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Scicluna J, Di Napoli R, Pirozzi D, Fraenza F, Cardillo M, Scavone C, Capuano A. Hepatobiliary disorders and Direct-Acting Antiviral (DAA) therapies: real-world evidence and insights from the EudraVigilance database. Expert Opin Drug Saf 2025:1-8. [PMID: 40243008 DOI: 10.1080/14740338.2025.2495180] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2024] [Revised: 03/06/2025] [Accepted: 03/17/2025] [Indexed: 04/18/2025]
Abstract
BACKGROUND The introduction of Direct-Acting Antivirals (DAA) brought about a breakthrough in the treatment of HCV. This study aims to analyze the hepatic safety profile of Harvoni® (sofosbuvir/ledipasvir), Epclusa® (sofosbuvir/velpatasvir), and Vosevi® (sofosbuvir/velpatasvir/voxilaprevir) through a review of the Individual Case Safety Reports (ICSRs) reported in EudraVigilance (EV). RESEARCH DESIGN AND METHODS ICSRs with adverse events (AE) belonging to the system organ class (SOC) hepatobiliary disorders were retrieved from the EV database. A descriptive analysis was performed. Reporting odds ratios (ROR) were calculated to assess the reporting frequency of hepatobiliary disorders among the DAA combinations. RESULTS Out of 5,552 ICSRs reported between January 2018 and December 2023, 1,942 were for Harvoni®, 3,180 for Epclusa® and 430 for Vosevi®. Three hundred and thirty-nine ICSRs reported 1,616 PT within the SOC hepatobiliary disorders. Harvoni® showed a statistically significant lower frequency of reporting for the hepatobiliary disorders SOC when compared to Epclusa® and Vosevi® (ROR, 0.33; 95% CI [0.26-0.41] and ROR 0.31; 95% CI [0.19-0.48], respectively). CONCLUSION Harvoni® showed a lower reporting frequency of hepatobiliary disorders and fewer drug ineffectiveness reports, suggesting it may be preferred over Epclusa® and Vosevi® in patients with preexisting liver or biliary conditions.
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Affiliation(s)
- John Scicluna
- Eu2P Programme, University of Bordeaux, Bordeaux, France
| | - Raffaella Di Napoli
- Campania Regional Centre for Pharmacovigilance and Pharmacoepidemiology, Naples, Italy
- Department of Experimental Medicine - Section of Pharmacology "L. Donatelli", University of Campania "Luigi Vanvitelli", Naples, Italy
| | - Daniele Pirozzi
- Campania Regional Centre for Pharmacovigilance and Pharmacoepidemiology, Naples, Italy
| | - Federica Fraenza
- Campania Regional Centre for Pharmacovigilance and Pharmacoepidemiology, Naples, Italy
- Department of Experimental Medicine - Section of Pharmacology "L. Donatelli", University of Campania "Luigi Vanvitelli", Naples, Italy
| | - Mirko Cardillo
- Campania Regional Centre for Pharmacovigilance and Pharmacoepidemiology, Naples, Italy
| | - Cristina Scavone
- Campania Regional Centre for Pharmacovigilance and Pharmacoepidemiology, Naples, Italy
- Department of Experimental Medicine - Section of Pharmacology "L. Donatelli", University of Campania "Luigi Vanvitelli", Naples, Italy
- Department of Life Sciences, Health, and Health Professions, Link Campus University, Rome, Italy
| | - Annalisa Capuano
- Campania Regional Centre for Pharmacovigilance and Pharmacoepidemiology, Naples, Italy
- Department of Experimental Medicine - Section of Pharmacology "L. Donatelli", University of Campania "Luigi Vanvitelli", Naples, Italy
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Wang HW, Zeng YS, Huang CF, Chen CY, Kuo HT, Tseng KC, Mo LR, Cheng PN, Tai CM, Hung CH, Lo CC, Chen CH, Lee PL, Yang CC, Chen CT, Lin CY, Hsieh TY, Chong LW, Lin CL, Hu JT, Yang SS, Kao JH, Liu CJ, Chuang WL, Huang JF, Yeh ML, Dai CY, Huang YH, Lin HC, Bair MJ, Wang SJ, Huang CW, Tsai MC, Wang CC, Su WW, Lin CW, Lin CL, Chu CH, Yu ML, Peng CY. Posttreatment FIB-4 score change predicts hepatocellular carcinoma in chronic hepatitis C patients: Findings from the Taiwan hepatitis C registry program. J Formos Med Assoc 2025:S0929-6646(25)00056-7. [PMID: 40023754 DOI: 10.1016/j.jfma.2025.02.014] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2024] [Revised: 01/27/2025] [Accepted: 02/07/2025] [Indexed: 03/04/2025] Open
Abstract
PURPOSE This study investigated whether Fibrosis-4 (FIB-4) score and its change can serve as predictors of hepatocellular carcinoma (HCC) development in patients with chronic hepatitis C (CHC) infection receiving direct-acting antivirals (DAAs). METHODS This study identified 9679 patients who completed DAA treatment and achieved sustained virologic response (SVR) from the Taiwan Nationwide Real-World HCV Registry Program, and their risk of HCC was analyzed. RESULTS Multivariable Cox regression analyses identified diabetes mellitus (DM), alpha-fetoprotein (AFP) level, and FIB-4 score as independent predictors of HCC in both Model 1 (baseline) and Model 2 (SVR). Change in FIB-4 score (△FIB-4) of < -0.9086 from baseline to SVR achievement was a significant predictor of HCC only in Model 2 (SVR). In Model 2 (SVR), DM (hazard ratio [HR]: 1.53, 95% confidence interval [CI]: 1.04-2.26, p = 0.033), FIB-4 score (≥3.25 vs. <3.25; HR: 2.40, 95% CI: 1.63-3.53, p < 0.001), △FIB-4 (greater reduction: <-0.9086 vs. smaller reduction: ≥-0.9086; HR: 1.85, 95% CI: 1.25-2.74, p = 0.002), and AFP level (≥20 vs. <20 ng/mL; HR: 16.40, 95% CI: 9.16-29.36, p < 0.001) were significant predictors of HCC. At 3 years, the cumulative HCC incidence was 10.67% in patients with an FIB-4 score of ≥3.25 upon achieving SVR and △FIB-4 of < -0.9086 and 1.72% in those with an FIB-4 score of <3.25 upon achieving SVR and △FIB-4 of ≥ -0.9086. CONCLUSIONS Posttreatment FIB-4 score and its change from baseline can be used to stratify HCC risk in patients with CHC receiving DAAs.
