concurrent portal hypertension to implement SS-combined PHRE predictions. Recently, the plasma von Willebrand factor (vWF) level/ platelet count ratio was introduced as a promising index biomarker of concurrent portal hypertension in hepatic venous pressure gradient-based studies.

Aims: This study aims to elucidate whether vWF/platelet ratio can serve as a promising, applicable surrogate biomarker to reflect SS values and changes in direct acting antiviral (DAA)-treated patients with chronic hepatitis C (CHC).

Methods: DAA-treated patients achieving an SVR from 2012 to 2022 were retrospectively screened. Previous studies revealed compatible levels of vWF antigen (Ag) levels acquired in citrated plasma compared with serum. Cryopreserved samples from a cohort of eligible patients with paired SS data at both baseline (TW0) and Week 24 after the end of treatment (PW24) were therefore used to quantitate vWF Ag levels through an ELISA.

Results: Of the 212 eligible patients with available SS data at both TW0 and PW24, the median age was 60 (interquartile range = 52–66) years. Seventy-four (34.9%) patients were male. Multiple linear regression

analysis using a stepwise model identified Δaspartate aminotransferase (coefficient = -0.265; 95% confidence [CI] = -0.525 – -0.005; P = 0.046), Δplatelet count (coefficient = -0.097; 95% CI = -0.160 – -0.033; P = 0.003), and ΔvWF/platelet ratio (coefficient = 0.322; 95% CI = 0.207 – 0.437; P< 0.001) to predict ΔSS values (percent changes from TW0 to PW24) (n = 212). The receiver operating characteristic analysis to diagnose “ΔSS > 0” by the single biomarker- ΔvWF/platelet ratio revealed an area under the curve of 0.825 (95% CI = 0.031; P <0.001). The linear regression model to predict “ΔSS > 0” by the ΔvWF/platelet ratio can be formulated as: ΔSS = 0.162 + 0.304 x ΔvWF/platelet ratio. Multiple linear regression analysis using a stepwise model identified Δaspartate aminotransferase (coefficient = -0.265; 95% CI = -0.525 – -0.005; P = 0.046), Δplatelet count (coefficient = -0.097; 95% CI = -0.160 – -0.033; P = 0.003), and ΔvWF/platelet ratio (coefficient = 0.322; 95% CI = 0.207 – 0.437; P < 0.001) to predict ΔSS values (percent changes from TW0 to PW24) (n = 212). In contrast, only Δα-fetoprotein (P < 0.001) and ΔSS (P = 0.046) were identified to correlate with ΔLS. Likewise, only Δaspartate aminotransferase (P <0.001), Δbilirubin (P = 0.005), and Δα-fetoprotein (P = 0.011) were identified to correlate with Δ alanine aminotransferase levels from TW0 to PW24. The vWF/ platelet ratio did not significantly correlate with LS and ALT changes. Moreover, multiple linear regression analysis using a stepwise model identified age (years) (coefficient = 0.014; 95% CI = 0.007 – 0.022; P = 0.016), LS values (m/ s) (PW24) (coefficient = 0.554; 95% CI = 0.400 – 0.708; P < 0.001), vWF level (ng/mL) (PW24) (coefficient = 0.001; 95% CI = 0 – 0.001; P < 0.001), vWF/platelet ratio (PW24) (coefficient = 0.002; 95% CI = 0.001 – 0.003; P < 0.001) to correlate with absolute SS values (m/s) at PW24 (n = 212). Conclusions: The current results imply that the vWF/ platelet ratio should be a biomarker to indicate the outcomes of portal pressure gradient rather than hepatic necroinflammation. The vWF/platelet ratio potentially can serve as a promising, applicable surrogate or alternative biomarker to reflect SS values and changes in DAA-treated CHC patients. Future studies should investigate whether combined utility of vWF/platelet ratio can enhance the prognostication in addition to utility of LS, platelet count, and SS values post-SVR.

61

ELF）、FIB-4、改

良 FIB-4、APRI 和 MAC-2 結合蛋白糖基化 異構體（M2BPGI）在預測治療後慢性

C 型

肝炎患者肝纖維化分期之效能 PERFORMANCE OF THE ENHANCED LIVER FIBROSIS (ELF) TEST, FIB-4, MODIFIED FIB-4, APRI, AND MAC-2 BINDING PROTEIN GLYCOSYLATION ISOMER (M2BPGI) IN PREDICTING LIVER FIBROSIS STAGE IN PATIENTS WITH CHRONIC HEPATITIS C AFTER ANTIVIRAL THERAPY

王鴻偉 賴學洲 許偉帆 陳昇弘 彭成元

中國醫藥大學附設醫院消化醫學中心

Background: Accurate noninvasive biomarkers of fibrosis status are important for hepatitis C virus (HCV) management.

Aims: The purpose of this study was to determine the ability of the fibrosis index based on the enhanced liver fibrosis (ELF) index, and other noninvasive biomarkers, including the Fibrosis-4 (FIB-4) index, modified FIB-4 index (mFIB-4), aspartate aminotransferase-to-platelet ratio (APRI) and mac-2 binding protein glycosylation isomer (M2BPGi) to predict the stage of liver fibrosis in patients with chronic hepatitis C after HCV eradication.

Methods: The ELF index was determined in 197 HCVinfected patients using commercial ELISA assays for the component elements of the index. Area under the receiver operating characteristic curve (AUROC) was used to evaluate the predictive performance of ELF at different stages of liver fibrosis as determined by liver histology (METAVIR stage), as well as to compare the efficacy of other noninvasive biomarkers of liver fibrosis by DeLong test. The optimal cutoff value of ELF to predict fibrosis status was determined by accuracy score.

Results: The numbers of patients with F1, F2, F3 and F4 were 80, 56, 27 and 34, respectively. The ELF index increased with histological stage of liver fibrosis and exhibited a linear relationship with METAVIR score in all subjects (r = 0.404, p < 0.001). The AUROCs for predicting significant fibrosis (F234), advanced fibrosis (F34), and cirrhosis (F4) in 197 participants were 0.641, 0.722, 0.762 for ELF; 0.729, 0.803, 0.814 for FIB-4; 0.639, 0.727, 0.790 for mFIB-4; 0.760, 0.777, 0.733 for APRI; and 0.668, 0.718, 0.745 for M2BPGi, respectively. The AUROCs of FIB-4 for predicting advanced fibrosis (F34), and cirrhosis

增強型肝纖維化檢測（

(F4) were numerically higher than those of ELF, whereas for predicting significant fibrosis (F234) the AUROC of FIB-4 was significantly higher than that of ELF. All differences in AUROCs between ELF and the other indices for predicting F34 and F4 were not statistically significant. In the post-treatment HCV cohort, an ELF cutoff of 9.14 predicted significant fibrosis (F234) with 72.6% sensitivity, whereas an ELF cutoff of 10.49 had 96.3% specific for predicting advanced fibrosis (F34) and a cutoff of 10.83 was 98% specific for predicting cirrhosis.

Conclusions: FIB-4 was superior to ELF and mFIB-4 in predicting significant fibrosis, whereas the performance of ELF was similar to FIB-4, mFIB-4, APRI and M2BPGi in predicting advanced fibrosis and cirrhosis in patients with chronic hepatitis C after HCV eradication.

62

Background: Direct-acting antiviral agents (DAAs) are effective to reduce incidence of hepatocellular carcinoma (HCC) and mortality among hepatitis C virus (HCV) patients. The beneficial impact of DAAs on outcomes in patients with intermediate to advanced HCC remains uncertain.

Aims: This study aimed to assess the survival of patients with Barcelona Clinic Liver Cancer (BCLC) stage B/C HCC following DAAs treatment.

Methods: From April 2015 to May 2022, consecutive 103 HCV-related HCC patients with BCLC stage B or C who had received DAAs therapy were retrospectively reviewed from Taipei Veterans General Hospital. Time to progression (TTP) and overall survival (OS) were assessed and factors associated with TTP and OS were analyzed.

Results: Of the 103 BCLC B/C HCC patients received DAAs, 86 patients were BCLC B and 17 patients were BCLC C. The mean age was 71 years old, and 66% had underlying cirrhosis. Most patients were within Child–Pugh class A (87.4%) and Albumin-bilirubin (ALBI) grade 1/2 (95.1%). Forty-two (40.8%) patients with active HCC during DAAs therapy. Of them, 76 (73.8%) patients received genotype-specific DAAs, and 27 (26.2%) patients received pan-genotypic DAAs. The sustained virological response (SVR) rate was 95.3% (82/86) in BCLC B, and 70.6% (12/17) in BCLC C, respectively. Seral AFP level > 200 ng/ml (HR, 2.474; p = 0.010) was the independent predictor of TTP. Presence of cirrhosis, ChildPugh B/C, seral AFP > 200 ng/ml, and fail to achieve SVR were independent risk factors associated with OS. A novel scoring system to predict OS into 3 groups was created based on the multivariate analysis. For the 86 BCLC B HCV-HCC patients, ALBI grade 2/3 (HR, 2.435; p = 0.026) was the only factor associated with unTACEable-progression (TTUP) in multivariate analysis.

Conclusions: DAAs could achieve a high SVR rate in BCLC B HCC patients even with active HCC. The novel model can be applied to predict survivals after DAAs therapy.

直接抗病毒藥物治療對於 C 型肝炎病毒感 染的中晚期肝細胞癌患者其腫瘤進展和存活

COVID-19 流行期間台灣山地地區 C 型肝炎 篩檢和治療的合作轉診模式

64

以 Sofosbuvir/Velpatasvir/Voxilaprevir 治療 NS5A 直接抗病毒藥物治療失敗之慢性 C 型 肝炎病患：台灣真實世界多中心世代研究 SOFOSBUVIR/VELPATASVIR/ VOXILAPREVIR FOR PATIENTS WITH CHRONIC HEPATITIS C VIRUS INFECTION PREVIOUSLY TREATED WITH NS5A DIRECT-ACTING ANTIVIRALS: A REAL-WORLD MULTICENTER COHORT IN TAIWAN

劉振驊1,2,3 彭成元4,5 劉俊人1,2,6 陳啟益7 羅清池8

曾國枝9,10 蘇培元11 高偉育12,13,14,15 蔡明璋16,17 董宏達18

Background: Mass screening and outreach clinics are commonly used for HCV treatment in rural areas in Taiwan. However, these methods need support from medical centers and usually decrease or even stop during COVID pandemic.

Aims: We aimed to develop a collaborative referral model between a primary care clinic (Liouguei district public health center, LDPHC) and a tertiary referral center (E-Da hospital) to increase HCV screening and treatment uptake in a mountainous region (Liouguei district) of southern Taiwan during the COVID-19 pandemic.

Methods: Once-in-a-lifetime hepatitis B and C screening service provided by Taiwan National Health Insurance was used for HCV screening. Provision of HCV screening as part of integrated services was performed in LDPHC. HCV-infected patients received a scheduled referral and took the shuttle bus provided by Kaohsiung City Municipal Government to E-Da hospital. HCV RNA testing and abdominal ultrasonography were performed on first visit, and DAAs were prescribed to HCV-viremic patients at the second visit.

Results: From October 2020 to September 2022, 1879 out of 3835 residents (49.0%) eligible for HCV screening received anti-HCV testing in LDPHC. Eighty-two residents were HCV-infected, with an anti-HCV seroprevalence of 4.4%. Seventy-nine HCV-infected patients needed referral, including 66 patients and 13 patients receiving anti-HCV testing from LDPHC and other clinics, respectively. Seventy patients (88.6%) were successfully referred. HCC was found in 4 patients, and all were HCV-viremic patients. Thirty-five out of the 38 HCV-viremic patients (92.1%) received DAA therapy. Thirty-two patients (91.4%) achieved SVR12 and all 3 patients who did not achieve SVR 12 were non-virologic failure.

Conclusions: The collaborative referral model described herein has demonstrated a good model of HCV screening, linkage to care and treatment in a remote mountainous region, even during COVID-19 pandemic. In addition, sustained referral is possible based on this routine referral model.

鄭浩材19,20 李輔仁21 黃嘉生22 黃克章23 施宇隆24

楊勝舜25,26,27 吳若玄28 賴學洲4,5 方佑仁3 陳柏岳7

黃國智8 曾志偉9,10 蘇維文11 張君照12,13,14 李佩倫18

陳志州18 張吉仰21 謝財源24 張崇信25 黃儀倢25

高嘉宏1,2,6,29

1 國立臺灣大學醫學院附設醫院內科部；2 國立臺灣大 學醫學院附設醫院肝炎研究中心；3 國立臺灣大學醫學 院附設醫院雲林分院內科部；4 中國醫藥大學消化醫學 中心；5 中國醫藥大學醫學院；6 國立臺灣大學臨床醫 學研究所；7 嘉義基督教醫院胃腸肝膽科；8 嘉義聖馬 爾定醫院內科部；9 大林慈濟醫院內科部；10 花蓮慈濟 大學醫學系；11 彰化基督教醫院胃腸肝膽科；12 臺北醫 學大學附設醫院胃腸肝膽科；13 臺北醫學大學醫學院； 14 臺北醫學大學消化醫學中心；15 臺北醫學大學癌症中 心；16 中山醫學大學附設醫院胃腸肝膽科；17 中山醫學 大學醫學院；18 柳營奇美醫院胃腸肝膽科；19 新北市立 土城醫院胃腸肝膽科；20 長庚大學暨長庚醫院胃腸肝膽 科；21 天主教輔仁大學附設醫院胃腸肝膽科；22 陽明醫 院胃腸肝膽科；23 中國醫藥大學北港附設醫院胃腸肝膽 科；24 國防醫學中心三軍總醫院胃腸科；25 臺中榮民總 醫院胃腸肝膽科；26 中山醫學大學醫學院；27 國立中興 大學生物醫學科學研究所；28 美國加州大學聖地牙哥分 校眼科部；29 國立臺灣大學醫學院附設醫院醫學研究部

Background: Real-world data are scarce about the effectiveness and safety of sofosbuvir/velpatasvir/ voxilaprevir (SOF/VEL/VOX) for retreating East Asian patients with hepatitis C virus (HCV) infection who previously received NS5A direct-acting antivirals (DAAs).

Aims: We conducted a multicenter study to assess the performance of SOF/VEL/VOX in patients who were not responsive to prior NS5A inhibitors in Taiwan.

Methods: Between September 2021 and May 2022, 107 patients who failed NS5A inhibitor-containing DAAs with SOF/VEL/VOX salvage therapy for 12 weeks were

戴啓明1 林鴻2 陳子皓1 陳志城3 曾政豪3 徐銘宏

1 義大醫院胃腸肝膽科 2 高雄六龜衛生所 3 義大癌治療醫院胃腸肝膽科

included at 16 academic centers. The sustained virologic response at off-treatment week 12 (SVR12) was assessed in the evaluable (EP) and per-protocol (PP) populations. The safety profiles were also reported.

Results: All patients completed 12 weeks of treatment and achieved an end-of-treatment virologic response. The SVR12 rates were 97.2% (95% confidence interval (CI): 92.1%-99.0%) and 100% (95% CI: 96.4%-100%) in EP and PP populations. Three (2.8%) patients were lost to offtreatment follow-up and did not meet SVR12 in the EP population. No baseline factors predicted SVR12. Two (1.9%) not-fatal serious adverse events (AE) occurred but were unrelated to SOF/VEL/VOX. Sixteen (15.0%) had grade 2 total bilirubin elevation, and three (2.8%) had grade 2 alanine transaminase (ALT) elevation. Thirteen (81.3%) of the 16 patients with grade 2 total bilirubin elevation had unconjugated hyperbilirubinemia. The estimated glomerular filtration rates (eGFR) were comparable between baseline and SVR12, regardless of baseline renal reserve.

Conclusions: SOF/VEL/VOX is highly efficacious and well-tolerated for East Asian HCV patients previously treated with NS5A inhibitor-containing DAAs.

HEPATITIS C IN-HOSPITAL CALL-BACK PROGRAM IN LOW PREVALENCE REGION OF TAIWAN- A REGIONALHOSPITAL RETROSPECTIVE STUDY

Background: Hepatitis C virus (HCV) is one of the major causes of chronic liver disease, cirrhosis and hepatocellular carcinoma. It has become possible to eliminate HCV by using Direct-acting antivirals (DAAs). In 2016, World Health Organization proposed eliminating hepatitis C as a public health threat by 2030. Therefore, the access of HCVinfected persons to diagnosis and treatment is important. Aims: To evaluate the efficacy of care cascade in call-back program and explore the features of responders.

Methods: From September 2013 to December 2021, 1296 HCV antibody-positive patients in Taipei city hospital RenAi branch were retrospectively enrolled into the in-hospital call-back program. After exclusion, 598 patients were eligible for call-back. At first, we send the call-back letter and then we call the patient on the phone. The features of patients with successful call-back and predictors of HCV viremia were investigated.

Results: The call-back rate, HCV RNA test rate, HCV RNA-positive rate and DAAs implementation rate were 9.5% (57/598), 100% (57/57), 66.7% (38/57) and 100% (38/38), respectively (Fig. 1). The distribution of HCV genotypes (GT) for GT1a/1b/2/3/6 was 8.3%/36.1%/36.1%/5.6%/2.8%, and 11.1% of them were unclassified. All patients achieve sustained virological response (SVR) by DAAs. Patients with HCV RNApositive had higher aspartate aminotransferase (AST) (58.62 ± 74.03 vs 24.53 ± 7.41, p = 0.005) and alanine aminotransferase (ALT) (64.97 ± 80.67 vs 22.67 ± 11.71, p = 0.003) than HCV RNA-negative patients (Table 1). In HCV RNA-positive group, 9 patients had cirrhosis and all of their Child-Pugh scores were 5. Patients with cirrhosis had higher total bilirubin level and FIB-4 score (Table 2). In a multivariate logistic analysis, independent factors associated with detectable HCV RNA were ALT ≥ 40 (IU/L) (Odds ratio: 5.278, p = 0.02, 95% CI: 1.305 - 21.343).

Conclusions: This HCV call-back program identified a significant proportion of patients with positive HCV

主題：肝腫瘤（二）

antibody that remained unevaluated for HCV RNA testing or therapy in the hospital. The therapeutic rate and SVR of DAAs both were 100%. In conclusion, the call-back program demonstrated the feasibility and efficacy for eliminating HCV in a regional hospital.

Background: Results from REFLECT trial showed a median overall survival (OS) of 13.6 months in patients with hepatocellular carcinoma (HCC) receiving lenvatinib monotherapy. Multiple systemic agents including pembrolizumab combination therapy have become available in recent years but their impact on survival remains unclear.

Aims: The aim of this study was to evaluate the survival outcomes of lenvatinib-based therapy in the era of multilines sequential therapy.

Methods: Consecutive 222 patients with unresectable HCC receiving lenvatinib-based therapy were retrospectively enrolled, including 110 patients with lenvatinib monotherapy and 112 patients with lenvatinib plus pembrolizumab combination therapy. Radiologic response, progression-free survival (PFS), OS and post-progression outcomes were evaluated.

Results: The median PFS and OS were 18 and 7.8 months, respectively, in patients within REFLCT criteria, and were 10.3 and 5.2 months, respectively, in patients beyond REFLCT criteria. The objective response rate (ORR) was 30.3% and 46% by RECIST1.1 and modified RECIST criteria, respectively. The ORR was not significantly different between patients within and beyond REFLECT criteria. In the overall cohort, the ORR, PFS and OS were not significantly different between patients with and without pembrolizumab combination therapy. By multivariate analysis, more than one organ involvement by HCC (hazard ratio (HR) = 1.516, p = 0.030), AFP > 200 ng/mL (HR = 1.828, p = 0.002), ALBI grade 2-3 (HR = 2.612, p < 0.001), and neutrophil-lymphocyte ratio >3 (HR = 2.155, p < 0.001) were independent predictors of OS.

In 137 patients with disease progression, 60.6% of them received second-line therapy, which was associated with

a significantly better post-progression survival (PPS) (7.8 vs. 2.4 months, p < 0.001). By multivariate analysis, ALBI grade at disease progression and second-line therapy were independent predictors of PPS.

Conclusions: Our study showed an improved OS as compared to the REFLECT trial. The availability of second-lines therapy and liver function reserve are important factors of survival after lenvatinib failure.

免疫相關不良反應在接受免疫檢查點抑制劑

INCIDENCE AND ROLE OF IMMUNERELATED ADVERSE EVENTS ON OUTCOMES IN PATIENTS WITH UNRESECTABLE HEPATOCELLULAR CARCINOMA UNDERGOING IMMUNE CHECKPOINT INHIBITORS

Background: Immune checkpoints inhibitors (ICIs) are recommended as the first-line and second-line systemic treatment for unresectable hepatocellular carcinoma (uHCC). Previous report suggests that the development of immunerelated adverse events (irAE) correlates favorable clinical outcomes.

Aims: However, it is not clear about the impact of different types of irAE on tumor response and the safety of rechallenge. Methods: From May. 2017 to Oct. 2022, 215 consecutive uHCC patients who received ICIs monotherapy or in combination with tyrosine kinase inhibitors (TKIs) as the first-line (n = 133) or second-line systemic therapy (n = 82) in Taipei Veteran General Hospital were retrospectively reviewed. The tumor responses were assessed according to RECIST 1.1 criteria. The grades of irAE were evaluated according to CTCAE v5.0.

Results: Of them, 40 (18.6%) developed at least grade 2 irAE (graded ≥2, irAE2), including 19 (8.8%) dermatitis, 9 (4.2%) hepatitis, 7 (3.3%) pneumonitis, and 5 (2.3%) miscellaneous. The irAE2 more frequently occurred during cycle 2 to cycle 4 of ICI treatment. Development of irAE2 was associated with higher objective response rate (ORR) (37.5% versus 7.4%) as well as disease control rate (80% versus 50.3%), and better progression free survival (PFS) (8.8 mo versus 4.4 mo). Among the 40 patients with irAE2, the median duration of steroid treatment (including methylprednisolone and oral steroid) was 6.57 weeks (range 0.14-27.6 weeks). Interestingly, 32 (80%) received ICI rechallenge after irAE subsided, and recurrence of irAE occurred in 9 (4 by dermatitis, 3 by hepatitis, and 2 by miscellaneous)

Conclusions: irAE2 is not uncommon for uHCC under ICIs therapy, which is associated with better ORR, DCR and PFS. Rechallenge of ICI may be safe for two thirds of the cases under closely surveillance.

治療的無法切除之肝細胞癌患者中之發生率 及其角色

果相關

HIGH TUMOR BURDEN IS ASSOCIATED WITH POOR SURVIVAL OUTCOME IN PATIENTS RECEIVING LENVATINIB PLUS PEMBROLIZUMAB FOR UNRESECTABLE HEPATOCELLULAR

CARCINOMA

Background: Lenvatinib plus pembrolizumab therapy for unresectable hepatocellular carcinoma (uHCC) showed encouraging results in an early-phase study but failed to meet the primary endpoint in the LEAP-002 trial. However, the real-world evidence of lenvatinib plus pembrolizumab as first-line or beyond first-line treatment is still unclear. Aims: This study aimed to investigate the efficacy of lenvatinib and pembrolizumb in the patients with uHCC in our cohort.

Methods: We retrospectively collected the patients with uHCC who received lenvatinib and pembrolizumab as firstline or beyond first-line therapy in Chang Gung Memorial Hospital from April 2019 to July 2021. All patients were followed till September 2022. High tumor burden were defined as Vp4 portal vein thrombosis (main trunk and/ or bilateral portal vein major branch), and/or bile duct invasion and/or tumor occupied ≥50% liver volume. Overall survival (OS), progression-free survival (PFS), and objective response by modified RECIST (mRECIST) were evaluated. Furthermore, we analyzed the predictors for survival outcome using a Cox regression model.

Results: A total of 66 patients receiving lenvatinib and pembrolizumab were recruited. Of them, 52 (78.8%) were male and 49 (74.2%) were BCLC stage C. At baseline, the median alpha-fetoprotein level was 211.30 ng/ml. 10 (15.2%) patients had main portal vein thrombosis, and 33 (50%) had extrahepatic metastasis. Regarding tumor burden, 30/65 patients (46.2%) were beyond the up-to11-criteria, and 26 (39.4%) had high tumor burden. There were 29 (43.3%) patients for first-line therapy and 37 patients for beyond first-line therapy. The median duration of treatment was 3.3 months, and the median duration of follow-up was 10.7 months. The objective response rate (ORR) and disease control rate (DCR) were 27% and 65%,

respectively. The median OS was 18.2 months, and the median PFS was 8.7 months. In the univariate analysis for OS, Vp4 portal vein thrombosis, out of up-to-11 criteria, and high tumor burden were independent predictors. Taking albumin-bilirubin (ALBI) grade, high tumor burden, and AFP response (defined as AFP decline ≥10% from baseline) into a multivariate Cox regression model, both high tumor burden and AFP response were significant prognostic factors for overall survival. As for PFS, AFP response was the only independent predictor in univariate analysis. The common treatment-related adverse events were diarrhea (22.7%) and hand-foot skin reaction (18.2%).

Conclusions: The lenvatinib plus pembrolizumab therapy has acceptable efficacy and safety profiles in the realworld setting. AFP response was the only predictor for PFS. Furthermore, high tumor burden and AFP response independently predicts poor overall survival in our cohort.

在不可切除的肝細胞癌且接受樂衛瑪與吉舒 達合併治療的患者高腫瘤負荷與較差存活結

徐毓均 林伯庭 滕威 蘇崇維 謝彝中 陳威廷 林成俊 林俊彥 林錫銘 林口長庚紀念醫院胃腸肝膽科

癌自癒併用癌思停合併體外放射治療用於高

independent predictor associated with shorter PFS (adjust HR: 3.187 [1.315-7.722], P = 0.0103; 2.757 [1.244-6.111], P = 0.0125). Combination with RT was an independent factor of longer OS; whereas, BCLC stage C had a trend of shorter OS (adjust HR: 0.322 [0.110-0.907], P = 0.0322; 2.862 [0.886-9.392], P = 0.0860). The incidence rates of severe (≥ grade 3) adverse events were not significant difference between patients with and without RT (11.1% vs. 18.8%, P = 0.4215).

Conclusions: The combination therapy with A+B and RT for high-risk HCC was safety and efficacy on higher rate of tumor response and probably prolonged OS. A prospective randomized trial is needed to validate our conclusions.

Background: Atezolizumab plus bevacizumab (A+B) was approved worldwide for advanced HCC based on IMbrave150 trail. The efficacy benefit of A+B for patients with high-risk HCC is still not satisfactory. External radiotherapy (RT) has been reported to offer excellent local tumor control.

Aims: This study aims to investigate the clinical efficacy and safety of this combination for high-risk HCC.

Methods: We retrospectively reviewed patients received A+B for high-risk HCC in a tertiary medical center. Highrisk HCC were defined as VP4 portal vein invasion (main trunk and/or bilateral portal vein major branch), and/or bile duct invasion and/or tumor occupied ≥ 50% liver. Objective response rate (ORR), progression free survival (PFS), and overall survival (OS) were evaluated according to modified Response Evaluation Criteria in Solid Tumors (mRECIST).

Results: A total of 61 patients with median age of 60.9-year-old, 75.4% male, 86.9% viral hepatitis infected, 73.8% Child-Pugh A, 80.3% BCLC stage C were 100% at least one of high-risk factor which including 30 with VP4 portal vein invasion, 1 with bile duct invasion and 47 with liver tumor occupancy of ≥ 50%. All of patients had A+B treatment and 16 (26%) of them had concurrent RT including 13 patients received proton radiation. The median A+B treatment duration were 3.5 months. After a median follow-up periods of 5.5 months, the rates of ORR for patients with and without RT were 43.8% and 17.8% (P = 0.0383). The median PFS was compared between concurrent RT and A+B alone (4.7 vs. 3.3 months, P = 0.6233). As for OS, patients with RT had significantly longer than patients without RT (not reached vs. 6.0 months, P = 0.0195). Multivariate analysis showed the BCLC stage C and liver tumor occupancy of ≥ 50% were

3 林口長庚紀念醫院放射腫瘤科 4 林口長庚紀念醫院腫瘤科 5 新北市立土城醫院腫瘤科

比較白蛋白為基準的肝臟功能模型（ALBI/ EZ-ALBI/PALB/PAL）與 MELD 對於接受 經動脈化療栓塞的肝癌患者預後 COMPARISON OF FOUR ALBUMINBASED LIVER RESERVE MODELS (ALBI/EZ-ALBI/PALB/PAL) AGAINST MELD FOR HEPATOCELLULAR CARCINOMA PATIENTS UNDERGOING TRANSARTERIAL CHEMOEMBOLIZATION

71 Lenvatinib 單用／合併 Pembrolizumab 與

Background: The severity of liver function reserve plays an important role in management of hepatocellular carcinoma (HCC). Non-invasive liver reserve models such as model for end stage liver disease (MELD), albumin-bilirubin (ALBI) and easy (EZ)-ALBI were used to evaluate liver dysfunction. The platelet-albumin-bilirubin (PALBI) score is used to assess liver function reserve in HCC patients. The plateletalbumin (PAL) score is recently proposed to assess liver function in surgical HCC patients.

Aims: We aimed to investigate the prognostic performance of four albumin-based liver reserve models (ALBI, EZALBI, PALBI, PAL) compared with MELD score in HCC patients undergoing transarterial chemoembolization.

Methods: A total 1038 treatment naïve HCC patients who received TACE as primary treatment were enrolled. Comparison of prognostic performance of liver function reverse models was examined by corrected Akaike information criteria (AICc) and homogeneity.

Results: Multivariate analysis revealed that serum albumin, serum creatinine, AFP > 200 ng/mL, vascular invasion, tumor size > 5 cm, ALBI grade 2-3, EZ-ALBI grade 2-3, PALBI grade 2-3, PAL grade 2-3 were independent prognostic predictors associated with survival. Of these, the PALBI grade had the highest homogeneity and lowest AICc value, followed by the ALBI grade, EZ-ALBI grade and PAL grade. Therefore, albumin-based liver reserve models were better prognostic performance than the MELD score.

Conclusions: Our study revealed that the PAL score is a better prognostic model to evaluate the liver function reserve in HCC patients undergoing TACE. The albumin-based liver function reserve models (ALBI, EZ-ALBI, PALBI, and PAL) are better models compared with the MELD score. The results needed to validate by other independent studies.

Background: The recent phase III LEAP-002 study showed negative results in the overall survival of lenvatinib plus pembrolizumab compared with lenvatinib monotherapy for unresectable hepatocellular carcinoma (uHCC) in the first-line setting. However, impressive survival outcomes with no unexpected side effects were still noted in both arms. Whether the combination therapy will have a better survival outcome compared to sorafenib is still unknown.

Aims: The study tried to evaluate the treatment response and outcomes of Lenvatinib monotherapy or plus pembrolizumab and sorafenib for uHCC in real-world firstline setting within LEAP-002 inclusion criteria.

Methods: From Jan. 2018 to Aug, 2022, 298 patients who received lenvatinib monotherapy or plus pembrolizumab and sorafenib for uHCC in the first-line setting with ChildPigh class A liver function were retrospectively enrolled in this study. The status of HCC was either in advanced HCC or failed by prior systemic therapy. The tumor responses were assessed with Response Evaluation Criteria in Solid Tumors (RECIST) v1.1.

Results: Of the 298 uHCC patients, the objective response rate (ORR) and disease control rate (DCR) were significantly higher in patients received lenvatinib monotherapy (26.5%, 69.9%) and lenvatinib plus pembrolizumab (37.6%, 75.3%) compared with sorafenib (11.5%, 44.6%). Although the overall survival were no different in these patients, Lenvatinib monotherapy or plus pembrolizumab showed significantly better progression free survival than sorafenib. And the further subgroup analysis showed that patient received sorafenib with progressive disease received immune check point inhibitor as the following treatment has significantly better survival

than those did not (23.5 vs. 12.7 months, p = 0.002).

Conclusions: Although lenvatinib monotherapy and lenvatinib plus pembrolizumab has no significantly better survival compared with sorafenib, the better response rate and PFS were still noted. And the following treatment after progression play an key role in survival.

末期腎病變病人其血紅素值於小腸膠囊內視 鏡檢查是否有出血時非好的指標 ASSESSMENT OF PATIENTS WITH ESRD AND THE FINDING OF BLEEDING IN CAPSULE ENTEROSCOPY, HEMOGLOBIN IS NOT A GOOD PREDICTOR OF BLEEDING

劉奕吾1 李騏宇1 陳銘仁1,2,3,4 林煒晟1,3,4 林錫泉

Background: Gastrointestinal (GI) bleeding can be divided into two board categories, upper and lower source of GI bleeding. Upper GI bleeding is much more common than lower GI bleeding (67/100,000 v.s. 36/100,000) and approximately 5% of all GI bleeding case is obscure GI bleeding (OGIB). Also, bleeding occurs in about 50% of patients with end-stage renal disease (ESRD) which may caused by platelet dysfunction.

Aims: Our aim of this study is to evaluate the patient underwent capsule enteroscopy (CE) with finding of ulcer and/or angiodysplasia. Is there any difference of bleeding parameters between patients with ESRD or non-ESRD group.

Methods: Totally 310 patients underwent capsule enteroscopy since 2005 till 2022 due to small bowel lesions. The patients performed CE due to obscure GI bleeding (OGIB) was 172 and non-OGIB was 138. We used methodology of student T test to check the correlation between each parameters and CE finding (ulcer and/or angiodysplasia) in patient with ESRD and non-ESRD patient.

Results: A total 310 were enrolled, 172 patients underwent CE due to OGIB and 138 patients due to non-OGIB. We excluded the patient without Hb data before CE which showed 153 in OGIB group and 114 in non-OGIB group. The average Hb level of OGIB showed 9.52 ± 2.2 mg/ dL and 12.49 ± 2.4 in non-OGIB group (p < 0.001). Also, we take ESRD into account. The patient with ESRD (n = 33) and non-ESRD (n = 234) group showed average Hb level of 8.77 ± 2.13 mg/dL and 11.07 ± 2.72 mg/dL, respectively (p < 0.001). In patient without ESRD and performed CE due to OGIB (n = 126) and non-OGIB (n = 108) showed Hb level 9.70 ± 2.32 mg/dL and 12.68 ± 2.24

主題：上消化道疾病（二） 72

mg/dL, separately (p < 0.001). In patient with ESRD and performed CE due to OGIB (n = 27) and non-OGIB (n = 6) showed Hb level 8.69 ± 1.97 mg/dL and 9.13 ± 2.9 mg/ dL, respectively (p = 0.651). In patient with ESRD and CE showed ulcer and/or angiodysplasia (n = 15), the average Hb showed 9.23 ± 2.44 mg/dL. In those without finding of ulcer and/or angiodysplasia (n = 18), the average Hb showed 8.39 ± 1.81 mg/dL, p = 0.267. In patient without ESRD and CE showed ulcer and/or angiodysplasia (n = 76), the average Hb showed 11.03 ± 2.78 mg/dL. In those without finding of ulcer and/or angiodysplasia (n = 158), the average Hb showed 871, p = 0.871.

Conclusions: Although the patient with underlying disease of ESRD may increasing the risk of bleeding tendency, but no significant difference between finding of ulcer and/ or angiodysplasia in capsule enteroscopy examination nor Hb level in those patient with tentative diagnosis of OGIB before CE. No matter the patient has ESRD or not, the Hb level is not correlated to the CE finding (ulcer and or angiodysplasia).

WITH MAGNIFYING NARROWBAND IMAGING AND LUGOL CHROMOENDOSCOPY IS EFFECTIVE FOR EARLY DETECTION OF ESOPHAGEAL SQUAMOUS CELL NEOPLASMS AMONG HEAD AND NECK

1

Background: Esophageal cancers and head and neck cancers are among top ten frequent cancers in Taiwan with increasing incidence. In patients with head and neck cancers, esophageal squamous cell neoplasms (ESCNs) are the most common second primary tumors with poor survival. Image enhanced endoscopy (IEE) with Lugol chromoendoscopy (LCE) or narrow band imaging combined with magnifying endoscopy (NBI-ME) both increased detection of esophageal dysplasia and cancer. Combination of LCE and NBI-ME may be more effective in detecting early ESCNs. In earlier study using LCE for evaluation of metachronous ESCNs in patients with prior early stage esophageal ESCNs, Grading of Lugol voiding lesions (LVLs) and alcohol use were related to the risk of metachronous ESCNs. However, the scenario in patients with head and neck cancer but without synchronous ESCNs wasn’t explored. The efficacy of combined LCD+NBI-ME was also less known. Limited data and instruction were available for surveillance in patients with head and neck cancer without co-existing ESCC.

Aims: To evaluate the performance of image enhanced endoscopic surveillance with NBI-ME and LCE among head and neck cancer patients without history of ESCNs. This study aimed to find out the suitable esophageal cancer surveillance program in patients with head and neck cancer.

Methods: From Apr, 2016, we routinely performed IEE

常規運用放大窄頻內視鏡與碘液染色進行影 像提升內視鏡篩檢可以有效早期發現頭頸癌

for surveillance of ESCNs in patients with history of head and neck cancer. The patients received NBI-ME first followed by LCE by 3 experienced endoscopists. Lugol voiding lesions (LVLs) were graded to the numbers of LVLs per endoscopic views and classified into 3 groups: A (absence of LVL lesion), B (1-9 lesions) and C (≥10 lesions). Endoscopic biopsies were obtained on suspicious early ESCNs. We selected patients who didn’t underwent esophageal dysplasia or malignancy at index endoscopy and received at least 2 IEE endoscopy from Apr, 2016 to Dec, 2019. The patients’ demographic profile, clinical data, endoscopy images and reports were obtained from our center’s IEE database.

