11 minute read
I) HCV
Free Paper
Section：HCV ①
EFFECTIVENESS OF GLECAPREVIR/PIBRENTASVIR FOR PATIENTS WITH HEPATITIS C AND COMPENSATED CIRRHOSIS IN A REAL-WORLD SETTING IN TAIWAN
Pei-Kai Su1, Te-Sheng Chang1,2 Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chang Gung Memorial Hospital, Chiayi, Taiwan1 College of Medicine, Chang Gung University, Taoyuan, Taiwan2
蘇培凱1 張德生1,2 嘉義長庚紀念醫院內科部腸胃肝膽科1 長庚大學醫學院2
Background: Real-world data regarding the effectiveness of glecaprevir/pibrentasvir (GLE/ PIB) for patients with hepatitis C virus (HCV) infection and compensated cirrhosis is limited, especially in the Asian population. Aims: Proving the effectiveness of glecaprevir/ pibrentasvir for patients with hepatitis C and compensated cirrhosis in a real-world setting. Methods: This retrospective cohort study included consecutive patients with chronic HCV infection and compensated cirrhosis treated with GLE/ PIB from August 2018 to January 2021 at Chang Gung Memorial Hospital in Chiayi, Taiwan. The diagnosis of cirrhosis was determined using acoustic radiation force impulse (> 1.98 m/s), fibrosis-4 index (> 6.5) or the presence of clinical, radiological, endoscopic, or laboratory evidence of cirrhosis and/or portal hypertension. Sustained virological response (SVR12) was defined as undetectable HCVRNA 12 weeks after the end of treatment. Adverse events (AEs) were also evaluated. Results: A total of 160 patients with HCV and compensated cirrhosis treated with GLE/PIB were enrolled: 57 for 8 weeks and 103 for 12 weeks. In the per protocol analysis, 95.7% (45/47) of the 8-week group and 100% (99/99) of the 12-week group achieved SVR; in the evaluable population analysis, 78.9% (45/57) of the 8-week group and 96.1% (99/103) of the 12-week group achieved SVR. Two patients had no response and did not attain SVR in the 8-week group, one of them had documented poor drug adherence. The AEs were numerically higher in the 12-week group compared to the 8-week group including pruritus (26.2% vs. 12.3%), fatigue (9.7% vs. 3.5%), and dizziness (7.8% vs. 1.8%). Laboratory abnormalities were also more common in the 12-week group. Total bilirubin elevation >3× the upper normal limit (UNL) was observed in 13.6% in the 12-week group and 5.3% in the 8-week group. Patients with alanine transaminase elevation >5× the UNL were very rare in both groups of patients. No AEs resulted in treatment discontinuation. Conclusions: GLE/PIB treatment for 8 weeks is as effective as that for 12 weeks in patients of Taiwanese ethnicity with HCV and compensated cirrhosis.
②
RISK STRATIFICATION OF HEPATOCELLULAR CARCINOMA INCIDENCE BY FIB-4-BASED PREDICTION MODEL IN PATIENTS WITH CHRONIC HEPATITIS C RECEIVING ANTI-VIRAL THERAPY: A NATIONWIDE REAL-WORLD TAIWANESE COHORT (T-COACH)
Hung-Wei Wang1,2, Pei-Chein Tsai3,4 , Chi-Yi Chen5, Kuo-Chih Tseng6 , Hsueh-Chou Lai1,7, Hsing-Tao Kuo8 , Chao-Hung Hung9, Shui-Yi Tung9 , Jing-Houng Wang10, Jyh-Jou Chen11 , Pei-Lun Lee11, Ron-Nan Chien12 , Chun-Yen Lin12, Chi-Chieh Yang13 , Gin-Ho Lo14, Chi-Ming Tai14, Chih-Wen Lin14 , Jia-Horng Kao15,16, Chun-Jen Liu15,16 , Chen-Hua Liu15,16, Sheng-Lei Yan17 , Ming-Jong Bair18, Wei-Wen Su19 , Cheng-Hsin Chu20, Chih-Jen Chen20 , Ching-Chu Lo21, Pin-Nan Cheng22 , Yen-Cheng Chiu22, Chia-Chi Wang23 , Jin-Shiung Cheng24, Wei-Lun Tsai24 , Han-Chieh Lin25, Yi-Hsiang Huang25 , Jee-Fu Huang3,4, Chia-Yen Dai3,4 , Wan-Long Chuang3,4, Ming-Lung Yu3,4 , Cheng-Yuan Peng1,2 Center for Digestive Medicine, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan1 School of Medicine, China Medical University, Taichung, Taiwan2 Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan3 School of Medicine and Hepatitis Research Center, College of Medicine, and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan4 