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Affiliation(s)
- Hung-Wei Wang
- School of Medicine, China Medical University, Taichung, Taiwan; Center for Digestive Medicine, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
| | - Yu-Syuan Zeng
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chung-Feng Huang
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chi-Yi Chen
- Division of Gastroenterology and Hepatology, Department of Medicine, Ditmanson Medical Foundation Chiayi Christian Hospital, Taiwan
| | - Hsing-Tao Kuo
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chi Mei Medical Center, Tainan, Taiwan
| | - Kuo-Chih Tseng
- Department of Internal Medicine, Dalin Tzu Chi Hospital, Chiayi, Taiwan; School of Medicine, Tzu Chi University, Hualien, Taiwan
| | | | - Pin-Nan Cheng
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Cheng Kung University Hospital, Tainan, Taiwan; College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Chi-Ming Tai
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, E-Da Hospital, Kaohsiung, Taiwan; College of Medicine, I-Shou University, Kaohsiung, Taiwan
| | - Chao-Hung Hung
- Division of Hepatogastroenterology, Department of Internal Medicine, Chia-Yi Chang Gung Memorial Hospital, Chiayi, Taiwan
| | - Ching-Chu Lo
- Division of Gastroenterology, Department of Internal Medicine, St. Martin De Porres Hospital, Chiayi, Taiwan
| | - Chien-Hung Chen
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, Taiwan
| | - Pei-Lun Lee
- Liouying Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chi Mei Medical Center, Tainan, Taiwan
| | - Chi-Chieh Yang
- Department of Gastroenterology, Division of Internal Medicine, Show Chwan Memorial Hospital, Taiwan
| | - Chun-Ting Chen
- Division of Gastroenterology, Department of Internal Medicine, Tri-Service General Hospital Penghu Branch, National Defense Medical Center, Taipei, Taiwan
| | - Chun-Yen Lin
- Department of Gastroenterology and Hepatology, Linkou Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Tsai-Yuan Hsieh
- Division of Gastroenterology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
| | - Lee-Won Chong
- Division of Hepatology and Gastroenterology, Department of Internal Medicine, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan; School of Medicine, Fu-Jen Catholic University, New Taipei City, Taiwan
| | - Chih-Lang Lin
- Liver Research Unit, Department of Hepato-Gastroenterology and Community Medicine Research Center, Chang Gung Memorial Hospital at Keelung, Chang Gung University, College of Medicine, Keelung, Taiwan
| | - Jui-Ting Hu
- Liver Center, Cathay General Hospital, Taiwan
| | - Sheng-Shun Yang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan
| | - Jia-Horng Kao
- Hepatitis Research Center and Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Chun-Jen Liu
- Hepatitis Research Center and Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Wan-Long Chuang
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Jee-Fu Huang
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ming-Lun Yeh
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chia-Yen Dai
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Yi-Hsiang Huang
- Healthcare and Services Center, Taipei Veterans General Hospital, Taipei, Taiwan; Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Han-Chieh Lin
- Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan; Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Ming-Jong Bair
- Division of Gastroenterology, Department of Internal Medicine, Taitung Mackay Memorial Hospital, Taiwan; Mackay Medical College, New Taipei City, Taiwan
| | - Szu-Jen Wang
- Division of Gastroenterology, Department of Internal Medicine, Yuan's General Hospital, Kaohsiung, Taiwan
| | - Chien-Wei Huang
- Division of Gastroenterology, Kaohsiung Armed Forces General Hospital, Kaohsiung City, Taiwan
| | - Ming-Chang Tsai
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chung Shan Medical University Hospital, Institute of Medicine, School of Medicine, Chung Shan Medical University, Taichung, Taiwan
| | - Chia-Chi Wang
- Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation and School of Medicine, Tzu Chi University, Taiwan
| | - Wei-Wen Su
- Department of Gastroenterology and Hepatology, Changhua Christian Hospital, Taiwan
| | - Chih-Wen Lin
- Division of Gastroenterology and Hepatology, E-Da Dachang Hospital, and School of Medicine, College of Medicine, I-Shou University, Kaohsiung, Taiwan
| | - Chih-Lin Lin
- Department of Gastroenterology, Renai Branch, Taipei City Hospital, Taipei, Taiwan
| | | | - Ming-Lung Yu
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
| | - Cheng-Yuan Peng
- School of Medicine, China Medical University, Taichung, Taiwan; Center for Digestive Medicine, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan.