Results: Total 179 patients received at least 2 IEE endoscopy in the study periods. Their mean age was 57.1 ± 8.4 years old with male dominant (n = 168, 97.7%). A total of 4 patients were found with metachronous ESCNs during follow-up. The duration for development of metachronous ESCNs was 477 to 717 days and the mean interval for development of metachronous ESCNs was 617.5 days. All patients received curative resection treatment for metachronous ESCNs. The group of LVL grade C had a higher risk of developing metachronous esophageal neoplasms than group of LVL grade A and B. (10.3% vs. 1.25% vs. 0% respectively, p = 0.005) In multivariate regression and Kaplan-Meier survival curve analysis, LVL type C had increased risk of esophageal cancer development (aOR: 144.53, p = 0.011). A total of 8 patients died during the study period, none of them had metachronous ESCNs.

Conclusions: (1) In patients with solely head and neck cancer, routine surveillance IEE with LCE + NBI-ME can timely detect early ESCNs with low ESCNs related mortality rate. (2) Patients with LVL type C had higher risk of ESCN development. (3) Annual surveillance may be considered sufficient to detect early ESCN.

探討食道薄荷油灌注對食道無效性收縮患者 其收縮功能之影響 IMPACT OF MENTHOL INFUSION ON ESOPHAGEAL PERISTALSIS IN PATIENTS WITH INEFFECTIVE ESOPHAGEAL MOTILITY

李宗晉

佛教慈濟醫療財團法人花蓮慈濟醫院肝膽腸胃科

Background: The cold receptor, transient receptor potential melastatin 8 (TRPM-8), is expressed in esophageal vagal afferents. Direct infusion of menthol into the esophagus can inhibit secondary peristaltic frequency via TRPM8 in healthy adults (Gastroenterology 2022). Ineffective esophageal motility (IEM) is a common motility disorder.

Aims: This study aimed to test the hypothesis that direct infusion of menthol into the esophagus alters esophageal peristaltic characteristics in patients with IEM.

Methods: Twenty patients with IEM (men 11, mean age 36, 21-60 years) were evaluated for primary and secondary peristalsis using high resolution manometry (HRM) with one mid-esophageal injection port. Primary peristalsis was assessed with ten water swallows, while secondary peristalsis was generated with rapid air injections of 20 mL. The study included two different sessions by randomly performing acute administration of placebo or menthol to assess their effects on esophageal peristaltic physiology. Frequency of primary and secondary peristalsis as well as relevant HRM parameters were explored.

Results: Menthol infusion didn’t change distal contractile integral (DCI) (p = 0.47), distal latency (p = 0.58), or complete peristalsis (p = 0.25). Menthol infusion had no effect on basal lower esophageal sphincter pressure (p = 0.32), esophagogastric junction contractile integral (p = 0.76), or integrated relaxation pressure (p = 0.38) of primary peristalsis. Infusion of menthol significantly decreased the frequency of secondary peristalsis (p = 0.002). There was no difference in DCI for secondary peristalsis for air injections of 20 mL (p = 0.27) between menthol infusion and the placebo.

Conclusions: Esophageal infusion of menthol significantly reduced peristaltic frequency of secondary peristalsis as induced by rapid air distension in IEM patients. Inhibitory modulation of secondary peristalsis from menthol infusion appears to be similarly present in both IEM patients and healthy adults, suggesting in the esophagus that activation of TRPM-8 by menthol can attenuate mechanosensitivity of secondary peristalsis regardless of the presence of IEM.

雷尉毅 梁書瑋 洪睿勝 翁銘彣 劉作財 易志勳 陳健麟

多重快速吞嚥 MACHINE LEARNING-ASSISTED CLASSIFICATION OF MULTIPLE RAPID SWALLOWS IN HIGH RESOLUTION MANOMETRY

76

運用食道過度警覺與臟器焦慮量表於生理性 酸暴露之胃食道逆流患者可協助症狀反應之 評估

ESOPHAGEAL HYPERVIGILANCE AND ANXIETY SCALE CAN EVALUATE SYMPTOM RESPONSE IN REFLUX PATIENTS WITH NORMAL ACID EXPOSURE

雷尉毅1 劉作財1 易志勳1 王仁宏2 洪睿勝1 翁銘彣1 梁書瑋1 陳健麟1 1 佛教慈濟醫療財團法人花蓮慈濟醫院肝膽腸胃科

Background: High-resolution manometry (HRM) is currently used to assess esophageal motility disorders. Multiple rapid swallows (MRS), one of the provocative testing, can increase the diagnostic yield in evaluating esophageal motor function. The interpretation of HRM relies on the Chicago Classification (CC) algorism and expert experience, which could lead to inter-rater disagreement.

Aims: This study aimed to develop an automated diagnostic platform utilizing machine learning and artificial intelligence (AI) methods to determine MRS responses based on raw HRM data.

Methods: The HRM studies of consecutive patients with MRS were collected and assigned labels of the contractile reserve, deglutition inhibition, integrated relaxation pressure (IRP), and esophageal motility diagnosis with CC diagnosis by expert interpreters. The two-stage MRS framework consisting of image processing and AI models was trained and tested. In the image processing stage, features of each MRS were developed by finding the region of interest and computing input pressure data to increase the learning effectiveness of AI model training. At the AI-level stage, three models based on convolutional neural networks (CNN) and fully connected networks (FCN) were conducted to derive the study diagnosis.

Results: The total dataset included 1,015 raw MRS data. A Nested Cross-Validation strategy was utilized for assessing the performance of AI models. The model for contractile reserve identification yielded an accuracy of 0.88 in the test dataset. The test accuracy of the deglutition-inhibition model and IRP model were 0.83 and 0.90, respectively. The mean absolute error of the IRP was 5.2 mmHg. The overall accuracy of the tested MRS framework by using three models was 0.89.

Conclusions: This is the first AI model to automatically identify the contractile reserve and deglutition-inhibition from raw HRM data. Our study demonstrates that the AI-assisted MRS modeling framework can not only reduce human tasks but also have great potential to improve HRM interpretation in clinical practice.

Background: Treatment for gastroesophageal reflux disease (GERD) patients with normal acid exposure is complicated by multiple psychophysiological factors. Esophageal hypervigilance and anxiety scale (EHAS), a novel questionnaire for the cognitive-affective evaluation of esophageal perception, has been demonstrated to correlate with symptoms severity of GERD. However, there was no study using EHAS for the evaluation of its correlation to symptom outcomes from GERD therapy.

Aims: The study aimed to investigate the interrelationships among the changes in GERD symptom severity, esophageal hypervigilance and anxiety, and psychosocial profiles after alginate suspension or proton-pump inhibitors (PPIs) therapy in GERD patients with normal acid exposure.

Methods: Consecutive patients with reflux symptoms and normal acid exposure on ambulatory pH-impedance monitoring were enrolled in this prospective, parallel study for comparing 8 weeks of treatment with Alginos Oral Suspension (sodium alginate 1,000 mg three times daily) with PPIs (once daily). The validated questionnaires including EHAS, GERD questionnaire (GERDQ), Pittsburgh Sleep Quality Index (PSQI), Taiwanese Depression Questionnaire (TDQ) score, and State-Trait Anxiety Inventory (STAI) score were used to evaluate patient-reported outcomes. The primary outcome was a response to anti-reflux therapy, defined as symptom improvement of GERDQ score at 8 weeks compared with baseline.

Results: Of 146 patients with normal acid exposure included (mean age: 47.9 years, range 24-72 years, female 63%), 75 (51.4%) patients were assigned to the alginate group, 71 (48.6%) to the PPIs group. Compared with baseline, both alginate and PPIs significantly reduced the GERDQ, total EHAS, PSQI, TDQ, and STAI after 8

運用機器學習於高解析度食道壓力檢測辨識

weeks of treatment (P < 0.001). However, there was no significant difference between groups in terms of GERDQ, EHAS, PSQI, TDQ, or STAI. In patients with symptom alleviation from therapy regardless of alginate or PPIs, a decrease in GERDQ level was significantly correlated with a decrease in EHAS (including subscales of anxiety and hypervigilance) (P < 0.01), PSQI (P < 0.05), TDQ (P < 0.05), and STAI score (P < 0.01).

Conclusions: This study showed that sodium alginate and PPIs have comparable effects on the alleviation of reflux symptoms and psychological distress in GERD patients with normal acid exposure. Our work demonstrated that alleviated EHAS status associated with reflux symptom improvement, suggesting that EHAS can be a novel metric to predict and assess symptom response in patients after GERD therapy.

77

探討食道無效性收縮對胃食道逆流症患者其 酸逆流負荷之影響：台灣多中心研究 EFFECT OF INEFFECTIVE

ESOPHAGEAL MOTILITY ON ACID REFLUX BURDEN IN PATIENTS WITH GERD: A MULTICENTER STUDY IN TAIWAN

劉作財1 雷尉毅1 曾屏輝2 王彥博3 王仁宏4 易志勳1

洪睿勝1 翁銘彣1 梁書瑋1 陳健麟1

1 佛教慈濟醫療財團法人花蓮慈濟醫院肝膽腸胃科

2 國立臺灣大學醫學院附設醫院胃腸肝膽科

Background: Ineffective esophageal motility (IEM) is the most commonly encountered abnormal manometric finding in gastroesophageal reflux disease (GERD). Diagnostic criteria for IEM in Chicago Classification version 4.0 (CC4.0) have been more stringent.

Aims: The aim of this study was to investigate the hypothesis of whether there is a difference in pHimpedance metrics between conclusive and inconclusive IEM in GERD patients.

Methods: We retrospectively analyzed patients with GERD symptoms referred to three medical centers who underwent high-resolution manometry (HRM) and offPPI 24-h impedance-pH monitoring. IEM patients were grouped as “conclusive IEM” and “inconclusive IEM” according to CCv4.0. The demographic information, GERD questionnaires, HRM, and esophageal reflux monitoring studies were compared between the two groups.

Results: Of 187 IEM patients included (51.2 ± 14.0 years, 97 female), 127 (68%) were identified as conclusive IEM and 60 (31%) as inconclusive IEM. There were no differences in age, gender, body mass index, GERDQ score, 4-second integrated relaxation pressure (IRP4s), LES resting pressure, and hiatal hernia among the groups. Conclusive IEM patients were more likely to have a higher upright acid exposure time (AET) (P = 0.028), higher upright (P = 0.008) and total reflux episodes (P = 0.007) compared to inconclusive IEM patients. Regarding the results of impedance testing, patients with conclusive IEM encountered more upright (P = 0.024) and total acid reflux events (P = 0.016) compared to inconclusive IEM. Ineffective peristalsis was significantly correlated with total reflux events (r = 0.152, P < 0.038).

Conclusions: This study demonstrated that the proportions

3 臺北榮民總醫院胃腸肝膽科 4 佛教慈濟醫療財團法人花蓮慈濟醫院醫學研究部

of ineffective swallows alter not only acid exposure time but also a number of reflux events. Our work supports the notion that IEM remains one of the crucial pathophysiological mechanisms leading to pathological acid reflux in GERD, and current CCv4.0 with more stringent criteria of IEM may better predict abnormal acid reflux burden in those patients.

78

定量糞便免疫化學法於不同臨界值檢測「結

直腸進行性腺瘤」之成果分析 PERFORMANCE OF QUANTITATIVE

FECAL IMMUNOCHEMICAL

TESTS

OF HUMAN HEMOGLOBIN FOR THE DETECTION OF ADVANCED COLORECTAL NEOPLASMS AT DIFFERENT CUTOFFS

Background: Fecal immunochemical test (FIT) has been widely applied for colorectal cancer (CRC) screening with adequate performance. Recent reports suggest the effectiveness of FIT could be affected by different brands and cutoff values. HM-JACKarc with a cutoff value at 30 (human hemoglobin ug/g feces) is a common quantitative measurement used in Taiwan for CRC screening in recent years. The reliable cutoff values remained unclear. Aims: This study aims to determine optimal cutoff values of FIT for the detection of advanced colorectal neoplasms (A-CRN) for average risk individuals between 40-75 years of age.

Methods: We conducted a retrospective study to assess the performance of FIT (HM-JACKarc) for detecting A-CRN (defined as: polyp sized ≥ 1.0cm or adenoma with villous component or severe dysplasia or cancer) at different cutoff values. We enrolled individuals, between 40-75 years of age, who participated in health check-ups and received FIT and colonoscopy concurrently. Outcome measurements include: Receiver operating characteristic curve for detecting A-CRN; FIT positivity rate at different cutoffs; Sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) for detecting A-CRN at different cutoffs. Increment of workload of colonoscopy at different cutoffs.

Results: A total of 9505 individuals (mean age: 53 y; M:F = 57.5%:42.5%) were enrolled between November 2015 and December 2018. A-CRNs were detected in 650 individuals (6.8%), including 21 cases of CRC. FIT positivity rates were 6.4%, 4.1% and 3.1% at the FIT cutoffs of 10, 20, and 30 (ug/g feces) respectively. The area under curve (AUC) for A-CRN was 0.60. The sensitivity

主題：下消化道疾病（二）

4 國立臺灣大學醫學院內科

of detecting A-CRN were 18.0%, 13.7% and 11.2% at the FIT cutoffs of 10, 20, and 30 (ug/g feces) respectively. The specificity of detecting A-CRN were 94.6%, 96.7% and 97.6% at the FIT cutoffs of 10, 20, and 30 (ug/g feces) respectively. The PPV of detecting A-CRN were 19.7%, 23.4% and 25.4% at the FIT cutoffs of 10, 20, and 30 (ug/ g feces) respectively. The NPV of detecting A-CRN were 94.0%, 93.8% and 93.7% at the FIT cutoffs of 10, 20, and 30 (ug/g feces) respectively. The increment of workload of colonoscopy were 106.5%; 32.3% and 0% at the FIT cutoffs of 10, 20, and 30 respectively.

Conclusions: Compared to the current FIT cutoff at 30 (ug/ g feces), lowering the cutoff value to 10 (ug/g feces) may significantly increase the sensitivity of FIT for detecting A-CRN by 60.7% (from 11.2% to 18.0%); however, a 106.5% increment on CFS workloads was accompanied. A balance between the test performance and colonoscopy workload should be critically evaluated to understand the cost-effectiveness of a FIT screening program.

79

維生素 D 缺乏症在發炎性腸道疾病的病患 有高度的盛行率 HIGH PREVALENCE OF VITAMIN D DEFICIENCY AMONG IBD PATIENTS

楊承達 黃秀萍 顏旭亨 彰化基督教醫院胃腸肝膽科

Background: Vitamin D deficiency is common in IBD patients. However, the data were limited in Taiwanese IBD patients.

Aims: This study aims to evaluate the prevalence and risks of vitamin D deficiency in a Taiwanese IBD cohort.

Methods: From January 2017 to December 2022, vitamin D level was checked in adult IBD patients in Changhua Christian Hospital, a medical center in central Taiwan. Risk factors for vitamin D were evaluated.

Results: Total 88 adult IBD patients, including 15 patients with Crohn’s disease and 73 patients with ulcerative colitis, were included in this study. The median age is 48.3 yearsold. The baseline characteristics and vitamin D level were shown in table 1. The median vitamin D level is 22.4 ± 7.7. 37 patients (42%) had vitamin D deficiency (vitamin D level < 20 ng/mL). Comparing patients with normal vitamin D level and deficiency, only female gender is statistically significant.

Conclusions: The prevalence of vitamin D deficiency in general adult population in Taiwan is 22.4%. However, in Taiwanese IBD population, the prevalence is much higher than general population.

80

患有發炎性腸道疾病的病人接受 COVID-19 疫苗注射後的效果及併發症之臨床結果分析 研究：中台灣一醫學中心之經驗 EFFECTIVENESS AND SAFETY OF COVID-19 VACCINE AMONG PATIENTS WITH INFLAMMATORY BOWEL DISEASE: A MEDICAL CENTER HOSPITAL-BASED STUDY IN CENTRAL TAIWAN 吳宜樺

1 中國醫藥大學附設醫院消化醫學中心

2 台灣小腸醫學會

3 台灣發炎性腸道疾病學會

Background: In 2020, the world faced the unprecedented crisis of coronavirus disease 2019 (COVID-19). Patients with Inflammatory bowel disease (IBD) remain highly concerned that either their disease or medications may increase the risk of severe COVID-19. Moreover, COVID-19 infection also resulted in many complications for IBD patients who were vaccinated. However, the association of IBD patients with COVID-19 who had been vaccinated receiving biologics, immunomodulators, or steroids therapies is lacking in Taiwan. Thus, we hypothesized that the first wave of the COVID-19 pandemic would have some effects on IBD patients who were vaccinated and performed this retrospective study. Aims: The aim of this study was to investigate the effectiveness and safety of COVID-19 vaccines in patients with IBD receiving biologics, immunomodulators, or steroids therapies in a medical center hospital in middle Taiwan.

Methods: From January 1980 to October 2022, a total of 286 consecutive patients with IBD (UC: 184 patients; CD: 102 patients), regularly followed at China Medical University Hospital, a tertiary referral center in central Taiwan, was enrolled into our current study. There were 155 patients had received vaccine for at least one dose. Finally, 51 patients who were vaccinated still suffered from COVID-19 with an infection rate of 32.9% (51/155). We analyzed the clinical manifestations of COVID-19-positive in IBD patients. The diagnostic criteria of COVID-19 infection were based on the positivity of COVID-19 rapid antigen test or polymerase chain reaction (PCR) test. Clinical characteristic, and treatment outcomes of all patients with COVID-19 who had been vaccinated were analyzed. Categorical variables were reported as counts

(percentages) and compared using the chi-squared test and Fisher’s exact test.

Results: A total of 184 patients with Ulcerative colitis (UC) was enrolled into our current study, 87 patients had received vaccine for at least one dose. Finally, 37 patients suffered from COVID-19 with an infection rate of 42.5% (37/87). Patients with UC (42.5%) presented significantly higher infection rate of COVID-19 than patients with CD (20.6%) (p < 0.05). (Table 1). The mean diagnostic age of these enrolled patients was 45.1years (ranging from 21 years to 85 years old). Male accounted for the majority of our all patients in the study (76.5%). The mean body weight was 62.4 kg (range, 44.0-94.5 kg). There were 87 patients (87/184; 47.2%) had received COVID-19 vaccine for at least one dose, and 80 patients (97/184; 52.7%) did not receive any dose of vaccine. The mean dose of COVID-19 vaccine was 2.17. The most common clinical manifestations were sore throat (26/37; 70.2%), followed by fever (24/37; 64.8%), cough (22/37; 59.4%), runny nose (13/37; 35.1%), fatigue 27.0% (10/37; 27.0%), muscle pain (8/37; 21.6%), headache (7/37; 18.9%), abdominal pain (3/37; 8.1%) and asthma (2/37; 5.0%). There were 21 patients using biologics (21/37; 56.7%) when diagnosed with COVID-19. The most common type of biologics used in patients with UC was Vedolizumab (7/21; 33.3%), followed by Adalimumab (6/21; 28.5%), Etrasimod (4/21; 19.0%), Infliximab (2/21; 9.5%), and Upadacitinib (1/21; 4.7%). There were no differences in the COVID-19 infection rate in different treatment groups among patients with UC (p > 0.05) (Table 2). All these patients had mild COVID-19 with a good outcome and none of these patients needed a hospitalization. A total of 102 patients with Crohn’s disease (CD) was enrolled into our current study, 68 patients had received vaccine for at least one dose. Finally, 14 patients suffered from COVID-19 with an infection rate of 20.6% (14/68). The mean diagnostic age of these enrolled patients was 39.5 years (ranging from 21 years to 84 years old). Male accounted for the majority of all patients in our present study (77.5%). The mean body weight was 60.4 kg (range, 44.0-90.5 kg). There were 68 patients (68/102; 66.6%) had received covid-19 vaccine for at least one dose, and 34 patients (34/102; 33.3%) did not receive any dose of vaccine. The mean dose of COVID-19 vaccine was 2.15. The most common clinical manifestations were sore throat (12/14; 85.7%), followed by fever (11/14; 78.5%), cough (10/14; 71.4%), runny nose (6/14; 42.8%), fatigue 5.8% (5/14; 35.7%), headache (3/14; 28.5%), abdominal pain (2/14; 14.2%), muscle pain (2/14;

14.2%) and asthma (1/14; 7.1%). There were 12 patients using biologics (12/14; 85.7%) when diagnosed with COVID-19. The most common type of biologics used in patients with CD was Vedolizumab (3/14; 21.4%), followed by Adalimumab (2/14; 14.2%), Etrasimod (2/14; 14.2%), Infliximab (2/14; 14.2%), and Upadacitinib (1/14; 7.1%). There were no differences in the COVID-19 infection rate in different treatment groups among patients with CD (p > 0.05) (Table 3). All these patients had mild COVID-19 with a good outcome and none of these patients needed a hospitalization.

Conclusions: Our current study showed the risk of COVID-19 in IBD patients is not specifically higher than the general population, despite IBD is usually considered a high risk of severe COVID-19. Our 51 patients with COVID-19 infection had a good outcome and none one needed hospitalization. Patients with UC presented significantly higher infection rate of COVID-19 than patients with CD. There were no differences in COVID-19 for different treatments among patients with UC and CD. The use of biologics or immunomodulators was not associated with an increased risk of COVID-19 in patients with IBD. The use of steroids was also not associated with an increased risk of COVID-19 in patients with IBD if steroids were held two weeks or decreased dosage before vaccinations. Furthermore, we found that IBD patients under adequate therapy can reduce the severity of COVID-19.

黏液生成與腺瘤偵測的影響：一先導性隨機 分組研究

IMPACT OF 25% AND 50% SALINE VERSUS WATER ON MUCUS PRODUCTION AND ADENOMA DETECTION IN THE LEFT COLON DURING WATER EXCHANGE

COLONOSCOPY – A PILOT RANDOMIZED TRIAL

鄭吉良1 郭彥麟1 蘇怡佳1 劉乃仁2 連昭明3 唐家沛4 謝毓錫4 Felix W. Leung5

1 中壢長榮醫院胃腸科

2 林口長庚紀念醫院胃腸肝膽科系

Background: Water-assisted colonoscopy increased left colon mucus production. Whether the increase can be altered by saline is not fully known.

Aims: We tested the hypothesis that saline infusion might reduce such mucus production in a dose-related manner. We also used the result to address the exploratory question whether adenoma detection could be affected.

Methods: In a randomized trial, patients were assigned to colonoscopy with CO2 insufflation, water exchange (WE) insertion with warm water, 25% saline, and 50% saline. The primary outcome was the Left Colon Mucus Scale (LCMS) score (5-point scale). Secondary outcomes included changes in the serum electrolytes before and after saline infusion and the adenoma detection rate (ADR), defined as the percentage of patients with ≥1 conventional adenomas in the left colon.

Results: There were 296 patients who completed the study, of whom 75 were randomized to the WE water group, 75 to the WE 25% saline group, 76 to the WE 50% saline group, and 70 to the CO2 group. Baseline demographics and colonoscopy indications were similar. The mean LCMS score for WE with water was significantly higher than those for WE with saline and CO2 (1.4 ± 0.8 [WE water] vs. 0.7 ± 0.6 [WE 25% saline] vs. 0.5 ± 0.5 [WE 50% saline] vs. 0.2 ± 0.4 [CO2]; overall P < 0.0001), with no significant difference between the 25% and 50% saline groups. The left colon ADR was highest in the 50% saline, followed by 25% saline, and water group (25.0%

比較換水大腸鏡使用 25% 生理食鹽水、 50% 生理食鹽水與蒸餾水灌注對左側大腸

vs. 18.7% vs. 13.3%) but the difference was not significant (P = 0.270 for WE water vs. WE 50% saline; possibly type II error). Logistic regression showed water filling was the only predictor of moderate mucus production (odds ratio, 33.3; 95% confidence interval, 7.2-153.2). No acute electrolyte abnormalities were documented indicating a safe modification.

Conclusions: In the current pilot study, WE stimulated mucus production was significantly inhibited and ADR was numerically increased in the left colon by 25% and 50% saline. Without significantly altering serum electrolytes, infusion of saline during insertion is a safe modification of WE colonoscopy. Evaluation of the impact of inhibition of WE stimulated mucus by saline on ADR may refine the outcome of WE.

Background: Chronic pain is one of the most prevalent health problems in our modern world, with millions of people debilitated by conditions such as back pain, headache, abdominal pain and arthritis. The chronic pain in these patients would affect their work productivity, sleep and daily activities. Patients seeking treatment for chronic pain often report difficulties with memory, concentration, and other cognitive functions. Schnurr and MacDonald have found that the patients seeking treatment for chronic pain report more memory problems than control subjects. Learning and memory have been evaluated psychometrically in chronic pain patients, with patients performing poorly compared with controls on parameters including spatial and verbal working memory capacity and recall, recognition memory and long-term spatial memory. Mixed findings concerning the correlation of subjective memory reports to objective memory complaints are not uncommon. It can be argued that subjective memory reports will be accurate if the subjective questionnaire assesses specific behaviors rather than general impressions of memory ability. Because everyday memory performance takes place within a specific context and with specific goals in mind, subjective memory assessment is more accurate when specific behaviors are queried, such as remembering to take medications. We therefore chose a wellcharacterized questionnaire that used specific instances to assess subjective memory performance, the Metamemory in Adulthood (MIA) questionnaire. Metamemory has been a significant part of memory research since the 1970s and refers to the ability to self-reflect on one’s own memory function, as well as more general knowledge of how memory works. This instrument contains seven scales that provide an index of several aspects of memory beliefs. Among various types of chronic pain syndromes, chronic visceral pain is frequently found in the patients with

functional gastrointestinal disorder (FGID), which is also highly prevalent in the general population. Irritable bowel syndrome (IBS), a common form of FGID, characterized by chronic and recurrent lower abdominal pain. IBS patients also report that cognitive function and mental alertness have declined. A limited number of studies of cognitive function in IBS suggest that IBS patients may exhibit impaired long-term and working memories. Whether the chronic visceral pain found in IBS patients is also associated with memory dysfunction remained unknown. We hypothesized that memory dysfunction is present in IBS patients. We used various questionnaires to explored memory function in IBS patients.

Aims: To evaluate correlation of memory function in patients with irritable bowel syndrome.

Methods: There were two groups of participants: 23 IBS patients and 26 healthy age-matched controls. All participants with the followings would be excluded from the sudy: regular use of tobacco, recreational drug use, a history of CNS disease or brain injury, education less than 10th grade, and evidence of a current psychiatric illness. All participants were evaluated by the following questionnaires: the hospital Anxiety and Depression Scale (HADS), Pain Catastrophizing Scale (PCS), meta-memory in Adulthood (MIA) questionnaire and IBS Quality of Life questionnaire (IBS-QOL). HADS is made up of 2 scales: anxiety and depression. The Chinese version of the scale is to evaluate the participants’ mood within one week before this study. Pincus et al 71 recommend the use of this instrument to assess anxiety and depression in chronic pain populations. PCS consists of 3 subscales to assess rumination, magnification, and helplessness, and also offers a total score regarding catastrophizing. Magnification refers to the tendency to exaggerate the threat value or seriousness of pain sensations. Rumination relates to the inability to divert attention away from pain. Finally, helplessness refers to pessimism in relation to one’s ability to cope with pain. The questionnaire in Chinese version was used in previous study. MIA questionnaire70 consists of 108 items that query participants about different aspects of memory beliefs and yields scores for seven different scales, including knowledge about memory, tendency to use effective strategies, perceived capacity, change in capacity, anxiety about memory performance, motivation to have a “good” memory, and self-efficacy or control over memory function. Individual items will rate on a five-point Likert scale where participants indicated their agreement with statements about memory. Older adults typically report lower memory

capacity, less stability (i.e., decreasing capacity), and lower self-efficacy over memory than young adults did. The psychometric properties of the MIA have been studied extensively, demonstrating good internal consistency and convergent validity with other metamemory instruments. The Rome III modular questionnaire was used to define IBS. The Rome III Modular Questionnaire is a selfadministered questionnaire for diagnosing functional GI diseases. Subjects were classify as having IBS according to their answers on the Rome III modular questionnaire. For IBS diagnosis, subjects required to have at least two of the three symptom criteria: (i) abdominal pain or discomfort relieved/improved by defecation; (ii) onset of pain associated with change in stool form (appearance); (iii) onset of pain associated with and/or stool frequency. A t-test was used to explore differences in group characteristics (age, BMI, education), HADS-anxiety (HADS-A), HADSdepression (HADS-D), PCS, IBS-QOL and MIA. Pearson product-moment correlations were calculated to assess the relationship between the MIA scales and PCS. These correlations were calculated separately for each group. Finally, as an additional measure to control for the influence of levels of anxiety on cognitive performance, participants meeting predefined criteria for possible co-morbid anxiety (a HADS-A score of ≥ 11) were excluded.

Results: Demographic and clinical characteristics in control and IBS. Groups did not differ significantly on age, BMI and education level. According to Rome III criteria, seven IBS patients were diarrhea predominant (IBS-D), three constipation predominant (IBS-C) and 13 were mixed (IBS-M). IBS patients HADS-D score (p < 0.001) and HADS-A score (p < 0.001) were higher than the those in healthy controls. IBS patients also showed significantly higher levels in PCS and IBS-QOL than control group (p < 0.01). Memory function in controls and IBS patients. IBS patients’ knowledge of memory function was similar to that of the age-matched controls (p = 0.24). IBS patients reported less use of strategies to support memory (p = 0.01), and less stability in memory capacity (p = 0.05). Correlations with objective memory performance and pain scale. A correlation analysis was carried out to identify relationships between memory performance (MIA) and pain catastrophizing scale (PCS). A negative relationship was identified between PCS scores and memory capacity (r = -0.391, p = 0.03) within the IBS group, but not in the healthy controls.

Conclusions: We found that the IBS patients have similar knowledge about memory as the controls did, but they

correctly perceive their memory capacity as lower. Beliefs about memory and self-report of memory problems are important in clinical practice because it is often not possible to do formal testing. Our results suggest that patients’ self-report about memory function using the MIA questionnaire appear to be accurate, and have important implications showing that IBS is a disorder in association with memory dysfunction. The results suggest that memory intervention programs to focus on improving self-efficacy may be helpful for IBS patients, which deserves further investigation.

發炎性腸道疾病相關之大腸癌：台灣多中心 聯合世代研究

CLINICAL CHARACTERISTICS, MANAGEMENT AND OUTCOMES OF COLITIS-ASSOCIATED COLORECTAL CANCER IN TAIWAN: A MULTICENTER COHORT STUDY

吳心耘1 魏淑鉁1 周仁偉2 顏旭亨3 林春吉4 蔣鋒帆5 鍾承軒6 林煒晟7 章振旺7 李柏賢8 郭家榮8 林敬斌9

許文鴻10 莊喬雄11 蔡騌圳12 馮意哲13 黃天祐14 1 國立臺灣大學醫學院附設醫院胃腸肝膽內科；2 中國

醫藥大學附設醫院胃腸肝膽內科；3 彰化基督教醫院胃

腸肝膽內科；4 臺北榮民總醫院大腸直腸外科；5 臺中

榮民總醫院大腸直腸外科；6 亞東紀念醫院肝膽腸胃內

科；7 馬偕紀念醫院胃腸肝膽內科；8 林口長庚紀念醫

院胃腸肝膽內科；9 中山醫學大學附設醫院肝膽腸胃內 科；10 高雄醫學大學附設中和紀念醫院胃腸內科；11 國 立成功大學醫學院附設醫院內科部；12

Background: The incidence and prevalence of inflammatory bowel disease (IBD) are increasing in Asian countries, including Taiwan. The management of colitisassociated colorectal cancer (CAC) is an important issue in clinical practice.

Aims: With the awareness and progress of CAC screening and surveillance, we aim to explore the clinical characteristics, treatment and outcomes of CAC in Taiwan. Methods: Data were retrospectively collected from 14 medical centers in Taiwan. The staging conformed to the AJCC (8th edition) for colorectal cancer. The clinical demographics, endoscopic findings, histology, medications, treatment modalities and outcomes were recorded and analyzed.

Results: From 1987 to 2022, a total of 65 patients were enrolled, with the median age of 56 and male predominance (66.2%). The ulcerative colitis (UC) to Crohn’s disease (CD) ratio was 12:1. Median IBD duration prior to CAC development was 13 years. Distal colon was the most common location (41.5%), followed by rectum (35.4%). Extensive colitis accounted for 77.2% for UC and 76.5% patients with Mayo endoscopic sub-score ≥2. The lesions appeared non-polypoid in 50.9% and ill-defined in 67.9%. Fortunately, white light endoscopy detected 85.9% such lesions. The percentage of CAC staging from 0 to 4 were 10.5%, 21.1%, 14%, 21.1%, and 33.3%, respectively.

高雄榮民總醫院 胃腸肝膽內科；13 奇美醫院胃腸肝膽內科；14 三軍總醫 院胃腸內科

Endoscopic resection could only be applied for 12.5% patients, while 68.7% received surgery, 43.8% endured chemotherapy, and 21.9% underwent radiotherapy. With a median follow up time at 21.5 months, 16.9% recurrence and 30.8% mortality were recorded. Median disease-free time was 13 months.

Conclusions: From our study, UC with longer disease duration and more extensive/inflammatory types would be the target groups for CAC screening and surveillance. White light endocsopy detected most lesions and the most common treatment for CAC was surgical intervention. In order to improve the outcomes, we should focus on diagnosing the CAC in earlier stages.

非酒精性肝炎所致之肝癌患者經根治性手術 後比起病毒性肝炎所致之肝癌有較短的復發 時間 SHORTER TUMOR RECURRENCE

Background: Non-alcoholic steatohepatitis (NASH) is an emerging cause of cirrhosis and hepatocellular carcinoma (HCC) worldwide. The outcomes for patients with NASHrelated HCC after curative treatment are still not well clarified.

Aims: Compare the overall survival (OS) and time to tumor recurrence (TTR) of NASH-related HCC with virusrelated HCC after surgical resection.

Methods: From January 2016 to December 2019, we retrospectively enrolled patients with HCC underwent curative resection. Their baseline characteristics, including etiology of liver disease, clinical features, and tumor pathological characteristics were collected. Primary outcomes were OS and TTR. A propensity-score matching analysis was performed to match NASH-related and HBVrelated HCC

Results: In total, 206 HCC patients with etiology of hepatitis B virus (HBV, n = 121), hepatitis C virus (HCV, n = 54), and NASH (n = 31) were enrolled. Of those virusrelated HCC, 84.0% achieved viral suppression. Patients with NASH-related HCC recurred significantly earlier than virus-related HCC (median TTR: 1108 days vs. non-reached, p = 0.03). By multivariate Cox-regression analysis, NASH-related HCC (HR = 2.27, 95% CI: 1.254.12), presence of satellite nodule (HR = 1.92, 95% CI: 1.01-3.65), presence of cirrhosis (HR = 1.65, 95% CI: 1.05-2.61), Child-Pugh stage B (HR = 4.59, 95% CI: 1.4015.09), and pre-surgical AFP level >20 ng/dl (HR = 1.76, 95% CI: 1.10-2.80) were factors associated with early recurrence . Factors associated with OS included recurrence of tumor (HR = 4.43, 95% CI: 1.72-11.42), BCLC stage B (HR = 12.57, 95% CI: 2.61-60.52), and tumors without capsulation (HR = 5.88, 95% CI: 1.59-21.70).

NASH-

主題：肝硬化及其他肝病（二） 84

related HCC had a similar OS to that of virus-related HCC. After propensity-score matching, NASH- related HCC had similar baseline characteristics comparing to HBV-related HCC. In both overall and propensity-score matching cohort, NASH-related HCC exhibited significantly shorter TTR than HBV-related HCC.

Conclusions: NASH-related HCC is associated with earlier tumor recurrence than virus-related HCC following curative resection, while their OS were comparable. Postsurgical surveillance is important to detect early HCC recurrence for patients with NASH-related HCC.

Background: Due to the nationwide hepatitis B vaccination program in Taiwan since 1984 and the development of antiviral therapy for hepatitis B virus (HBV) infection and hepatitis C virus (HCV) infection and the increased prevalence of nonalcoholic fatty liver disease, the etiology of liver related complication such as cirrhosis and hepatocellular carcinoma (HCC) has changed.

Aims: This study aimed to analyze the incidence and outcome of viral related and non viral related HCC.

Methods: We retrospectively analyzed patients with HCC from January 2011 to December 2020 at our institution. Viral hepatitis was defined as positive hepatitis B surface antigen or positive anti-HCV antibody.

Results: A total of 2748 patients with HCC were enrolled. Among these, viral-related HCC were 2188 and nonviralrelated HCC were 560. The median age diagnosed was 65.2 in the viral HCC group and 69.6 in the non-viral HCC group (P < 0.001). The early-stage HCC, including BCLC stage 0 and stage A, was higher in the viral group, 52.9% versus 33.6% (P < 0.001). Alcohol use was higher in the nonviral group 39.9% versus 30.1% (P < 0.001). There was no difference in sex and body mass index. Nonviral HCC increased slightly from 18.8% to 21.8% during the last 5 years without statistical difference (P = 0.053). Overall survival was higher in the viral group 54.4 months versus 20.5 months (P < 0.001). In the early stage of HCC, overall survival was higher in the viral group (P < 0.001), but there were no statistical differences in stage B, C or D of BCLC compared to these two groups.

Conclusions: Non-viral HCC has been trending to increase in recent years. Overall survival was lower in non-viral HCC. It may be related to a lower portion of early HCC detected in nonviral HCC. Further studies may be required to identify risk factors, such as fatty liver disease, for this group.

THE OUTCOME OF HEPATOCELLULAR CARCINOMA IN VIRAL AND NON VIRAL CAUSE

利用循環腫瘤細胞偵測早期肝癌 CIRCULATING TUMOR CELLS AS A DIAGNOSTIC BIOMARKER FOR EARLY STAGE HEPATOCELLULAR CARCINOMA

3

4 國立臺灣大學臨床醫學研究所

Background: Early diagnosis with prompt treatment is key in the management of hepatocellular carcinoma (HCC) because of improving outcomes. Circulating tumor cells (CTC) have been developed as a biomarker for the diagnosis of several cancers.

Aims: Our aim is to establish a platform using CTC for the diagnosis of early-stage HCC.