Department of Internal Medicine, Chiayi Christian Hospital, Chiayi, Taiwan5 Department of Internal Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chia-Yi; School of Medicine, Tzuchi University, Hualien, Taiwan6 School of Chinese Medicine, China Medical University, Taichung, Taiwan7 Division of Hepatogastroenterology, Department of Internal Medicine, Chi-Mei Medical Center, Tainan, Taiwan8 Division of Hepatogastroenterology, Department of Internal Medicine, Chiayi Chang Gung Memorial Hospital, Chiayi, Taiwan9 Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung Taiwan10 Division of Gastroenterology and Hepatology, Chi-Mei Medical Center, Liouying, Tainan, Taiwan11 Division of Hepatology, Department of Gastroenterology and Hepatology, Linkou Medical Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan12 Division of Gastroenterology, Department of Internal Medicine, Show-Chwan Memorial Hospital, Changhua, Taiwan13 Division of Gastroenterology and Hepatology, Department of Medicine, E-Da Hospital, and School of Medicine, I-Shou University, Kaohsiung, Taiwan14 Graduate Institute of Clinical Medicine, National Taiwan University, College of Medicine, Taipei, Taiwan15 Division of Gastroenterology and Hepatology, National Taiwan University Hospital, Taipei, Taiwan16 Division of Gastroenterology, Department of Internal Medicine, Chang Bing Show-Chwan Memorial Hospital, Changhua, Taiwan17 Division of Gastroenterology, Department of Internal Medicine, Taitung Mackay Memorial Hospital, Taitung, Taiwan18 Division of Gastroenterology, Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan19 Division of Gastroenterology, Department of Internal Medicine, Mackay Memorial Hospital, Taipei, Taiwan20 Department of Internal Medicine, St. Martin De Porres Hospital - Daya, Chiayi, Taiwan21
Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Cheng Kung University Hospital and College of Medicine, National Cheng Kung University, Tainan, Taiwan22 Division of Gastroenterology, Department of Internal Medicine, Tzuchi Hospital, The Buddhist Tzuchi Medical Foundation, New Taipei, Taiwan23 Division of Gastroenterology and Hepatology, Department of Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan24 Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan25 FIB-4 為主的預測模型可區分慢性 C 型 肝炎患者接受抗病毒治療後之肝癌發 生風險：台灣全國性 C 型肝炎世代研 究
王鴻偉1,2 蔡佩倩3,4 陳啟益5 曾國枝6 賴學洲1,7 郭行道8 洪肇宏9 董水義9 王景弘10 陳志州11 李佩倫11 簡榮南12 林俊彥12 楊基滐13 羅錦河14 戴啟明14 林志文14 高嘉宏15,16 劉俊人15,16 劉振驊15,16 顏聖烈17 白明忠18 蘇維文19 朱正心20 陳志仁20 羅清池21 鄭斌男22 邱彥程22 王嘉齊23 鄭錦翔24 蔡維倫24 林漢傑25 黃怡翔25 黃志富3,4 戴嘉言3,4 莊萬龍3,4 余明隆3,4 彭成元1,2 中國醫藥大學附設醫院內科部消化醫學中心1 中國醫藥大學醫學系2 高雄醫學大學附設中和紀念醫院肝膽胰內科暨肝 炎防治中心3 高雄醫學大學醫學系、肝炎研究中心、液態生物 檢體暨世代研究中心4 嘉義基督教醫院內科部5 嘉義大林慈濟醫院內科部暨慈濟大學醫學系6 中國醫藥大學中醫系7 奇美醫學中心內科部胃腸肝膽科8 嘉義長庚紀念醫院內科部胃腸肝膽科系9 高雄長庚紀念醫院內科部胃腸肝膽科系暨長庚大 學醫學系10 柳營奇美醫院胃腸肝膽科11 林口長庚紀念醫院胃腸肝膽科系12 秀傳紀念醫院內科部胃腸肝膽科13 義大醫院內科部胃腸肝膽科暨義守大學醫學系14 國立臺灣大學臨床醫學研究所15 國立臺灣大學醫學院附設醫院內科部胃腸肝膽科16 彰濱秀傳紀念醫院內科部胃腸肝膽科17 台東馬偕紀念醫院內科部胃腸肝膽科18 彰化基督教醫院內科部胃腸肝膽科19 台北馬偕紀念醫院內科部胃腸肝膽科20 天主教聖馬爾定醫院內科部21 國立成功大學醫學院附設醫院內科部胃腸肝膽科 暨國立成功大學醫學系22 台北慈濟醫院內科部胃腸肝膽科23 高雄榮民總醫院內科部胃腸肝膽科24 臺北榮民總醫院內科部胃腸肝膽科25
Background: Non-invasive liver fibrosis indices have been widely utilized to predict liver fibrosis status and even liver-related complications, including hepatocellular carcinoma (HCC) in patients with chronic hepatitis C (CHC). Aims: We aimed to stratify HCC risks by noninvasive fibrosis index-based risk model in a realworld nationwide Taiwanese chronic hepatitis C cohort (T-COACH). Methods: T-COACH is a nationwide hepatitis C virus registry cohort between 2003 and 2015 from 23 hospitals with a median follow-up period of 4.49 years (Q1-Q3: 2.63-7.15 years). A total of 1589 patients who had received IFN-based therapy with both baseline and end of follow-up (EOF) clinical data