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Wang S, Huang C, Chang T, Lo C, Hung C, Huang C, Chong L, Cheng P, Yeh M, Peng C, Cheng C, Huang J, Bair M, Lin C, Yang C, Kuo H, Hsieh T, Lee T, Lee P, Wu W, Lin C, Su W, Yang S, Wang C, Hu J, Mo L, Chen C, Huang Y, Chang C, Huang C, Chen G, Kao C, Tai C, Liu C, Lee M, Tsai P, Dai C, Kao J, Lin H, Chuang W, Tseng K, Chen C, Wang S, Yu M. Real-world efficacy and safety of universal 8-week glecaprevir/pibrentasvir in patients with chronic hepatitis C with early chronic kidney disease or pre-end-stage renal disease: Insights from a nationwide hepatisis C virus registry in Taiwan. Kaohsiung J Med Sci 2025; 41:e12929. [PMID: 39829106 PMCID: PMC11827544 DOI: 10.1002/kjm2.12929] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/27/2024] [Revised: 12/06/2024] [Accepted: 12/13/2024] [Indexed: 01/22/2025] Open
Abstract
An 8-week regimen of glecaprevir/pibrentasvir is recommended for treatment-naïve patients with chronic hepatitis C (CHC). In alignment with the Taiwanese government's objective to eliminate hepatitis C by 2025, this study aimed to provide real-world evidence on the use of this regimen in treatment-naïve patients with chronic kidney disease (CKD) by using data from the Taiwan Association for the Study of the Liver HCV Registry (TACR). CKD was defined by an estimated glomerular filtration rate (eGFR) of <60 mL/min/1.73 m2 or higher with proteinuria persisting for over 3 months. Patients were categorized as having early CKD (eGFR ≥45 mL/min/1.73 m2) or pre-end-stage renal disease (pre-ESRD) (eGFR <45 mL/min/1.73 m2). Among 1072 patients who received at least one dose of the regimen, 1054 had available data for assessing sustained virologic response at 12 weeks posttreatment (SVR12). The overall SVR12 rate was 99.6%, with rates of 99.7% for pre-ESRD patients and 99.6% for early CKD patients. Subgroup analysis showed 100% efficacy for genotype 3 and dyslipidemia, 99.5% for diabetes, 99.4% for cardiovascular disease, 96.9% for a history of cerebral vascular accident, and 95.5% for patients with a history of drug injection or HIV co-infection. Adverse events were reported in 16.8% of patients, with 0.8% experiencing serious events, and only two cases were treatment-related. Renal function significantly improved, with overall eGFR increasing from 39.2 to 41.9 mL/min/1.73 m2. Early CKD patients showed an eGFR rise from 53.5 to 57.1, while pre-ESRD patients improved from 27.1 to 29.2 at SVR12. The study concluded that the 8-week regimen is highly effective, well-tolerated, and associated with significant renal function improvement in treatment-naïve CHC patients with both early CKD and pre-ESRD.