Methods: We conducted a prospective study to include healthy volunteers and patients of liver disease in National Taiwan University Hospital. An 8ml blood sample was collected and peripheral blood mononuclear cells (PBMC) were isolated, fixed and incubated with the capture antibody (CA). CA bound PBMCs were injected into the Cell Reveal and the CTCs were captured through the V-BioChip system. (CytoAurora Biotechnologies, Inc., Hsinchu, Taiwan). The chip was stained by antibody sets of EBF (GPC3 and CK7) and EAQ (PanCK and FOXM1). Candidates for CTCs on the chip were automatically identified and normalized for further analysis.

Results: Between August 2021 and June 2022, we enrolled a total of 11 healthy donors, 2 cirrhotic patients and 26 patients with HCC BCLC stage 0/A. The median number of GPC3+ CTC was 0 (25-75% percentile: 0-2), 3 (1-5), and 5.5 (2.8-9.3) in healthy, cirrhosis, and HCC-BCLC 0/A groups, respectively. Compared with healthy control, the median number of GPC3+ CTC was significantly greater in the BCLC-0/A HCC group (P < 0.001). The median number of PanCK+ CTC was 0 (0-2), 0.5 (0-1), and 2 (1-3) in healthy, cirrhosis, and HCCBCLC 0/A groups, respectively, and the PanCK+ CTC was significantly greater in the HCC group compared with healthy ones (p=0.013). There is no significant difference in CK7+ CTC or FOXM1+ CTC between HCC and non-HCC patients.

Conclusions: The CTC is a promising biomarker for diagnosis of early stage HCC, specifically the GPC3+ and PanCK+ CTC. Further validation study in patients with different stage of liver diseases is needed.

長期 Obeticholic Acid 可以改善非酒精性脂 肪肝小鼠的心臟功能受損

CHRONIC OBETICHOLIC ACID

TREATMENT AMELIORATES-RELATED CARDIAC DYSFUNCTION IN NASH MICE

Background: Farnesoid X receptor agonists inhibit the activation of the NLRP3 inflammasome and provide a potential therapeutic target for NLRP3-dependent inflammatory diseases. The FXR agonist obeticholic acid (OCA) improves hepatic steatosis and inflammation by inhibiting hepatic and macrophage NLRP3 inflammasome activation. In diabetic mice, FXR activation improves myocardial dysfunction by inhibiting cardiac inflammation and fibrosis. Accordingly, this study aimed to evaluate the mechanisms and effects of chronic treatment with the FXR agonist on cardiac inflammasome-mediated cardiac dysfunction in NASH mice.

Aims: This study evaluate the in vivo and in vitro effects and mechanisms of 2-weeks of Foresaid X receptor (FXR) agonist, obeticholic acid (OCA), treatment on the Treg dysregulation-related cardiac dysfunction in NASH mice (NASH-OCA) at systemic, tissue and cellular levels.

Methods: To create NASH mice, 12-week-old C57BL/6 mice were fed with20-week high-fat and methionine and choline deficiency (MCD) diet (HFMCD). NASH-OCA group were continuously receiving 2-week steroidal FXR agonist, obeticholic acid (OCA, a semi-synthetic bile acid acting as an FXR ligand, 10mg/kg/day, using the azert osmotic pump) from the (21st to 22nd) week after HFMCD feeding. Then, cardiac function were measured by echocardiography. Body composition (fat and lean mass) was measured by computed tomography. Cardiac and serum levels of caspase-1, IL-1 beta, creatine kinase (CK) and cardiac troponin were measured. Cardiac inflammation and interstitial fibrosis was measured.

Results: Lower cardiac FXR/SHP and higher inflammasome (IL-1 beta and caspase-1) expression was observed in the hearts of NASH group mice. Significantly, chronic FXR agonist treatment reversed the abovementioned dysregulated markers in NASH mouse hearts.

5 國立臺灣大學醫學院附設醫院醫學研究部

Significantly lower FS, lower LVEF, lower SV, and higher LV mass were observed in the NASH group. Additionally, positive correlations were noted between the percentage of the OCA-increased FS and the magnitude of the OCAincreased levels of FXR. After chronic FXR agonist treatment, the above-mentioned cardiac dysfunctions were normalised in NASH-OCA mice. Meanwhile, the severe cardiac inflammation and fibrosis of NASH mice was decreased after chronic FXR agonist treatment.

Conclusions: In general, chronic FXR activation is a potential strategy to inhibit cardiac inflammation, cardiac fibrosis, cardiac apoptosis, and cardiac hypocontractility, restore the cardiac function, and subsequently improve cardiac dysfunction in NASH mice.

單核苷酸多態性

與胰腺癌風險的

Pancreatic cancer is a highly fatal disease and can be associated with the susceptibility from the genetic variation. There is growing evidence that aberrant expression of microRNAs (miRNAs) is associated with the development and progression of pancreatic cancer.

Aims: The aim of this study is to examine the effect of a single nucleotide polymorphism (SNP) rs1347093 (C>A), lying in the upstream regulatory region of microRNA-216b (miR-216b), on the transcriptional activity and to explore the role of miR-216b in pancreatic cancer.

Methods: Luciferase reporter assay, quantitative real-time PCR, and Western blotting were performed.

Results: In patients with pancreatic cancer, the genetic variation rs1347093 (C>A) was observed. In Taiwanese population, the allele frequencies for the C and A at rs1347093 were 96.16% and 3.84%, respectively. Our study further suggested that SNP rs1347093 (C>A) can lead to the lower transcriptional activity. In pancreatic cancer, miR-216b-5p and miR-216b-3p expressions were significantly down-regulated. In addition, highly expressed beclin-1 in pancreatic cancer is a target gene of miR-216b5p.

Conclusions: This study may expand the knowledge of pancreatic cancer risk through miR-216b-related SNP rs1347093.

PATIENTS WITH NON-ALCOHOLIC FATTY LIVER DISEASE AND MUTANT TYPE OF ALCOHOL DEHYDROGENASE

1B/ALDEHYDE DEHYDROGENASE

2 GENE INCREASE THE RISK OF ELEVATED ALANINE TRANSAMINASE

Background: Patients with non-alcoholic fatty liver disease (NAFLD) share the similar pathophysiological presentations with patients of alcohol liver disease. Alcoholic metabolic enzymes related genes, alcohol dehydrogenase 1B (ADH1B) and aldehyde dehydrogenase2 (ALDH2) genes, may be associated with the pathophysiology in NAFLD patients. Aims: This study aims to analyze the association between ADH1B/ALDH2 gene polymorphism and serum metabolic factors, body statures, hepatic steatosis/fibrosis status in patients with NAFLD.

Methods: Patients with NAFLD were included. All participants received serum biochemistry data, abdominal ultrasonography (US) and fibroscan (fibrosis evaluation Kpa; steatosis evaluation, CAP db/m). ADH1B gene SNP s1229984 and ALDH2 gene SNP rs671 polymorphism were analyzed.

Results: From 2021/12/1 to 2022/11/30, constitutional 65 patients were included. The mean age was 54.7 ± 12.4 y/ o. Forty (61.5 %) was female. The gene allele distributions of ADH1B were mutant type (AA 38/65, 58.5%; GA 19/65, 29.2%) and wild type (GG 8/65, 12.3%); ALDH2 mutant (AA 1/65, 1.5%; GA 28/65, 43.1%) and wild type (GG 35/65, 55.4%). No association between body mass index (BMI), serum metabolic factors (sugar, lipid profile), hepatic steatosis (CAP)/fibrosis (Kpa) and ADH1B/ALDH2 gene allele distribution was found in this study. But ALT value was associated with gene allele. Patients with both wild type of ADH1B/ALDH2 allele have a lower value of ALT than those with mutant type (standardized coefficients β = -0.273, p = 0.04).

Conclusions: High percent of mutants type ADH1B allele (57/65, 87.7%) and ALDH2 allele (26/65, 40.0%) were found in our patients with NAFLD. No association was found between ADH1B/ALDH2 gene allele, BMI, and hepatic steatosis/fibrosis. Patients with both mutant type of ADH1B/ALDH2 allele have a higher value of ALT than those with wild type.

非酒精性脂肪肝病人之 ADH1B／ALDH2 基因型態變異與丙氨酸轉胺酵素（ALT）之 相關性

李承儒 陳立偉 林志郎 胡瀞之 錢政弘 簡榮南 基隆長庚紀念醫院胃腸肝膽科

壁報展示 第一部分：肝

P.001

C 肝患者的 ANA 型態表現：單一醫學中心 之分析

ANA PATTERNS OF HEPATITIS C INFECTED POPULATION: A SINGLE CENTER RETROSPECTIVE ANALYSIS

Background: A previous study reported a 30% prevalence of various autoantibodies among patients with hepatitis C virus (HCV) infection. The International Consensus on Anti-nuclear antibody (ANA) Patterns was recently introduced to classify ANA patterns based on immunoassay on HEp-2 cells. There is no previous report with this newly developed classification to evaluate patients with HCV infection.

Aims: The study aims to study the prevalence and pattern of ANA patterns among HCV-infected patients.

Methods: We retrospectively analyzed the medical records of patients with HCV infection from September 2020 to June 2021 at our institution. A positive ANA is defined as a titer of more than 1:320. We compared patient features among the positive and negative groups.

Results: Overall, 258 patients were enrolled—184 patients with negative ANA and 74 patients (28.7%) with positive ANA. The mean age was 67.3 in ANA positive group and 61.2 ANA negative group. Female was prominent with ANA positive and accounted for 63.5%. The most detected ANA pattern was AC-1 (homogeneous) (25.9%), followed by AC-4 (fine speckled) (25.2%) and AC-21 (antimitochondrial antibody) (9.6%). In ANA positive group, we found a trend of lower HCV viral load (5.72 log10 IU/ ML vs. 6.02 log10 IU/ML), lower alanine aminotransferase level (39.5 U/L vs. 44 U/L), and higher advanced fibrosis (F3 and F4) (38.5% vs. 26.1%). In addition, higher positive ANA (more than 1:640) is significantly associated with lower estimated glomerular filtration rate (eGFR) (77.76 vs. 87.94 mL/min/1.73m2, P=0.044).

Conclusions: A high prevalence (28.7%) of ANA was found in patients with chronic hepatitis C. The presence of positive ANA is not related to the severity of their hepatic manifestation. However, higher positive ANA was significantly associated with lower eGFR.

P.002 Neutrophil-to-lymphocyte Ratio（NLR）預 測晚期肝細胞癌患者接受 PD-1/PD-L1 抑制 劑之治療反應

A HIGHER BASELINE NEUTROPHILTO-LYMPHOCYTE RATIO PREDICTED THE PROGRESSION OF DISEASE IN PATIENTS WITH ADVANCED HEPATOCELLULAR CARCINOMA

RECEIVING PD-1/PD-L1 INHIBITORS

Background: Regarding immune checkpoint inhibitors for hepatocellular carcinoma (HCC), one of the major challenges is the lack of predictive biomarkers. This study aimed to investigate potential predictors of tumor response for patients with advanced HCC treated with programmed cell death-1 (PD-1)/programmed cell death ligand-1 (PDL1) inhibitors.

Aims: In this study, we investigated potential predictors of treatment response for patients with advanced HCC treated with PD-1/PD-L1 inhibitors.

Methods: This retrospective observational study included patients with locally advanced or metastatic HCC who received PD-1/PD-L1 inhibitors. Demographics, disease characteristics, baseline laboratory data, HCC stage, previous therapies, tumor responses, adverse events (AEs), and survival were collected. Univariate and multivariate Cox proportional hazard regression analyses were used to evaluate the potential predictors of progressive disease (PD).

Results: A total of 38 patients were included. Among them, 3 (7.9%) patients had complete response, 10 (26.3%) partial response, 5 (13.2%) stable disease, and 20 (52.6%) PD. The objective response rate and disease control rate were 34.2% and 47.4%, responsively. Grade 3/4 and grade 5 AEs were reported in 10 (26.3%) and 3 (7.9%) patients, respectively. Multivariate analysis revealed that only neutrophil-to-lymphocyte ratio (NLR) was independently associated with PD (HR = 1.109, 95% CI = 1.004-1.225, P = 0.041).

Conclusions: This study observed that baseline NLR > 2.5 increased 10% of higher risk of PD after PD-1/PD-L1 inhibitors in patients with advanced HCC patients.

楊芳琦 蘇培元 蕭舜文 顏旭亨 陳洋源 彰化基督教醫院胃腸肝膽科

吳亮寬 林裕鴻 牟聯瑞 台南市立醫院腸胃肝膽科

P.003

EIGHT-WEEKS OF GLECAPREVIR/ PIBRENTASVIR IS WELL TOLERATED AND YIELDS HIGH SUSTAINED VIROLOGICAL RESPONSE IN HCVINFECTED TREATMENT-NAIVE PATIENTS WITH COMPENSATED CIRRHOSIS: THE CREST STUDY

Cornberg M1, Abergel A2, Aghemo A3, Ahumada A4, Andreoni M5, Asselah T6, Bhagat A7, Butrymowicz I7 , Carmiel M8, Chodick G9,10, Conway B11, Gasbarrini A12, Hüppe D13, Jorquera Plaza F14, Lampertico P15,16 , Manzano Alonso ML17, Myles L18, Persico M19, Ramji A20, Sarrazin C21, Semizarov D7, Song Y7, Villa E22, Weil C9, Uriz Otano JI23,24

1Department of Gastroenterology, Hepatology and Endocrinology, Hannover Medical School, Hannover, Germany; 2CHU Estaing, UMR 6602 CNRS Université d’Auvergne, Clermont Ferrand, France; 3Department of Biomedical Sciences, Humanitas University, and Department of Gastroenterology, Humanitas Research Hospital IRCCS, Rozzano, Italy; 4Liver Unit, Hospital General Universitario Gregorio Marañón, Madrid, Spain; 5University of Tor Vergata, Rome, Italy; 6Service d’Hépatologie, Hôpital Beaujon, INSERM UMR 1149, Université de Paris, Clichy, France; 7AbbVie Inc., North Chicago, IL, USA; 8Liver Unit, Galilee Medical Center, Nahariya, Israel. The Azrieli Faculty of Medicine, BarIlan University, Zefat, Israel; 9Maccabitech, Maccabi Healthcare Services, Tel-Aviv, Israel; 10Sackler Faculty of Medicine, Tel-Aviv University, Tel-Aviv, Israel; 11Vancouver Infectious Diseases Center and Simon Fraser University, Vancouver, Canada; 12Internal Medicine and Gastroenterology, Fondazione Policlinico Universitario A. Gemelli IRCCS, Rome, Italy; 13Gastroenterologische Gemeinschaftspraxis Herne, Herne, Germany; 14Digestive System Service, Complejo Asistencial Universitario de León, IBIOMED and CIBERehd, León, Spain; 15Foundation IRCCS Ca’ Granda, Ospedale Maggiore Policlinico, Policlinico – Division of Gastroenterology and Hepatology – CRC ‘AM and A Migliavacca’ Centre for Liver Disease, Milan, Italy; 16University of Milan, Milan, Italy; 17Liver Unit, Hospital Universitario 12 De Octubre, Madrid, Spain; 18Barrie GI Associates, Barrie, Ontario, Canada; 19Dipartimento di Medicina Clinica Medica, Epatologica e Lungodegenza, AOU OO. RR. San Giovanni di Dio Ruggi e D’Aragona, Salerno, Italy; 20University of British Columbia, Vancouver, BC, Canada; 21Department

of Internal Medicine and Liver Center, St. Josefs-Hospital Wiesbaden and Viral Hepatitis Research Group, GoetheUniversity Hospital Frankfurt, Frankfurt, Germany; 22UC Gastroenterologia, Dipartimento di Specialità Mediche, Azienda Ospedaliera Universitaria di Modena, Modena, Italy; 23Navarra Institute for Health Research (IdiSNA), Pamplona, Spain; 24Department of Gastroenterology, Liver Unit, Complejo Hospitalario de Navarra, Pamplona, Spain

Background: The direct-acting antiviral glecaprevir/ pibrentasvir (G/P) is approved for 8-week treatment of chronic hepatitis C genotypes (GT) 1–6 in patients with or without compensated cirrhosis (CC).

Aims: To support clinical trials findings, this study assessed real-world effectiveness and safety in treatment-naïve (TN) patients with CC treated with 8-weeks’ G/P, with a focus on challenging-to-treat patients with advanced liver disease (platelets < 150,000/µl, elasticity > 20 kPa [FibroScan®, Echosens, Paris, France]), or both, and special populations such as drug users, human immunodeficiency virus coinfection, and psychiatric disorders.

Methods: Here we present updated interim results from the CREST study, an ongoing, noninterventional, multicenter study including data from Canada, Germany, Israel, Italy, France, and Spain. The primary endpoint was sustained virologic response at posttreatment Week 12 (SVR12) based on the modified analysis set (MAS) which excluded patients who discontinued G/P for reasons other than nonvirologic failure or with missing SVR12. Safety and laboratory abnormalities were assessed on the full analysis set.

Results: Of 437 patients who received ≥ 1 dose of G/P, 24.5% (107/437) had GT3, 46.0% (189/411) had platelets < 150,000/µl, 16.4% (61/373) had elasticity > 20 kPa, and 9.8% (36/366) had platelets < 150,000/µl and elasticity > 20 kPa. Of 375 patients in the MAS with data available, SVR12 was reached by 371 (98.9%). SVR12 was 97.7% (84/86) in patients with GT3, 99.4% (165/166) in those with platelets < 150,000 /µl, 98.1 % (53/54) in those with elasticity > 20 kPA, and 100% (32/32) in those with both elasticity > 20 kPa and platelets < 150,000/µl. Of 117 (26.8%) patients with an adverse event (AE), 5 (1.1%) had a serious AE (SAE), with 1 (0.2%) discontinuing the study drug due to an AE. None of the SAEs were drug related. The most common AEs (> 5%) were fatigue (9.6%; 42/437) and headache (6.4%; 28/437). Of 421 patients with laboratory data available, 9 (2.1%) and 10 (2.4%) had alanine or aspartate aminotransferase, respectively, > 5x

upper limit of normal.

Conclusions: In this real-world cohort, 8-week G/P therapy was well-tolerated, with SVR12 rates similar to those in clinical trials. These results support the use of G/P therapy in TN patients with CC, regardless of liver disease severity or GT, including GT3. Additional efficacy data in special populations will be presented at the congress.

P.004

Ezetimibe 治療減少肝硬化大鼠氧化態低密

EZETIMIBE TREATMENT REDUCES OXIDIZED LOW-DENSITY

LIPOPROTEIN AND INTRAHEPATIC FAT ACCUMULATION IN BILIARY CIRRHOSIS RATS

Background: In chronic liver disease, chronic inflammation is attributed to an increase of oxidative stress, and which increases the concentration of oxidized low-density lipoprotein (ox-LDL). On the other hand, intrahepatic fat accumulation is a critical factor of fibrogenesis. Intrahepatic steatosis and ox-LDL further exacerbate hepatic inflammation and fibrosis.

Aims: This study aims to test the effect of ezetimibe on cirrhotic rats and investigates its effects on ox-LDL and liver fibrosis.

Methods: Biliary cirrhosis was induced in Sprague-Dawley rats with common bile duct ligation (BDL). Sham-operated rats served as surgical controls. The ezetimibe (10 mg/kg/ day) or vehicle were administered in the sham-operated or BDL rats for 4 weeks. Four weeks later, the hemodynamic parameters, biochemistry data, oxidative stress were evaluated. The plasma level and intrahepatic ox-LDL were also examined. The hepatic tissue was examined and various proteins were analyzed to explore the possible mechanism of ox-LDL on liver fibrosis.

Results: BDL rats presented cirrhotic pictures with hyperlipidemia and elevated ox-LDL levels compared to the control group. Ezetimibe treatment did not influence hemodynamic and biochemistry data of BDL rats; however, it significantly reduced oxidative stress, plasma levels of ox-LDL and tumor necrosis factor α. Although ezetimibe did not improve hepatic inflammation and liver fibrosis, it ameliorated intrahepatic fat accumulation and reduced intrahepatic ox-LDL. In addition, ezetimibe treatment up-regulated hepatic lectin-like oxidized low-density lipoprotein rececptor-1 protein expressions in BDL rats.

Conclusions: Ezetimibe reduced plasma and intrahepatic ox-LDL in cirrhotic rats. Furthermore, it ameliorated intrahepatic fat accumulation and oxidative stress. However, it did not influence hepatic fibrosis and inflammation of biliary cirrhotic rats.

P.005

結合 CRARITY 及αFP 預測無法切除肝腫

瘤病人接受 Anti-PD-1 免疫治療之預後 COMBINED CRAFITY SCORE AND α-FETOPROTEIN RESPONSE PREDICTS TREATMENT OUTCOMES IN PATIENTS WITH UNRESECTABLE HEPATOCELLULAR CARCINOMA RECEIVING ANTI-PROGRAMMED DEATH-1 BLOCKADE–BASED IMMUNOTHERAPY 張哲睿

response: patients with a CRAFITY score of 0/1 and AFP response (Group 1), those with a CRAFITY score of 2 and no AFP response (Group 3), and those who did not belong to Group 1 or 3 (i.e., Group 2). The combination of CRAFITY score and AFP response could predict disease control and could predict PFS compared with CRAFITY score or AFP response alone. The combination of CRAFITY score and AFP response was also an independent predictor of OS (Group 2 vs. Group 1, HR: 4.513, 95% CI: 1.990–10.234; Group 3 vs. Group 1, HR: 3.551, 95% CI: 1.544–8.168).

Conclusions: In conclusion, our findings indicated that the combination of CRAFITY score and AFP response could predict disease control, PFS, and OS in patients with uHCC receiving PD-1 blockade–based immunotherapy.

Background: Biomarkers for predicting the treatment efficacy of immune checkpoint inhibitor (ICI)-based therapy in patients with unresectable hepatocellular carcinoma (uHCC) are crucial.

Aims: Previous studies demonstrated that C-reactive protein and alpha-fetoprotein (AFP) in immunotherapy (CRAFITY) score at baseline predicted treatment outcomes and that patients with uHCC with AFP response, defined as >15% decline in AFP level within the initial 3 months of ICI-based therapy, had favorable outcomes when receiving ICI-based therapy. However, whether the combination of CRAFITY score and AFP response can be used to predict the treatment efficacy of programmed death-1 (PD-1) blockade–based therapy in patients with uHCC remains unclear.

Methods: We retrospectively enrolled 110 consecutive patients with uHCC from May 2017 to March 2022 from two hospitals. The median ICI treatment duration was 2.85 (1.67–6.63) months, and 87 patients received combination therapies.

Results: The objective response and disease control rates were 21.8% and 46.4%, respectively. The duration of progression-free survival (PFS) and overall survival (OS) was 2.87 (2.16–3.58) months and 8.20 (4.23–12.17) months, respectively. We categorized patients into three groups based on CRAFITY score (2 vs. 0/1) and AFP

B 型肝炎肝失償病人接受貝樂克治療短期預 後：單一醫學中心經驗 SHORT–TERM OUTCOMES OF DECOMPENSATED CHRONIC HEPATITIS B PATIENTS TREATED WITH ENTECAVIR: REAL-WORLD EXPERIENCE OF ONE SINGLE MEDICAL CENTER

P.007

貝樂克治療 B 型肝炎肝硬化且肝失償病人： 單一醫學中心經驗

ENTECAVIR FOR PATIENTS WITH HEPATITIS

B DECOMPENSATED CIRRHOSIS: REAL-WORLD EXPERIENCE OF ONE SINGLE MEDICAL CENTER

Background: Entecavir (ETV) is recommended as firstline therapy for chronic hepatitis B (CHB).

Aims: The aim of the study was to elucidate the short-term outcomes of ETV-treated decompensated CHB patients.

Methods: From Jan 2009 to Dec 2021, a total of 244 CHB patients with hepatic decompensation, defined as: total serum bilirubin level ≥ 2 mg/dL, prolongation of prothrombin time ≥ 3 s or an international normalized ratio (INR) > 1.5 upper limit of normal who received ETV in Taichung Veterans General Hospital were enrolled for analysis. The risk factors of 3 month-mortality were analyzed.

Results: Of 244 patients, 185 (71%) were male, with a mean age of 56.07 ± 15.51 years, 48 (19.6%) were positive for HBeAg and 109 patients (44.7%) had cirrhosis. The median survival time was 28.48 ± 39.23 months. The median baseline HBV DNA level was 6.22 ± 1.4 log IU/ml and the median baseline model for end-stage liver disease scores (MELD) was 20.56 ± 7. Baseline MELD, baseline HBV DNA levels, ascites and hepatic encephalopathy were associated with 3 month-mortality.

Conclusions: This study demonstrated baseline MELD score, baseline HBV DNA levels, ascites and hepatic encephalopathy were significant predictor of 3 monthmortality in decompensated CHB patients

Background: Entecavir (ETV) is recommended as firstline therapy for chronic hepatitis B (CHB).

Aims: The aim of the study was to elucidate the clinical outcomes of ETV-treated CHB patients with decompensated cirrhosis.

Methods: From Jan 2009 to Dec 2021, a total of 109 CHB cirrhotic patients with hepatic decompensation, defined as: total serum bilirubin level ≥ 2 mg/dL, prolongation of prothrombin time ≥ 3 s or an international normalized ratio (INR) > 1.5 upper limit of normal who received ETV in Taichung Veterans General Hospital were enrolled for analysis. The risk factors of short-term and long-term mortality were analyzed.

Results: Of 109 patients, 81 (71%) were male, with a mean age of 59.62 ± 13 years and 15 (13.8 %) were positive for HBeAg. The median survival time was 11.1 ± 42 months. The median baseline HBV DNA level was 6.23 ± 1.53 log IU/ml and the median baseline model for end-stage liver disease scores (MELD) was 22.77 ± 7. Baseline MELD score, ascites and hepatic encephalopathy were independently associated with the 3-month, 1-year and 3-year mortality.

Conclusions: The liver reserve was crucial for the clinical outcomes in ETV-treated CHB patients with decompensated cirrhosis.

黃凌嵩1 黃儀倢1 張崇信1 李少武1 李騰裕1 童春芳1 廖思嘉1 葉宏仁2 楊勝舜1 張繼森1 1 臺中榮民總醫院腸胃科 2 童綜合醫院腸胃科

HEPATIC ARTERY INFUSION CHEMOTHERAPY (HAIC) WITH OR WITHOUT RADIATION THERAPY (RT) FOR HEPATOCELLULAR CARCINOMA WITH MAJOR PORTAL VEIN INVASION

COMPARISON OF THE DAAS

TREATMENT OUTCOMES IN PATIENTS WITH HEPATITIS C VIRUS INFECTION BETWEEN INCARCERATED PATIENTS AND OUTPATIENTS

Background: Hepatocellular carcinoma (HCC) patients with major portal vein invasion (MPVI) present with very poor outcomes. Hepatic artery infusion chemotherapy (HAIC) and radiation therapy (RT) have both been found to be effective for advanced HCC with MPVI.

Aims: To compare the therapeutic outcomes of our “new HAIC regimen (combining chemoinfusion with lipiodol embolization) with and without concurrent RT, before and after propensity score matching (PSM), in treating HCC patients with MPVI.

Methods: 140 patients (Group A) with MPVI received HAIC alone and 35 patients (Group B) underwent concurrent HAIC and RT between 2002 and 2018. The Modified Response Evaluation Criteria in Solid Tumors (mRECIST) was adopted to assess the therapeutic objective response rate (ORR). The Kaplan-Meier curve was used to calculate progression-free survival (PFS) and overall survival (OS) between the two groups. Univariate and multivariate analyses by Cox’s regression model were used to assess survival outcomes.

Results: In the initial cohort, higher ORR and PFS were found in the concurrent RT group (80 vs 66.4% and 9 vs 8 months, respectively) but shorter OS (10.5 vs 14.5 months, p = 0.039) were observed. After PSM, the OS was 10.5 and 13 months without reaching significance (p = 0.441). Multivariable Cox regression analysis revealed that the significant factors for adjusting hazard ratios for OS were Child-Pugh classification, AFP level, and hepatic vein invasion.

Conclusions: Our new regimen of HAIC is effective in treating advanced HCC patients with MPVI and may be adopted as the first-line therapy. Concurrent RT provided no additional clinical benefits, with equal or shorter OS.

Background: The prevalence of chronic hepatitis C (HCV) is relatively high among incarcerated individuals ranging from 3%~38% globally. So far direct-acting antivirals (DAAs) has revolutionized the management of CHC with high SVR rates in the general population. DAAs are preferred in custodial settings because of more shorter treatment courses.

Aims: Prison population are thought to have younger age and less comorbidities than outpatients in regards to receiving DAAs therapy. Also, better drug compliance was one of the important reasons due to adequate duration of prison sentences for completing the full course of antviral treatment. Thus, we aimed to conduct a retrospective cohort study to analyze the compositions of characteristics and treatment outcomes (sustained viral response, SVR) between these two groups.

Methods: A total of 148 anti-HCV and HCV ribonucleic acid (RNA) positive patients including 48 incarcerated patients and 100 outpatients in Chi-Mei hospital from July 2021 to February 2022. They were treated with sofosbuvir/velpatasvir or glecaprevir/pibrentasvir. Among all the patients, we excluded patients that be treated second times with HCV recurrence. The SVR 12 was the primary outcome and age/sex distribution, HCV genotype distribution, biochemistry, fibrosis score, lost-to-follow-up were measured as the secondary outcomes.

Results: Forty-eight incarcerated HCV patients and one-hundred HCV outpatients were enrolled for this analysis. The patients in the incarcerated group were male predominant (95.8% vs 52%), more younger (46.83 ± 7.03 vs 60.03 ± 13.2 years), had significantly different genotype distribution (type 6 predominant vs type 2 predominant), higher Hb (14.9 ± 1.54 vs 13.7 ± 1.79 g/dL), albumin (4.34 ± 0.31 vs 4.1 ± 0.47 g/dL), total and direct bilirubin (1.05 ± 0.46 vs 0.74 ± 0.39, 0.44 ± 0.2 vs 0.35 ± 0.2 mg/ dL) but lower ALT (52.02 ± 37.2 vs 77.24 ± 76.17 IU/L), AST (38.46 ± 21.77 vs 59.59 ± 53.59 IU/L) compared to

肝動脈化療是否合併放射治療對合併主門靜 脈侵犯肝癌之療效比較

P.009

丙型肝炎的篩檢與治療：比較監獄與門診病 人的直接作用抗病毒藥物治療效果

張瑄元 楊畯棋 孫啟書 馮意哲 郭行道

許銘仁 奇美醫院胃腸肝膽科

HCV patients in the outpatient group. SVR was achieved in 31 incarcerated group and 92 outpatient group, so the intention-to-treat SVR were 64.5% and 92% respectively. There were 15(including 11 early release and 3 prison transfer) and 5 patients lost to follow up respectively and 2 patients expired in outpatient group finally. Perprotocol SVR were 93.9% and 98.92% respectively. Lower intention-to-treat SVR is achieved in the incarcerated patients (64.5% vs 92%, p = 0.000).

Conclusions: Indeed, incarcerated patients in our analysis partially confirmed our hypothesis of being significantly more male person, younger ages compared to the outpatient group. Though intention-to-treat SVR was significant lower than outpatient group which may due to early releases, prison transfer, insufficient of insight for full treatment course. Per-protocol SVR revealed no significant difference between two groups. That would be a mighty evidence to instigate the HCV survey on incarcerated patients from the beginning of sentence.

P.010

A REAL-WORLD STUDY IN EFFICACY

COMPARISONS OF HEPATIC ARTERIAL INFUSION CHEMOTHERAPY, TYROSINE KINASE INHIBITOR AND RADIOTHERAPY IN ADVANCED HEPATOCELLULAR CARCINOMA WITH MACROVASCULAR INVASION

黃冠凱4 李青記2 吳泓璁1 林毅志3 張定宗4 陳炯瑜4 莊喬雄4 蔡宏名5 郭欣瑜4

1 國立成功大學附設醫院內科部

2 國立成功大學附設醫院臨床醫學研究中心 3

Background: Hepatocellular carcinoma (HCC) is one of the common digestive cancers in Taiwan and the third leading cause of cancer-related deaths worldwide. Portal vein tumor thrombosis (PVTT) is present in 1040% of HCC patients at diagnoses, which usually results in worsening liver function, higher incidence of blood metastasis, complications associated with portal hypertension, and intolerance to treatment. In the past, Sorafenib was the only recommended therapy in HCC patients with PVTT by guidelines but with limited effectiveness. Recently, numerous phase-III trials have reported different agents beyond Sorafenib with promising anti-tumor activities and safety. However, the consensus for the treatment of such patients with advanced HCC is limiting.

Aims: Our study aims to recognize a anti-tumor agent with better efficacy and acceptable safety profiles for patients of HCC complicated with PVTT.

Methods: Adults diagnosed with HCC, who treated hepatic arterial infusion chemotherapy (HAIC), from November 2016 to December 2020 at National Cheng Kung University Hospital were retrospectively included. Exclusion criteria included patients without macrovascular invasion, those diagnosed with hepato-cholangiocarcinoma, those died prior to the first radiographic survey, those with Vp1 or Vp2 invasion, those with hepatic vein tumor thrombus or atypical image pattern of tumor thrombus, and those receiving HAIC combined with regimens other than TKI, radiotherapy (such as radiofrequency thermal

比較肝動脈灌注化學治療、標靶藥物、放射 線治療在晚期肝癌合併大血管侵犯病患的治 療效果之真實世界研究

國立成功大學附設醫院外科部

4 國立成功大學附設醫院肝膽腸胃科 5 國立成功大學附設醫院影像醫學部

ablation or immunotherapy). The eligible patients were categorized in the following groups: (i) HAIC alone, (ii) HAIC plus tyrosine kinase inhibitor (TKI), and (iii) HAIC, TKI, plus radiotherapy. The assessed outcomes included the progression-free survival (PFS), overall survival time, objective response rate (ORR), and adverse reaction. We evaluated the radiologic responses of the tumors by modified Response Evaluation Criteria in Solid tumors (mRECIST). The outcomes between three groups were compared by the Scheffe’s multiple comparison test. In multivariable analyses, the variable (P < 0.05 in univariate analysis) and the propensity score, consisted of the patient age, the Eastern Cooperative Oncology Group (ECOG) score, Child–Pugh stage, Cancer of the Liver Italian Program (CLIP) score, were forced entry in the Coxregression model.

Results: The total 69 patients were categorized in the groups of HAIC alone (14 patients, 20.3%), HAIC plus TKI (39, 56.5%), and HAIC, TKI, plus radiotherapy (16, 23.2%). A significantly dissimilar proportion of AFP > 400 between the HAIC alone, HAIC plus TKI, and HAIC, TKI, plus radiotherapy groups (66.67% vs. 42.86% vs. 20%) was disclosed. The higher proportion of Child–Pugh stage A in the HAIC plus TKI (82.05%) and HAIC, TKI, plus radiotherapy (93.75%) groups was exhibited, compared to that in the HAIC alone group (64.29%). The higher proportion of the Cancer of the Liver Italian Program (CLIP) = 2-5 in the HAIC alone (100%) and HAIC plus TKI (92.31%) groups was observed, compared to that in the HAIC, TKI, plus radiotherapy group (68.75%). In further analyses for outcomes, the significantly shorter median (95% CI) of the overall survival time in the HAIC alone (3.3 [1.9-4.8] months) was discovered, compared to that in HAIC plus TKI (13.8 [6.0-15.8] months) (P = 0.024), or HAIC, TKI, plus radiotherapy (14.5 [8.8-23.7] months) (P = 0.015) groups, respectively. However, no significant difference (P = 0.999) between the HAIC plus TKI and HAIC, TKI, plus radiotherapy groups was noticed. The lower median (95% CI) of the PFS in the HAIC alone group (2.1 [0.6-2.9] months) was exhibited (P = 0.002), compared to that in the HAIC, TKI, plus radiotherapy group (11.3 [5.5-17.9] months). But no significant difference (P = 0.263) in median (95% CI) of the PFS between the HAIC alone and HAIC plus TKI (3.2 [2.2-5.4] months) group was disclosed, and that in the HAIC plus TKI and HAIC, TKI, plus radiotherapy groups was similar (P = 0.528). On the aspect of radiologic responses of the tumors, lower Vessel ORR in the HAIC alone group than

that in the HAIC, TKI, plus radiotherapy group (P = 0.010), but no significant different between the HAIC alone and HAIC plus TKI groups (P = 0.622). The patient proportion of adverse events in three group revealed no statistically difference (P = 0.500). After adjusting the propensity score consisted of the patient age, the Eastern Cooperative Oncology Group (ECOG) score, Child–Pugh stage, Cancer of the Liver Italian Program (CLIP) score, Cox regression model revealed the adjusted hazard ratio (AHR) (95% CI) for mortality in the HAIC plus TKI and HAIC, TKI, plus radiotherapy groups were respectively 0.17 (0.08 – 0.40) and 0.31 (0.12 – 0.81), compared to the HAIC alone group. The AHR (95% CI) for PFS in the HAIC plus TKI and HAIC, TKI, plus radiotherapy groups were respectively 0.27 (0.13 – 0.57) and 0.21 (0.08 – 0.54), compared to the HAIC alone group.

Conclusions: Compared to the HAIC alone group, our study revealed the significant longer overall survival time in the HAIC plus TKI and HAIC, TKI, plus radiotherapy groups, the longer PFS in the HAIC, TKI, plus radiotherapy group, and the more favorable vessel ORR in the HAIC, TKI, plus radiotherapy group. In sum, compared to HAIC monotherapy, combination therapy with TKI, radiotherapy, or both might impart benefits in patients with advanced HCC, with the lack of difference in the occurrences of adverse events. Accordingly, the ideal strategy for patients with advanced HCC with macrovascular invasion might be multimodal, using a combination of several locoregional therapy and personalized systemic therapy. However, a prospective randomized controlled trial involving the larger patient population is needed for evaluating the efficacy of HAIC combination therapy in the future.