available were analyzed by Cox proportional hazards models for risk of HCC after adjustment for competing mortality. Results: Of 1589 patients, 1363 (85.8%) patients achieved sustained virological response (SVR). A total of 88 (5.5%) patients suffered HCC during 7762 person-years of follow-up. Patients with SVR had 1, 3, 5, 10-year cumulative HCC incidence rates of 0.55%, 1.87%, 3.48% and 8.35%, respectively. According to receiver operating characteristic curve analysis, FIB-4 at baseline and EOF showed remarkable and similar diagnostic performance in distinguishing HCC (area under the curve [AUC] FIB-4 at baseline: 0.832, EOF: 0.829; DeLong test, P = 0.813). According to the Cox proportional hazards model, non-SVR (adjusted hazards ratio [HR]: 1.92, P = 0.008), diabetes mellitus (adjusted HR: 2.11, P = 0.005) and FIB-4 at EOF (adjusted HR: 5.60, P < 0.0001) were significant predictors of HCC. Risk score models were developed to predict HCC according to HR. In model 1 (by sum of risk score), the 10-year cumulative incidence rates of HCC were 43.35% in patients with high risk (score 9-10), 25.48% in those with intermediate risk (score 6-8) and 4.06% in those with low risk (score 3-5).
While in model 2 (by number of risk predictor), the 10-year cumulative incidence rates of HCC were 39.64% in patients with high risk (at least two risk predictors), 19.12% in those with intermediate risk (with one risk predictor) and 2.52% in those with low risk (without any risk predictor). Conclusions: The FIB-4-based prediction model at EOF could help stratify the risk of HCC in patients with CHC after anti-viral therapy.
③
CLUSTER ANALYSIS OF PATIENTS WITH METABOLIC-ASSOCIATED FATTY LIVER DISEASE
Tung-Han Ho1, Chun-Nan Chen1 , Sheng-Wei Cheng1, Fat-Moon Suk1 , Gi-Shih Lien1, Ming-Shun Wu1,2 Division of Gastroenterology, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan1 Division of Gastroenterology and Hepatology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan2 利用集群分析分類新陳代謝相關脂肪 肝病人
何東翰1 陳俊男1 鄭勝偉1 粟發滿1 連吉時1 吳明順1,2 臺北市立萬芳醫院消化系內科1 臺北醫學大學醫學院醫學系消化內科2
Background: Metabolic associated fatty liver disease (MAFLD) is identified in patients with hepatic steatosis and concurrently the three metabolic conditions: obesity, diabetes and metabolic dysregulation, either alone or in combination. MAFLD is slowly progressive, the present cut-off value of the subtypes of MAFLD diagnosed by different metabolic conditions is insufficient to reflect the progression and outcome of such disease. Aims: This study aims to classify the subtypes of MAFLD by cluster analysis and depict the characteristics of these subtypes of MAFLD. Methods: The data were retrieved from the Taipei Medical University-Wan Fang Hospital in Taiwan. We define the positive criteria of MAFLD by correlation method. After cluster analysis and optimal classification, the clinical and biochemical features in different MAFLD subtypes were compared. Results: After the correlation analysis, triglyceride (TG), alanine aminotransferase (ALT), insulin, homeostasis model assessment-insulin resistance (HOMA-IR), TG-HDL (high-density lipoprotein cholesterol) ratio are the positive criteria of MAFLD. The optimal number of clusters is three. The biomarkers including controlled attenuation parameter (CAP), HDL, HOMA-IR, TG-HDL ratio
were noted for their significant difference of each variable among 3 clusters. The different severity of steatosis in the three clusters was showed in the box plot indicated that the status of MAFLD is different in the three groups. Conclusions: The results suggest that this new clustering is a better approach to identify patients with MAFLD. CAP, HDL, HOMA-IR and TG-HDL ratio may be the effective predictive biomarkers for worsening condition of MAFLD.