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Affiliation(s)
- Szu‐Jen Wang
- Graduate Institute of Clinical MedicineKaohsiung Medical UniversityKaohsiungTaiwan
- Division of Hepatogastroenterology, Department of Internal MedicineShin Huey Shin HospitalKaohsiungTaiwan
- Division of Gastroenterology, Department of Internal MedicineYuan's General HospitalKaohsiungTaiwan
| | - Chung‐Feng Huang
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis CenterKaohsiung Medical University Hospital, Kaohsiung Medical UniversityKaohsiungTaiwan
- Ph.D. Program in Translational Medicine, College of MedicineKaohsiung Medical University, Academia SinicaKaohsiungTaiwan
| | - Te‐Sheng Chang
- Division of Hepatogastroenterology, Department of Internal MedicineChiaYi Chang Gung Memorial HospitalChiayiTaiwan
- College of MedicineChang Gung UniversityTaoyuanTaiwan
| | - Ching‐Chu Lo
- Division of Gastroenterology, Department of Internal MedicineSt. Martin De Porres HospitalChiayiTaiwan
| | - Chao‐Hung Hung
- Division of Hepatogastroenterology, Department of Internal MedicineKaohsiung Chang Gung Memorial HospitalKaohsiungTaiwan
| | - Chien‐Wei Huang
- Division of GastroenterologyKaohsiung Armed Forces General HospitalKaohsiungTaiwan
| | - Lee‐Won Chong
- Division of Hepatology and Gastroenterology, Department of Internal MedicineShin Kong Wu Ho‐Su Memorial HospitalTaipeiTaiwan
- School of MedicineFu‐Jen Catholic UniversityNew Taipei CityTaiwan
| | - Pin‐Nan Cheng
- Division of Gastroenterology and Hepatology, Department of Internal MedicineNational Cheng Kung University Hospital, College of Medicine, National Cheng Kung UniversityTainanTaiwan
| | - Ming‐Lun Yeh
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis CenterKaohsiung Medical University Hospital, Kaohsiung Medical UniversityKaohsiungTaiwan
- Hepatitis Research Center, College of Medicine; Center for Liquid Biopsy and Cohort ResearchKaohsiung Medical UniversityKaohsiungTaiwan
| | - Cheng‐Yuan Peng
- Centers for Digestive Medicine, Department of Internal MedicineChina Medical University HospitalTaichungTaiwan
- School of MedicineChina Medical UniversityTaichungTaiwan
| | - Chien‐Yu Cheng
- Division of Infectious Diseases, Department of Internal Medicine, Taoyuan General HospitalMinistry of Health and WelfareTaoyuanTaiwan
| | - Jee‐Fu Huang
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis CenterKaohsiung Medical University Hospital, Kaohsiung Medical UniversityKaohsiungTaiwan
- Hepatitis Research Center, College of Medicine; Center for Liquid Biopsy and Cohort ResearchKaohsiung Medical UniversityKaohsiungTaiwan
- School of Medicine and Doctoral Program of Clinical and Experimental Medicine, College of Medicine and Center of Excellence for Metabolic Associated Fatty Liver DiseaseNational Sun Yat‐sen UniversityKaohsiungTaiwan
| | - Ming‐Jong Bair
- Division of Gastroenterology, Department of Internal MedicineTaitung Mackay Memorial HospitalTaitungTaiwan
- Mackay Medical CollegeNew Taipei CityTaiwan
| | - Chih‐Lang Lin
- Liver Research Unit, Department of Hepato Gastroenterology and Community Medicine Research Center, Chang Gung Memorial Hospital at Keelung, College of MedicineChang Gung UniversityKeelungTaiwan
| | - Chi‐Chieh Yang
- Department of Gastroenterology, Division of Internal MedicineShow Chwan Memorial HospitalChanghuaTaiwan
| | - Hsing‐Tao Kuo
- Division of Gastroenterology and Hepatology, Department of Internal MedicineChi Mei Medical CenterYongkang DistrictTainanTaiwan
| | - Tsai‐Yuan Hsieh
- Division of Gastroenterology, Department of Internal MedicineTri Service General Hospital, National Defense Medical CenterTaipeiTaiwan
| | - Tzong‐Hsi Lee
- Division of Gastroenterology and HepatologyFar Eastern Memorial HospitalNew Taipei CityTaiwan
| | - Pei‐Lun Lee
- Division of Gastroenterology and Hepatology, Department of Internal MedicineChi Mei Medical CenterTainanTaiwan
| | | | - Chih‐Lin Lin
- Department of Gastroenterology, Renai BranchTaipei City HospitalTaipeiTaiwan
| | - Wei‐Wen Su
- Department of Gastroenterology and HepatologyChanghua Christian HospitalChanghuaTaiwan
| | - Sheng‐Shun Yang
- Division of Gastroenterology and Hepatology, Department of Internal MedicineTaichung Veterans General HospitalTaichungTaiwan
| | - Chia‐Chi Wang
- Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation and School of MedicineTzu Chi UniversityTaipeiTaiwan
| | - Jui‐Ting Hu
- Liver CenterCathay General HospitalTaipeiTaiwan
| | - Lein‐Ray Mo
- Division of GastroenterologyTainan Municipal Hospital (Managed By Show Chwan Medical Care Corporation)TainanTaiwan
| | - Chun‐Ting Chen
- Division of Gastroenterology, Department of Internal MedicineTri Service General Hospital, National Defense Medical CenterTaipeiTaiwan
- Division of Gastroenterology, Department of Internal Medicine Tri Service General Hospital Penghu BranchNational Defense Medical CenterTaipeiTaiwan
| | - Yi‐Hsiang Huang
- Division of Gastroenterology and Hepatology, Department of MedicineTaipei Veterans General HospitalTaipeiTaiwan