P.011

脂肪肝對乳癌的影響 THE IMPACT OF FATTY LIVER DISEASE ON BREAST CANCER

Background: Breast cancer is the most common cancer among women in Taiwan and worldwide, with an annual incidence of two million cases. Fatty liver disease is one of the most common chronic liver diseases. Metabolic components are important risk factors for the development of both fatty liver disease and breast cancer. During the follow up using ultrasonography, many women with breast cancer were found to have fatty liver.

Aims: The aim of this study was to investigate the association between fatty liver and breast cancer and the impact of fatty liver disease on breast cancer.

Methods: From June 1998 to June 2020, 526 patients were diagnosed with tissue-proven breast cancer at the ChengChin general hospital Chung-Gang branch. They were classified as breast cancer with fatty liver group (B+F, No.272) and brest cancer without fatty liver group (BF, No.254). Ultrasonography was performed using a 3.5 mHz transducer. Patients were evaluated on the basis of age, BMI, clinical variables, coexistence of viral hepatitis, survival time, stage and use of hormone therapy. Data were statistically analyzed using the chi-squared test & student’s t-test. Analysis of survival was performed using the Kaplan-Meier method.

Results: Demographic data including average age, BMI, clinical laboratory data, coexistence of viral hepatitis, use of hormone therapy and existence of fatty liver are summarized in table 1 and table 2. The existence of fatty liver disease in patients with breast cancer did not influence the prognosis (figure). But the breast cancer with fatty liver group was found to have higher BMI, higher HbA1C, GOT, GPT, ALP, Hb and platelet values.

Conclusions: The survival was not influenced by the existence of fatty liver in patients with breast cancer. But the breast cancer patients with fatty liver disease have higher BMI, HbA1C, serum transaminases, Hb and platelet values than those without fatty liver disease.

P.012

使用甲型胎兒蛋白、白蛋白與腫瘤負荷分數 建立一個術前的模型預測早期肝細胞癌的微 血管侵犯 A NEW MODEL BASED ON PREOPERATIVE AFP, ALBUMIN, AND TUMOR BURDEN SCORE FOR PREDICTING MICROVASCULAR INVASION IN EARLY-STAGE HCC

張源升1 黃鼎森1 王植熙2 劉約維2 蔡明釗1,3

1 高雄長庚紀念醫院內科部

2 高雄長庚紀念醫院一般外科

3 高雄長庚紀念醫院肝膽腸胃科

Background: Microscopic vascular invasion (MVI) has been demonstrated as a strong risk factor associated with tumor recurrence and poor overall survival among hepatocellular carcinoma (HCC) patients after resection, but the preoperative prediction of MVI is still challenging. Aims: We aimed to build and validate a novel model to predict MVI in the preoperative setting.

Methods: We retrospectively collected 857 patients with Barcelona Clinic Liver Cancer (BCLC) stage 0 or A HCC who underwent primary resection at Kaohsiung Chang Gung Hospital between January 2001 and June 2016. The patients were randomized into derivation (n = 648) and validation groups (n = 209). Logistic regression analysis was used to screen out independent risk factors for MVI and further constructed a predictive model for MVI. Prediction performance was compared by the area under the receiver operating characteristic curve (AUC).

Results: The multivariable logistic regression analysis of the training cohort found that alpha-fetoprotein (AFP) ≥20 ng/mL (OR = 1.96, 95% CI: 1.41–2.73, p < 0.001), albumin <3.5 g/dL (OR = 1.48, 95% CI: 1.06–2.05, p = 0.019) and tumor burden score (TBS) ≥8.6 (OR = 2.54, 95% CI: 1.49–4.35, p = 0.001) to be independent risk factors for MVI. The three factors were chosen to build a model for prediction of MVI. The AUC for the training and validation group was 0.619 (95% CI: 0.575–0.663) and 0.642 (95% CI: 0.562–0.722), respectively, and the calibration plot showed good performance of the prediction model, with a low mean absolute error at 0.01.

Conclusions: The new model comprised AFP, albumin, and TBS that can predict risk of MVI for early-stage HCC.

李政祺 黃仁杰 辛政憲 陳鄭弘堯 何士奇 澄清綜合醫院中港分院胃腸肝膽科

P.013

肝內微型核糖核酸在活體肝移植患者之原生 肝組織內的調控表現 THE ROLE OF HEPATIC MICRO-RNAS IN NATIVE LIVER OF LIVING DONOR LIVER TRANSPLANTATION

林淑賢1,2 王植熙2,3 邢福柳2,4 趙景華1,2

1 高雄長庚紀念醫院肝膽胃腸科系

2 高雄長庚紀念醫院肝臟移植中心

3 高雄長庚紀念醫院一般外科

4 高雄長庚紀念醫院解剖病理科

Background: Living donor liver transplantation (LDLT) is considered a life-saving strategy for patients with endstage liver disease, acute liver failure and hepatocellular carcinoma (HCC). MicroRNAs (miRNAs) are involved in regulating gene expression related to various disease phenotypes and statuses.

Aims: The aim of this study is to explore the hepatic miRNAs signatures in native liver that correlate with the primary liver disease leading to LDLT.

Methods: This study totally enrolled 80 patients, including 70 cirrhotic and 10 non-cirrhotic patients undergoing LDLT. Among the 70 cirrhotic patients, 54.3% (38/70) of them had cirrhosis only, and 45.7% (32/70) of them had LC with concurrent HCC. By using quantitative real-time RT-PCR confirmation, different hepatic miRNAs (miR122, miR-301, miR-133a, and miR-21) expression levels in native liver tissue were identified. Based on specific primary liver disease for LDLT, patients were divided into variant subgroups for hepatic miRNAs signatures analysis.

Results: Compared to non-cirrhotic patients, cirrhotic patients had significant up-regulation of miR-301 and miR-21 (p < 0.05) and down-regulation of miR-133a (p < 0.05). For patients with LC and concurrent HCC, they had marked high expression of miR-122 and low expression of miR-301 and miR-133a (p < 0.05), compared to cirrhotic patient only. In the LC only subgroup, patient with alcoholism or HBV/HCV infection had down-regulation of miR-122 (p < 0.05) compared to those with other etiology of LC. For patients had LC and concurrent HCC, miR122, miR-301 and miR-133a was highly expressed in cases with alcoholism and HBV/HCV infection (p < 0.05). At the meanwhile, miRNA-21 was significantly up-regulated in cases of alcoholic cirrhosis with hepatic steatosis (p < 0.05), but down-regulated in cases of viral related cirrhosis with hepatic steatosis (p < 0.05); Patients with viral related cirrhosis with hepatic steatosis also had obviously up-

regulated miR-122 than those without hepatis steatosis (p < 0.05). Finally, miR-133a was up-regulated for alcoholic LC patients with HCC, and down-regulated in the group of virus-related LC patients with HCC (p < 0.05).

Conclusions: Our study demonstrated that specific hepatic miRNAs in native liver expressed in correlation with the primary liver disease leading to LDLT. The expression patterns of miRNAs may serve as potential diagnostic biomarkers in the setting of LDLT.

P.014

病態性肥胖病人接受減重手術非酒精性脂肪 肝疾病的脂質組學特徵 THE PLASMA LIPIDOMIC PROFILES

醫院外科部消化外科；3 臺北醫學大學醫學院外科學

科；4 臺北醫學大學消化醫學研究中心；5 臺北醫學大

學附設醫院病理部；6 臺北醫學大學醫學院病理學科；7

臺北醫學大學萬芳醫院病理實驗部；8 臺北醫學大學萬

芳醫院病理實驗部；9 臺北醫學大學附設醫院胃腸科； 10 臺北醫學大學營養學院；11 臺北醫學大學台北癌症中

心；12 臺北醫學大學代謝與肥胖科學研究所；

Background: Nonalcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease worldwide and affects 20-30% of the general population. Triglycerides are mostly associated with these pathologies, but other lipid moieties seem to be involved in the development and severity of NAFLD.

Aims: This prospective cohort study aims to use lipidomic analysis to investigate lipidomic profile features before and after bariatric surgery.

Methods: Lipidomics was performed using ultra-highperformance liquid chromatography–tandem mass spectrometry on plasma samples from a prospective cohort study involved morbidly obese patients who underwent sleeve gastrectomy at Taipei Medical University Hospital between October 2016 and December 2020. Venous blood samples were collected before surgery and 6 months postoperatively. Wedge liver biopsy was performed during surgery and significant liver fibrosis was defined as a fibrosis score > 2. We selected healthy obesity (n = 10), nonalcoholic steatohepatitis (NASH) with mild liver fibrosis (F0-1) (n = 20) and NASH with significant liver fibrosis (n = 20) patients.

Results: The distribution of total lipids before and after sleeve gastrectomy between the three groups was presented in partial least square-discriminant analysis and samples were scattered in different area, revealing the different dataset detected. There are no lipid species were identified difference before and after surgery in healthy obesity

group. There are 66 lipid species were identified difference before and after surgery in NASH with mild liver fibrosis group. There are 102 species were identified difference after surgery in NASH with significant liver fibrosis group. The fold changes of cholesterylesters (22:5), ceramides (Cer) (34:0), Cardiolipin (CL) (57:0), CL (75:0), CL (78:2), Phosphatidic acid (PA) (40:4), phosphatidylcholine (PC) (36:1), PC (36:5), PC (40:6), phosphatidylethanolamine (PE) (38:6), PE (40:4), phosphatidylglycerol (PG) (34:0), phosphatidylglycerolphosphate (PGP) (36:1), PGP (38:4), PGP (40:4), phosphatidylinositol (PI) (38:4), phosphatidylserine (PS) (42:4), triacylglyceride (TG) (50:6), TG (59:6) were significant difference before and after surgery between the three groups.

Conclusions: Lipid species were associated with NASH and liver fibrosis before and after bariatric surgery. CE (22:5) and TG (50:6) may be proposed as a lipid metabolite to predict NASH with liver fibrosis in morbidly obese patients.

13 臺北醫 學大學附設醫院營養研究中心

P.015

以巴塞隆納臨床肝癌分期預後與治療策略治 療屏東地區原發性惡性肝腫瘤之臨床回溯性

THE CLINICAL FEATURES AND ASSOCIATED FACTORS OF PRIMARY LIVER CANCER TREATED IN ACCORDANCE WITH BCLC STAGING AND TREATMENT STRATEGY – A RETROSPECTIVE COHORT STUDY IN PING-TUNG COUNTY

Background: Liver cancer can usually be classified by histology as either hepatocecullar carcinoma (HCC) or cholangiocecullar carcinoma (CCC). It displays features of both hepatocecullar and biliary epithelial differentiation. More than 80% of primary liver cancers are HCC and usually occur in cirrhotic liver related hepatitis B or C virus, alcohol use, with a male predominance. Another CCC is the second most common, accounting for 10-15%, with established risk factors of intrahepatic biliary stone, primary sclerosing cholangitis, parasite infection and chemical carcinogen exposure.

Aims: Current Barcelona Clinical Liver Cancer (BCLC) staging guideline for primary liver cancers treatment recommended liver resection, radiofrequency ablation (RFA), transarterial chemoembolization (TACE), radiation therapy (RT), chemotherapy, and best supportive care as treatment strategy. However, whether there is a difference between these two cancers in the extent of pattern of progression, treatment indication and prognosis prediction has not been clarified thus far. In the present study, we aimed to analyze the clinical features and evaluate predictive factors associated with primary liver cancer.

Methods: We conducted a retrospective cohort study and enrolled patients at Pao-Chien hospital, Ping-Tung between Jan 2016 and Dec 2017. Seventy two patients with primary liver cancers, HCC 62 (86.1%) and CCC 10 (13.9%), treated in accordance with BCLC staging and strategy were enrolled based on clinical decision-making and treatment recommendation responsible from multidisciplinary tumor

board team. Data were originally collected a mean period of 6.42 years of follow-up and 1.38 years for treated cohort. Results: The total 72 patients comprised of male 46 (77.6%), cirrhosis 51 (70.8%) predominance, and had a mean age (70.9 ± 11.9) years, PT (INR) (1.09 ± 0.18), platelet 182.3 ± 113.2 (x103/uL), APRI 1.71 ± 2.05, FIB4 6.34 ± 6.76. Cox-regression univariate analysis revealed aged 60 (HR 2.049, CI 1.014-4.139, P = 0.046), PT (INR) (HR 19.783, CI 5.582-66.540, P < 0.001), Total bilirubin (HR 1.104, CI 1.035-1.178, P = 0.003), AFP (HR 1.000, CI 1.000-1.000, P = 0.001), APRI (HR 1.210, CI 1.082-1.352, P = 0.001), FIB-4 (HR 1.048, CI 1.013-1.085, P = 0.006), Child-Pugh (HR 2.969, CI 2.021-4.362, P < 0.001), AJCC (HR 1.222, CI 1.066-1.400, P = 0.004) and BLCL (HR 1.910, CI 1.476-2.470, P < 0.001) were associated with treatment of primary liver cancer. Base on Cox proportional hazards multivariate analysis, AFP (HR 1.000, CI 1.0001.000, P = 0.01), Child-Pugh (HR 1.756, CI 1.065-2.897, P = 0.027) and BLCL (HR 1.538, CI 1.116-2.120, P = 0.009) were independent predictive factor for treatment of primary liver cancer. Logistic regression univariate analysis showed FIB-4 > 3.25 (HR 9.053, CI 1.735-46.708, P = 0.009), cirrhosis (HR 37.5, CI 4.325-325.140, P = 0.001), HBV (HR 10.241, CI 1.223-85.781, P = 0.032), AJCC (HR 6.171, CI 1.446-26.344, P = 0.014) and BLCL (HR 2.043, CI 1.023-4.071, P = 0.042) were associated with treatment of primary liver cancer. Logistic regression multivariate analysis demonstrated cirrhosis (HR 0.038, CI 0.004-0.407, P = 0.007) was independent predictive factor for treatment of primary liver cancer.

Conclusions: Elevated serum AFP has a predictive value for long term risk of HCC development in cirrhotic patients. BCLC treatment strategy help guide an individualized approach to clinical decision-making, according to tumor burden and cancer related symptoms in prognosis prediction.

P.016

反覆經動脈化學栓塞治療中期肝癌的療效 THE RESPONSE OF REPEATED TRANSARTERIAL CHEMOEMBOLIZATION FOR INTERMEDIATE-STAGE HEPATOCELLULAR CARCINOMA

2

Background: Transarterial chemoembolization (TACE) has been widely used in the treatment for intermediate-stage hepatocellular carcinoma (HCC).

Aims: This study aims to investigate the outcome of repeated TACE, and find indicators for early complete response (CR).

Methods: The responses of 54 patients with intermediatestage HCC treated with repeated TACE were retrospectively evaluated during February 2016 and February 2021. The response measured after each TACE was based on mRECIST criteria via dynamic CT or MRI. The liver function was evaluated by ALBI score. The statistical analysis were performed by Student’s t test, chi-square test and logistic regression as appropriate.

Results: Among the 54 patients received first TACE, 9 (16%) patients achieved CR. Of 32 patients received second TACE, one (3.1%) patient reached CR. Among 25 patients received a third session of TACE, 4 (16%) showed CR. Of 16 patients underwent four sessions of TACE, 3 (18.7%) achieved CR. Compared to patients without CR after first TACE, patients with CR after first TACE had significantly higher level of albumin (4.19 ± 0.49 g/dl vs. 3.80 ± 0.46 g/dl, P = 0.046), lower level of AST (33.44 ± 19.65 U/L vs. 55.24 ± 49.97 U/L, P = 0.049) and ALP (71.20 ± 23.29 U/L vs. 113.46 ± 57.78 U/L, P = 0.041), and lower alpha fetoprotein (AFP) levels (8.79 ± 11.92 vs. 2696.19 ± 8166.51 ng/dL, P = 0.012). However, multivariate analysis did not show significant factor associated with CR after first TACE. The mean of ALBI score was significantly increased after the forth (-2.469 ± 0.730) and fifth (-2.241 ± 0.558) TACE.

Conclusions: Repeated TACE treatment was effective for patients with intermediate-stage HCC. Although multivariate analysis showed no significance, lower AFP level, and better hepatic function were observed in HCC BCLC class B patients experiencing CR after their first TACE. Deterioration of liver function occurred after repeated TACE.

P.017

年輕醫療人員 C 型肝炎預防篩檢 HEPATITIS C VIRUS SCREENING IN YOUNG HEALTHCARE WORKER

林欣妮

1 長庚醫療財團法人高雄長庚紀念醫院管理部

2 長庚醫療財團法人高雄長庚紀念醫院家庭醫學科

3

Background: Needlestick injuries (NSI) expose healthcare workers risk to Hepatitis C. Based on results of domestic epidemiologic studies, the national screening of hepatitis B and C has launched in Taiwan since Sep 2020. The ages of examinee are limited between 45 and 79 years. In the past 3 years, 278 needlestick injury events occurred at our hospital, and 43 (15.5%) were exposed to hepatitis C virus.

Aims: This present study aims to investigate the prevalence of young healthcare workers.

Methods: All healthcare worker between 30 to 44 years old at a medical center in the southern were invited to anti-HCV screening. Baseline information collected, including gender, department, age, seniority, and history of needlestick injury. Screening tool was blood survey to check Anti-HCV antibody. Then, the correlation between the positive rate of Anti-HCV Ab and needlestick injury events in young people was investigated.

Results: This is a cross-sectional study with 460 participants. None of participants was positive for antiHCV. Among them, 82 people had experience in needlestick injury (17.8%). Hepatitis C virus infection after needlestick injury was not found to be significantly associated in this study. Therefore, hepatitis C virus infection was the low prevalence in young papulation.

Conclusions: The current study concluded that the prevalence of anti-HCV in young health worker was quite low. We suggest that they might not be the priority group of HCV screening.

何家瑋1 陳墨繁2 翁詩涵3 陳韻正2 林志陵1

1 臺北市立聯合醫院仁愛院區消化內科

臺北市立聯合醫院仁愛院區影像醫學科

3 臺北市立聯合醫院教學研究部

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

P.018

健保給付蕾莎瓦改善晚期肝癌的五年存活率 REIMBURSEMENT OF SORAFENIB IMPROVED 5-YEAR SURVIVAL OF PATIENTS WITH ADVANCED HEPATOCELLUAR CARCINOMA (HCC)

黃惠玲1,2 吳帆2 張德生3 沈建亨3 盧勝男4

1 嘉義長庚紀念醫院護理部

2 國立中正大學資訊管理系

3 嘉義長庚紀念醫院肝膽胃腸科

4 高雄長庚紀念醫院肝膽胃腸系

Background: Sorafenib was approved to be the first target therapy agent of hepatocelluar carcinoma (HCC) based on SHARP and Asia-Pacific trials. It prolonged overall survival for 2.3~2.8 month with a hazard ratio of 0.68~0.69. It has been reimbursed by National Health Insurance in Taiwan since Aug. 1 2012. The first 2nd line target therapy agent, regorafenib, was also reimbursed after Jun. 1 2019.

Aims: To evaluate the survival benefit of reimbursement of sorafenib for the candidates of target therapy, we conducted this retrospective analysis.

Methods: Patients met all the 3 criteria were defined as candidates of sorafenib treatment, i.e. (i). BCLC stage C, (ii). Child-Pugh class A and (iii) not initially treated by surgical resection or local ablation. The study period was between Aug. 1 2012 and Jun 1 2019 and the control period was between Jan 1 2011 and Jul 31 2015. All candidates were enrolled. We reviewed their cancer registration database in a regional hospital and abstracted age, gender, BCLC stage, data of diagnosis, data of death or censor, and initial treatment modality. Medical records of subjects, who survived for 5 years, were also review. Kaplan-Meier survival curve with log rank test was used for survival analysis.

Results: A total of 225 candidates with 214 (95.1%) events (deaths) were recruited in the study period and 48 with 100% events were recruited in the control period. The survival was significant longer in study group (p = 0.029). The median survival times were 0.7 years for the study group and 0.4 years for the controls. Their 5-year survival rates were 7.8% and 2.1%, respectively. Sixteen subjects survived for more than 5 years in the study group, while only 1 in the control. Among 16 patients, 13 (81.2%) were treated by target therapy with or without other combinations.

Conclusions: In the study period, patient with advanced HCC had longer median survival times and higher 5-year survival rate. Target therapy plays a significant role of longer survival. Reimbursement of sorafenib did show significantly but minimal survival benefit.

P.019 早期和晚期肝細胞癌患者腸道菌群的變化 DISTINCT GUT MICROBIOTA ALTERATIONS IN PATIENTS WITH EARLY-STAGE AND ADVANCED-STAGE HEPATOCELLULAR CARCINOMA

Background: Gut microbiota alterations play a key role in the development of hepatocellular carcinoma (HCC); however, little is known about the changes in gut microbiota diversity during the progression of HCC.

Aims: We aimed to characterize the differences in the GM diversity and composition of patients with early-stage HCC and advanced-stage HCC.

Methods: This cross-sectional study examined stool samples from adults with early-stage HCC (n = 31) and advanced-stage HCC (n = 44). The taxonomic composition of the gut microbiota was determined by 16S ribosomal RNA gene sequencing of stool samples.

Results: There was no significant difference in the alphadiversity of the gut microbiota between groups; however, beta-diversity was significantly different between the earlystage and advanced-stage groups. Further analysis indicated that the genus Veillonella, family Enterobacteriaceae, order Enterobactriales, and class Gammaproteobacteria were more abundant in the advanced-stage group than the earlystage group.

Conclusions: Patients with early-stage and advancedstage HCC exhibit different patterns of gut microbiota diversity. Furthermore, specific taxa—including Veillonella, Enterobacteriaceae, Enterobacteriales, and Gammaproteobacteria—are enriched in patients with advanced-stage HCC; these taxa may promote the progression of HCC by allowing accumulation of lipopolysaccharides (LPS).

P.020

HIGHER PREVALENCE OF OCCULT

HBV INFECTION IN HBSAG-/HBCAB+ PATIENTS WITH HEPATOBILIARY CANCERS RECEIVING ANTIVIRAL PROPHYLAXIS

Background: According to the criteria of Taiwan’s National Health Insurance, patients with HBsAg negative and antiHBc positive can receive antiviral prophylaxis to prevent HBV reactivation since Mar. 2021. However, the data about prevalence and clinical characteristics of resolved HBV infection (RBI) and occult HBV infection (OBI) in such population is limited in Taiwan.

Aims: The study is to analyze the prevalence and clinical characteristics of RBI and OBI in HBsAg- and anti-HBcAb+ patients with malignancy receiving antiviral prophylaxis.

Methods: We retrospectively collected 345 HBsAg-/HBcAb+ patients with malignancy receiving antiviral prophylaxis from Mar. 2021 to Nov. 2022. RBI was defined as undetectable HBV DNA and HBsAg-/HBcAb+. OBI was defined as detectable HBV DNA and HBsAg-/HBcAb+.

Results: Of the 345 patients, 334(96.8%) patients were RBI, and 11 (3.2%) patients were OBI. The HBV viral load of OBI ranged from <10 (detected but below lower limit of quantification) to 236 IU/mL. The mean age of RBI and OBI was 62.4 years and 62.8 years. 193 (57.8%) of RBI and 7 (63.6%) of OBI was male. There was no statistical difference of age, gender, BMI, type of malignancy, DM, hypertension, and kidney disease between the two groups. 274 (79.4%) patients were classified as oncology included 7 (3%) OBI and 71 (20.6) patients were classified as hematology malignancy included 4 (6%) OBI. The prevalence of OBI in each type of malignancy in descending order were hepatobiliary cancer (43%, 3/7), leukemia (13%, 2/15), myeloma (13%, 1/8), colon cancer (4%, 1/24), breast cancer (3%, 2/59), lymphoma (2%, 1/48), and other solid cancer (<1%, 1/184), respectively.

Conclusions: The prevalence of OBI is low in HBsAg-/ HBcAb+ patients receiving antiviral prophylaxis but the patients with hepatobiliary cancers had the highest prevalence of OBI. We need to pay more attention to monitor the drug compliance during antiviral therapy in such high-risk patients to prevent HBV reactivation.

P.021

感染 HBV 的孕婦有較低的 DNA 檢測率但 較高的治療率：一個醫學中心的經驗 LOWER TESTING RATE OF HBV DNA BUT HIGHER TREATMENT RATE AMONG PREGNANCY WOMEN WITH HBV INFECTION: A MEDICAL CENTER EXPERIENCE

林靜君

蘇培元 林婉瑜 顏旭亨 彰化基督教醫院胃腸肝膽科

Background: Antiviral therapy is recommended to reduce the rates of vertical transmission in pregnancy women with viral load more than 10^6 IU/mL during the third trimester and was implemented by Taiwan’s National Health Insurance since Feb. 2018. The data about HBV testing and care among these pregnancy women is limited in Taiwan.

Aims: The study is to analyze the clinical characteristics and HBV testing among pregnancy women with HBV infection in a medical center.

Methods: We retrospectively collected 218 pregnancy women with HBV infection from Feb. 2018 to Nov. 2022. All patients had visited our obstetrics outpatient clinic at least once. Patients had no data of HBeAg were excluded. Finally, 184 patients were included into the study. Results: The mean age of the 184 pregnancy women with HBV infection was 37.1 years old included 22 (12%) HBeAg+ patients. 129 of 184 patients had regular prenatal cares in our hospital while only 76 of 129 (58.9%) patients had completed HBV DNA test. 7 of 76 (9.2%) patients had HBV viral load more than 10^6 IU/mL and all these patients (100%) received antiviral therapy during third trimester. In the pregnancy women with both available data of HBeAg and HBV DNA (n = 88), the ratio of women had therapeutic level of HBV viral load (>10^6 IU/mL) is higher in HBeAg+ women (6/13, 46.2%) than HBeAgwomen (1/75, 1.3%).

Conclusions: To eliminate mother-to-child transmission of HBV, low HBV DNA testing in pregnancy women with HBV infection is an important issue that need to be resolved. We need to make more practical strategies to increase the testing rate, especially in HBeAg+ pregnancy women.

接受抗病毒預防治療的 HBsAg-／HBcAb+ 肝膽癌患者有較高的隱匿性 HBV 感染盛行 率

林婉瑜 蘇培元 曾雅慧 顏旭亨 彰化基督教醫院胃腸肝膽科

P.022

慢性 C 肝及 B 肝合併感染病人接受 C 肝口 服抗病毒藥物治療引起 B 肝活化相關肝炎

萬芳醫院及基隆醫院經驗 CLINICAL RELAPSE RELATED TO REACTIVATION OF HEPATITIS B IN PATIENTS OF CHRONIC HEPATITIS C WITH HEPATITIS B VIRUS INFECTION TREATED WITH DIRECT ACTING ANTIVIRALS – THE EXPERIENCE OF WAN–FANG AND

Background: Because the Asia-Pacific area is hyperendemic for HBV exposure for adults who were born before the mass HBV vaccination program. Approximately 10% of HCV viremic patients were seropositive for HBsAg. When HCV is eradicated with DAA, HBV reactivation (HBVr) may occur. A meta-analysis study demonstrated that only 9% of HBV/HCV co-infected patients who received DAA treatment developed HBVrrelated hepatitis (Lancet Gastroenterol. Hepatol. 2018, 3, 172–180).

Aims: This study aimed to reveal the difference between medical center and regional hospital about patient’s characteristics and medical care. In addition, we tried to explore the predictive factor of HBVr related clinical relapse in HBV/HCV co-infected patients under DAA treatment.

Methods: From Jan 2017 to Nov 2021, 432 cases of Wan Fang hospital and 259 cases of Keelung hospital with HCV viremia received DAA were collected. Finally 29 cases and 21 cases with co-infected HBV in respective hospital who had at last 6 months follow-up post HCV SVR or off antiHBV prophylaxis were enrolled. In addition, 48 cases were selected to assess the HBVr related clinical relapse except one liver cirrhosis and one HIV cases with keeping Nuc use.

Results: The 50 cases cohort included 30 men and 20 women with a median age of 61 (39 – 84) years old at entry and a 21.7 ± 12.7 months follow-up. Liver cirrhosis, HCC and HIV comorbidity were 5, 1 and 1 respectively. The median HCV RNA level was 5.78 (2.73 – 7.38) log10 IU/ml and HCV SVR was 96% post DAA. All cases were negative HBe Ag and 23 (46%) had detectable HBV DNA. The median HBV DNA level was 2.32 (1.15~4.87) log10

IU/ml and high HBV DNA (>2000 IU/ml) was 4 (8%). Age, sex, pre treated liver function test, PT, AFP, HCV RNA level, genotype distribution and HBV DNA level had no significantly difference between two hospitals except all cirrhosis cases and lower platelet count in Wan-Fang hospital. Total 18 cases (36%) received Nuc prophylaxis and only one case was in Keelung hospital. Whether the use of Nuc prophylaxis was not related to HBV DNA level or detectable HBV DNA. 6 cases (12.5%) had HBVr related clinical relapse during following–up (4 cases in Keelung hospital and 2 cases in Wan-fang hospital). Two cases had reused Nuc and one of them was expired. We used clinical relapse as dependent variable and age, sex, cirrhosis, ALT > 2x, log10 HCV RNA, HCV SVR and HBV DNA > 2000 IU/ml as independent variables. Single variate logistic regression models showed only HBV DNA > 2000 IU/ml significantly related to the presence of relapse (HR: 20.5, 95% CI: 1.506 – 279.002. P = 0.023). But Multivariate logistic regression models showed only log10 HCV RNA was significantly related (HR: 11.23, 95% CI: 1.373 –91.855, P = 0.024).

Conclusions: From our small study, the incidence of HBVr related clinical relapse was 12.5%. The lower rate of Nuc prophylaxis in Keelung hospital was related to decision of doctor and financial reason of patient. HCV RNA level was the only significant factors for clinical relapse in our limited data.

P.023

單獨使用或合併肝動脈化學藥物灌注治療與 免疫檢查點抑制劑於治療併大血管侵犯之晚

期肝癌 台灣單一醫學中心之臨床經驗

HEPATIC ARTERIAL INFUSION

CHEMOTHERAPY AND IMMUNE

CHECKPOINT INHIBITORS, ALONE OR IN COMBINATION, IN ADVANCED HEPATOCELLULAR CARCINOMA WITH MACROVASCULAR INVASION: A SINGLE-CENTRE EXPERIENCE IN TAIWAN

江健銘1 吳叡森1 洪子鈞1 吳泓璁1 林毅志2 張定宗1

王崇騰1 劉紋君1 謝名宗1 吳毅晉1 陳柏潤1 陳炯瑜1

林聖翔3,4,5 莊喬雄1 陳煌斌1 蔡宏名6 郭欣瑜1,3

1 國立成功大學醫學院附設醫院內科部

2 國立成功大學醫學院附設醫院外科部

3 國立成功大學醫學院臨床醫學研究所

4 國立成功大學醫學院公共衛生研究所

5 國立成功大學醫學院附設醫院生物統計諮詢中心

6 國立成功大學醫學院附設醫院影像醫學部

Background: The presence of vascular invasion is associated with poor survival in advanced hepatocellular carcinoma.

Aims: We compared the effectiveness of hepatic arterial infusion chemotherapy and immune checkpoint inhibitors, alone or in combination, in patients with advanced hepatocellular carcinoma.

Methods: This retrospective study analysed overall response, vascular response and survival in patients with unresectable hepatocellular carcinoma and macrovascular invasion receiving at least one dose of hepatic arterial infusion chemotherapy, immune checkpoint inhibitors or hepatic arterial infusion chemotherapy plus immune checkpoint inhibitors.

Results: A total of 130 patients were included. There was no significant difference in overall response between three groups. Objective response rate of vascular thrombi was significantly different between three groups (p = 0.023). Post hoc Bonferroni correction showed that vascular objective response rate was significantly higher in patients treated with combination therapy than those treated with hepatic arterial infusion chemotherapy (p = 0.014). For responses in portal vein tumour thrombus, objective response rate was significantly different between three groups (p = 0.013), and post hoc Bonferroni correction showed that patients treated with combination therapy

significantly had higher objective response rate (p = 0.005) than those treated with hepatic arterial infusion chemotherapy. The 12-month overall survival and progression-free survival rates were 31.4% and 24.6% in patients treated with immune checkpoint inhibitors, 44.9% and 21.2% in those treated with hepatic arterial infusion chemotherapy, and 67.5% and 33.2% in those treated with combination therapy, respectively. There were no significant differences in overall survival (p = 0.1268) and progression-free survival (p = 0.0913) between three groups.

Conclusions: Hepatic arterial infusion chemotherapy combined with immune checkpoint inhibitors had a superior response of portal vein tumour thrombus compared to hepatic arterial infusion chemotherapy and immune checkpoint inhibitors alone. Future studies are needed to address the survival benefit of the combination therapy in advanced hepatocellular carcinoma with macrovascular invasion.

P.024

在標準以上的肝癌存活期是 C 肝盛行偏鄉 整合性肝病照顧計畫的最終成果

ABOVE STANDARD SURVIVAL OF HEPATOCELLULAR CARCINOMA AS FINAL OUTCOMES OF COMPREHENSIVE HEPATOLOGY CARE PROGRAMS IN A REMOTE HCVENDEMIC AREA

卓韋儒1 黃惠玲2 邱文南1 胡錦鴻1 黃東榮3 張德生1,4 盧勝男4,5

1 雲林長庚紀念醫院肝膽胃腸科

2 嘉義長庚紀念醫院護理部

3 雲林長庚紀念醫院胸腔科

4 嘉義長庚紀念醫院肝膽胃腸科

5 高雄長庚紀念醫院肝膽胃腸系

Background: Two nearby Townships, Mailiao and Taihsi, located in northern coast of Yunlin county and are endemic for hepatitis C virus (HCV) infection and hepatocellular carcinoma (HCC). Under the feedback programs of the local petrochemical corporation, all residents were invited to an annual health examination in these 10 years. Items concerning HCC screening were included, i.e HBsAg, antiHCV, AFP and abdominal ultrasonography. About 50% of residents underwent health examination at least once. The Chang Gung Memorial Hospital Yunlin Branch (YLCGMH) in Mailiao executed health examination and provided postexamination care. HCV viremia was detected in more than 1000 patients and most of them have been treated by interferon-based or direct-acting anti-viral agent (DAA) in the hospital. The YLCGMH is a 100-bed local hospital has facilities of almost all items of laboratory test, CT and MRI, but has only limited facilities on HCC treatment. Aims: To evaluate HCC survival as final outcomes of the comprehension hepatology care programs, we conducted this retrospective study.

Methods: A biweekly hepatology clinic established in October 2017 and accepted internal and external referral patients with uncommon or severe liver diseases, mostly HCC. Patients with newly diagnosed HCC or recurrence after treatment were transferred to CGMH Chiayi branch (CYCGMH) for further management. The CYCGMH is a 1300-bed reginal hospital with full facilities and abundant experience of HCC treatment. All HCC cases referred from YLCGMH to CYCGMH during 5-year period after October 2017 were enrolled. Characteristics of patients joined the screening program (screening group) were

compared with those who didn’t participate the screening program (control group). BCLC-stage-specific survival was analyzed. BCLC-stage-specific survival was analyzed.

Results: A total of 77 patients were enrolled, including 53 in screening group and 24 in control group. Screening group has more cases diagnosed in early stage (BCLC stage 0+A 86.8% vs 62.5%, p = 0.028), best liver function reserve (ALBI grade I 77.3% vs 50%, p = 0.031) and longer survival (p=0.036). The median survivals were >5 years, 3.3 years and 0.5 years in BCLC stage 0+A, B and C, respectively. They were above the expectations of BCLC guideline 2022 in stages 0, A and B.

Conclusions: This successful comprehensive hepatology care model in remote endemic area showed screening of hepatitis and HCC, and linkage to accessible high quality care results in good HCC survival.

Background: Chronic hepatitis C virus (HCV) infection is one of the leading causes of liver cirrhosis, hepatic decompensation, hepatocellular carcinoma (HCC), and liver transplantation candidacies. It has been estimated that liver cirrhosis developed approximately 10%–20% of patients over 20–30 years after HCV infection with a 3%–6% annual risk of hepatic decompensation and a 1%–5% annual risk of HCC. Successful antiviral treatment response brings huge beneficial effect on long-term outcome for patients with chronic hepatitis C (CHC). However, the risk of hepatic decompensation and future development of HCC are not entirely eradicated after cure of HCV infection, especially for patients with advanced liver disease.

Aims: At present, real-world data evaluating the long-term incidence of disease progression for CHC patients with liver cirrhosis after treating with Peg-IFN plus ribavirin (RBV) with or without SVR are scarce in Taiwan.

Methods: Between January 2011 to June 2018, a total of 79 consecutive CHC patients with compensated liver cirrhosis who treated with Peg-IFN plus RBV by the investigators were enrolled. History of HCC before the initiation of PegIFN, prior liver transplantation and early terminate antiviral therapy with short follow-up period (<1 year) were excluded. For patients who failed to Peg-IFN plus RBV, all oral direct-acting antivirals (DAAs) were provided for rescue therapy and treatment responses were recorded. The primary end point analyzed was the cumulative incidence of disease progression after Peg-IFN initiation, defined as the occurrence of any of the following: (1) liver decompensation events (ascites, variceal hemorrhage, hepatic encephalopathy, or jaundice), (2) de novo HCC, (3) need for liver transplantation, or (4) death. The date of the

first event was determined for cumulative failure curves. Death was categorized further as liver-related and non–liver-related. The cumulative incidence of liver disease progression was measured by Kaplan-Meier statistical method and compared by log rank test.