④
HEPATITIS B CO-INFECTION MAY ALLEVIATE FIBROSIS REGRESSION IN CHRONIC HEPATITIS C PATIENTS TREATED WITH DIRECT-ACTING ANTIVIRALS
Cheng-Er Hsu1, Yen-Chun Liu1,2, Ya-Ting Cheng1,2, Wen-Juei Jeng1,2, Rong-Nan Chien1,2, Chun-Yen Lin1,2, I-Shyan Sheen1,2 Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou Branch, Taoyuan, Taiwan1 College of Medicine, Chang Gung University, Taoyuan, Taiwan2 合併 B 型肝炎感染，可能減輕全口服 抗 C 肝病毒藥物改善肝纖維化的效果
徐正二1 劉彥君1,2 鄭雅婷1,2 鄭文睿1,2 簡榮南1,2 林
俊彥1,2 沈一嫻1,2 林口長庚紀念醫院胃腸肝膽科1 長庚大學醫學院2
Background: High sustained virological response (SVR) rate (>95%) and fibrosis regression could be achieved by 8-24 weeks of direct acting antivirals treatment (DAA) in patients with chronic hepatitis C virus (HCV) infection. However, in chronic hepatitis C (CHC) patients co-infected with hepatitis B virus (HBV), reactivation of HBV were reported during DAA treatment which may even lead to increase ALT level or hepatitis events. Aims: This study aims to compare the fibrosis regression proportion between patients with monoHCV and HBV + HCV dual infection who achieved SVR after DAA treatment. Methods: CHC patients with / without HBV co-infection who received DAA treatment and achieved SVR12 from March 2015 to December 2019 in Chang Gung Memorial Hospital, Linkou branch were enrolled. Those with available liver stiffness measurements (LSM) before and during 1-year follow-up were recruited into analysis. LSM assessed by transient elastography (TE, Fibroscan) were prospectively recorded at baseline and after SVR The exclusion criteria were human immunodeficiency virus co-infection, age < 18 years old while starting DAA treatment, unable to complete DAA treatment course, no SVR. The criterion of fibrosis regression is LSM decreased over 30% after DAA treatment. Propensity score
matching adjusting pretherapy age, ALT, platelet, LSM, gender were done at 1:3 ratio before comparison between mono-HCV and HBV + HCV infected patients. Results: Among 906 patients enrolled, 853 patients were HCV mono infection, 53 patients were HCV and HBV co-infection. The median age was 63 year-old, 39.8% male, 63.8% genotype 1 and the median level of HCV RNA was 6.2 log10 IU/mL. Patients with HBV + HCV coinfection are more likely to be younger age (61.8 vs. 63.2, P=0.29), male (54.7% vs. 38.9%, P=0.02) and lower pretherapy LSM level (8.3 vs. 10.2 kPA, P=0.11) while HCV RNA, HCV genotype, pretherapy ALT, platelet, BMI and type 2 DM proportion were comparable. After PSM with 1 to 3 ratio, higher proportion of mono-HCV infected patients achieved LSM improvement >30% after DAA treatment comparing to dual HBV + HCV infection (32.1% vs. 24.5%, P=0.3) Conclusions: The regression of fibrosis after DAA treatment may be alleviated by HBV co-infection. Further validation study should be conducted to provide robust evidence of this issue.
⑤
COMPARISON OF EFFICACY AND SAFETY BETWEEN PANGENOTYPIC HCV DIRECTACTING ANTIVIRAL AGENTS: EPCLUSA VERSUS MAVIRET – A SINGLE CENTER DATA IN SOUTHERN TAIWAN
Chun-Yu Lin, Chien-Hung Chen, Tsung-Hui Hu, Jing-Houng Wang, Chao-Hung Hung, Sheng-Nan Lu Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan C 型肝炎全基因型口服抗病毒藥宜譜 莎與艾百樂的藥效與安全性比較 ─ 台 灣南部單一醫學中心的資料分析
林俊宇 陳建宏 胡琮輝 王景弘 洪肇宏 盧勝男 高雄長庚紀念醫院內科部胃腸肝膽科 Background: Eight-week glecaprevir/pibrentasvir (Maviret) and 12-week sofosbuvir/velpatasvir (Epclusa) leads to a high rate of sustained virological response at post-treatment week 12 (SVR12). Aims: To compare the efficacy and safety of 8-week Maviret and 12-week Epclusa in all patients and specific populations. Methods: This study included total 972 patients who received 8-week Maviret (n=487) and 12week Epclusa (± Ribavirin) (n=485) treatment from August 2018 to October 2020. Results: Of the 972 patents, 925 completed DAA treatment and post-treatment week12. Of the 925 patients, there was no significant difference in patients who achieved SVR12 between Epclusa and Maviret (452/458, 98.69% vs. 464/467, 99.36%; p=0.302) groups. Among the patients without SVR12, 3 were treatment failure and 3 were relapsers in Epclusa group, and all 3 were relapsers in Maviret group. There was a similar SVR12 rate in different HCV genotypes (1a, 1b, 2, 3, 6) between Epclusa and Maviret groups. There was also no significant difference in SVR12 rate between Epclusa and Maviret groups in HBV co-infection (46/47, 97.9% vs 33/33, 100%), compensated cirrhosis (97/100, 97% vs. 23/23,