- Institute of Clinical Medicine, School of MedicineNational Yang‐Ming Chiao Tung UniversityTaipeiTaiwan
| | - Chun‐Chao Chang
- Division of Gastroenterology and Hepatology, Department of Internal MedicineTaipei Medical University HospitalTaipeiTaiwan
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, School of Medicine, College of MedicineTaipei Medical UniversityTaipeiTaiwan
| | | | | | - Chien‐Neng Kao
- National Taiwan University Hospital Hsin‐Chu BranchHsinchuTaiwan
| | - Chi‐Ming Tai
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, E‐Da HospitalI‐Shou UniversityKaohsiungTaiwan
- School of Medicine for International Students, College of MedicineI‐Shou UniversityKaohsiungTaiwan
| | - Chun‐Jen Liu
- Hepatitis Research Center and Department of Internal MedicineNational Taiwan University HospitalTaipeiTaiwan
| | - Mei‐Hsuan Lee
- Institute of Clinical MedicineNational Yang‐Ming Chiao Tung UniversityTaipeiTaiwan
| | - Pei‐Chien Tsai
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis CenterKaohsiung Medical University Hospital, Kaohsiung Medical UniversityKaohsiungTaiwan
- Hepatitis Research Center, College of Medicine; Center for Liquid Biopsy and Cohort ResearchKaohsiung Medical UniversityKaohsiungTaiwan
| | - Chia‐Yen Dai
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis CenterKaohsiung Medical University Hospital, Kaohsiung Medical UniversityKaohsiungTaiwan
- Hepatitis Research Center, College of Medicine; Center for Liquid Biopsy and Cohort ResearchKaohsiung Medical UniversityKaohsiungTaiwan
| | - Jia‐Horng Kao
- Hepatitis Research Center and Department of Internal MedicineNational Taiwan University HospitalTaipeiTaiwan
| | - Han‐Chieh Lin
- Division of Gastroenterology and Hepatology, Department of MedicineTaipei Veterans General HospitalTaipeiTaiwan
- Institute of Clinical Medicine, School of MedicineNational Yang‐Ming Chiao Tung UniversityTaipeiTaiwan
| | - Wang‐Long Chuang
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis CenterKaohsiung Medical University Hospital, Kaohsiung Medical UniversityKaohsiungTaiwan
| | - Kuo‐Chih Tseng
- School of MedicineTzuchi UniversityHualienTaiwan
- Department of Internal Medicine, Dalin Tzu Chi HospitalBuddhist Tzu Chi Medical FoundationChiayiTaiwan
| | - Chi‐Yi Chen
- Division of Gastroenterology and Hepatology, Department of MedicineDitmanson Medical Foundation Chiayi Christian HospitalChiayiTaiwan
| | - Shu‐Chi Wang
- Department of Medical Laboratory Science and BiotechnologyKaohsiung Medical UniversityKaohsiungTaiwan
| | - Ming‐Lung Yu
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis CenterKaohsiung Medical University Hospital, Kaohsiung Medical UniversityKaohsiungTaiwan
- Hepatitis Research Center, College of Medicine; Center for Liquid Biopsy and Cohort ResearchKaohsiung Medical UniversityKaohsiungTaiwan
- School of Medicine and Doctoral Program of Clinical and Experimental Medicine, College of Medicine and Center of Excellence for Metabolic Associated Fatty Liver DiseaseNational Sun Yat‐sen UniversityKaohsiungTaiwan
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Lu MY, Chuang WL, Yu ML. The role of artificial intelligence in the management of liver diseases. Kaohsiung J Med Sci 2024; 40:962-971. [PMID: 39440678 DOI: 10.1002/kjm2.12901] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/11/2024] [Revised: 09/24/2024] [Accepted: 09/24/2024] [Indexed: 10/25/2024] Open
Abstract
Universal neonatal hepatitis B virus (HBV) vaccination and the advent of direct-acting antivirals (DAA) against hepatitis C virus (HCV) have reshaped the epidemiology of chronic liver diseases. However, some aspects of the management of chronic liver diseases remain unresolved. Nucleotide analogs can achieve sustained HBV DNA suppression but rarely lead to a functional cure. Despite the high efficacy of DAAs, successful antiviral therapy does not eliminate the risk of hepatocellular carcinoma (HCC), highlighted the need for cost-effective identification of high-risk populations for HCC surveillance and tailored HCC treatment strategies for these populations. The accessibility of high-throughput genomic data has accelerated the development of precision medicine, and the emergence of artificial intelligence (AI) has led to a new era of precision medicine. AI can learn from complex, non-linear data and identify hidden patterns within real-world datasets. The combination of AI and multi-omics approaches can facilitate disease diagnosis, biomarker discovery, and the prediction of treatment efficacy and prognosis. AI algorithms have been implemented in various aspects, including non-invasive tests, predictive models, image diagnosis, and the interpretation of histopathology findings. AI can support clinicians in decision-making, alleviate clinical burdens, and curtail healthcare expenses. In this review, we introduce the fundamental concepts of machine learning and review the role of AI in the management of chronic liver diseases.