Results: Mean age of enrolled patients starting Peg-IFN was 59.8 ± 9.3 years, 60.8% of them was female, and mean pre-treatment HCV RNA was 5.98 ± 0.91 log10 IU/ mL. After therapy with Peg-IFN plus RBV, 50.6% of them achieved SVR. The median follow-up period post first dose Peg-IFN was 109 months (mean value: 98.3 ± 32.5, range: 16 to 143 months). 31 of 39 (79.5%) patients who failed Peg-IFN plus RBV received all oral DAAs as rescue and 30 of them (96.8%) achieve SVR. A total of 39 (49.4%) patients developed liver disease progression during study period, 18 in SVR and 21 in Peg-IFN failure group. For cirrhotic patients achieved SVR by Peg-IFN + RBV (n = 40), incidence to have liver disease progression at 2, 5, 8, and 11 years was 17.6%, 28.4%, 41.1% and 58.0%, respectively. For Peg-IFN failure (n = 39) but majority of them successfully rescued by all-oral DAAs, the incidence to have liver disease progression at 2, 5, 8, and 11 years was 12.8%, 34.6%, 51.4% and 64.1%, respectively (P = 0.584). De novo HCC is the most common event of liver disease progression, responsible for 77.7% in Peg-IFN SVR and 57.1% in Peg-IFN failure patients, respectively.

Conclusions: Despite viral clearance by Peg-IFN, the longterm risk to develop liver disease progression still existed for CHC patients with liver cirrhosis. For cirrhotic CHC patients who failed therapy with Peg-IFN, future incidence of liver disease progression could be negatively modified, at least in part, by successful DAAs rescue. Continuing surveillance of HCC and other liver-related events should be arranged for patients with advanced liver disease after antiviral therapy.

直接抗病毒藥物治療南台灣一監獄慢性 C 型肝炎受刑人 DIRECT-ACTING AGENTS FOR THE TREATMENT OF CHRONIC HEPATITIS C DETAINEES IN A PRISON OF SOUTHERN TAIWAN

relapser was treated with 12w Epclusa for GT 6. Conclusions: These IDU detainees are significantly younger and less advanced fibrosis/cirrhosis in comparison with previous hospital-based CHC population. Genotype 6, 1a and 3 HCV among intravenous drug abuse detainees are much higher than in general population while the common GT 1b and 2 comprise only. DAAs achieved a very high SVR12 rate (99.3%). Routine HCV testing is recommended to be included in health examination as well as HBV/HIV upon arrival at prison.

Background: WHO estimates that 71 million people worldwide were chronically infected with hepatitis C virus (HCV) in 2017. Globally, 23% of new HCV infections and one in three HCV deaths are attributable to injecting drug use (IDU). Intravenous drug users carry an extremely high prevalence of HCV infection after the outbreak of HIV/ HCV since 2003 in Taiwan. Various genotype and subtypes of HCV, such as genotype 3, 6a, 6n, 6k, were introduced from Thailand and Yunnan, China. To achieve the goal of HCV elimination in 2025, it is necessary to screen and treat this special population to prevent further transmission.

Aims: To screen and treat detainees with chronic hepatitis C in prison.

Methods: From Jan. 2019, our institute set up a GI OPD weekly to screen and treat HCV in Tainan Second Prison. A total of 152 detainees with HCV viremia were treated according to reimbursement of National Health Insurance Administration.

Results: All 152 CHC detainees are male with IDU history, mean age was 45.8 ± 5.5 years old; comorbidities including 2 with cancer (1 thyroid, 1 HCC), 5 with diabetes, 22 with dyslipidemia, 19 with HBV coinfection, and 8 with cirrhosis (by ultrasonography). FIB-4 scores were F0: 112, F1: 27, F2: 7, F3: 3 F4: 3. Sixty-four (42%) were GT 6, followed by GT 1a (39, 26%), 1b (19, 12%), GT 3 (15, 10%), GT 2 (11, 7%) and mixed types (4, 3%). Seventyeight detainees were treated with 8w Maviret, 36 with Epclusa, 33 with Harvoni, 3 with Epclusa/Ribavirin, 1 with 12w Maviret, and only one DAA experienced relapser was treated with 12w Vosevi. Twelve detainees were paroled before 12w post treatment follow-up despite of pretreatment inquiry of parole timeline. Two detainees died during treatment, one due to aortic dissection and refusal of surgical intervention (Child-Pugh B cirrhosis, Epclusa/ Riba) and the other one with thyroid cancer history died in prison unnoticed (Maviret). The overall SVR12 rate of completed follow-up is 99.3% (137/138). The only one

P.026

董宏達1,2 林政衡1,2 吳昱勳1,2 李佩倫1,2 陳志州1,2 黃婷儀2 1 柳營奇美醫院胃腸肝膽科 2 柳營奇美醫院肝病中心

P.027

POST-PROGRESSION TREATMENT

OUTCOMES OF SORAFENIB

FOLLOWED BY REGORAFENIB FOR UNRESECTABLE HEPATOCELLULAR CARCINOMA ‒ EXPERIENCE AT A MEDICAL CENTER

Background: Hepatocellular carcinoma (HCC) remains to be one of the leading causes of cancer-related death in Taiwan. Sorafenib is one of the first-line systemic treatments for advanced HCC. The pivotal RESORCE trial showed that regorafenib was effective as second-line therapy for patients with advanced HCC who progressed on first-line sorafenib. Real-world data are needed to assess clinical outcomes in the setting of daily practice in Taiwan.

Aims: Our purpose was to present real-world experience with post-progression treatment outcomes of sorafenib followed by regorafenib for unresectable HCC.

Methods: From Jan 2017 to July 2022 at MacKay Memorial Hospital, we retrospectively reviewed the medical records of HCC patients who had received sorafenib-regorafenib sequential therapy, and in total, 55 patients who received sorafenib followed by regorafenib are enrolled in this study. Response evaluation was done based on mRECIST every two to four months after treatment. Survival analysis was calculated by using the Kaplan-Meier method.

Results: A total of 55 patients was enrolled and male predominant (n = 48, 87.2%). The median age of these patients was 64.5 years. The proportion of patients positive for HCV Ab and HBsAg, and alcoholic liver disease were 69%, 20%, and 18.2%, respectively. Most patients belonged to Child-Pugh score A (n = 47, 85.4%). The proportion of patients with BCLC stage B and C were 41.8% and 56.4%, respectively. Fourteen cases (25.5%) and 26 cases (47.3%) had portal vein thrombosis and extrahepatic spread, respectively. Most of the patients had disease progression (n = 43, 78.2%). The median progression free survival (PFS) after sorafenib was 6 months and after regorafenib was 3

months. The median overall survival (OS) of these patients after the time of diagnosis was 61 months. The median OS after sorafenib followed by regorafenib was 38 months, and after regorafenib was 22 months, respectively.

Conclusions: Compared to the clinical trial study of sorafenib-regorafenib sequential and regorafenib therapy, our real-world data showed longer OS of the patients receiving sorafenib followed by regorafenib. Post-progression treatment will play an essential role in prolonging survival. These need more further prospective studies to validate.

Regorafenib 繼 Sorafenib 治療無法切除肝細 胞癌症患者失敗後的治療結果 一個醫學

3 馬偕醫學院

P.028

成人預防保健受檢者接受 B、C 型肝炎篩檢： 台灣北部一醫院統計 SCREENING OF HEPATITIS B AND C IN ADULT PREVENTIVE HEALTH CARE SERVICE: STATISTICS FROM A HOSPITAL IN NORTHERN TAIWAN

林政寬1 施雅麗1 張桂芬1 陳志道2

1 亞東紀念醫院肝膽胃腸科

2 亞東紀念醫院家醫部

Background: In Taiwan, screening of hepatitis B and C once in a lifetime during adult preventive health care service is provided by Health Promotion Administration, and extended to 45- to 79-year-old adults or more than 40-year-old indigenous peoples since September 28, 2020. Detection of the unawareness patients is crucial in the treatment and prevention of further complications of chronic liver disease.

Aims: We aim to analyze the seropositive rate of HBsAg and anti-HCV in adults receiving hepatitis screening in a hospital in northern Taiwan.

Methods: A hospital-based retrospective review was conducted on the subjects who underwent hepatitis B and C screening in the integrated preventive care center of Far Eastern Memorial Hospital from October 2020 to July 2022. Serology of HBsAg and anti-HCV were detected by Roche Cobra e801 with Elecsys® HBsAg II and Anti-HCV II immunoassay for the qualitative determination. The positivity was defined as ≥0.9 COI.

Results: Totally 10170 subjects received hepatitis B and C screening in the study period. There were 44.6% of the subjects with 1st code of ID card from the Taipei metropolitan area (Taipei, New Taipei City, and Keelung). Totally 1038 patients (10.21%) with HBsAg carrier and 162 patients (1.59%) with anti-HCV positivity were found, included 15 patients (0.15%) combined HBsAg and HCV carrier. HBsAg seropositivity was 10.78% in male patients and 9.75% in female patients. The positive rate was higher in 45- to 59-year-old groups (12.87% in 45- to 49-year; 12.09% in 50- to 59-year), and 1st code of ID card from Kinmen County (14.29%), Pingtung County (12.95%), and Changhua County (12.8%). In the Taipei metropolitan area, Taipei City was 10.01% and New Taipei City was 9.84%. The seropositivity of anti-HCV was 1.37% in male patients and 1.77% in female patients. The positive rate was higher in 60- to 79-year-old groups (2.1% in 69- to 79-year; 1.5% in 60- to 69-year), 1st code of ID card from Kaohsiung

City (4.17%), Chiayi County (3.71%), and Taichung City (3.53%). In the Taipei metropolitan area, Taipei City was 1.14% and New Taipei City was 1.08%.

Conclusions: Taipei metropolitan area has a low prevalence of hepatitis C, but the same prevalence of hepatitis B as other Taiwan regions. Realization of the seropositive rate in different age and geographic populations helps in the detection of high-risk persons in the screening program.

Background: Portal hypertension and hepatic encephalopathy (HE) leads to many lethal complications in liver cirrhotic patients. Recent studies suggest that gut microbiota plays a critical role in pathogenesis of portal hypertension and hepatic encephalopathy.

Aims: Fructooligosaccharides are prebiotic that affect microbiota. This study aimed to investigate the impacts of fructooligosaccharides on portal hypertension-related derangements, hepatic encephalopathy and gut microbiota in cirrhotic rats.

Methods: Sprague-Dawley rats received bile duct ligation to induce cirrhosis or sham operation as control. BDL and sham rats received oral vehicle or fructooligosaccharides daily. Experiments were performed when liver cirrhosis developed.

Results: Fructooligosaccharides did not precipitate liver fibrosis in sham or cirrhotic rats. However, it decreased hepatic vascular resistance significantly (P = 0.03). Vasodilation-related protein expressions of phospho - Akt (P = 0.008) and GCH1 (P = 0.01) upregulated significantly in liver in fructooligosaccharides-treated group. Although locomotor functional test did not demonstrate improvement in fructooligosaccharides-treated group, fructooligosaccharides reduced oxidative stress in liver and brain. In fecal microbiota analysis, Dubosiella increased significantly in fructooligosaccharides-treated group.

Conclusions: In conclusion, fructooligosaccharides reduced hepatic vascular resistance and brain oxidative stress. The beneficial effects of fructooligosaccharides in cirrhotic patients deserves further investigation.

Background: PIVKA-II (Des-gamma-carboxy prothrombin, DCP) is a type of abnormal prothrombin secreted by HCC and proven to be a useful serum marker in the diagnosis of HCC as Alpha-Fetoprotein (AFP). Microvascular invasion (MVI) is a histological feature that indicates aggressive behavior of HCC and perceived as an independent predictor for disease free and overall survival of HCC patients. In some reports, PIVKA-II is recognized to be helpful in the predication of MVI among HCC patients. However, there are a few studies to discuss the association between PIVKA-II level and presence of MVI in detail.

Aims: This retrospective single center study is to analyze the PIVKA-II level in prediction of microvascular invasion and other prognostic factors in patients with resected HCC. Methods: Retrospectively, the patients with resected HCC who received PIVKA-II test before the liver resection were collected at our institution from January 1, 2021 to September 31, 2022. The patients who had pathological diagnosis of HCC from surgical specimens were enrolled and split into two groups according to PIVKA-II level. We analyzed these patient’s histopathological characteristics and clinical data.

Results: There were 68 patients with resected hepatic tumors receiving PIVKA-II test before liver resection, and a total of 67 patients with pathological diagnosis of HCC were enrolled. The optimal cut-off level of PIVKA-II in our data for univariate analysis that predicted MVI was 77 ng/ml, based on appropriate data analysis, thus the patients were split into two groups (group A and B, PIVKA-II cutoff level of 77 ng/ml). Group A composed of 33 patients with PIVKA-II level < 77 ng/ml and group B composed of

P.029

在肝硬化合併肝腦病變之大鼠果寡醣能減少

潘俊傑1,2 許劭榮1,2 黃惠君1,2 黃怡翔1,2 侯明志1,2 李發耀1,2 1 臺北榮民總醫院胃腸肝膽科 2 國立陽明交通大學醫學系

34 patients with PIVKA-II level ≥ 77 ng/ml, and the median age was 63.5 ± 9.97 and 62.1 ± 14.2 years, respectively. Both groups were male predominant (84.8% vs. 64.7%). The prevalence of HBV, HCV, and chronic viral hepatitis (HBV or HCV) infection was 72.7%, 24.8%, and 90.9% in the group A, and 54.8%, 11.8%%, and 73.5% in the group B. The proportion of patients with well-compensated liver cirrhosis (Child-Pugh score A), and functional compromise or decompensated liver cirrhosis (Child-Pugh score B and C) was 97.0% and 3.0% in the group A, and 91.2% and 8.8% in the group B. The proportion of patients with BCLC stage C or D in two groups was 3.0% and 35.3%, respectively. The mean of AFP level in the group A and B was 800.3 ± 4356.7 and 6247.6 ± 22209.1 ng/ml, and the mean of tumor size of liver resection in the group A and B was 1.98 ± 1.11 and 5.58 ± 4.82 cm. The proportion of surgical method with lobectomy in two groups is 0.0% and 14.7%. In histopathology, the proportion of poor differentiated HCC in two groups was 12.1% and 11.8%, respectively. The proportion of macrovascular invasion and microvascular invasion was 0.0% and 6.1% in the group A, and 8.8% and 58.8% in the group B. The characteristics of patients between two groups were not significantly different in age, gender, viral hepatitis, Child-Pugh score, AFP level, surgical method, tumor differentiation and macrovascular invasion. There was a higher proportion of patients who belonged to BCLC stage C or D in the group B (n=12, 35.3%), compared to the group A (n=1, 3.0%) (p=0.001). The mean of tumor size of liver resection in the group B is significantly larger than the group A (5.58 ± 4.82 vs.1.98 ± 1.11 cm) (p < 0.001). The proportion of presence of microvascular invasion (MVI) in HCC was higher in the group B, compared to the group A (58.8% vs. 6.1%) (p < 0.001).

Conclusions: The HCC patients with PIVKA-II level ≥ 77 ng/ml detected before liver resection have a higher proportion of advanced BCLC stage (BCLC C or D), and larger tumor size in surgical specimens, and significantly higher proportion of microvascular invasion in HCC, suggesting high recurrence rate and poor long-term survival.

P.031

與微塑料暴露引起的新生兒肝損傷 MELATONIN IS BETTER THAN RESVERATROL IN ALLEVIATING MATERNAL HIGH FAT DIET PLUS MICROPLASTICS EXPOSURE IN NEONATE OFFSPRING LIVER INJURY

刁茂盟 Khai-Lun Kong 高雄長庚紀念醫院兒科

Background: Maternal high-fat diet and exposure of microplastics can impact the accumulation of liver fat in the offspring, which can cause liver cirrhosis. Melatonin and resveratrol has been reported in alleviating high-fat diet or exposure of microplastics injury.

Aims: To study the possible beneficial effects of melatonin or resveratrol in neonate offspring liver injury through both maternal high-fat diet (1st hit) and microplastics exposure (2nd hit).

Methods: After confirmation of pregnancy, pregnant females Sprague-Dawley rats were randomly divided for the maternal high-fat diet exposure paradigm (HFD) or normal diet (NCD) until delivery. The others were fed with microplastics as NCDL: NCD + microplastics (5 μm, 100 μg/L), NCDH: NCD + microplastics (5 μm, 1000 μg/L), HFDL: HFD + microplastics (5 μm, 100 μg/L), HFDH: HFD + microplastics (5 μm, 1000 μg/L). Oral melatonin and resveratrol were given in the NCDL, NCDH, HFDL and HFDH. The offspring was sacrificed 7 days after delivery (PD7).

Results: In offspring liver, the western blot of cleaved caspase 3 expression with cellular apoptosis increased in HFDH (P < 0.05) but not NCDL, NCDH and HFDL, which in the four groups cleaved caspase 3 expression decreased (P < 0.05) more in the melatonin than resveratrol administration. The phospho-AKT expression increased in NCDL, NCDH, HFD, HFDL and HFDH (P < 0.05) which were decreased (P < 0.05) more in the melatonin than resveratrol administration. The MDA, lipid peroxidation, expression were increased in HFD, HFDL, HFDH groups (P < 0.05), which was decreased more in melatonin than resveratrol in HFDL but decreased more in the resveratrol than melatonin in HFDH groups.

Conclusions: Cellular apoptosis was alleviated more in melatonin than resveratrol in the neonate offspring liver after maternal microplastics plus HFD. The lipid peroxidation was alleviated more in the melatonin than resveratrol in maternal low dose microplastics plus HFD.

褪黑激素優於白藜蘆醇降低母體高脂肪飲食

P.032

抗生素使用於接受內視鏡組織黏膠注射胃靜 脈曲張病患之預防感染的效果：期中分析 ANTIBIOTIC PROPHYLAXIS IN PATIENTS UNDERGOING ENDOSCOPIC INJECTION OF CYANOACRYLATE FOR PRIMARY AND SECONDARY PREVENTION OF GASTRIC VARICEAL BLEEDING: INTERIM ANALYSIS

2 國立陽明交通大學醫學系

5

Background: Antibiotic prophylaxis is an integral part for the management of acute variceal bleeding in cirrhotic patients. However, it is unclear whether prophylactic antibiotic usage is benefit for the patients without acute gastric variceal bleeding (GVB) treated by elective gastric variceal obturation (GVO).

Aims: This randomized trial aimed to evaluate the efficacy of prophylactic antibiotics in patients treated by elective GVO.

Methods: Patients with gastric varices but without acute GVB were enrolled in Taipei Veterans General Hospital and randomized to the prophylactic antibiotic group (ertapenem 1 g iv. 30 mins before GVO) and the control group (without antibiotic usage) in a 1:1 ratio. The primary outcome was the incidence of bacteremia in 24 hours after GVO. Secondary outcomes were any infection, GVB and overall survival in 2 months.

Results: From May 2017 to December 2021, 49 patients were enrolled and randomized to the antibiotic group (n = 24) and the control group (n = 25). All patients received GVO and the assigned treatment successfully. The blood culture results were negative at 30 mins, 4 hrs and 24 hrs after GVO in both groups. The cumulative probability of any infection (p = 0.0768) and GVB (p = 0.6677) were not significantly different between the two groups. In multivariate analysis, concurrent hepatocellular carcinoma was the only independent factor associated with GVB after GVO (HR: 8.176, 95% CI: 1.10160.692, p = 0.040). No patient dead in both groups within 2 months.

Conclusions: According to the preliminary results, the administration of prophylactic antibiotics may not have additional benefits for patients without acute GVB treated by elective GVO. Final conclusions will be made after the study is completed in the near future.

P.033

補充凝結芽孢桿菌 TCI711 益生菌對脂肪性

肝病患者之影響：初期研究

EFFECTS OF BACILLUS COAGULANS

TCI711 SUPPLEMENTATION ON PATIENTS WITH NON-ALCOHOLIC FATTY LIVER DISEASE: A PRELIMINARY STUDY

簡御如1 黃奕文2,3,4 張甄2 謝榮鴻1 楊明達5

1 臺北醫學大學保健營養學系

2 臺北醫學大學附設醫院消化內科

Background: Bacillus coagulans reduces hepatic lipid accumulation and inflammatory biomarkers in patients with non-alcoholic fatty liver disease.

Aims: We aim to investigate the effects of Bacillus coagulans TCI711 supplementation on the amount of fatty change (Controlled Attenuation Parameter, CAP) and fibrosis score on FibroScan in patients with non-alcoholic fatty liver disease.

Methods: All subjects received blood testing and FibroScan before and after supplementation. A randomized, double-blind study design was used to assign 16 subjects into the treatment group 1 (n = 8) or placebo group 2 (n = 8). All participants consumed either one capsule of Bacillus coagulans TCI711 probiotic or placebo once per day for 8 weeks. Data was analysed by two-way mixed-design ANOVA.

Results: Pre-treatment GPT was 28.1 ± 12.0 and 38.8 ± 22.7, became 24.2 ± 10.0 and 39.0 ± 23.9 post treatment, in group 1 and 2, respectively. Pre-treatment CAP score was 296.9 ± 66.7 and 341.8 ± 41.5, became 291.0 ± 70.5 and 330.4 ± 47.4 dB/m post treatment, in group 1 and 2, respectively. Pre-treatment fibrosis score was 4.5 ± 1.0 and 5.5 ± 1.9 in group 1 and 2, respectively. Post treatment fibrosis score was significantly lower in group 1 than 2 (4.0 ± 1.0 vs. 6.9 ± 3.1, p < 0.05).

Conclusions: Lower fibrosis score in treatment group might be due to lower hepatic inflammation after Bacillus coagulans TCI711 supplementation. Further study is needed to confirm these finding.

P.034

病毒性肝炎在膽管癌患者身上扮演的角色 THE ROLE OF THE HEPATITIS VIRUSES IN PATIENTS WITH BILE DUCT CANCER: EXPERIENCE AT ONE MEDICAL CENTER

P.035

的重要代償及保護機制

Background: Bile duct cancer, cholangiocarcinoma (CCA), including intrahepatic cholangiocarcinoma (iCCA) and extrahepatic cholangiocarcinoma (eCCA), is a highly lethal cancer. Several associated risk factors would have effects on the incidence and prognosis of CCA. The retrospective study discusses the evidence implicating viral hepatitis (HBV and HCV) has correlations with different anatomical sites of CCA, but has not been revealed in Taiwan.

Aims: Our purpose was to evaluate the association of viral hepatitis with different anatomical sites of CCA.

Methods: The medical records of patients with CCA in MacKay Memorial Hospital from Jan. 1st, 2015 to Feb. 28th, 2021 were reviewed retrospectively. The patients with histologically proven CCA were enrolled. The Chi-square test and t-test were applied for the analysis of potential risk factors between patients with iCCA and eCCA. Survival analysis was calculated by using the Kaplan-Meier method.

Results: A total of 136 patients with histologically proven CCA were collected and 48% of patients were male. The mean age was 65 ± 11.1 years. The patients were comprised of two groups; the iCCA group (n = 74) and the eCCA group (n = 62). There were no differences between iCCA and eCCA groups in age (64.3 ± 11.4 versus 65.8 ± 10.9 years, P = 0.43), sex, intrahepatic duct (IHD) stone, post-cholecystectomy, NASH/ NAFLD, and liver cirrhosis. However, there were significant differences in symptomatic (P < 0.005), cholelithiasis (P = 0.029), and bilirubin level (P < 0.005). Moreover, we found that more patients had viral hepatitis in the iCCA than eCCA group (49% versus 13%, P < 0.005). There was no significant difference in cumulative survival curves between the iCCA and eCCA group (P = 0.424). There was also no difference in survival curves for CCA patients in the viral and non-viral groups (P = 0.487). Furthermore, there was also no difference in survival curves for iCCA patients in the viral and non-viral groups (15.3 ± 22.6 versus 19.7 ± 21.4 years, P = 0.37).

Conclusions: Our real-world data showed that the patient with iCCA had a higher infection rate of virus hepatitis than eCCA. However, virus hepatitis did not cause an effect on the survival of iCCA patients.

Background: Hepatic encephalopathy is a lethal complication of liver cirrhosis and is derived from neuroinflammation and hyperammonemia. Meningeal lymphatics drain the waste and maintain the homeostasis of the brain. Our published study suggested that enhanced meningeal lymphangiogenesis in early cirrhosis ameliorated neuroinflammation and HE. However, meningeal lymphatic function in advanced liver cirrhosis has not been surveyed. Aims: This study aimed to evaluate the role of meningeal lymphatic system in advanced liver cirrhosis.

Methods: Liver cirrhosis was induced in male SpragueDawley rats by common bile duct ligation. Early cirrhosis or late cirrhosis developed 4 or 6 weeks after operation, respectively. In addition, sham or deep cervical lymph node ligation were performed in parallel groups with advanced liver cirrhosis.

Results: Rats with advanced liver cirrhosis had more severe portal hypertensin, portosystemic collateral shunting, and hyperammonemia. However, there was no significant differences in the severity of hepatic encephalopathy and neuroinflammation between early and advanced cirrhotic rats. Interestingly, advanced liver cirrhosis group had meningeal lymphangiogenesis, increased brain clearance function and meningeal lymphatic drainage. Blocking meningeal lymphatic drainage by deep cervical lymph nodes ligation significantly exacerbated hepatic encephalopathy in rats with advanced liver cirrhosis.

Conclusions: In conclusion, meningeal lymphangiogenesis developed in advanced liver cirrhosis and prevented the deterioration of neuroinflammation and hepatic encephalopathy. Meningeal lymphangiogenesis is an important physiological compensatory mechanism of hepatic encephalopathy in advanced liver cirrhosis.

簡銘陞 李庚頷 王蒼恩 洪建源 林慶忠 劉家源 陳銘仁 王鴻源 張經緯 馬偕紀念醫院肝膽腸胃科

腦膜淋巴管新生是晚期肝硬化大鼠肝腦病變

P.036

COVID-19 大流行時期接受全基因型直接抗 病毒藥物治療的 C 型肝炎患者其藥物交互 作用的真實世界經驗

REAL WORLD EXPERIENCE OF DRUG-DRUG INTERACTIONS FOR HCV PATIENTS RECEIVING PANGENOTYPIC DIRECT-ACTING ANTIVIRALS IN THE ERA OF COVID-19 PANDEMIC

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. However, drug-drug interactions (DDIs) must be avoided when used in combination with other medications, especially with the possible concomitant use of COVID-19 infection antivirals during the COVID-19 pandemic.

Aims: This study aimed to access the potential DDIs of concomitant drugs with pan-genotypic DAAs and COVID-19 infection antivirals, and actual incidence of DDIs in real-world experience.

Methods: From January 2022 to October 2022, consecutive 116 HCV patients receiving pan-genotypic DAAs were retrospectively enrolled in Taipei Veterans General Hospital. The number of comedications and their potential DDIs with three pan-genotypic DAA regimens and three COVID-19 infection antivirals were analyzed. The actual incidence of DDIs during DAAs treatment were also investigated.

Results: The mean age was 60.9 years old, with male predominant (55.2%). Of them, 12 (10.3%) patients had cirrhosis, and 24 (20.7%) patients had diabetes mellitus. Most patients were within Child–Pugh class A (109/116, 94.0%). The distribution of HCV genotypes was 8.6 % in GT 1a, 36.2% in GT 1b, 39.7% in GT 2, 6.9 % in GT 6, and 8.6% in indeterminate genotype, respectively. Of them, 43 (37.1%) patients received GLE/PIB, 69 (59.5%) received SOF/VEL ± RBV, and 4 (3.4%) received SOF/ VEL/VOX as DAAs regimen. Noteworthy, four patients had COVID-19 infection during DAAs treatment course.

The rates of ETVR and SVR12 were 97.6 % and 95.3%.

The mean number of concomitant medications was 2.01. The distribution of concomitant drugs was 64.7% with no

concomitant drug, 11.2 % with 1-3 drugs, 11.2 % with 4-6 drugs, 9.5 % with 7-9 drugs, and 3.4% had more than 9 drugs, respectively. In potential contraindicated (red) DDI class, GLE/PIB was the most prevalent (7.3%), followed by SOF/VEL/VOX (6.4%), and SOF/VEL (1.8%) for non-cirrhosis and compensated cirrhosis patients; and no red DDI occurred in decompensated cirrhosis patients. In addition, the percentage of patients without potential DDIs was higher with SOF/VEL (79.8%) than with the other regimens. The potential red DDIs were predominantly with lipid‐lowering agents for DAAs. For potential red DDI class with COVID-19 infection antivirals, Nirmatrelvir/Ritonavir was the most prevalent (6%), followed by Remdesivir (0.9%), and no potential DDIs with Molnupiravir. For COVID-19 antivirals, the potential red DDIs was mainly with central nervous system drugs. Finally, the actual incidence of DDIs during DAAs treatment showed no red DDI occurred for all patients, and GLE/PIB was the most prevalent (93%) of no potential DDIs.

Conclusions: The potential DDIs between these comedications differed, with the most potential DDIs occurring with GLE/PIB and Nirmatrelvir/Ritonavir. After careful assessment of comedications and their potential DDIs, the actual incidence of DDIs could be reduced, and optimize safety in real-world practice.

P.037

放射治療合併系統性療法在晚期肝癌合併靜 脈血栓患者的存活效益評估 SURVIVAL BENEFITS OF COMBINED RADIOTHERAPY WITH SYSTEMIC THERAPY FOR ADVANCED HEPATOCELLULAR CARCINOMA PATIENTS WITH VENOUS THROMBOSIS

黃弘睿1 藍耿欣1,3,4 黃怡翔1,2 侯明志1,3

1 臺北榮民總醫院腸胃科

2 國立陽明交通大學臨床醫學研究所

3 國立陽明交通大學醫學系

4 國立陽明交通大學藥理學研究所

Background: Radiotherapy (RT) is a local treatment modality for patients with hepatocellular carcinoma (HCC) with portal vein thrombosis (PVT), hepatic vein thrombosis (HVT) and inferior vena cava (IVC) thrombosis.

Aims: To evaluate the prognostic factors and efficacy of RT in combination with systemic therapy in HCC with venous thrombosis.

Methods: This retrospective study included 261 HCC patients with PVT, HVT or IVC thrombosis. Twenty-nine patients received treatment of RT combined with systemic therapy, targeted therapy or immune checkpoint inhibitors. Two hundred and thirty-two patients received systemic therapy alone.

Results: Among 261 patients, the medium overall survival was 9.3 months with the combination of RT and systemic therapy vs. 6.5 months with systemic therapy alone (p value: 0.037). Survival at 6, 9 and 12 months was 79.3%, 58.6%, 41.4% and 45.3%, 35.8%, 30.6%, respectively.

Conclusions: In patients with advanced HCC and venous thrombosis, survival was significantly longer in those treated with RT combined systemic therapy than with systemic therapy alone.

P.038

C 型肝炎病毒非結構蛋白質 5A Ser235 磷酸 化在 NS5A 二聚體形成及病毒複製之基因型 特異性功能意義

GENOTYPE-SPECIFIC FUNCTIONAL SIGNIFICANCE OF HCV NS5A SER235 PHOSPHORYLATION IN NS5A DIMERIZATION AND VIRAL REPLICATION

藍耿欣 黃怡翔 侯明志

臺北榮民總醫院胃腸肝膽科

Background: HCV NS5A is a dimeric phosphoprotein responsible for HCV replication. Yet, the functional significance of NS5A Ser235 phosphorylation in HCV lifecycle has never been unambiguously defined.

Aims: The aim of this study is to elucidate the role of NS5A Ser235 phosphorylation in NS5A dimerization and resistance to direct-acting antiviral agents.

Methods: A series of NS5A mutants were constructed by site-directed mutagenesis in HCV genotype 1b Con1 strain and genotype 2a JFH1 subgenomic replicons. NS5A dimerization assay was performed by inter-molecular crosslinking using glutaraldehyde in Huh-7.5.1 cells transfected with Con1 subgenomic replicons, JFH1 subgenomic replicons or FLAG-tagged NS5A plasmids. Resistance to NS5A inhibitors was determined in Huh-7.5.1 cells transfected with Con1 or JFH1 reporter subgenomic replicons followed by luciferase assay.

Results: The genotype 2a JFH1 NS5A phosphomimetic S235D mutant formed a dimer that is resistant to disruption by NS5A inhibitors. Ser235 phosphorylation and ensuing dimerization of the NS5A resistance-associated substitution Y93H did not require other non-structural proteins that are indispensable for wild-type NS5A function in genotype 2a JFH1 but not in genotype 1b Con1 strain.

Conclusions: This study demonstrated genotypic differences in the role of Ser235 phosphorylation coupled with NS5A dimerization and replication between HCV genotype 1b and 2a.

P.039

PROPHYLACTIC BROAD SPECTRUM ANTIBIOTICS IS ASSOCIATED WITH LOWER RISK OF INFECTION IN INTUBATED PATIENTS WITH ACUTE VARICEAL BLEEDING

廖思涵1,2 簡國龍3,4 陳祈玲3,5,6 許辰陽3 陳健弘1,2,7 陳秀熙3 高嘉宏2,5

1 國立臺灣大學醫學院附設醫院癌醫中心分院綜合內科 部消化科

2 國立臺灣大學醫學院附設醫院腸胃肝膽科

Background: In patients with liver cirrhosis presenting with acute variceal bleeding, bacterial infection is an important issue. Previous studies has been already demonstrated that prophylactic antibiotics could reduce risk of bacterial infection and rebleeding. However, there are still considerable numbers (10-20%) of bacterial infection even under prophylactic antibiotics.

Aims: To explore the risk factors of bacterial infection in intubated patients with acute variceal bleeding.

Methods: From 2016 to 2022, 54 patients with variceal bleeding and intubation were reviewed. Thirteen of them under active infection upon variceal bleeding, 41 of them developed bacterial infection after variceal bleeding. Choice of prophylactic antibiotics, type of sequential infection and mortality in 6 weeks were reviewed.

Results: Of the 41 patients with variceal bleeding and intubation, 20 (48.8%) of them developed sequential bacterial infection. On multivariate analysis, broad spectrum prophylactic antibiotics was associated with lower infection rate, but not 6 weeks mortality. Hepatic encephalopathy, nasogastric tube insertion and acute on chronic liver failure were associated with higher infection rate. Acute on chronic liver failure was associated with higher 6 weeks mortality.

Conclusions: Broad spectrum prophylactic antibiotics might lower sequential bacterial infection in patient with variceal bleeding and intubation.

3 國立臺灣大學公衛學院流行病學與預防醫學研究所

4 國立臺灣大學醫學院附設醫院心臟內科

5 國立臺灣大學臨床醫學研究所

Background: To reduce the incidence of hepatocellular carcinoma (HCC), three change points of interventions have been implemented in Taiwan, including hepatitis B vaccination from 1984, universal health care from 1995, and antiviral therapy from 2004.

Aims: The primary aim of this study was to predict when and how the elimination of virus-related HCC could be achieved by adding large-scale antiviral therapy to the causal chains of interventions with deep machine learning method.

Methods: The digital twin design was envisaged to produce the virtual group after learning parameters that governed the direct and indirect causal chains of three change-point interventions, including the gradual expansion of antiviral therapy when making allowance for the heterogeneity of demographic and geographic variations. Bayesian causal graphic model was adopted to estimate when and how eliminating virus-related HCC with the incidence less than 4 per 100,000 could be achieved with large-scale antiviral therapy.

Results: Based on the incidence predicted by the virtual group after learning the long-term time trend of HCC incidence pertaining to three-change points of direct and indirect causal chains, the elimination of virus-related HCC in Taiwan would be achieved by the end of 2045 when a further 10,042 virusrelated HCC incident cases could be averted after treating 159,992 and 34,624 chronic hepatitis B and C patients with large-scale antiviral therapy, respectively.

Conclusions: We demonstrate how to use the digital twin design with Bayesian casual graphic model to achieve the elimination of virus-related HCC when adding largescale antiviral therapy to the existing three change-point interventions for HCC.

胃食道靜脈出血並插管的病患使用預防性廣 效抗生素與較低的感染率有關

陳宥任1,2 侯明志1,2 黃怡翔1,2 1 臺北榮民總醫院胃腸肝膽科 2 國立陽明交通大學醫學院

P.040

以深度機器學習預測台灣病毒性肝炎相關肝 癌根除的潛在性 PREDICTING THE POTENTIAL OF ELIMINATING VIRUS-RELATED HEPATOCELLULAR CARCINOMA IN TAIWAN BY DEEP MACHINE LEARNING

6 國立臺灣大學醫學院附設醫院外科部

7 國立臺灣大學醫學院

Background: Various treatments are available for patients with liver cancer; however, patients often experience serious symptoms after treatment, such as stomach discomfort, fever, loss of appetite, anxiety, or liver cancer recurrence, thereby affecting their quality of life (QOL).

Aims: To improve the QOL of patients with liver cancer, this study investigated the posttreatment lifestyle of sixty patients.

Methods: A self-reported structured questionnaire and a modified Chinese version of the Health Enhancement Lifestyle Profile (HELP-C) were used to collect the demographic data and to assess patients’ overall posttreatment lifestyle, respectively.

Results: Significant differences were observed between the overall posttreatment lifestyle and the demographic variables of age, ethnicity, education level, marital status, chronic diseases, and posttreatment complications (p < 0.05). Significant differences (p < 0.05) were observed in the HELP-C domains of diet, leisure, and activities of daily living (ADL) between the sexes. The scores for diet (9.66 ± 4.21) and leisure (4.33 ± 2.03) in women were significantly lower (p < 0.05) than those in men (13.13 ± 4.98 and 6.17 ± 2.37, respectively), indicating that women with liver cancer should be more concerned about diet and leisure after surgery. However, the score for ADL was significantly higher (p < 0.05) in women (17.90 ± 5.15) than in men (13.48 ± 2.56), indicating that men should focus on improving ADL.

Conclusions: This research provides reference clinical data on the posttreatment lifestyle of patients with liver cancer to improve their QOL.

P.042

比較慢性

測力 COMPARISONS OF PREDICTABILITY BETWEEN PRE- AND POST-THERAPY ALPHA FETOPROTEIN FOR HEPATOCELLULAR CARCINOMA IN CHRONIC HEPATITIS C PATIENTS AFTER VIRAL ERADICATION

Background: Alpha fetoprotein (AFP) is a useful biomarker for hepatocellular carcinoma (HCC) surveillance but also a biomarker reflecting bridging hepatic necrosis during inflammation, which level will be reduced if hepatic inflammation be improved. It remained unknown whether the predictability for HCC occurrence using the AFP levels before and after DAA treatment would be different.

Aims: The study aims to compare the predictive performances of AFP before and after pre-DAA treatment for HCC in CHC patients with and without advanced chronic liver disease (ACLD).

Methods: CHC patients achieved SVR by interferon-free DAA, whose AFP levels were both available before and after DAA therapy were enrolled. The ACLD was defined as LSM ≥ 10 kPa and/or FIB-4 ≥ 3.25 and/or ultrasound signs of cirrhosis. The prediction for HCC occurrence between pre-DAA and end-of-treatment (EOT) were compared by area under receiver operating characteristic curve (AUROC). The optimal cut-off value of AFP for prediction of HCC was calculated by Youden Index.

Results: A total of 883 patients were enrolled with mean age of 63 years old, 41% patients of male and 70% patients of ACLD. The AUROCs for predicting HCC by pre-DAA AFP vs. EOT AFP were comparable (0.730 vs. 0.754, P = 0.258). The optimal cut-off value for HCC prediction was lower in AFP at EOT of 3 ng/mL than pretherapy AFP of 6 ng/mL, both with sensitivity >80% and NPV > 95%.

After stratifying pre-DAA ACLD status, EOT AFP showed significant better predictability for HCC than pretherapy AFP in ACLD patients (0.702 vs. 0.645, P = 0.014) while the pre-DAA AFP had superior predictability for HCC to the EOT AFP in non-ACLD CHC patients (0.928 vs. 0.831, P = 0.005). If stratifying by pretherapy ALT levels ≥2 times

肝癌患者治療後生活方式：一探索性研究 POSTTREATMENT LIFESTYLE OF PATIENTS WITH LIVER CANCER: AN EXPLORATORY STUDY

顏聖烈

C 型肝炎使用全口服抗病毒藥開 始與結束治療之甲型胎兒蛋白對於肝癌的預

(X) versus <2X upper limit of normal (ULN), AFP level at EOT had better predictability for HCC than pre-DAA AFP (0.746 vs. 0.676, P = 0.023) in CHC patients with pre-DAA ALT ≥ 2X ULN, while the two timepoints AFP levels’ predictability appeared to be comparable in those with preDAA ALT < 2X ULN.

Conclusions: EOT AFP level is superior to pre-DAA AFP level for HCC prediction among patients with pre-DAA ALT > 2X ULN while it appeared comparable among ACLD patients or those with pre-DAA ALT < 2X ULN. In non-ACLD patients, pre-DAA AFP is better than EOT AFP for HCC prediction.

P.043

COVID-19 大流行相關的肝癌患者生存中的 維生素 D 系統和 ACE2 基因組學：從真實

世界的大數據到實驗室分子生物學 VITAMIN D SYSTEM AND ACE2

GENOMICS IN LIVER CANCER

PATIENTS’ SURVIVAL ASSOCIATED WITH COVID-19 PANDEMIC: FROM REAL-WORLD BIG DATA TO LABORATORY MOLECULAR BIOLOGY

楊光祖1,2,3,4,5 康水成1 李明義6 顏家祺7 謝博軒2 許郡倫2 葉彥秀8 葉耀宗9 稅皓靄2 林雅雯2 戴嘉言10 余明隆11 吳登強10 蔡成枝12 洪志勳13 董乃昀3 鄭文隆3 胡翔崴3 許秉毅14 司徒惠康15 許惠恒15

1 高雄市立民生醫院肝膽腸胃內科；2 國防醫學院醫學

科學研究所；3 國際創新生醫技術研究院；4 美國西南 大學；5 國際學士院；6 高雄市立民生醫院內科部心臟 內科；7 高雄市立民生醫院骨科；8 台大醫學院微生物 學科暨研究所；9 輔英科技大學；10 高雄醫學大學附設 中和紀念醫院；11 中山大學；12 高雄長庚紀念醫院；13 義守大學；14 中國醫藥大學附設安南醫院；15 國家衛生 研究院

Background: During 2019-2022, COVID-19 pandemic has a great impact on global health, economics, and psychosocial status of people. Previous studies revealed that vitamin D level was associated with patients infected with COVID-19. Angiotensin-Converting Enzyme 2 (ACE2) as a potential diagnostic and prognostic biomarker influencing patients’ metabolic pathway in COVID-19 infection. On the other hand, the metabolic role of ACE2 in liver cancer patients is still unaddressed via molecular biology till now.

Aims: To conduct a real-word big data and laboratory molecular biology networking in liver cancer patients. Methods: We downloaded the prevalence and the death rates of liver cancer. Metabolic information and pathways regarding ACE2 and vitamin D system was retrieved from HPA. STRING database showed proteomics of ACE2. Finally, we searched the survivals of liver cancer patients regarding ACE2-vitamin D system associated genomic markers.

Results: As shown in Figure 1, liver cancer prevalence and death rates were higher in Asia-Pacific region than Europe and Latin America. Table 1 shows ACE2 metabolic summary, mainly about transport reactions. Figure 2 illustrated detailed metabolic signaling pathway of ACE2

and proteomics informatics. Figure 3 shows 10-year survivals of liver cancer patients on the basis of vitamin D system relevant genomic markers.

Conclusions: We demonstrated that ACE2/CYP2E1/ CYP4V2/COQ6/CYP2R1 were statistically significant associated with liver cancer patients’ 10-year survivals.

第二部分：消化道及膽胰疾病 P.044

大腸平滑肌瘤：病歷系列 COLONIC LEIOMYOMA: CASE SERIES

林連福1 黃彼得1 許秋潤2

1 童綜合醫院肝膽腸胃科

2 童綜合醫院解剖病理科

Background: Gastrointestinal leiomyoma commonly occurs in the esophagus and stomach. Colonic leiomyoma is rare, accounting for only 3% of all gastrointestinal smooth muscle tumors. [Mod Pathol. 2001;14:950-956. World Journal of Gastroenterology. 2015;21:1091–1098. Journal of the American College of Surgeons. 2004;198:134-146. Gastroenterology Research. 2016;9:105–107. American Journal of Roentgenology. 1955;74:246-255.] These tumors are usually asymptomatic and are detected incidentally in routine colonoscopy [Hong Kong Med J. 1997;3:325-327.] The common locations of colon leiomyoma are descending colon and sigmoid colon [World J Surg. 2000;24:430–436. J Med Assoc Ga. 1991;80:667–683.], with 43% of colon leiomyomas less than 0.5 cm in size [World J Surg. 2000;24:430–436.]. The lesions usually present as sessile type, although pedunculated type can also be seen. The surface pattern can mimic epithelial polyps during colonoscopy [Gastroenterology Research. 2016;9:105–107. The Korean Journal of Gastroenterology. 2016;68:179–185.].

Aims: The aim of this study is to report our clinical experience on colonoscopic morphology by Paris classification [Endoscopy. 2002;34:226–36.], mucosal surface characteristics, and methods of resection of colonic leiomyomas.

Methods: From Jan. 2018 to Oct. 2022, 5 cases of colonic leiomyoma from a total of 2163 cases of colonoscopy were analyzed. Transparent cap fitted water exchange colonoscopy was used for routine colonoscopy. The instruments used were CF290L Olympus Optical Co., Ltd., Tokyo, Japan, water infusion pump with room-temperature water, and Olympus distal attachment (transparent cap) D-201-13404. Pethidine and midazolam or intravenous propofol sedation were used. The colonoscopic morphological pictures [Paris classification] and mucosal pattern by NICE (NBI International Colorectal Endoscopic Classification based on narrow-band images) classification were reviewed. The endoscopic resections were performed with cold snare polypectomy or cold endoscopic mucosal resection. The pathological diagnosis of leiomyoma was made based on microscopic findings of spindle cell pattern,

positive SMA (smooth muscle antigen) immunochemical staining, and negative staining for CD (cluster of differentiation)117, CD34, and DOG 1(discovered on gastrointestinal stromal tumors protein 1).

Results: There were 4 female patients, and 1 male patient, with the mean age of 60.2 (51-74 years). Three lesions were found in sigmoid colon, 1 in transverse colon, and the remaining in hepatic flexure. Normal mucosal patterns were found in 3 cases and the remaining 2 cases mimic the adenoma pattern NICE type 2. Cold endoscopic mucosal resection was performed in 3 cases, and cold snare polypectomy in two. Two cases with normal mucosal pattern retained nearly the same colonoscopic pictures after submucosal indigo carmine solution injection, and the lesions were firm in consistency leading to the suspicion of superficial subepithelial lesions. There were no colonoscopic diagnoses of colonic leiomyomas before the pathology results, and no complications after endoscopic resection were encountered.

Conclusions: Colon leiomyomas are rare smooth muscle tumors, detected incidentally during colonoscopy, and usually present with sessile forms. They can mimic epithelial lesion, and can be resected endoscopically. Lesions with normal mucosal pattern, retaining of colonoscopic morphology after submucosal solution injection, and firm consistency after resection, should lead to the suspicion of superficial subepithelial lesions.

P.045

發炎性腸道疾病患者的服藥順從性和衛教成 效之研究

MEDICATION ADHERENCE AND EFFECTS OF HEALTH EDUCATION IN PATIENTS WITH INFLAMMATORY BOWEL DISEASE

Background: Medication adherence is important in inflammatory bowel disease (IBD). Poor adherence is associated with more frequent disease flare, increased cost, and disability.

Aims: This study aims to evaluate medication adherence and effects of health education.

Methods: From January 2020 to December 2020, 64 adult IBD patients were invited for an online questionnaire for evaluation of medication adherence and effects of health education in Changhua Christian Hospital.

Results: Total 64 adult IBD patients completed study questionnaires included 32 patients with Crohn’s disease (CD) and 32 patients with ulcerative colitis (UC). The baseline characteristics were showed in table 1. For medication adherence, most patient were highly or moderately adherent and reported never or sometimes forgot to take medication (100% for steroids, 88-93% for other kinds of medications), as shown in table 2. For the usefulness of disease education, medication education, and scheduling of an outpatient clinic, 10.9~12.5% of patients felt useful and 78.1% of them felt very useful, as shown in table 3.

Conclusions: In contrast to other studies, our study showed higher adherence rate which might be the effects from health education.

楊承達 黃秀萍 陳洋源 顏旭亨 彰化基督教醫院胃腸肝膽科

P.046

ABO 血型與發炎症性腸病的關係 THE ASSOCIATION BETWEEN ABO BLOOD TYPE AND INFLAMMATION BOWEL DISEASE: A HOSPITAL-BASED STUDY IN CENTRAL TAIWAN

Background: Earlier reports have reported that the ABO blood type may link with multiple diseases, such as malignancy, autoimmune disease and even inflammatory bowel disease (IBD). However, the role of the ABO blood type with IBD remains controversial.

Aims: Therefore, we performed a retrospective study to explore the relationship between ABO blood type and IBD in a tertiary medical center.

Methods: We collected retrospectively 156 Taiwanese IBD patients (44 Crohn disease (CD) and 112 ulcerative colitis (UC)) diagnosed and followed at Changhua Christian Hospital from June 1990 to July 2022. We analyzed the clinical pattern of characteristics and ABO blood type groups.

Results: A total of 156 patients were included. The proportion of ABO blood type in UC was 30 (26.7 %) in blood type A, 29 (25.8 %) in blood type B, 5 (4.4%) in blood type AB, and 48 (42.8 %) in blood type O. Of 44 CD patients, 9 (20.4%) were blood type A, 12 (27.2 %) were blood type B, 3 (6.8 %) were blood type AB, and 20 (45.4 %) were blood type O. The mean diagnostic age of patients was 39.37 years in UC and 36.98 in CD. Males accounted for the majority of both groups (58.04% in UC and 77.27% in CD). Comparing IBD (UC and CD) and the general population, there was no statistically significant association of ABO blood type distribution between these three groups (p = 0.92 in UC; p = 0.69 in CD). There was also no preference between UC and CD groups compared with ABO blood types (p = 0.82). In the subgroup analysis, there were no significant differences in gender, diagnosed age, disease locations, and disease behavior between different ABO blood groups in UC and CD.

Conclusions: Our analysis showed no difference in all characteristics between IBD and blood type. ABO blood type might not be associated with IBD prevalence among the patients in this study.

P.047

糞便移植治療難治性和復發性困難梭狀桿菌 感染的療效和安全性 台灣北部三級中心 的經驗 EVALUATION OF THE EFFICACY AND SAFETY OF FECAL MICROBIOTA TRANSPLANTATION FOR REFRACTORY AND RECURRENT CLOSTRIDIOIDES DIFFICILE INFECTION ‒ EXPERIENCES OF A TERTIARY CENTER IN NORTHERN TAIWAN

李瑋瑋1 陳介章2 鍾承軒1 曾柏鈞

Background: Gut microbiota are associated with human health and many diseases, including Clostridioides difficile infection (CDI), which has climbing incidence globally. Fecal microbiota transplantation (FMT) has been demonstrated as an alternative treatment for recurrent CDI. In Taiwan, FMT has been indicated for recurrent and refractory CDI since September 2018; however, the efficacy and safety have never been reported.

Aims: We aimed to evaluate the efficacy and safety of FMT for recurrent and refractory CDI at a tertiary hospital in northern Taiwan.

Methods: We collected clinical data from consecutive patients who received FMT for recurrent or refractory CDI between October 2019 till December 2021 at Far Eastern Memorial Hospital. The primary and secondary outcomes were cured by FMT without relapse within 10 weeks after initiating therapy and FMT-related adverse events (AEs), respectively. The administration of FMT was through colonoscopic injection with 300 mL of stool suspension (60 g stool) from eligible donors into the terminal ileum or cecum of recipients. The stool donors could be 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 post-transplant stool specimens from four patients using 16S rRNA gene sequencing.

Results: Total 14 (6 female and 8 male) patients received FMT during study period. The majority of indications for FMT were refractory Clostridioides difficile-associated

葉菀婷 許翠純 陳洋源 顏旭亨 彰化基督教醫院內科部肝膽腸胃科

diarrhea (CDAD) (85.71%). Eight (57.1%) were severe CDI. The mean (± SD) age and Charlson comorbidity index (CCI) of patients were 78.4 (± 14.15) years old and 6.86 (±2.74) respectively. All patients received FMT via colonoscopy. Among 14 patients, 10 (71.43%) patients were cured without relapse within 10 weeks after the first injection of donor feces. Four (28.57%) failure cases all died because of underlying diseases, not CDI related. More than half (57.1%) of patients did not have any adverse event, and the most common adverse event was transient diarrhea (21.4%). There were four patients who completed the microbial diversity of pre- and post-transplant stool specimens achieved successful engraftment with microbiota similar to donors. The increased diversity of post-FMT fecal microbiota was shown significantly increased in Simpson index and Shannon index.

Conclusions: This study has demonstrated FMT as an efficient and safe treatment for refractory and recurrent CDI. The clinical success rate was 71.43% with acceptable FMT-related AE within 10 weeks. Further studies are needed to elucidate the long-term outcome.

P.048

共衛政策介入之效果：花蓮縣的經驗分享 THE PREVALENCE OF VITAMIN D INSUFFICIENCY AND DEFICIENCY IN ELDERS AND THE EFFECT OF PUBLIC HEALTH POLICY INTERVENTION: AN EXPERIENCE OF HUALIEN COUNTY, TAIWAN 蕭宇超 張雲傑

Background: Vitamin D deficiency and insufficiency were an important health issue among the world. Vitamin D insufficiency and deficiency would cause negative effects on multiple systems especially bone density, such as osteomalacia which may have a great effect on the life quality of elders. Early detection and intervention were important for people with vitamin D deficiency and insufficiency.

Aims: This study aimed to reveal the prevalence of vitamin D deficiency and insufficiency of elders in Hualien and to evaluate the effect of public health policy intervention.

Methods: This study was a retrospective cohort study, and the subjects were collected from the health examination sponsored by the government from 2020 to 2021 in Hualien. People over 65-years-old and aboriginal people over 55-year-old could optionally attend the examination. According to different levels of serum vitamin D, people were classified as sufficiency (>32 ng/ml), insufficiency (20-32 ng/ml), deficiency (8-20 ng/ml), and severe deficiency (<8 ng/ml). Intervention for vitamin D insufficiency and deficiency included education and vitamin D supplement.

Results: 7598 subjects in 2020 health examination and 6303 subjects in 2021 health examination were included. In 2020, elders without enough vitamin D were 55.53% (insufficiency: 46.05%, deficiency: 9.19%, and severe deficiency: 0.29%). Females were more prominent on vitamin d deficiency and insufficiency than male (61.92% vs 46.61%). In 2021, elders without enough vitamin D were 44.46% (insufficiency: 35.97%, deficiency: 8.31%, and severe deficiency: 0.17%). Females still had more severe vitamin D deficiency and insufficiency than male (50.61% vs 36.18%). According to different districts, Fengbin and Hualien city were the top two districts with vitamin d deficiency and insufficiency among 13 districts in Hualien. Total 3102 subjects had twice check of serum vitamin D

維他命 D 不足及缺乏於年長者之盛行率及

朱家祥

level in 2020 and 2021. The average serum vitamin D level was significantly increased in 2021 compared with 2020 (33.54 ng/mL (± 11.30) in 2020 and 36.42 ng/mL (± 13.37) in 2021, p < 0.05).

Conclusions: Vitamin D deficiency and insufficiency were prominent in Hualien. Public health policy seems to improve this condition.

P.049

同日無痛檢查先做胃鏡與先做腸鏡之差異 WHEN PERFORMING ESOPHAGOGASTRODUODENOSCOPY AND COLONOSCOPY UNDER SEDATION AT THE SAME DAY, IS DOING LOWER ENDOSCOPY FIRST ANY DIFFERENT?

林憲宏1 王豊裕2 張婉芬3 李俊毅4 徐魁堯5 林奎佑6 林齊宣1 李孟達1 郭長豐7

1 台北仁濟院附設仁濟醫院胃腸科

Background: Esophagogastroduodenoscopy (EGD) and colonoscopy are performed under sedation more often in recent years. Anesthesiologists think EGD under sedation is riskier because more sedation is needed to suppress the gag reflex while the airway is occupied by the endoscopist. When EGD and colonoscopy are performed at the same day, EGDs usually are done first. If colonoscopies were done first, would there be any difference? If EGDs are performed after colonoscopy, they will still be in sedation and little additional dose will be needed. Patients will also have more time to pass out gas inflated at colonoscopy, if EGDs were performed after colonoscopy. This might reduce the incidence of post-procedure pain.

Aims: We want to know, when doing upper and lower endoscopies at the same day, whether there are any differences if colonoscopies were done first.

Methods: We prospectively record patients’ conditions from April 11 to October 7, 2022, for 138 outpatients who received upper and lower endoscopies at the same day. The mean age was 61.8 years (range 25-91), and 89 (64.5%) were women. Colonoscopies were done first for 67 patients from April to June 2022 (group A). EGDs were done first for 71 patients from July to October 2022 (group B). Endoscopy were performed by 5 endoscopists. Anesthesia was given by 3 anesthesiologists. Anesthetics include alfentanil, propofol, and midazolam. One of the anesthesiologists did not use midazolam.

Results: The induction dose and total dose of anesthetics were comparable between groups A and B. The mean induction dose of alfentanil of group B was slightly lower

than that of group A (group B 0.30 mg [standard deviation 0.12] vs. group A 0.35 mg [0.15], P = 0.058). The mean endoscope insertion time to cecum of group A was 8.33 minutes (5.43), significantly longer than that of group B (5.28 minutes [3.78], P = 0.00023). The awakening time of group A was longer than that of group B (8.33 minutes [5.43] vs. 4.97 minutes [3.53], P = 0.01). Hypoxemia (SpO2 < 90%) occurred in 7 cases, all women (P = 0.05). The mean body mass index (BMI) of those with hypoxemia was 26.5 (1.1), significantly higher than those without hypoxemia (23.5 [3.6], P < 0.0001). The mean awakening time of those with hypoxemia was slightly longer than that of those without hypoxemia (8.0 minutes [3.5] vs. 5.6 minutes [3.6], P = 0.058). There were borderline significant differences between groups A and B regarding the occurrence of hypoxemia (5/62 vs. 2/69, P = 0.058). The mean examination time of those with hypoxemia was 26.1 minutes (8.4), comparable to that of those without hypoxemia (28.7 minutes [10.1], P = 0.50). Hypotension was defined as drop of systolic blood pressure of more than 20 mmHg to lower than 90 mmHg. Hypotension occurred in 26 cases. The mean pre-anesthesia blood pression of those with hypotension was significantly lower than those without hypotension (pre-anesthetic systolic blood pressure 128.7 mmHg [18.5] vs. 141.3 mmHg [21.8], P = 0.0069; pre-anesthetic diastolic blood pressure 73.3 mmHg [11.9] vs. 80.4 mmHg [11.7]; P = 0.0065). Incidence of hypotension occurred more often during anesthesia by one of the anesthesiologists who did not use midazolam (19/72 vs. 7/66, P = 0.018). Only 7 patients complained of pain after procedure (group A 4/67 vs. group B 3/71), probably due to the use of carbon dioxide for gas inflation. The results of this study showed that there were no significant anesthetics dose differences between groups A and B, probably because the details of the dose titration of anesthetics were difficult to record, and the dosing habits of the anesthesiologists probably were fixed whether upper or lower endoscopies were done first. The relatively lower alfentanil induction dose is probably due to less need for analgesia during upper endoscopy. The shorter cecum insertion time when upper endoscopy was performed first, was probably due to more relaxation of patients at the time of colonoscopy after the sound sleep during the upper endoscopy period. The longer awakening time of group B was probably due to the dosing at pharyngeal insertion for control of gag reflex while EGD usually ends within 3-5 minutes. The occurrence of hypoxemia was only related to BMI.

Conclusions: This study shows that the doses of anesthetics were comparable whether EGDs or colonoscopies were done first. The cecum insertion times were longer and awakening times were also longer if colonoscopies were done first. The occurrence of hypoxemia was only related to patients’ BMI.

P.050

病患的胰臟癌發生率 CHOLECYSTECTOMY DECREASE INCIDENCE OF PANCREATIC CANCER IN PATIENTS WITH CHOLEDOCHOLITHIASIS UNDERWENT ENDOSCOPIC SPHINCTEROTOMY OR PAPILLARY BALLOON DILATATION

翁立翰1 蔡明璋1,2 林俊哲1,2 汪奇志1,2 1 中山醫學大學附設醫院肝膽腸胃內科

Background: Endoscopic sphincterotomy (EST) or papillary ballon dilatation (EPBD) were all recommended for choledocholithiasis in patients with or without symptoms. In addition, elective laparoscopic cholecystectomy (CCY) is recommended after endoscopic clearance of choledocholithiasis for patients with acute cholangitis, according to Tokyo guidelines. Several metaanalysis and population-based cohort study in Korea show increase risk of malignancy in patients after CCY, especially pancreatic cancer, but majority included patients with gallstones compared with patients accepted CCY, rather than choledocholithiasis. We performed a retrospective cohort study to investigate its relevance. Aims: Evaluate the potential risk of pancreatic cancer in patients underwent cholecystectomy after EST and ERPD, especially in choledochlithiasis.

Methods: We performed the retrospective cohort study that comprises about 23 million beneficiaries who were enrolled in Health Insurance Program, Taiwan from 2011 to 2017. We accessed data from Taiwan’s Health and Welfare Data Science Center. We identified the patients hospitalized for the major diagnosis including choledocholithiasis or cholangitis and first time treated with EST or EPBD. Initially, there were 55459 patients selected, and the patients who had missing of demographics data, aged <18 years at admission, and cholecystectomy before admission were excluded. There were 14068 patients who underwent CCY within 2 months after the admission as intervention group, and 38259 patients who did not have CCY as comparison group. The additional analysis of propensity score matching (PSM) was also performed to reduce the confounding bias after balance the measured characteristics between the study groups. Finally, 13330

pairs of PSM CCY and non-CCY patients were selected for analysis (Figure 1). The pancreatic cancer was identified from the information on the Cancer Registry Database. All study individuals were followed from the index date until the occurrence of study event, death, or end of study. The incidence rate and 95% confidence interval (CI) were calculated by considering the Poisson distribution. Kaplan–Meier survival curves were plotted to compare the 7-year cumulative probability of developing pancreatic cancer. The log-rank test was performed to determine the overall homogeneity of hazard rate functions among study groups. After the proportional hazard assumption was tested, the univariate and multivariable Cox proportional hazards regression was used to estimate the hazard ratio (HR) of exposure to CCY on the risk of pancreatic cancer. All statistical analyses were conducted by using SAS version 9.4. The significance level of 0.05 was used for hypothesis test.

Results: At last, total 26660 patients were enrolled in our retrospective study. Analysis of these patients showed 56% reduction in cumulative incidence probability of pancreatic cancer in CCY group (Figure 2, adjust Hazard ratio = 0.44, 95% CI = 0.27-0.72, Kaplan–Meier survival curves). In addition, analysis of cumulative all cancer mortality probability showed 47% reduction. (Figure 4, adjust Hazard ratio = 0.53, 95% CI = 0.47-0.61, Kaplan–Meier survival curves). But cumulative pancreatic cancer mortality probability showed no significant difference between two groups. (Figure 3, adjust Hazard ratio = 0.72, 95% CI = 0.47-1.10, Kaplan–Meier survival curves). According to above results, even we reduce the incidence of pancreatic cancer but the general prognosis of it was not changed in current medical treatment. But, cumulative all cancer mortality was reduced, and we consider CCY in patients with choledocholithiasis can reduce mortality of other malignancy.

Conclusions: Cholecystectomy in choledocholithiasis patients, who underwent EST/EPBD, could reduce incidence of pancreatic cancer in our retrospective study. In addition, it could reduce probability of all cancer mortality but not pancreatic cancer mortality.

膽囊切除術降低針對膽管結石進行過內視鏡 括約肌切開術或者內視鏡乳突氣球擴張術的

P.051

三軍總醫院 Mallory-Weiss Tear 之回顧性研 究

A RETROSPECTIVE STUDY OF MALLORY-WEISS TEAR IN TRISERVICE GENERAL HOSPITAL

P.052

腫瘤基質中成纖維細胞生長因子 -21 的表現 與中期胰臟癌的預後相關

STROMAL EXPRESSIONS OF FIBROBLAST GROWTH FACTOR-21 ASSOCIATE WITH OUTCOMES OF RESECTABLE INTERMEDIATE-STAGED PANCREATIC ADENOCARCINOMA

黃冠榕

Background: Mallory-Weiss tear is a laceration at the junction of the stomach and the esophagus associated with forceful vomiting and retching. It often leads to bleeding from submucosal arteries which are self-limited with conservative management. Hence, there was few discuss about endoscopic management of Mallory-Weiss tear.

Aims: We aimed to evaluate the possible clinical traits and the prognostic factors in the patients with Mallory-Weiss tear treated by endoscopic management.

Methods: We conducted a retrospective review of 21 esophagogastroduodenoscopy for 19 patients with MalloryWeiss tear treated by endoscopy from May 2017 to April 2022 at Tri-Service General Hospital. We analyzed the patient’s clinical presentation, laboratory data and outcomes. Results: There were 17 males and 2 females. The median of length of hospitalization after endoscopic management is 8 days (range, 0 to 122). Six patients (31%) expired. Among them, five patients had the medical record with either cancer or history of cancer. The causes of death were attributed to septic shock in four patients, pneumonia in one patient and colon adenocarcinoma with peritoneal carcinomatosis and bowel obstruction in one patient. Endoscopic managements included 8 records (38%) with endoscopic hemoclip, 7 records (33%) with Epinephrine injection, 3 records (14%) with Argon plasma coagulation (APC), 1 record (4%) with monopolar coagulation with hot biopsy, 1 record (4%) with endoscopic hemoclip combined with Epinephrine injection and 1 record (4%) with monopolar coagulation with hot biopsy combined with Epinephrine injection. Two patients required secondary hemostasis, one with primary hemostasis of monopolar coagulation, and the other with primary hemostasis of APC. 13 patients (61%) presented with hematemesis or fresh bloody gastric drainage (Hemoglobulin, mean: 10.92 ± 2.41 mg/dL). Eight patients (39%) presented without hematemesis or fresh bloody gastric drainage (Hemoglobulin, mean: 9.5 ± 1.25 mg/dL).

Conclusions: Mallory-Weiss tear is a self-limited disease. Hemostasis with monopolar coagulation or APC might be related to higher risk of rebleeding and repeated hemostasis.

Background: Pancreatic cancer has become one of the top ten lethal cancers in Taiwan and is still limited by the unsatisfactory treatment outcomes. The abundant desmoplasia in the tumor microenvironment with stromal fibrosis may account for this struggle.

Aims: The aim of this study is to investigate the role of fibroblast growth factor-21 (FGF-21), which is associated with stromal fibrosis, in the clinical outcomes of resectable intermediate-staged pancreatic adenocarcinoma (PDAC).

Methods: The archive tissue of pancreatic tumor from 52 patients who underwent surgical resection and adjuvant chemotherapy in Taipei Veterans General Hospital for their intermediate-staged PDAC (clinically stage II assessed by AJCC 8th criteria) was obtained and investigated for the expressions of FGF-21. Among them, 43 samples could be examined in both tumor and non-tumor parts. Progressionfree survival (PFS) and overall survival (OS) were calculated.

Results: During the follow-up period, 42 deaths developed and the median overall survival was 16.5 months (95% CI: 12.5 – 20.5). Patients with higher expressions of FGF-21 in the cancer stroma had a significantly better OS compared with the counterpart (OS: 20.4 vs. 13.2 months, p = 0.023). Besides, significantly better OS (27.6 vs 14.8 months, p = 0.009) and PFS (9.6 vs. 5.4 months, p = 0.023) were also observed in whom a higher expression of FGF-21 was noted at tumor part than non-tumor part.

Conclusions: The higher expression of FGF-21 in cancer stroma was found to be associated with better survival benefits in patients who underwent surgical resection and adjuvant chemotherapy for intermediate-staged pancreatic adenocarcinoma. This finding suggests a potential role of FGF-21 in prediction of clinical outcomes of these patients.

陳彥圻1,2 黃天祐1 張維國1 謝財源1 陳鵬仁1 1 三軍總醫院胃腸肝膽科 2 花蓮國軍總醫院腸胃內科

P.053

在腸道重建術後的惡性膽道狹窄，經由內視 鏡置放金屬支架引流術的預後 THE OUTCOMES OF ENDOSCOPIC BILIARY DRAINAGE FOR MALIGNANT BILIARY STRICTURE IN SURGICALALTERED ANATOMY WITH SELFEXPANDABLE METAL STENTS

王堯生 黃千睿 陳炯瑜

國立成功大學醫學院附設醫院胃腸肝膽科

Background: Endoscopic retrograde cholangiopancreatography (ERCP) in surgical-altered anatomy (SAA) is technical challenging. Surgical altered anatomy was indicated gastrojejunostomy (GJ) bypass surgery, subtotal gastrectomy with Billroth II(B-II) reconstruction, pancreatoduodenectomy (PD) with or without Braun’s procedure, and any types of roux-en-y reconstruction (RY). Short type enteroscope with or without balloon overtube assistance is always required. To treat malignant biliary obstruction by endoscopic drainage in SAA is a more advanced issue. Malignant biliary obstruction in SAA may be due to primary or cancer recurrent at bile duct or anastomosis after previous operation. Metal stent is recommended option for malignant biliary obstruction. ERCP in such those malignant disease may be failed due to long limbs, adhesions, difficult cannulation or unstable or poor scope position. However. there were limited reports in the worldwide.

Aims: To study the clinical outcome of endoscopic biliary drainage for malignant biliary stricture in surgical-altered anatomy with self-expandable metal stent.

Methods: Patients who had been performed biliary drainage with metal stents for malignant obstructive jaundice in surgical-altered anatomy enrolled in National Cheng Kung University Hospital from 2020 to 2022 retrospectively. All patients were performed ERCP by short type enteroscope (Olympus, SIF-H290S) with transparent hood. Single balloon overtube was applied for patients in roux-en-y reconstruction or some long efferent limbs of gastrojejunostomy on demand. Types of metal stents were chosen according to clinical requirements. Electric medical records were reviewed. Characteristics of patients, cancer, locations of stricture, outcomes, and complications of endoscopy were analyzed.

Results: Twenty-six patients were enrolled in this study finally with 12 men and 14 women. Their mean age was 64.5 y/o (range: 30 ~ 90 y/o). The causes of malignant

stricture were mostly pancreatic cancer (57.7%, n = 15), followed by bile duct cancer (23.1%, n = 6), and gastric cancer (15.4%, n = 4). The target site showed naïve papilla 46.2%, n = 12, and the others were hepaticojejunostomy. The technically successful rate was 88.5%, and the clinical success rate was 76.9%. Recurrent biliary obstruction was 35%, n = 10. The Median and IQR of stent patency time were 81.5 [32.75-199.75] days. Medial survival after stenting around 105 days was present. In subgroup analysis, The distribution and technical success rate of altered anatomy was subtotal gastrectomy with Billroth II was 85.7%, n = 6; gastrojejunal bypass for gastric outlet obstruction was 60%, n = 3; pancreatoduodenectomy (PPPD or Whipple operation) was 100%, n = 12, and rouxen-y reconstruction was 100%, n = 2. The complications included one cholangitis, one pancreatitis, and one progressive jaundice due to clinical failure.

Conclusions: Endoscopic biliary drainage with selfexpandable metal stent by ERCP for malignant obstructive jaundice in patients with surgically altered anatomy is clinically applicable. The clinical success and complications were acceptable. Endoscopy may be failed to target site or failed biliary cannulation, and the rescuing method could be performed by rendezvous or antegrade method.

P.054

內視鏡黏膜下剝離術：單一區域醫院臨床經 驗 ENDOSCOPIC SUBMUCOSAL DISSECTION: CLINICAL EXPERIENCE IN A DISTRICT HOSPITAL IN CENTRAL TAIWAN

Background: Endoscopic submucosal dissection (ESD) has become a standard therapy for large early gastrointestinal (GI) neoplasms with the aim of obtaining en bloc specimens. Several studies have shown the technique to be safe and effective in reducing local recurrence rate with higher curative rates compared to endoscopic mucosal resection (EMR). However, most studies in Taiwan involved large medical centers.

Aims: To report our clinical experience with ESD and to assess it’s therapeutic outcome in a single district hospital in central Taiwan.

Methods: From October 2016 to October 2022, a total of 39 ESD procedures were performed in our hospital. The clinicopathological data, ESD-related complications and clinical outcomes were retrospectively collected and studied.

Results: The average age of enrolled patients was 60.5 years with 27 males and 12 females. The locations of the lesions were: colon (21), stomach (9), esophagus (8) and duodenum (1). The en bloc resection rate was 92.3% (accepted proficiency bench mark >90%) while the histologic margin-negative (R0) resection was 94.8% (accepted proficiency benchmark >80%). Histopathologic diagnosis of the lesions identified 14 carcinomas and 10 pre-malignant lesions. Four cases had procedure-related complications, including 2 esophageal strictures, 1 massive bleeding and 1 intra-procedure perforation which was successfully managed with hemoclipping. There was no procedure-related mortality but 2 cases developed local recurrence during follow-up. ESD was aborted in one case due to technical difficulty and was converted to surgery. There was a loss of follow-up in 7 patients.

Conclusions: ESD is an effective and safe technique in the management of large early GI neoplasms. Our outcomes are comparable with other studies in medical centers and achieved the accepted proficiency benchmarks.

Background: Colorectal cancer (CRC) screening is recently recommended for average-risk individuals starting at age 45 years according to the updated international guidelines. Adenoma detection rate (ADR) is a key quality measure for colonoscopy (CFS). The current benchmark of ADR is 25% for screening colonoscopy beginning at age 50 years. ADR among age 45-49 years adults remained not clear.

Aims: This study aims to evaluate ADR of screening colonoscopy for average-risk individuals age between 4549 y.

Methods: We enrolled participants for health examination with complete colonoscopy between Jan. 2014 and Feb. 2020 in our hospital. CFS examined at age younger than 40 years and CFS with the indication of surveillance were excluded. ADR is defined as CFS with at least one colorectal adenoma detected among all CFS. ADR were compared among different age groups: 40-44 y, 45-49 y and ≥50 y. A p value <0.05 (Chi-squared Test) is considered as significant.

Results: There were 28511 CFS completed in the study period. After excluding CFS examined at age younger than 40 years (n = 5100) and CFS for surveillance (n = 5221), a total of 18190 CFS were enrolled for analysis. The overall ADR was 34.7% (6318/18190). ADR of age groups 4044 y, 45-49 y and ≥50 y were 25.8% (843/3271), 29.1% (977/3361) and 38.9% (4498/11558) respectively, (p < 0.001).

Conclusions: There is a significant gap of ADR among different age groups. Our results suggested that lowering the screening age may lower the average level of ADR. However, the current benchmark of screening ADR (25%) could remain unchanged if CRC screening begins at age 45 y.

劉博堃 黃彼得 童綜合醫療社團法人童綜合醫院胃腸肝膽科

P.056

胃輕癱於糖尿病患族群中之盛行率 ─ 一個 多中心研究之期中分析 INTERIM ANALYSIS OF PREVALENCE FOR GASTROPARESIS IN DIABETES MELLITUS PATIENTS ‒ A MULTICENTER STUDY IN TAIWAN

金寧煊1 陳健麟2 洪睿勝2 翁銘彣2 雷尉毅2 王文 3,4 徐銘宏5 陳華芬6,7 吳彥雯8 鍾承軒1,9

1 亞東紀念醫院肝膽胃腸科

2 花蓮慈濟醫院肝膽腸胃科

3 義大醫院內科部

4 義守大學醫學院

Background: Gastroparesis is one of the complications of diabetes mellitus (DM). However, the epidemiology of gastroparesis in DM patients is not well-established.