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Affiliation(s)
- Ming-Ying Lu
- Division of Hepatobiliary, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- School of Medicine and Hepatitis Research Center, College of Medicine and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan
- School of Medicine and Doctoral Program of Clinical and Experimental Medicine, College of Medicine and Center of Excellence for Metabolic Associated Fatty Liver Disease, National Sun Yat-sen University, Kaohsiung, Taiwan
| | - Wan-Long Chuang
- Division of Hepatobiliary, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- School of Medicine and Hepatitis Research Center, College of Medicine and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ming-Lung Yu
- Division of Hepatobiliary, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- School of Medicine and Hepatitis Research Center, College of Medicine and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan
- School of Medicine and Doctoral Program of Clinical and Experimental Medicine, College of Medicine and Center of Excellence for Metabolic Associated Fatty Liver Disease, National Sun Yat-sen University, Kaohsiung, Taiwan
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Hong CM, Su TH, Hsu SJ, Tseng TC, Liu CH, Yang HC, Kao JH, Chen PJ, Cheng PN, Hung CH, Peng CY, Chen CH, Lin CY, Kuo HT, Lin HC, Huang YH, Chen CY, Lin CL, Tsai PC, Zeng YS, Dai CY, Chuang WL, Huang JF, Huang CF, Yeh ML, Yu ML, Liu CJ. Addition of neutrophil-to-lymphocyte ratio to Pre-DAA FIB-4 does not increase prediction value for de novo liver complications in hepatitis C. J Formos Med Assoc 2024:S0929-6646(24)00511-4. [PMID: 39488497 DOI: 10.1016/j.jfma.2024.10.024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2024] [Revised: 07/28/2024] [Accepted: 10/25/2024] [Indexed: 11/04/2024] Open
Abstract
BACKGROUND AND AIMS Direct-acting antiviral agents (DAAs) achieve high sustained virologic response (SVR) in chronic hepatitis C patients; yet a proportion of patients still experience de novo liver complications after SVR. Identification of risk factors is clinically important. FIB-4 index is a useful noninvasive tool to assess fibrosis, while neutrophil-to-lymphocyte ratio (NLR) is a biomarker for systemic inflammation. Our study aimed to investigate whether the addition of NLR can increase the prediction power of pre-DAA FIB-4 for de novo liver complications after SVR. METHODS We recruited patients via The Taiwan HCV Registry (TACR) and National Health Insurance Registry Database. The inclusion criteria were patients who achieved SVR12 after DAA and were followed for at least 24 months after SVR12. Liver complications included ascites, hepatic encephalopathy, variceal bleeding, and HCC. RESULTS Totally 7657 patients were recruited from 2013 to 2018. Among them, 3674 patients (48.0%) had a FIB-4 value > 3.25 and 491 patients (6.4%) had a NLR >4 before DAA. After two-year of follow-up after SVR 12, 214 patients (2.8%) developed de novo liver complications. Factors associated with liver complications included male gender, diabetes mellitus, hyperlipidemia, chronic kidney disease, and pre-DAA FIB-4 >3.25 in multivariate analyses. Addition of NLR slightly did not increase the power of predicting liver complications. CONCLUSIONS The overall incidence of de novo liver complications after SVR is low during short-term follow-up. Elevated pre-DAA FIB-4 is associated with de novo liver complications after SVR, whereas the addition of pre-DAA NLR does not increase the prediction power.
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Affiliation(s)
- Chun-Ming Hong
- Division of Hospital Medicine, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Tung-Hung Su
- Division of Gastroenterology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Shih-Jer Hsu
- Division of Gastroenterology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Tai-Chung Tseng
- Department of Medicine Research, National Taiwan University Hospital, Taipei, Taiwan
| | - Chen-Hua Liu
- Division of Gastroenterology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Hung-Chih Yang
- Division of Gastroenterology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Jia-Horng Kao
- Division of Gastroenterology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Pei-Jer Chen
- Division of Gastroenterology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan; Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan
| | - Pin-Nan Cheng
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Cheng Kung University Hospital, Tainan, Taiwan
| | - Chao-Hung Hung
- Division of Hepatogastroenterology, Department of Internal Medicine, ChiaYi Chang Gung Memorial Hospital, Taiwan; Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Taiwan
| | - Cheng-Yuan Peng
- Center for Digestive Medicine, Department of Internal Medicine, China Medical University Hospital, School of Medicine, China Medical University, Taichung, Taiwan
| | - Chien-Hung Chen
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Taiwan
| | - Chun-Yen Lin
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou Branch, Taiwan
| | - Hsing-Tao Kuo
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chi Mei Medical Center, Taiwan
| | - Han-Chieh Lin
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Yi-Hsiang Huang
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Chi-Yi Chen
- Division of Gastroenterology and Hepatology, Department of Medicine, Ditmanson Medical Foundation Chiayi Christian Hospital, Taiwan
| | - Chih-Lin Lin
- Department of Gastroenterology, Renai Branch, Taipei City Hospital, Taipei, Taiwan
| | - Pei-Chien Tsai
- Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Yu-Syuan Zeng
- Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Chia-Yen Dai
- Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Wan-Long Chuang
- Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Jee-Fu Huang
- Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Chung-Feng Huang
- Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Ming-Lun Yeh
- Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Ming-Lung Yu
- Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Chun-Jen Liu
- Division of Gastroenterology, Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan.
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Ji F, Tran S, Ogawa E, Huang CF, Suzuki T, Wong YJ, Toyoda H, Jun DW, Li L, Uojima H, Nozaki A, Chuma M, Tseng CH, Hsu YC, Ishigami M, Honda T, Atsukawa M, Haga H, Enomoto M, Trinh H, Preda CM, Vutien P, Landis C, Lee DH, Watanabe T, Takahashi H, Abe H, Asai A, Eguchi Y, Li J, Wang X, Li J, Liu J, Liang J, Lam CPM, Huang R, Ye Q, Pan H, Zhang J, Cai D, Wang Q, Huang DQ, Wong G, Wong VWS, Li J, Do S, Furusyo N, Nakamuta M, Nomura H, Kajiwara E, Yoon EL, Ahn SB, Azuma K, Dohmen K, An J, Song DS, Cho HC, Kawano A, Koyanagi T, Ooho A, Satoh T, Takahashi K, Yeh ML, Tsai PC, Yasuda S, Zhao Y, Liu Y, Okubo T, Itokawa N, Jun MJ, Ishikawa T, Takaguchi K, Senoh T, Zhang M, Zhao C, Alecu RI, Xuan Tay W, Devan P, Liu JK, Kozuka R, Vargas-Accarino E, Do AT, Maeda M, Chuang WL, Huang JF, Dai CY, Cheung R, Buti M, Niu J, Xie W, Ren H, Lim SG, Wu C, Yuen MF, Shang J, Zhu Q, Ueno Y, Tanaka Y, Hayashi J, Yu ML, et alJi F, Tran S, Ogawa E, Huang CF, Suzuki T, Wong YJ, Toyoda H, Jun DW, Li L, Uojima H, Nozaki A, Chuma M, Tseng CH, Hsu YC, Ishigami M, Honda T, Atsukawa M, Haga H, Enomoto M, Trinh H, Preda CM, Vutien P, Landis C, Lee DH, Watanabe T, Takahashi H, Abe H, Asai A, Eguchi Y, Li J, Wang X, Li J, Liu J, Liang J, Lam CPM, Huang R, Ye Q, Pan H, Zhang J, Cai D, Wang Q, Huang DQ, Wong G, Wong VWS, Li J, Do S, Furusyo N, Nakamuta M, Nomura H, Kajiwara E, Yoon EL, Ahn SB, Azuma K, Dohmen K, An J, Song DS, Cho HC, Kawano A, Koyanagi T, Ooho A, Satoh T, Takahashi K, Yeh ML, Tsai PC, Yasuda S, Zhao Y, Liu Y, Okubo T, Itokawa N, Jun MJ, Ishikawa T, Takaguchi K, Senoh T, Zhang M, Zhao C, Alecu RI, Xuan Tay W, Devan P, Liu JK, Kozuka R, Vargas-Accarino E, Do AT, Maeda M, Chuang WL, Huang JF, Dai CY, Cheung R, Buti M, Niu J, Xie W, Ren H, Lim SG, Wu C, Yuen MF, Shang J, Zhu Q, Ueno Y, Tanaka Y, Hayashi J, Yu ML, Nguyen MH. Real-world Effectiveness and Tolerability of Interferon-free Direct-acting Antiviral for 15,849 Patients with Chronic Hepatitis C: A Multinational Cohort Study. J Clin Transl Hepatol 2024; 12:646-658. [PMID: 38993510 PMCID: PMC11233980 DOI: 10.14218/jcth.2024.00089] [Show More Authors] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/07/2024] [Revised: 05/08/2024] [Accepted: 05/22/2024] [Indexed: 07/13/2024] Open
Abstract
Background and Aims As practice patterns and hepatitis C virus (HCV) genotypes (GT) vary geographically, a global real-world study from both East and West covering all GTs can help inform practice policy toward the 2030 HCV elimination goal. This study aimed to assess the effectiveness and tolerability of DAA treatment in routine clinical practice in a multinational cohort for patients infected with all HCV GTs, focusing on GT3 and GT6. Methods We analyzed the sustained virological response (SVR12) of 15,849 chronic hepatitis C patients from 39 Real-World Evidence from the Asia Liver Consortium for HCV clinical sites in Asia Pacific, North America, and Europe between 07/01/2014-07/01/2021. Results The mean age was 62±13 years, with 49.6% male. The demographic breakdown was 91.1% Asian (52.9% Japanese, 25.7% Chinese/Taiwanese, 5.4% Korean, 3.3% Malaysian, and 2.9% Vietnamese), 6.4% White, 1.3% Hispanic/Latino, and 1% Black/African-American. Additionally, 34.8% had cirrhosis, 8.6% had hepatocellular carcinoma (HCC), and 24.9% were treatment-experienced (20.7% with interferon, 4.3% with direct-acting antivirals). The largest group was GT1 (10,246 [64.6%]), followed by GT2 (3,686 [23.2%]), GT3 (1,151 [7.2%]), GT6 (457 [2.8%]), GT4 (47 [0.3%]), GT5 (1 [0.006%]), and untyped GTs (261 [1.6%]). The overall SVR12 was 96.9%, with rates over 95% for GT1/2/3/6 but 91.5% for GT4. SVR12 for GT3 was 95.1% overall, 98.2% for GT3a, and 94.0% for GT3b. SVR12 was 98.3% overall for GT6, lower for patients with cirrhosis and treatment-experienced (TE) (93.8%) but ≥97.5% for treatment-naive patients regardless of cirrhosis status. On multivariable analysis, advanced age, prior treatment failure, cirrhosis, active HCC, and GT3/4 were independent predictors of lower SVR12, while being Asian was a significant predictor of achieving SVR12. Conclusions In this diverse multinational real-world cohort of patients with various GTs, the overall cure rate was 96.9%, despite large numbers of patients with cirrhosis, HCC, TE, and GT3/6. SVR12 for GT3/6 with cirrhosis and TE was lower but still excellent (>91%).