Aims: In this study, we aimed to evaluate the prevalence of gastroparesis among DM patients in Taiwan.

Methods: Between July 2021 and December 2022, we prospectively enrolled consecutive patients with DM from multicenter (FEMH, Hualian branch of TCH and EDAH) in Taiwan. All patients answered a structured questionnaire of Gastroparesis Cardinal Symptom Index (GCSI), underwent blood tests, esophagogastroduodenoscopy (EGD) and gastric emptying scintigraphy (GES) (Fig.1). Those with mechanical obstruction, pregnancy, breastfeeding, post-gastric surgery, contraindications for EGD or GES, medications influencing gastric motility in the past one week or chronic disorders including hypothyroidism, psychological or rheumatological diseases were excluded. Abnormal GES finding (T1/2 longer than 85 minutes and gastric emptying 1-hr retention more than 65%) was defined as gastroparesis.

Results: A total of 68 (37 women, 31 men) patients were enrolled. The prevalence of gastroparesis in DM patients was 16.18% (n = 11). DM patients with gastroparesis were younger (mean, 49.27 vs 59.43 year-old, p = 0.024), reported higher GCSI score (mean 2.54 vs 1.65, p = 0.016), more prokinetics use (90.91 vs 45.61%, p < 0.001) and diabetic nephropathy (63.63 vs 24.56%, p = 0.036) than those without gastroparesis. No statistically significance in gender, body mass index, systolic blood pressure, blood

pressure deficit, waist, DM type, HbA1c, urine protein or albumin level was noticed between those with and without gastroparesis (Table 1). There was a non-significant very low correlation (r = 0.147 and p = 0.230) between GCSI and GES results analyzed by Pearson correlation test. (Table 2).

Conclusions: The prevalence of gastroparesis in DM patients in Taiwan was 16.18%. Those with gastroparesis were prone to be younger and complicated with nephropathy. Further enrollment of more DM patients is warranted.

P.057

ENHANCED ESOPHAGEAL ACID SENSITIVITY IS ASSOCIATED WITH RESPONSE TO PROTON PUMP INHIBITORS IN SYMPTOMATIC PATIENTS DESPITE NORMAL ACID EXPOSURE

Background: Altered acid sensitivity may occur in patients with gastroesophageal reflux disease (GERD). Patients with typical GERD symptoms and normal acid exposure time (AET) are classified as either reflux hypersensitivity (RH) or functional heartburn (FH), who may or may not respond to proton pump inhibitors (PPIs) therapy.

Aims: This study aimed to test the hypothesis of whether esophageal acid sensitivity could predict the PPI response in symptomatic patients despite normal AET.

Methods: We prospectively recruited adult patients with heartburn sensation and/or acid regurgitation diagnosed with RH (AET < 4%, positive symptom association probability, SAP) or FH (AET < 4%, negative SAP) on the basis of 24-h impedance-pH monitoring off PPI. Mucosal integrity was evaluated using mean nocturnal baseline impedance (MNBI). All participants completed validated questionnaires assessing patient-reported outcomes, including the GERD questionnaire (GERDQ) and the esophageal hypervigilance and anxiety scale (EHAS). Symptom response was defined as at least a 50% reduction in GERDQ score. Infusion of hydrochloric acid (0.1 N) into the mid-esophagus was performed to evaluate for acid sensitivity, during which the time to initial typical symptom perception (lag time) was recorded. Potential factors influencing PPIs response were identified using a generalized linear model.

Results: Of 74 study participants (age 21-64 years, 63.5% women), who completed the study, 40 had RH, and 34 had FH. PPIs response was seen in 33 patients (44.6%), 50.0% in RH, and 44.1% in FH. There was no significant difference in age, gender, BMI, reflux symptom severity, EHAS, AET, MNBI, or PPI response rate between patients with RH and FH. RH patients had a shorter lag time than FH patients (60.6 sec vs. 105.4 sec, P = 0.048). In a generalized linear regression model evaluating potential factors predicting PPIs response, only shorter time (β =

-0.131, CI = -0.261 ~ -0.002, P = 0.047) and lower MNBI (β = -0.267, CI = -0.458 ~ -0.076, P = 0.007) correlated with PPI response.

Conclusions: Enhanced acid sensitivity (shorter lag time) and lower mucosal integrity are independently associated with PPIs response in patients with RH and FH. Lower mucosal integrity indicating mucosal acid damage, and esophageal acid sensitivity indicating early symptom reporting, could therefore serve as physiomarkers of PPIs response in symptomatic patients despite normal AET.

正常食道酸曝露之逆流症患者其食道酸敏感 度增加與質子幫浦抑制劑成效相關

洪睿勝 翁銘彣 梁書瑋 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肝膽腸胃科

P.058

巴瑞特氏食道患者其食道警覺及焦慮程度低 於胃食道逆流症各分型患者 PATIENTS WITH BARRETT’S ESOPHAGUS ARE RELATED TO LOWER ESOPHAGEAL HYPERVIGILANCE AND ANXIETY SCALE COMPARED WITH OTHER PHENOTYPES OF GASTROESOPHAGEAL REFLUX DISEASE

Background: Patients with Barrett’s esophagus (BE) usually have serious gastroesophageal reflux. However, they often have few reflux symptoms and lower sensitivity to acid. The esophageal hypervigilance and anxiety scale (EHAS) is a novel questionnaire for the cognitive-affective evaluation of visceral sensitivity.

Aims: We hypothesized that BE patients have lower EHAS levels than gastroesophageal reflux disease (GERD) patients without BE.

Methods: We prospectively recruited patients with typical GERD symptoms (heartburn sensation and/or acid regurgitation) underwent esophagogastroduodenoscopy for erosive esophagitis evaluation. Those with negative endoscopy underwent 24-hour impedance-pH monitoring for further phenotyping. At the same time, newly diagnosed BE patients were prospectively enrolled. Validated scores for patient-reported outcomes, including the GERD questionnaire (GERDQ) and EHAS, were recorded for all participants.

Results: We enrolled 453 patients, aged 22-65 years (mean, 50.4), of whom 46.4% were male; 58 had BE, 117 had erosive esophagitis (EE), 49 had non-erosive reflux disease (NERD), 107 had reflux hypersensitivity (RH), and 122 had functional heartburn (FH). BE patients were male predominant (70.7%), older (mean, 56.6), with more hiatal hernia (31.0%), and smokers (29.3%). BE patients had lower GERDQ scores and EHAS than all the others (P < 0.001); EE patients had lower EHAS than those with NERD, RH, and FH (P < 0.001). On Pearson’s correlation, EHAS positively correlated with GERDQ scores (r = 0.284, P < 0.001).

Conclusions: This study demonstrates that patients with BE were characterized with lower EHAS as compared with other phenotypes of GERD. Our work indicates that BE patients had less reflux symptom burden and esophageal hypervigilance and anxiety. This may explain why the evaluation of GERD symptoms alone is unreliable for BE identification.

P.059

台灣版雪梨吞嚥問卷在口咽吞嚥困難病患的 驗證

VALIDATION OF TAIWANESE SYDNEY

SWALLOW QUESTIONNAIRE IN PATIENTS WITH OROPHARYNGEAL DYSPHAGIA

Background: Oropharyngeal dysphagia is easily overlooked. Screening may improve early detection and prevent complications, such as pneumonia or death. The Eating Assessment Tool (EAT-10) has been validated for dysphagia screening in Taiwan. The Sydney Swallow Questionnaire (SSQ) is a self-reported questionnaire validated in several languages and regions except for Taiwan.

Aims: This study aims to test the consistency, reliability, and validity of the Taiwanese SSQ for oropharyngeal dysphagia screening.

Methods: This study prospectively recruited patients with oropharyngeal dysphagia symptoms in the clinic of the Hualien Tzuchi Hospital. Exclusion criteria were recent oropharyngeal surgery in three months, esophageal disease, and older than 85 years. A cohort of healthy volunteers without dysphagia was recruited for the normative range. Participants filled out the SSQ and EAT-10 after inclusion. Manometric data of 10 mL IDDSI Level 0 bolus swallows were recorded after insertion of a high-resolution impedance catheter to the pharynx, and data were analyzed to derive the Swallow Risk index (SRI) from Swallow Gateway online platform. Internal consistency was evaluated with the Cronbach alpha coefficient. The SSQ was rechecked two weeks later to determine test-retest reliability by intraclass correlation coefficient. Validity was assessed by Kendall’s tau correlation coefficient between SSQ and EAT-10 as well as SSQ and SRI.

Results: Thirty-eight patients with oropharyngeal dysphagia and thirty-four healthy volunteers without dysphagia were recruited. Ten patients were excluded due to esophageal obstruction (n = 7), esophageal candidiasis (n = 1), absent esophageal contractility (n = 1), and old age (n = 1). Only eight patients completed the manometric study. The internal consistency (Cronbach alpha) of the first SSQ was 0.95. The intraclass correlation coefficient (ICC) of each question between the test and retest ranged from 0.72 to 1.00, and the ICC of the total score was 0.94. The

翁銘彣 梁書瑋 洪睿勝 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肝膽腸胃科

梁書瑋 洪睿勝 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肝膽腸胃科

Kendall’s tau-b correlation coefficients were 0.77 (p < 0.01) between SSQ and EAT-10 and 0.57 (p = 0.02) between SSQ and SRI. The upper limit of the normative range derived from healthy volunteers was 39.2.

Conclusions: SSQ displayed excellent internal consistency and test-retest reliability in Taiwanese patients with oropharyngeal dysphagia. SSQ exhibited a high correlation with EAT-10 and a moderate correlation with SRI.

P.060

內視鏡切除術治療胃黏膜腫瘤的療效及安全 性 台灣單一中心的 5 年經驗

EFFICACY AND SAFETY OF ENDOSCOPIC SUBMUCOSAL DISSECTION FOR THE TREATMENT OF GASTRIC MUCOSAL NEOPLASIA ‒ A 5-YEAR SINGLE-CENTER EXPERIENCE IN

Background: Initially pioneered in Japan in the 1990s, the application of endoscopic submucosal dissection (ESD) on gastrointestinal lesions has been wildly accepted after development for decades. For gastric mucosal and submucosal tumors, ESD now serves as the first-line standard treatment in Japan, and has cumulatively been certified as effective as surgical interventions in other countries. The most significant advantage of ESD is that it facilitates en bloc and R0 resection for early gastric cancers (EGC) regardless of their locations and sizes, providing a precise pathological diagnosis and simultaneously lowering the local recurrence risk with a less invasive approach. However, there are some undeniable concerns of ESD, including potential complications and possible tumor recurrence.

Aims: In contrast to the condition in Japan, there are limited data and reviews regarding the outcomes and complications of ESD in Taiwan, especially on gastric mucosal tumors. This study is consequently aimed to report a single-center experience in ESD-treated gastric mucosal lesions.

Methods: The retrospective study analyzed patients who underwent ESD for gastric mucosal lesions between January 2018 and September 2022 at Taipei Medical University Hospital (TMUH), Taipei, Taiwan. Patients with submucosal lesions were excluded from this study. Based on a single-center experience, we evaluated the rate of residual disease, local recurrence, and complications after ESD, all of which were influenced by some possible factors we were trying to figure out.

Results: There were 24 patients with 25 gastric mucosal lesions in total who received ESD in TMUH during the five years (January 2018 to September 2022). The mean

size of those lesions was 2.95 cm (0.5 – 6.3 cm). En bloc was practical in 88.0% (22/25) cases, and 2 cases (8.0%) reached piecemeal resection. One (4.0%) ESD was terminated because of poor vision of the submucosal plane caused by severe submucosal fibrosis. Up to 21 cases (84.0%) were histopathologically described as neoplasms (ranging from low-grade dysplasia to adenocarcinoma), and 13 cases (52.0%) were confirmed to be adenocarcinoma. There were 19 (90.5%) cases reaching R0 resection and 2 (9.5%) were incomplete resections within these 21 cases. With a mean follow-up period of 8.2 months (3 –24 months), one case (4.0%) was diagnosed with residual lesion and another one (4.0%) with local recurrence in previous R0 resections. The disease-free survival and disease-specific survival at 12 months was 92% and 100% respectively. Major bleeding events that required component therapy or hemostatic interventions including endoscopic, radiological and surgical treatments occurred in 4 procedures (16.0%). All of them were resected wound bleeding, but one case combined with esophageal-cardiac junction laceration (Mallory-Weiss syndrome) caused by severe post-procedural vomiting. Three (12.0%) of these four bleeding events were located at antrum and achieved hemostasis after endoscopic interventions. The other one (4.0%), which occurred at cardia, achieved hemostasis with trans-arterial embolization (TAE) after failure of endoscopic hemostasis. Non gastric perforation nor procedure-related death was observed.

Conclusions: This study showed that ESD is an effective resection technique for gastric mucosal lesions. The efficacy outcomes of ESD in this study were similar to the results presented in the literature, with a procedure success rate reaching 96.0% and the disease-free survival rate of 92%. Due to the limitation of small sample size and the relatively short follow-up duration in this study, further randomized control trial with larger sample size and longer follow-up period should be conducted in the future.

P.061

ENDOSCOPIC SURVEILLANCE FOR SECOND PRIMARY TUMORS IN HEAD AND NECK CANCER PATIENTS USING AN ADDITIONAL ORAL-PHARYNXLARYNX OBSERVATION

楊志偉 黃天祐 陳鵬仁 張維國 三軍總醫院腸胃科

Background: Advances in image enhanced endoscopy, such as narrow-band imaging with magnifying endoscopy, can improve detection of early-stage esophageal.

Aims: This study aims to evaluate the role of UGI endoscopy early detection second primary tumors, in patients with head and neck cancer, at the oral cavity, pharynx, larynx, and esophageal region.

Methods: Between December 2015 and December 2019, an adult cohort of 2,849 patients underwent 3,275 UGI endoscopies with oral-pharynx-larynx examination. We investigate the presenting symptoms, incidence, location, and stages of observable malignant neoplasm during routine upper GI endoscopy.

Results: A total of 2,849 (87%) patients successful received the upper GI endoscopy with oral-pharynx-larynx screening examination. Second primary tumors (n = 12, 9.3%) were found in patients with known 129 history of head and neck cancers. Two patients with synchronous second primary tumors and ten patients with metachronous second primary tumors were diagnosed. Newly diagnosed tumor (n = 4, 0.15%) were observed in 2,720 patients with upper GI endoscopy with symptoms of globus sensation, dysphagia, or acid regurgitation.

Conclusions: Periodic upper GI endoscopy is recommended used in patients with history of head and neck cancers, because high prevalence of second primary tumor. Routine upper GI endoscopy may detect early stage of head and neck cancer in asymptomatic patients. An additional oral-pharynx-larynx screening examination should be an integral part of routine upper GI endoscopy.

利用常規上消化道內視鏡口腔咽喉觀察頭頸 癌患者之次發性腫瘤

P.062

THE EFFECT OF EXERCISE TRAINING AND PROBIOTICS INTAKE ON THE GUT MICROBIOME AND PHYSICAL HEALTH OF IRRITABLE BOWEL SYNDROME

高英捷1 何士奇1 黃仁杰1 趙偉丞2 1 澄清綜合醫院中港分院胃腸內科

Background: Irritable bowel disease is a disorder of abnormal bowel function, characterized by abdominal pain or cramps combined with changes in bowel function, including abdominal distention, diarrhea, or constipation. Patients with irritable bowel disease are often associated with depression or bipolar disorder, and it has long been considered a psychosomatic illness rather than purely physical one. Probiotics have been shown to have preventive and ameliorative effects on such disease.

Aims: In recent years, exercise training has also been considered a feasible approach to irritable bowel disease, and it has been associated with the improvement of various physical and mental indicators. However, only a few studies have investigated the correlation between exercise and probiotic interventions on the symptoms of irritable bowel patients. Therefore, this study aims to investigate the effects of exercise training and probiotic supplementation on the gut microflora and health status in patients with irritable bowel disease.

Methods: Thirty patients with irritable bowel disease confirmed by two gastroenterologists were enrolled in this study. The subjects were randomly divided into three groups: exercise training + placebo group, exercise training + probiotic group, and probiotic-only group. These groups were given exercise training twice a week and probiotic supplementation twice a day for six weeks. The IBS-QOL, BSRS-5, and stool samples were collected before and after the experiment for further analyses.

Results: In this study, 31 subjects with irritable bowel disease were enrolled, with 21 females and 10 males and an average age of 38 years old. After six weeks of exercise training and probiotic supplementation, the results of the questionnaire showed that the exercise training + probiotic group and the exercise + placebo group showed a significant decrease in the score of irritable bowel life questionnaire (p < 0.01); Significant diffference in microflora of Klebsiella, Prevotellaceae and Patescibacteria

was also noticed in the exercise training + probiotic group (p < 0.05).

Conclusions: After six weeks of exercise training combined with intake of probiotics, the quality of daily life of patients with irritable bowel disease could be improved much. In the analyses of microflora, it is found that exercise training combined with intake of probiotics is correlated with the change in gut microflora in patients with irritable bowel disease. It also means that the change in gut microflora may be closely related to the improvement of symptoms of irritable bowel disease.

運動訓練與益生菌補充對於腸躁症患者其腸 道微生物相影響

2 中興大學組織工程與再生醫學博士學位學程

BLOOD STREAM INFECTION DETERMINED SURVIVAL OF TPN-SUPPLEMENTED PATIENTS WITH SEVERE UNCONTROLLED GASTROINTESTINAL DISORDERS

Background: Total parenteral nutrition (TPN) supplementation is commonly needed for patients with severe uncontrolled gastrointestinal (GI) disorders. In whom, blood stream infection (BSI) is one of the most serious complications, but the risk factors to develop BSI is not fully investigated.

Aims: The aim of this study is to investigate the risk factors to occurrence of BSI during TPN supplementation and its impacts on survival in patients with uncontrolled GI disorders.

Methods: From January 2018 to February 2019, 222 patients were supplemented with TPN for uncontrolled gastrointestinal disorders. Among them, 195 who lived more than 2 weeks were enrolled. Baseline characteristics, indications and formula of TPN were analyzed. Risk factors to develop BSI, including bacteremia and fungemia, and predictors to overall survival (OS) were respectively calculated by binary logistic regression and COX regression model.

Results: During the median follow-up time of 10.0 months (interquartile: 1.0 – 37.4), 46 (24%) patients developed BSI. Significant hyperbilirubinemia, hyponatremia and longer duration of TPN supplementation were observed in patients who developed BSI compared with the counterpart. In multivariate analysis, prolonged TPN supplementation longer than 18 days was an independent risk factor to the development of BSI. Otherwise, the TPN formula was not significantly associated with the occurrence of BSI. In addition, patients who developed BSI had a significantly poorer survival benefit compared with the others (OS: 3.7 vs. 16.6 months, p = 0.032). In multivariate analysis, development of BSI (adjusted hazard ratio [aHR]: 1.32, p = 0.041), TPN supplied via Port-A catheter (aHR: 1,65, p = 0.020), administration of immunosuppressive agents (aHR: 1.71, p = 0.021), presence of underlying cirrhosis (aHR: 2.425, p = 0.027) and end stage renal disease (aHR: 2.423, p – 0.024) were independent predictors to mortality.

Conclusions: Development of BSI independently predicted overall survival in patients who received TPN supplementation for their uncontrolled gastrointestinal disorders. Prolonged TPN supplement would significantly increase the risk of BSI. Cautious application and optimal adjustment of TPN would be considered in these patients.

P.063

在全靜脈營養支持下之嚴重不可控腸胃道疾 病病患，血流感染決定後續之存活率

謝秉翰 李沛璋 楊宗杰 蘇建維 黃怡翔 侯明志 臺北榮民總醫院胃腸肝膽科

P.064

胃癌腦膜轉移患者的臨床特徵與預後分析： 臺灣單一醫學中心的經驗 CYTOLOGICALLY PROVEN LEPTOMENINGEAL CARCINOMATOSIS IN GASTRIC CANCER PATIENTS: EXPERIENCE IN A TERTIARY REFERRAL CENTER

郭震亞1 張為淵2 林明燦3 孫家棟4 蔡上傑5 張晉豪6

鄭祖耀6,7

1 天主教輔仁大學附設醫院胃腸肝膽科

2 國立臺灣大學醫學院附設醫院新竹分院胃腸肝膽科

3 國立臺灣大學醫學院附設醫院外科部

4 國立臺灣大學醫學院附設醫院病理部

5 國立臺灣大學醫學院附設醫院醫學研究部

6 國立臺灣大學醫學院附設醫院癌醫中心分院檢驗醫學 部

7 國立臺灣大學醫學院附設醫院胃腸肝膽科

Background: Gastric cancer (GC) ranking 9th in incidence among all kinds of malignancies in Taiwan, and leptomeningeal carcinomatosis (LMC) is a rare but devastating complication of advanced GC. The reported incidence may be underestimated because of the non-specific clinical presentation and the suboptimal accuracy of the confirmation tests. Despite advances in multidisciplinary care, the prognosis for patients with LMC remains poor.

Aims: We aimed to review our experience with LMC in GC patients at a tertiary referral center in Taiwan to analyze the clinical features and survival outcomes.

Methods: All patients with a malignant diagnosis of cerebrospinal fluid (CSF) cytology at the National Taiwan University Hospital were reviewed from January 2002 to December 2018. The survival analysis was calculated by the Kaplan-Meier method. Univariate and multivariate Cox proportional hazards regression analysis were used to identify factors associated with survival.

Results: We identified 18 patients with a diagnosis of GCrelated LMC. LMC occurred in approximately 0.45% of GC patients during this period. Nine (50%) were male, and the median age was 58.5 years old. The most frequent neurological symptom of these patients was altered mental status (72.2%), followed by headache (44.4%) and nausea/ vomiting (44.4%). Intracranial hypertension was noted in 87.5% with the mean opening pressure to be 385.3 mmCSF. Intrathecal (IT) chemotherapy was administered to nine patients, principally with methotrexate alone (55.6%).

Fourteen patients received CSF drainage by ventriculoperitoneal shunt or external ventricular drainage via Ommaya reservoir for relieving intracranial hypertension. In the univariate Cox proportional hazards regression analysis, the poor ECOG performance status (>2), absence of other metastases, and absence of CSF drainage were all prognostic factors of poor survival.

Conclusions: LMC was a rare manifestation of GC and was associated with an extremely poor survival when the performance status was poor at presentation. CSF drainage may have some impact on the survival duration in selected cases with LMC.

P.065

EUS-FNB 在胰臟腫瘤的角色作用 THE ROLE OF EUS-GUIDED FNB IN PANCREATIC TUMOR: A SINGLE CENTER EXPERIENCE

Background: Endoscopic ultrasound (EUS) is an essential method for detection, characterization, and differential diagnosis of solid pancreatic lesions. EUS-guided fineneedle biopsy is an accurate and safe technique to confirm differential diagnosis of solid pancreatic lesions, staging of suspected or proven pancreatic cancer, and cytological and histological proof of unresectable pancreatic cancer.

Methods: A single center retrospective study that included total 25 patients in Taipei Medical University Hospital who performed EUS-guided fine-needle biopsy for solid pancreatic tumor. EUS-FNB was performed using linear echoendoscope with slow-pull fanning technique. Tissue acquisition was done with 20 gauge biopsy needle. Samples were included in formalin without rapid on-site evaluation and send for histopathology. Parameters including general characteristics, site of the lesion, EUS appearance, histological findings and treatment status were reviewed in detail in all cases.

Results: A total of twenty cases diagnosed as pancreatic adenocarcinoma, age is ranging from 38 to 86 years. Among them; 18 patients were male and 8 were female. Most patients were presented abdominal pain and fullness, body weight loss and jaundice, few patients were incidental sona and CT follow up finding. Size were ranged 17 to 70 mm hypoechoic tumor. Location of tumors were 4 cases in uncinate process; 1 case in neck; 7 cases in head; 5 cases in body to tail; 2 cases in tail and two patients from liver due to altered anatomical structure. Sixteen cases were diagnosed pancreatic adenocarcinoma, four cases were diagnosed metastatic tumor (from lung, nasal cavity, breast and uterus), four cases were chronic inflammation with fibrosis, and one case was failed. Among them, only two patients received surgery and the rest received chemotherapy and supportive treatment. There was one major complication (3.85%) of aspiration pneumonia.

Conclusions: Endoscopic ultrasound-fine needle biopsy has been established to be an important tool in the management of pancreaticobiliary disease and is used for screening, staging, histological confirmation and palliative treatment. But, the accuracy is affected by several factors such as different needle types and sizes and techniques, and also operator skill and experience.

P.066

以健保資料庫分析台灣地區發炎性腸炎住院 率之趨勢 HOSPITALIZATION TRENDS FOR INFLAMMATORY BOWEL DISEASES IN TAIWAN

Background: The trend of inflammatory bowel disease (IBD) hospitalization rates differed between developed countries and developing countries due to varied epidemiologic stages. The global trend of reducing the hospitalization rate has been reported, mostly from Western countries.

Aims: To our knowledge, there is a lack of populationbased data in regard to the hospitalization rate in Asian countries, where the incidence and prevalence of IBD are increasing significantly in recent decades. We aim to identify the temporal change of average annual percentage change (AAPC) in hospitalization rate and hospitalization days of IBD, and compare the difference between prebiologic and post-biologic eras in Taiwan.

Methods: The statistical data were obtained from January 2001 to December 2017 in this nationwide populationbased study by using National Health Insurance (NHI) database with coverage of almost the whole population (99.7%). The all-cause hospitalization rate of patients with Crohn’s disease (CD) or ulcerative colitis (UC) could be evaluated with the coding of IBD by International Classification of Disease (ICD), 9th and 10th version codes in catastrophic illness certificate (CIC) registration of NHI dataset. Firstly, we updated the incidence and prevalence rate of IBD in Taiwan. Secondly, the AAPC rate and its temporal change were explored. In addition, the parameters of hospitalization were analyzed including the length of hospital stays and admission codes. Finally, since biologics are available and reimbursed since 2011 in Taiwan, we compared the outcomes between pre-biologic and postbiologic eras.

Results: Among our analysis, a total of 3925 patients were registered for catastrophic IBD illness, 1179 of CD and 3251 of UC, from 2001 to 2017 in Taiwan. The incidence rate and prevalence rate in IBD patients increased from 0.62

林寶英 黃唯誠 簡錫淵 高偉育 張君照 臺北醫學大學附設醫院肝膽腸胃內科

and 2.43 per 100,000 population in 2001 to 2.16 and 19.16 per 100,000 population in 2017, respectively. The agestandardized hospitalization rates of IBD were increasing for IBD (AAPC, 1.93%; 95% CI, -1.30 to 5.18), CD (AAPC, 2.94%; 95% CI, -3.76 to 9.63), and UC (AAPC, 1.75%; 95% CI, -0.84 to 4.33). The average hospitalization day in IBD reached a peak in 2003 with parallel downward trends in both UC and CD. There was a marked reduction in the mean hospitalization days of IBD in post-biologic era, from 2011 to 2017, when compared with pre-biologic era, from 2001 to 2010 (19.5 days versus 23.4 days per hospitalization, p = 0.002).

Conclusions: The increasing trends in the incidence and prevalence of IBD were observed in Taiwan, which was similar to the epidemiological pattern in other industrialized areas. The hospitalization rate also increased with a rise in IBD prevalence. However, we observed the significantly shorter hospitalization days in post-biologic era, which might be contributed to the advancement in clinical treatments.

P.067

否合併膽囊破裂與肝膿瘍的關聯 THE CONNECTION OF CHOLECYSTITIS WITH/WITHOUT RUPTURE OF GALLBLADDER AND LIVER ABSCESS IN PATIENT WITH GALLSTONE: A SINGLE MEDICAL CENTER’S EXPERIENCE IN TAIWAN

Background: There are many people have gallstones. Some people suffered from biliary colic and even cholecystitis that cause symptoms. Gallbladder (GB) rupture may exist in little part of these cases. Besides, for pyogenic liver abscess from biliary origin, gallstones or biliary obstruction by choledocholithiasis are the main risk factor.

Aims: To evaluate the risk factors and parameters which may affect the severity, risk, complications of liver abscess in patients with gallstones, acute cholecystitis with or without GB rupture.

Methods: We collected the patients in China medical university hospital from Nov., 2011 to Jun., 2021 retrospectively who have gallstones or sludges and suffered from pyogenic liver abscess. For total 127 patients, we divided them into two groups that with or without GB rupture. Then we analyzed the basic data, underlying disease, laboratory data, admission dates and mortality rate with Chi-Square test in categorical variable and MannWhitney U test in continuous variable. Then for further analysis, patients with common bile duct (CBD) stone or patients with bile duct dilatation and hyperbilirubinemia were selected who are more likely to cause liver abscess via biliary origin.

Results: In table 1, there are significant increase of age in group of GB rupture (median: 72 vs. 64, p = 0.008) and lower aspartate aminotransferase (AST) level in group of GB rupture (25 vs. 41, p = 0.042). Patients in group of GB rupture have diabetes mellitus in majority (81%, p = 0.027). Percutaneous transhepatic gallbladder drainage (PTGBD) is much more frequently used in patients with GB rupture (57.1% vs. 18.9%, p = 0.001) For the location of liver abscess, in the group of GB rupture, the abscess are always (100%) adjacent to GB, and only few patients have abscess both adjacent and non-adjacent to GB coexist (19%) (p < 0.001); while in the group of GB without

中部一醫學中心之經驗：膽結石、膽囊炎是

鄭幸弘 莊世杰 楊其穎 黃文信 中國醫藥大學附設醫院消化系內科

rupture, there are only 40.6% patients with abscess adjacent to GB and 53.7% patients with abscess not adjacent to GB and 5.6% patients with both adjacent and non-adjacent abscess co-exist. However, there was no significant difference in the two groups in gallstones number, size, and choledocholithiasis or not. The data discloses increased level in group of GB rupture with white blood cell (WBC) count, alkaline phosphatase (Alk-p), r-glutamyl transferase (r-GT) and less cholecystectomy at the admission course though no significant difference. In table 2, there are smaller GB stones size in group of GB rupture (12 vs. 6.95 mm, p = 0.049).

Conclusions: Therefore, we could recognize that elder people or patients with DM have increased risk of GB rupture when they suffered from gallstone and liver abscess. PTGBD is much more frequently used in GB rupture patient that may relate to the severity of local inflammation. For patients with gallstones and ruptured GB, liver abscess adjacent to GB could be always noted. We should keep in mind that if abscess adjacent to GB, GB rupture should be considered. The limitations of this study are small sample size that no significant difference of WBC, Alk-p, r-GT level though increased level in group of GB rupture. Operation with cholecystectomy tends to avoid in that admission course, that operation risk such as adhesion, complications may increase in group of GB with rupture though no significant difference. The admission dates, mortality rate are no significant difference in these two groups.

P.068

CLINICAL UTILIZATION OF MULTIPLEX REAL-TIME PCR

TEST IDENTIFYING DIARRHEA

ETIOLOGY IN PATIENT WITH ACUTE GASTROENTERITIS: A SINGLE INSTITUTE EXPERIENCE IN TAIWAN

黃柏儒1 吳宜樺1 張凱智1 王英哲2 鄭庚申1,4 薛博仁

Background: Acute gastroenteritis (AGE) is a common infection disease and its clinical syndrome is defined by vomiting, diarrhea, and nausea, fever, abdominal pain. Viral gastroenteritis is a self-limiting disease with better prognosis. Bacterial gastroenteritis is different, some patients with warning signs or risk factors for severe disease, such as bloody diarrhea, persistent vomiting, dehydration, dizziness, or losing consciousness. Etiological diagnosis of AGE can be challenging and complicated due to wide range of potential pathogens including viruses, parasites, diseases, or bacteria. Early identification of the pathogen and administration of targeted antimicrobial therapy is an important factor in managing patients with AG complicated with warning signs, including bloodytinged diarrhea, dehydration, dizziness, fever or drowsy consciousness.

Aims: The aim of this study was to investigate the pathogens of patients with AGE complicated with warning signs or risk factors for severe disease in a teaching hospital of middle Taiwan.

Methods: We retrospectively reviewed the medical records of patients diagnosed as AGE with warning signs or risk factors for severe disease at our hospital from September 2021 to October 2022. These patients all had warning signs risk factor of severe diseases and we used Biofire filmarray gastrointestinal (GI) panel for identifying pathogens. This GI panel is an automated multiplex PCR test for rapid detection of total 22 pathogens, including 13 bacteria, 5 viruses and 4 parasites in approximately one hour.

Results: A total of 126 patients with AGE complicated with warning signs or risk factors for severe disease were

臨床應用快速多標的核酸檢測於急性腸胃炎 患者的病因診斷：中部一醫學中心之經驗

enrolled into this study. 105 patients need hospitalization for further therapy; 21 patients only follow up at OPD. There were 61 males and 65 females, with a male-tofemale ratio of 0.94:1. The mean age was 55.65 years (range, 18-94 years). The detection rate by GI panel is 46.03% (58/126), mono-pathogen infection (51/58, 87.9%) is predominant. Only 7 cases had multiple infection, including 6 cases of double pathogens (10.3%), 1 case of triple pathogens infection (1.7%). Total 9 kinds pathogens was detected. Clostridium difficile (20/58, 34.4%) accounted for the major of these pathogens. Followed by salmonella in thirteen (13/58, 22.4%), Enteroaggregative E. coli (EAEC) in ten (10/58, 17.2%), Campylobacter in 9 (9/58, 15.5%), Norovirus GI/GII in six (6/58, 10.3%), Enteropathogenic E.coli (EPEC) in four (4/58, 6.89%),Vibrio (parahaemolyticus, vulnificus & cholerae) in two (2/58, 3.4%), Cryptosporidium in one (1/58, 1.7%) and shiga-like toxin-producing E. coli (STEC) in one patient (1/58, 1.7%). All these patients with a good outcome and none of these patient death or morbidity due to acute gastroenteritis.

Conclusions: According to the result our study, bacterias is the predominant pathogens (52/58, 89.6%). l showed only 6 case is viral gastroenteritis. Hence, empiric antibiotic therapy is necessary for patient with warm signs of severe disease or past history. Although AGE is usually considered as self-limited disease accompanied with good prognosis. In some patient, such as old age or past history of systemic diseases complicated with warm signs of severe disease should be considered GI panel for early identifying targeted pathogens.

P.069

內視鏡超音波導引胰管會合與引流術：東南

EUS GUIDED PANCREATIC DUCT INTERVENTION, DRAINAGE AND RENDEZVOUS: EXPERIENCES IN A LOCAL HOSPITAL IN SOUTHEASTERN TAIWAN

吳佳憲 陳煥霖 白明忠 台東馬偕紀念醫院胃腸肝膽科

Background: EUS guided pancreatic duct intervention includes two main techniques of rendezvous technique (EUS-RV), and transmural stent insertion. In case of pancreatic duct stricture / obstruction, it has been one more and more popular salvage treatment other than surgery or percutaneous external drainage if endoscopic transpapillary pancreatic drainage fails. In expert operator’s hands, high rates of technical / clinical success were reported with more than 25% adverse events rates. Despite development of dedicated devices, EUS pancreatic intervention remains technique challenging.

Aims: We retrospectively evaluated efficacy, safety, and clinical outcomes of EUS-guided pancreatic duct interventions in our hospital.

Methods: I performed nine consecutive EUS-guided pancreatic duct interventions to assist ERCP in six patients (mean age 60 y/o, range 20~90) between June 2016 and August 2022. The etiology of pancreatic duct stricture / obstruction including chronic pancreatitis, pancreatic divisum with pancreatic duct stricture, traumatic pancreatic injury. I firstly performed EUS-RV if the papilla was intact and endoscopically accessible, otherwise I performed EUStransmural stent insertion. We retrospectively evaluated technical success, clinical success, adverse event of procedure, and follow-up results.

Results: In the six enrolled patients, three had pancreatic divisum with main pancreatic duct stricture with upper stream dilatation, two had traumatic pancreatic injury and the other one had chronic pancreatitis related pancreatic duct stricture with upper stream dilatation. Overall technical success rate was 89% (8/9). There was no immediate procedure related bleeding, or GI tract perforation. In the first pancreatic divisum case, I performed EUS-RV and successfully inserted the wire into main pancreatic duct and reaching duodenum but failed to insert the stent transpapillary from duodenum side. I then inserted one 5Fr plastic stent into the main pancreatic duct with the

台灣一區域教學醫院的經驗

assistance of coaxial electric cautery catheter. He remained free of symptoms for two months. Recurrent pancreatitis was noted 2 months later and X-ray showed dislodgment of the transmural pancreatic stent. I performed another session of transmural stenting with 5Fr plastic stent smoothly. He remained free of pancreatitis for more than half year. For the other two divisum cases and one traumatic pancreatic injury case, I performed EUS-RV and successfully inserted the wire into duodenum. Then I switched to duodenoscope and completed transpapillary pancreatic drainage with plastic stents. In the other traumatic pancreatic injury case, CT revealed complete interruption of pancreatic duct at pancreatic neck with fistula tract connecting to the tail portion of pancreatic duct. I performed transmural pancreatic duct stenting but failed. I then targeted the fistula tract for puncture and then inserted one 7Fr double pigtail plastic stent from stomach into the fistula tract. Three months later, stent was dislodged and one 5 cm fluid collection at pancreatic neck, connecting the tail portion of pancreatic duct. I performed EUS guided transmural stent insertion from tail portion of pancreatic duct into the pseudocyst. The patient remained free of symptoms for more than 12 months till now. In the chronic pancreatitis case, he underwent EUS-RV assisted pancreatic duct stenting because of duodenum obstruction by duodenal intramural hematoma. Three months later, I tried transmural pancreatic stenting due to persisted duodenal obstruction, but failed to dilate the tract with bougie dilatation catheter. Then I switched to EUS-RV and successfully inserted pancreatic duct stent. Later, patient underwent regular ERCP every 3 months for p stent exchange since resolution of the duodenal hematoma.

Conclusions: EUS-RV and EUS-transmural pancreatic duct stent insertion appeared relatively safe and effective treatment modality. Key for technical success including dedicated accessories and experienced endosonographer.

Background: Deep enteroscopy, including single balloon enteroscopy (SBE) and double balloon enteroscopy (DBE), is a novel endoscopic technique designed to evaluate and treat small-bowel disease. Although there is substantial literature addressing DBE and its impact on the diagnosis and management of small-bowel disease, there are limited data available on the clinical utility of SBE.

Aims: To evaluate the clinical utility of SBE in small bowel disease.

Methods: Data on patients with suspected of small bowel disease, who underwent SBE from November 2008 to July 2022 was collected from MacKay Memorial Hospital, a tertiary medical center in Taiwan. The demographic, clinical, procedural, and outcome data of SBE were collected and analyzed.

Results: A total of 401 patients underwent of 570 procedures. Antegrade and retrograde approaches were used in 283 and 287 of subjects, respectively. There were 169 patients received bidirectional procedures and 105 patients had tried to evaluate the entire small bowel. The success rate of total small bowel evaluation was 73.3% (77/105). The indicatios of SBE included obscure GI bleeding 47.1% (189/401), chronic abdominal pain32.4% (130/401), Chronic diarrhea11.7% (47/401), small bowel tumor 6.7% (27/401), suspected Crohn’s disease 1.2% (5/401) and others 0.7% (3/401). The diagnostic yield of SBE was 63.3% (254/401) included ulcer 15.2% (61/401), small bowel tumor 7.7% (31/401), polyposis syndrome 9.2% (37/401), angioectasia 12.2% (49/401), small bowel diverticulum 5.2% (21/401), lymphangiectasia 4% (16/401), Crohn’s disease 9.5% (38/401) and others 5.7% (23/401). In this study, the therapeutic SBE is 26.7% (107/401). There were 6 patients had significant complications after SBE (1.5%), and all cases recovery after conservative treatments. There are limitations of this study which including a singlecenter experience and retrospective study.

Conclusions: SBE demonstrated a high diagnostic yield and it seems to be a safe and effective method for performing deep enteroscopy.

P.071

利用傳統膠囊內視鏡與環景側照膠囊內視鏡

significantly higher than 25% by EC-10 (P = 0.013). The Z line detection rate was 60% by CapsoCam and was also significantly higher than 25% by EC-10 (P = 0.003). The diagnostic yield of P2 lesion was similar by two types (EC-10 56.3%, Cpasocam 50%, P = 0.723) (Table). The diagnostic concordance (kappa value) betweenEC-10 and CapsoCam was also strong for P2 lesions (κ = 0.815). The evaluation time was comparable between two types. (EC-10 54.56 min, Capsocam 59.56min, P = 0.309). The capsule transit time, image performance and complete capsule transit rate were similar between groups. (Table) 1 patient experienced both capsule endoscopes retention due to jejunal tumor related stenosis and were resolved by endoscopy. Less noises were noted by CapsoCam compared with EC-10 (0% V.S. 37.5%, P = 0.007).

Background: Video capsule endoscopy (VCE) is useful in evaluation of patients with suspected small bowel bleeding. Conventional capsule endoscopy can detect small bowel lesions with its wide-view lens while blind spots on the lateral side may not be visible. Panoramic side view capsule endoscope with four cameras surrounding the capsule endoscope that can obtain a 360° lateral view of gastrointestinal tract was developed in recent years. In earlier study comparing two earlier versions of capsule endoscope, the diagnosis rate was comparable. Both types of capsule endoscopes had updated versions with longer battery time, better resolution, and new reading software. No comparative study was available in comparing the performance of these newer models of capsule endoscopy.

Aims: To compare the detection rate of duodenal papilla, Z line and diagnostic yield of conventional capsule endoscope [Olmypus endocapsule 10 (EC-10), Olympus Co. Japan] and panoramic side view [CapsoCam Plus (CapsoCam), CapsoVision, US] capsule endoscope.

Methods: We prospectively enrolled 20-85 years old patients with suspected small bowel bleeding. Patients received split dose 4 liter Polyethylene glycol preparation prior to capsule endoscope ingestion with 10ml simethicone fluid preparation. Then the patient ingested EC-10 followed by CapsoCam 1.5 hours after or in reverse order in a randomized order. Two experienced endoscopist independently read the capsule endoscopy result.

Results: 16 patients (7 male and 9 female) were enrolled in this study with half (n = 8) patients receiving EC-10 first. Patients’ mean age were 65.81 years (range 50-86) with mean body mass index 25.53 kg/m 2. The ampulla vater detection rate was 68.5% by CapsoCam which was

Conclusions: The diagnostic yield and examination completion rate of CapsoCam Plus capsule endoscope was comparable with Olympus EC-10 capsule endoscope with high concordance. The detection rate of ampulla vater and Z line was higher by CapsoCam plus capsule. Less technical issues were encountered by CapsoCam plus capsule endoscope.

4 國立陽明交通大學醫學系

5 高雄榮民總醫院台南分院胃腸科

P.072

巴瑞特氏食道組織學診斷的一致性分析研究

AN AGREEMENT ANALYSIS STUDY OF HISTOLOGY IN THE BARRETT’S ESOPHAGUS

questions. 10 cases were agreed to have IM and 8 cases did not have IM. In one case, one person was in favor of IM, one was against IM, and the other two were unsure. In another case, two people objected to having IM, and the other two were not sure.

Background: Barrett’s esophagus is one of the most common diseases encountered by gastroenterologists and is related to the occurrence of esophageal adenocarcinoma. At present, the most accepted definition of diagnosis of Barrett’s esophagus is that the observation of specific mucosal changes by endoscope: endoscopic suspected esophageal metaplasia (ESEM), coupled with biopsy pathological examination to confirm intestinal metaplasia (IM). Pathological diagnosis is the key to the diagnosis of Barrett’s esophagus, so establishing the consistency of pathological diagnosis is the cornerstone of all Barrett’s esophagus research.

Aims: For agreement analysis of histology in the Barrett’s Esophagus, we compare the diagnostic consistency of intestinal metaplasia between different pathologists in pathological examination.

Methods: From the medical records of patients undergoing endoscopy in our hospital, the specific mucosal changes (endoscopic suspected esophageal metaplasia (ESEM)) observed under endoscopy were screened out, and biopsy were also taken for histological diagnosis. After reading the pathological slide photos, we would remove all the data that can identify the patient’s information. Then we make picture files for the pathologist to judge whether there is intestinal metaplasia, and to study the consistency of the pathological diagnosis. The subjects of the research questionnaire are pathology specialists in our hospital who are willing to join the research. The excluded object is the pathologist who participated in the presiding of this research project. There are a total of 20 questions in each questionnaire. For each question, two pathological photos obtained from ESEM are placed. The two pathological photos are hematoxylin and eosin stain with magnification of 40 times and magnification of 100 times. Ask about intestinal metaplasia.

Results: Finally, four questionnaires are finished. Five pathologists in our hospital, except for one researcher, the other four have finished the research questionnaire. Among the 20 questions, all subjects answered the same for 18

Conclusions: If we only look at magnification of 40 times and magnification of 100 times of hematoxylin and eosin stain, the agreement of pathologists were not 100%. Pathological diagnosis is the key to the diagnosis of Barrett’s esophagus. Perhaps the addition of other staining methods or careful observation using other magnifications can further increase the consistency of pathological diagnosis. There were not enough questionnaire questions and subjects in this experiment. Further research is needed in the future to explore the agreement of histology in the Barrett’s Esophagus.

陳昱宗1 張吉仰1 李昱儀2

1 輔大醫院內科部

2 輔大醫院病理科

利用病歷回顧探討代謝手術對肥胖患者術後 的影響 A STUDY TO EXPLORE THE POSTOPERATIVE IMPACTS OF METABOLIC SURGERY IN OBESE PATIENTS USING MEDICAL RECORD REVIEW

female case had an abnormal kidney injury (eGFR < 30 ml/ min/1.73m2 & PRE-CKD = 4) one year later.

Conclusions: Metabolic surgery is indeed one of the most effective weight loss methods to treat morbid obesity. Through long-term monitoring, we can observe the percentage of weight loss trends and improve the management of related-chronic diseases in obese.

Background: The obesity epidemic has become a serious public health problem in developed and developing countries. Two main types of metabolic surgeries, restrictive and malabsorptive, are both effective in the treatment of obesity. However, the effectiveness of metabolic surgery in long-term monitoring remains an understudied issue.

Aims: This study was a retrospective case-control study. Our objective was to establish a model to predict the effectiveness of metabolic surgery.

Methods: From April 2016 to September 2022, a total of 39 morbidly obese patients (male/female = 18/21, mean age = 44.7 ± 12.4 years old) were enrolled at Tainan Municipal Hospital (managed by Show Chwan Medical Care Corporation); among them, 21 (male/female = 10/11, mean age = 40.8 ± 11.6 years old) underwent gastrectomy. We analyze factors that can affect the outcome of the surgery, including gender, age, other chronic diseases, and physiological functions. All observation data were performed before, at three, six months, and one year after the surgery. Using the Mann-Whitney U test and the Chi-square test to perform nonparametric analysis, find independent variables, and further use the multivariate logistic regression to predict the factors of effectiveness of metabolic surgery.

Results: Through blood tests, we found that the control group (obese w/o surgery) had a significantly higher proportion of anemia (43.8% vs. 4.8%, p = 0.014), chronic inflammation (62.5% vs. 23.8%, p = 0.018), and kidney problems (eGFR < 60 ml/min/1.73m2 & PRE-CKD ≥ 3: 44.4% vs. 9.5%, p = 0.034) than that in the case group. The surgery significantly improved the liver inflammation index (AST/ALT) and postprandial blood glucose (GluAC) of the cases. However, due to aging and diabetes, 1

科

P.074

食道鱗狀細胞癌經術前化放療的療效比較 COMPARISON OF THERAPEUTIC OUTCOMES IN ESOPHAGEAL SQUAMOUS CELL CARCINOMA FOLLOWING NEOADJUVANT CHEMORADIOTHERAPY

余方榮1,2 劉又瑋2,3 陳以勳1 李瑞英3 吳宜珍1,2

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 高雄醫學大學附設中和紀念醫院胸腔外科

Background: Patients with locally advanced esophageal squamous cell carcinoma (ESCC) following neoadjuvant chemoradiotherapy (nCRT) may not always receive resection despite the possible achievement of a pathologic complete response (pCR) being associated with superior survival benefit.

Aims: We aimed to compare outcomes among ESCC patients with or without pCR and those refusing surgery.

Methods: In total, 111 medically operable, noncervical ESCC patients after the same protocol of nCRT (platinum/5-fluorouracil plus radiation 50Gy) were prospectively enrolled between 2011 and 2021. Eightythree of them underwent esophagectomy comprising pCR (n = 32) and non-pCR (n = 51), while 28 operable patients declined surgery (refusal-of-surgery group). Predictors and survival data were analyzed.

Results: In terms of esophagectomy, 38.5% (32/83) patients achieved pCR. The pCR group exhibited better pretreatment performance status than the non-pCR group (adjusted odds ratio: 0.11, 95% confidence interval: 0.030.58; p = 0.01). Among pCR, non-pCR, and refusalofsurgery groups, the 5-year overall survival (OS) rates were 56%, 29% and 50% (p = 0.08) and progression-free survival (PFS) rates were 52%, 28% and 36% (p = 0.07) respectively. The pCR group had significantly better OS and PFS than the non-PCR group (adjusted hazard ratio: 2.33 and 1.93, p = 0.02 and 0.049 respectively) but not the refusal-of-surgery group.

Conclusions: Better pretreatment performance status is associated with higher chance of pCR. Consistent with previous studies, we found attainment of pCR confers the best OS and PFS. Suboptimal OS in the refusal-of-surgery group reflects some of them would have residual disease in addition to complete remission. Further studies are needed to identify prognostic factors of pCR to select candidates who could validly decline esophagectomy.

P.075

膽囊炎合併膽管炎接受經皮膽囊引流術和治 療性內視鏡逆行胰膽管攝影術且大於 80 歲 病人的預後 OUTCOME IN OCTOGENARIANS WITH CONCURRENT CHOLECYSTITIS AND CHOLANGITIS RECEIVING PERCUTANEOUS TRANSHEPATIC GALLBLADDER DRAINAGE AND INTERVENTION ENDOSCOPIC RETROGRADE CHOLANGIOPANCREATOGRAPHY 李知育1,3

Background: Acute cholecystitis (AC) with concurrent cholangitis is a life-threatening disease in elder patients. Aims: We aimed to investigate the outcomes after endoscopic papillary balloon dilation (EPBD) versus endoscopic sphincterotomy (EST) in patients aged ≥ 80 years with moderate to severe AC who received percutaneous transhepatic gallbladder drainage (PTGBD).

Methods: From January 2008 to February 2021, patients receiving PTGBD and intervention endoscopic retrograde cholangiopancreatography (ERCP) in Taipei Veterans General Hospital were retrospectively enrolled. Clinical outcomes including recurrent AC, other biliary events, complications of ERCP and survival days were recorded. Outcomes between patients who received EPBD versus EST were compared. Kaplan-Meier model was used to interpret the overall survival.

Results: Total 104 patients with AC following PTGBD and subsequent ERCP were enrolled. Overall survival was 6.3 ± 0.5 year. The overall ERCP-related complication rate was low (0.04%) in this elderly population. The overall recurrent rate of AC, cholangitis, and pancreatitis after interventive ERCP were 20.4%, 11.5%, 1%, respectively. Eighty-one patients underwent EPBD, while 23 patients underwent EST. Baseline characteristics were similar between two groups. There was no statistically difference in terms of recurrent AC (19.0% vs. 30.4%, p = 0.275), cholangitis (12% vs. 9%, p = 0.633), and pancreatitis (1% vs. 0%, p = 0.597) between patients who received EPBD versus EST. The ERCP-related complication rates and biliary tract related mortality rates did not differ between

EPBD and EST (2.4% vs. 8.6%, p = 0.299; 2% vs. 4%, p = 0.639). The 1-year cumulative incidence of recurrent AC after EPBD or EST was 14.8% and 26% (p = 0.198), respectively.

Conclusions: ERCP is a safe procedure in the octogenarians, with low rates of recurrent AC and other biliary events. Also, there was no different outcomes in octogenarian with moderate-to-severe cholecystitis and concurrent cholangitis receiving subsequent EPBD or EST.

P.076

膠囊內視鏡對克隆氏症之診斷及治療決策上 的運用：一個台灣醫學中心之經驗

THE UTILIZATION OF CAPSULE

ENDOSCOPY IN DIAGNOSIS AND TREATMENT GUIDANCE FOR CROHN’S DISEASE: A MEDICAL CENTER

EXPERIENCE IN TAIWAN

Background: Capsule endoscopy (CE) has revolutionized our ability to visualize the small bowel mucosa. This modality is a valuable tool for the diagnosis of suspected small bowel Crohn’s disease (CD) and for monitor of disease activity in patients with established small bowel CD. Guidelines recommend routine small bowel assessment in patients with new diagnosed of CD to assess prognosis.

Aims: The purpose of this retrospective single-center study was to evaluate the utilization of CE in patients with suspected or established CD. We compared the differences of clinical baseline characteristics between patients with suspected CD or established CD. We also examined the effect on management decisions by CE and correlation between biochemical markers and therapy escalation.

Methods: From September 2005 to December 2022 at MacKay Memorial Hospital, we retrospectively reviewed the medical records of patients with suspected or established CD, who underwent CE. We analyzed patients’ baseline data and also performed Logistic regression to determine associations between biochemical and endoscopic measures of disease activity, with therapy escalation.

Results: A total of 20 patients (9 with suspected CD and 11 with established CD) was enrolled and analyzed. The median age of these patient was 42.65 years and 55% (11/20) of patients was male. Seventy percent of patients (14/20) had complete examination of CE. One case (5%) of capsule retention occurred in patients with established CD. There was no significant difference of clinical baseline characteristics between patients with suspected CD and established CD, except immunomodulators usage before CE (p = 0.002) and colonic involvement in CD (p = 0.008). CE resulted in therapy escalation in 75% (15/20) patients,

including 77.8% (7/9) of newly diagnosed CD and 72.7% (8/11) of patients with established CD whose disease was active. No significant correlation between therapy escalation and biochemical markers, including C-reactive protein (p = 0.399), erythrocyte sedimentation rate (p = 0.647), white blood cell count (p = 0.343), hemoglobin (p = 0.399) and colon involvement in CD (p = 0.766), was found.

Conclusions: CE allows safe and accurate evaluation of the mucosa of small bowel in patients with suspected or established CD. This modality has expanded our understanding of the inflammatory burden of CD outside the colon and the terminal ileum. The ability of CE to detect small bowel lesions may determine disease activity and guide treatment of CD.

P.077

單氣囊小腸鏡在疑似克隆氏症的臨床效用： 一個單一中心臨床經驗

THE CLINICAL EFFICACY OF SINGLEBALLOON ENTEROSCOPY FOR SUSPECTED CROHN’S DISEASE: A SINGLE-CENTRE EXPERIENCE IN TAIWAN

Background: Crohn’s disease (CD) can involve any part of the gastrointestinal tract and 10–30% of patients with CD have small bowel involvement.1 The diagnosis of CD with involvement of the small bowel remains a major challenge even after the development of capsule endoscopy and double-balloon enteroscopy, and is considered underestimated.

Aims: The aim of the present study was to evaluate the efficacy of single-balloon enteroscopy (SBE) for small bowel evaluation for patient with clinical suspicion of CD. Methods: Patients underwent SBE for suspected CD from November 2008 to July 2022 in MacKay Memorial Hospital were collected. We analyzed patients’ baseline data and endoscopic findings and the utility, including diagnostic efficacy and therapeutic decision-making of SBE.

Results: Total 30 patients received SBE for suspected CD were enrolled, and 21(70%) of the patients were diagnosed as CD with small bowel involvement, while 9 (30%) were excluded after SBE. Abdominal pain was significantly more frequent in patient later been diagnosed with CD (p < 0.05). Presence of aphthous ulcer (p = 0.020), longitudinal ulcer (p = 0.001) and stricture (p = 0.003) on SBE help establishing the diagnosis of CD, as well as ileocecal valve involvement (p = 0.001). After SBE, medication including 5-ASA, AZA, corticosteroid and biological agents were applied almost exclusively on patients with CD (p = 0.001).

Conclusions: SBE possess high diagnostic value for patient with clinical suspicion of CD. Typical features including aphthous ulcer, longitudinal ulcer and stricture help establishing the diagnosis, and guide the subsequent medical treatment.

P.078

第一次化療後升高的血小板／淋巴球比率和 嗜中性球／淋巴球比率在食道癌接受同步放 射化療的患者有較好的存活率 ELEVATED PLATELET-TOLYMPHOCYTE RATIO AND NEUTROPHIL-TO-LYMPHOCYTE RATIO AFTER FIRST CYCLE OF CHEMOTHERAPY AND BETTER SURVIVAL IN ESOPHAGEAL CANCER PATIENTS RECEIVING CONCURRENT CHEMORADIOTHERAPY

prechemotherapy PLR < 375.

Conclusions: Our study showed that low levels of prechemotherapy PLR and NLR were associated with better OS and DSS. Elevated platelet count and NLR after first cycle of CHT were associated with better OS. Elevated PLR and NLR after first cycle of CHT were associated with better DSS.

Background: Prognostic factors for poor survival have been proposed in esophageal squamous cell carcinoma (SCC) patients receiving concurrent chemoradiotherapy (CCRT). Elevated pretreatment platelet-to- lymphocyte ratio (PLR) and neutrophil-to- lymphocyte ratio (NLR) significantly predicted poor overall survival (OS), disease free survival (DFS) and cancer-specific survival (CSS) for esophageal cancer patients.

Aims: We conducted a retrospective study on hematological profile after first cycle of chemotherapy for esophageal SCC patients receiving CCRT.

Methods: From January 2008 to December 2017, a total of 420 patients with esophageal SCC were enrolled. All included patients had undergone CCRT. Complete blood count, differential count, NLR, and PLR before chemotherapy (CHT) and after first cycle of CHT were obtained. Univariate and multivariate Cox regression analyses were used to assess the association between survival and patient, disease, and treatment characteristics.

Results: On univariate analysis, significant factors for OS and DSS included ECOG performance status, clinical staging, operation, cisplatin dose, prechemotherapy NLR and PLR, and elevated postchemotherapy NLR. On multivariate analysis, ECOG performance status 0–I, Clinical staging I–II, Operation, cisplatin dose >150 mg per square meter, prechemotherapy PLR < 375, and postchemotherapy platelet count ≥ 150000/ µL were independent factors for predicting better OS. Independent factors for predicting better DSS included ECOG performance status 0–I, Clinical staging I–II, Operation, cisplatin dose >150 mg per square meter, and

P.079

胃癌篩檢的困境：血清澱粉樣蛋白 A 異構 物的診斷模型可否成為可能的解決方案？ GASTRIC CANCER SCREENING DILEMMA: WOULD SERUM AMYLOID A VARIANT BASED DIAGNOSTIC MODEL BE A POSSIBLE SOLUTION?

2 高雄市立大同醫院內科部

4 衛生福利部屏東醫院內科部

5 高雄醫學大學醫學系

6 高雄巿立小港醫院內科部

Background: Gastric carcinoma is a global malignant disease. It is most prevalent in East Asia, Central, and Eastern Europe, and Latin America. Symptoms of early gastric cancer are generally mild and non-specific. Once symptoms appear, they often progress to the later stage, which is one of the primary reasons for its relatively poor prognosis. However, reliable non-invasive screening tools remain unavailable.

Aims: Developing a reliable, non-invasive tool that can be widely used in diagnosis or screening for gastric cancer is essential. In this article, we try to design a study to evaluate the potential use of novel biomarkers, namely Serum Amyloid A for gastric cancer screening.

Methods: Nanoprobes affinity mass spectrometry was used to enrich, identify and quantify serum amyloid A variants. Next, develop a bioinformatics algorithm as a diagnostic model to distinguish the patient from moderate-high gastric cancer at low risk. To validate the usefulness of this model, we are conducting a retrospective cohort study to study the feasibility of amyloid serum A as a biomarker for gastric cancer screening. Between 2017 and 2021, the cohort had adult patients newly diagnosed with primary gastric cancer from endoscopic pathology. Besides, CEA was checked and compared with the SAA result. This study was reviewed and approved by the Kaohsiung Medical University Hospital’s Human Trials Review Board (IRB) and each participant provided informed consent.

Results: A total of 360 patients were classified as neoplasia (120), inflammatory (120), and healthy gastric mucosa (120). The sensitivity, specificity, positive predictive value, and negative predictive value of the diagnostic model for differentiating between gastric carcinoma and

non-gastric carcinoma were 80.8%, 70.0%, 57%, and 88%, respectively. This model also has a 70.8% positive predictive value and a 77.6% negative predictive value for separating gastric carcinoma of the gastritis patient. Sensitivity, specificity, PPV, and NPV of serum CEA at a cutoff of 5 ng/mL to differentiate each group was also checked, respectively.

Conclusions: The diagnostic model based on biocomputer algorithms of the Amyloid Serum A variant may be a potential solution to the dilemma of gastric cancer screening for its acceptable diagnostic value for gastric carcinoma comparable to serum CEA, which is invalid for gastric cancer.

P.080

石綿勞工發生胃癌的風險增加：台灣 35 年 回溯性世代研究

INCREASED RISK OF STOMACH

CANCER IN ASBESTOSEXPOSED WORKERS: A 35-YEAR

RETROSPECTIVE COHORT STUDY IN TAIWAN

2 國家衛生研究院國家環境醫學所

3 國立臺灣大學職業醫學暨工業衛生研究所

4 國立臺灣大學環境職業醫學部

5 高雄醫學大學環境職業醫學博士學程

6 高雄醫學大學環境職業醫學研究中心

7 高雄醫學大學醫學研究所

8 國立臺灣大學衛生政策與管理研究所

9 國立成功大學公共衛生研究所

10 國立成功大學環境職業醫學研究所

Background: Asbestos is termed “the magic mineral” with excellent properties in heat resistance, thermal and electrical insulation, tensile strength, and has gained extensive use in various industries, including architecture construction, ship building, heat insulation, friction materials, and textiles [1]. The global consumption of asbestos and related products reached the peak in the 1980s. However, many countries prohibit the use of asbestos product due to its adverse health effects, such as being a human carcinogen for decades.

Aims: Asbestos has been recognized as a human carcinogen for more than three decades, associated with malignant mesothelioma, cancer of lung, larynx, and ovary. Epidemiological studies and meta-analysis have shown some positive association between asbestos and stomach cancer. In this study, we aimed to explore cancer risks of workers potentially exposed to asbestos in Taiwan.

Methods: The asbestos occupational cohort was established from 1950 to 2015 based on administrative databases of labor insurance, and EPA regulatory datasets for asbestos reporting, followed by the Taiwan Cancer Registry (TCR) for the period 1980-2015. We conducted this retrospective cohort study and the occurrence of potentially asbestos related cancer was examined with TCR using specific histopathological evidence. Standardized incidence ratio (SIR) for cancer were computed for the whole cohort using reference rates of the general population, and also reference labor population.

Results: Compared with the general population, SIR of the asbestos occupational cohort for the stomach cancer increased both in males (1.05, 95% confidence interval [CI]: 1.02-1.09) and females (1.10, 95% CI: 1.01-1.18). The risk of stomach cancer significantly increased in males (1.21, 95% CI: 1.16-1.25), and females (1.16, 95% CI: 1.081.25) as compared with the reference labor population. SIR for female lung cancer increased, but that for laryngeal or ovarian cancer did not have significant difference. Compared with the reference labor population, the agestandardized incidence rate ratios (RR) of the asbestos occupational cohort showed significant increased cancer risk of pleura (RR = 2.18), lung (RR = 1.09), and larynx (RR = 1.23) in males.

Conclusions: This 35-year cohort study of asbestosexposed workers in Taiwan may collaborate the positive association with stomach cancer. Further studies are needed to verify causality through examining the doseresponse relationship considering occurrence of malignant mesothelioma.

P.081

利用人工智慧判讀早期胃癌分期 USING AI FOR EARLY GASTRIC CANCER STAGING

Background: Early gastric cancer (GC) has an excellent 5-year survival rate more than 95%. For early gastric cancer, endoscopic submucosal dissection is a widely accepted treatment for those T1a without lymph nodule metastasis patients. In the past, endoscopic ultrasound is a gold standard tool for tumor staging. However, the inconsistency of inspection quality makes it’s restrictive.

Aims: Artificial Intelligence (AI) now is widely applied to many medical filed. So, we conduct this study to investigate the possibility of AI to help early gastric cancer staging.

Methods: We propose a hybrid approach to classify the T1a and T1b polyps with small sample size. The hybrid method consists of the data preprocessing and image recognition. Our data preprocessing including data augmentation, image processing, and Cycle GAN. The data processing can enhance the feature extraction process and solve the problem of limited sample size. The image recognition we use the method called you only look once (YOLO), which is a method combining location of the polyp and classified the selected image. More specifically, we adopt the YOLOV4. With batch size of 64 and subdivisions of 14, learning rate of 0.0001and max-batch size of 4000, we can reach the best classifying model.

Results: With only 441 T1a images and 542 T1b images, we can build a model that can classified the image with sensitivity equals 88.95% and specificity equals 97.47%. The overall accuracy of 93.85%.

Conclusions: AI can provide an objective and precise method for early gastric cancer staging.

並促進自噬 NICLOSAMIDE, A G9A INHIBITOR, SUPPRESSES CELL VIABILITY AND PROMOTES AUTOPHAGY IN GASTRIC CANCER

蔡一民1 林姵妏2 朱曼菱2 劉玉雯2 劉校生2 吳登強1,3

高雄醫學大學附設中和紀念醫院胃腸內科

Background: Gastric cancer is the third leading cause of cancer death globally, and G9a/EHMT2 (a histone methyltransferase) is overexpressed and plays an oncogenic role in gastric cancer tumorigenesis.

Aims: This study aims to clarify whether niclosamide is a G9a inhibitor, which suppresses cell viability and promotes autophagy in gastric cancer cell.

Methods: Gastric cancer cells (AGS) were treated with niclosamide. Autophagic activity and G9a in AGS cells was determined by Western blotting. Cell viability was determined by MTT. To determine niclosamide is a G9a inhibitor, which suppresses cell viability and promotes autophagy in gastric cancer cell.

Results: Our current findings are as the following: (1) AGS cell was treated with niclosamide increased autophagic activities. (2) niclosamide is a G9a inhibitor. (3) niclosamide suppresses cell viability in gastric cancer cell. Conclusions: We reveal that niclosamide, a G9a inhibitor, suppresses cell viability and promotes autophagy in gastric cancer.

陳聰興1 李捷2 葉大森3

1 林口長庚紀念醫院胃腸肝膽科系

2 國立中山大學資訊管理學系

3 林口長庚醫院一般外科系

P.082

G9a 抑制劑 Niclosamide 抑制胃癌細胞增殖

P.083

探討間質幹細胞對胃癌細胞能量代謝的調節 INVESTIGATE THE REGULATION OF MESENCHYMAL STEM CELLS ON THE ENERGY METABOLISM OF GASTRIC CANCER CELLS

張哲墉

Background: Gastric cancer is a very common digestive tract cancer in Asian countries, and the death rate caused by gastric cancer ranks third in the world. Mesenchymal stem cells (MSCs) may be involved in the development of cancer. Altered energy metabolism contributes to more ATP source, and the growth and metastasis of cancer through up-regulating the uptake of energy-rich metabolites such as lactate, ketone bodies and glutamate et al.

Aims: In this study, we will investigate the regulation of mesenchymal stem cells on the energy metabolism of gastric cancer cells.

Methods: We explored the effect of MSCs on regulation of energy metabolism proteins MCT1, SLC6A14, OXCT1 and OXCT2 of gastric cancer cells, using RT and q-PCR assays. We measured the levels of lactate, ketone bodies, glutamate and ATP in human gastric cancer cells, using ELISA.

Results: Compared with human bone marrow-derived mesenchymal stem cells (BMMSCs), adipose-derived mesenchymal stem cells (ADSCs) significantly induced higher expressions of MCT-1, SCL6A14, OXCT-1/2 and ACAT-1 in human AGS gastric cancer cells. The levels of lactate, glutamate, ketone body and ATP were then measured in human AGS gastric cancer cells. We observed that ADSCs significantly upregulate lactate, glutamate, ketone body and ATP levels in human AGS gastric cancer cells.

Conclusions: These results suggest that ADSCs may be involved in the development of gastric cancer through regulating energy metabolism.

Background: The gastric cancer- and normal-organoids from the cancerous parts or iPS cells were established several years ago. Owing to the remarkable degree to which they recreate the cellular diversity observed in the human stomachs, they have attracted significant interest as a novel model system for precision medicine. However, many questions remain about the extent to which these cultures recapitulate gastro development and mechanism of Helicobacter pylori infected cancer progression.

Aims: The effect of the growth factors for cancer progression by Helicobacter pylori on stomach organoids were examined.

Methods: Previously, we reported that the Hepatocyte derived growth factor (HGDF) and TNF-alpha dependent pathways were crucial for cancer development using 2-D gastric cancer cells infected with Helicobacter pylori

Results: TNFα is defined as the upstream partner of HGDF in 2-D culture system, however, in 3-D organoids culture, HDGF and TNFα are independent in the case of infection of Helicobacter pylori. The invasion activity induced by Helicobacter pylori was inhibited by TNFα, but not by HDGF.

Conclusions: Here, we identified the heterogeneity of the cancer progressions derived from human gastric organoids in response to the Hepatocyte derived growth factor (HGDF) and TNF-alpha (TNFα) dependent pathways during the infection by Helicobacter pylori on stomach organoids. This difference is due to the heterogeneity of the signaling between 2-D and 3-D cultivation system.

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

P.085

THE SECRETOMICS OF GASTRIC CANCER TRANSPLANTED WITH THE MITOCHONDRIA PURIFIED WITH GASTRIC EPITHELIAL CELL

蔡旻軒1 劉忠榮1 王俊偉1,2 黃斌3 吳登強1,2 盧建宇1,2

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 高雄醫學大學生物醫學暨環境生物學系

Background: Mitochondrial transfer/transplantation applied to regulate the cancer physiologies has been well reported in the recent decade. Mitochondria regulates the bioenergenic, calcium balance, oxidative species, steroidogenesis, and metabolites generated from TCA cycle. In our previous study revealed that mitochondria purified from gastric epithelial cell GES-1 and be transferred into gastric cancer cell AGS and therefore leaded to a reduced carcinogenic AGS. Secretomics study currently aims on exosome that is one of extravesicles (EVs). By using the Nanoparticle tracking analysis (NTA), the amount of exosome secreted from AGS transplanted with GES-1 mitochondria was increased.

Aims: To investigate the secretomics of gastric cancer transplanted with the mitochondria from gastric epithelial cells.

Methods: In the MasSpec analysis, 84 proteins were identified and the relative expressions of these proteins were calculated in the AGS transplanted with GES-1 mitochondria.

Results: The IPA analysis indicated that theses exosome involved in the metastasis of cancer cell. In the co-culture system, the exosome purified from AGS transplanted with GES-1 mitochondria showed a significant uptake by endothelial cell as compare to the exosome secreted by wild type AGS, which implies that exogenous transplantation of mitochondria can facilitate the absorption of secreted exosome and then promotes the landing of exosome to the endothelial cell and also the MET process in the tumor growth.

Conclusions: Therefore, the malignance of gastric cancer can be possibly regulated by changing the features of secreted exosome under diverse mitochondrial transplantation.

P.086

成年腐蝕性患者的住院死亡因素分析 THE RISK FACTORS OF IN-HOSPITAL MORTALITY AMONG 557 ADULT PATIENTS WITH CAUSTIC INGESTION: THE COHORT STUDY, 1999-2014

1 新北市立土城醫院（委託長庚醫療財團法人興建經

Background: Ingestion of caustic agents causes severe gastrointestinal (GI) tract injury and induces many lifethreatening complications. Ingesting strong acids causes coagulation necrosis/eschar formation and limit penetration, whereas strong alkalis are rigorous for their penetrating nature associated with saponification/liquefaction effects. Aims: To estimate the mortality in adults with caustic ingestion and provide main risk factor for predicting inhospital mortality.

Methods: We analyzed 1999-2014 data from Chang Gung Memorial Hospital, Taiwan. All adults with caustic ingestion underwent urgent esophagogastroduodenoscopy (EDG) within 24 hours after arriving at our hospital. The mortality of in-hospital and after-discharge were all clearly recorded. Results: Among 557 adult patients admitted with caustic injuries, 343 (61.6%) required hospitalization. Total 128 in-hospital patients needed advanced treatment defined as ICU (intensive care unit) care and/or receiving surgical intervention and the length of stage was 22.3 ± 19.1 compared with admission patient (15.9 ± 14.7; P valve: <.0001). PH valve (P valve: 0.0012), endoscopic grade (3b, OR: 8.14, 95% CI: 4.17, 15.90, P valve: <.0001) and surgical intervention (HR: 0.05, 95% CI: 0.01, 0.23, P valve: <.0001) were independent risk factor for poor outcome. Old age was the main co-factor of in-hospital mortality under ventilator used. Renal injury was the co-factor of in-hospital mortality in non-shock patients. Aspiratory pneumonia and respiratory failure are main risk factors of mortality after discharge (P valve: 0.0214, 0.0041 respective).

Conclusions: The composite score of endoscopy-base and shock demonstrated an excellent predictive ability for inhospital mortality in patients with caustic ingestion.

利用胃上皮細胞粒線體移植胃癌細胞之分泌 體學研究

P.087

內視鏡超音波導引下進行膽汁引流術對於膽 管阻塞的有效性和安全性：台灣多中心研究 EFFICACY AND SAFETY OF ENDOSCOPIC ULTRASONOGRAPHYGUIDED BILIARY DRAINAGE (EUS-GUIDED BD) FOR BILIARY OBSTRUCTION: A MULTICENTER STUDY IN TAIWAN

謝政霖

1 國立臺灣大學醫學院附設醫院新竹臺大分院內科部

2 國立臺灣大學醫學院附設醫院綜合診療部內視鏡科

3 台東馬偕紀念醫院胃腸肝膽科

4 三軍總醫院胃腸肝膽科

5 中國醫藥大學附設醫院消化系內科

6 臺中榮民總醫院胃腸肝膽科

7 高雄醫學大學附設中和紀念醫院胃腸內科

8 新光吳火獅紀念醫院胃腸肝膽科

9 台北慈濟醫院胃腸肝膽科

10 國立臺灣大學醫學院附設醫院胃腸肝膽科

Background: Recently, EUS-guided BD procedure has been utilized after failed ERCP and the technical success rate is around 90% from published studies. In addition, issue about EUS-guided BD as primary modality for treatment of biliary obstruction has been analyzed by randomized trial. The advantage is not only time-consuming by difficult ERCP, for example: hepatic hilar stricture or surgical-altered anatomy with unreachable major papilla; but also concerning about possible complication, such as pancreatitis. Currently, no available data or consequence about conditions of EUSguided BD in Taiwan.

Aims: To analyze the efficacy and safety of EUS-guided BD procedure in Taiwan.

Methods: Multicenter retrospective observational study.

Results: A total of 84 patients from 8 hospitals underwent EUS-guided BD and most of them are malignant biliary obstruction (88.1%). The overall technical and clinical success rate are 85.7% and 85.7%, respectively. The mean procedure time is 64.5 ± 3.4 minutes. During mean followup time of 220.7 ± 28.8 days, the mean recurrent biliary obstruction (RBO) is 69.4 ± 12.9 days. The frequency of early and late complication rate are 26.2% and 10.7%, respectively. There are no mortalities related with procedure.

Conclusions: Our result from Taiwan multi-centers demonstrate EUS-guided BD is an alternative choice for biliary obstruction with acceptable safety and efficacy when performed by EUS expert.