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Affiliation(s)
- Fanpu Ji
- Department of Infectious Diseases, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China
| | - Sally Tran
- Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University Medical Center, Palo Alto, CA, USA
| | - Eiichi Ogawa
- Department of General Internal Medicine, Kyushu University Hospital, Fukuoka, Japan
| | - Chung-Feng Huang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung
- Hepatitis Research Center, College of Medicine and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung
| | - Takanori Suzuki
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
| | - Yu Jun Wong
- Gastroenterology & Hepatology, Changi General Hospital, Singhealth, Singapore
- Singhealth Duke-NUS Medicine Academic Clinical Program, Singapore
| | - Hidenori Toyoda
- Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Dae Won Jun
- Department of Internal Medicine, Hanyang University, College of Medicine, Seoul, Korea
- Hanyang Institute of Bioscience and Biotechnology, Hanyang University, Seoul, Korea
| | - Liu Li
- Department of Hepatology, The Third People's Hospital of Kunming City, Kunming, Yunnan, China
| | - Haruki Uojima
- Department of Gastroenterology, Internal Medicine, Kitasato University School of Medicine, Sagamihara, Japan
| | - Akito Nozaki
- Gastroenterological Center, Yokohama City University Medical Center, Yokohama, Japan
| | - Makoto Chuma
- Gastroenterological Center, Yokohama City University Medical Center, Yokohama, Japan
| | - Cheng-Hao Tseng
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, E-Da Cancer Hospital, Kaohsiung
| | - Yao-Chun Hsu
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, E-Da Cancer Hospital, Kaohsiung
| | - Masatoshi Ishigami
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Takashi Honda
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Masanori Atsukawa
- Division of Gastroenterology and Hepatology, Nippon Medical School, Tokyo, Japan
| | - Hiroaki Haga
- Department of Gastroenterology, Yamagata University Faculty of Medicine, Yamagata, Japan
| | - Masaru Enomoto
- Department of Transfusion Medicine and Department of Hepatology, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan
| | - Huy Trinh
- San Jose Gastroenterology, San Jose, CA, USA
| | - Carmen Monica Preda
- Gastroenterology & Hepatology Department, Clinic Fundeni Institute, Bucharest, Romania
| | - Phillip Vutien
- Division of Gastroenterology and Hepatology, University of Washington, Seattle, WA, USA
| | - Charles Landis
- Division of Gastroenterology and Hepatology, University of Washington, Seattle, WA, USA
| | - Dong Hyun Lee
- Department of Gastroenterology, Good Gang-An Hospital, Busan, Korea
| | - Tsunamasa Watanabe
- Division of Gastroenterology and Hepatology, St. Marianna University School of Medicine, Kawasaki, Japan
| | - Hirokazu Takahashi
- Liver Center, Saga University Hospital, Saga, Japan
- Division of Metabolism and Endocrinology, Saga University Faculty of Medicine, Saga, Japan
| | - Hiroshi Abe
- Division of Gastroenterology and Hepatology, Shinmatsudo Central General Hospital, Chiba, Japan
| | - Akira Asai
- 2nd Department of Internal Medicine, Osaka Medical and Pharmaceutical University, Osaka, Japan
| | - Yuichiro Eguchi
- Liver Center, Saga University Hospital, Saga, Japan
- Locomedical General Institute, Locomedical Eguchi Hospital, Saga, Japan
| | - Jie Li
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China
| | - Xiaozhong Wang
- Affiliated Traditional Chinese Medicine Hospital of Xinjiang Medical University, Urumqi, Xinjiang, China
| | - Jia Li
- Department of Gastroenterology and Hepatology, The Second People's Hospital of Tianjin, Tianjin, China
| | - Junping Liu
- Department of Infectious Diseases, Henan Provincial People's Hospital Affiliated to Zhengzhou University, Zhengzhou, Henan, China
| | - Jing Liang
- Department of Gastroenterology and Hepatology, The Third Central Hospital of Tianjin, Tianjin, China
| | - Carla Pui-Mei Lam
- Department of Medicine, The University of Hong Kong, Hong Kong, China
| | - Rui Huang
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China
| | - Qing Ye
- Department of Gastroenterology and Hepatology, The Third Central Hospital of Tianjin, Tianjin, China
| | - Hongying Pan
- Department of Hepatology, Zhejiang Provincial People's Hospital Affiliated to Zhejiang University, Hangzhou, Zhejiang, China
| | - Jiajie Zhang
- Department of Hepatology, Zhejiang Provincial People's Hospital Affiliated to Zhejiang University, Hangzhou, Zhejiang, China
| | - Dachuan Cai
- Department of Infectious Diseases, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Qi Wang
- Center of liver diseases, Beijing Ditan Hospital Affiliated to Capital Medical University, Beijing, China
| | - Daniel Q Huang
- Division of Gastroenterology and Hepatology, National University Hospital, Singapore
- Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Grace Wong
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China
- State Key Laboratory of Digestive Disease, The Chinese University of Hong Kong, Hong Kong, China
| | - Vincent Wai-Sun Wong
- Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Hong Kong, China
| | - Junyi Li
- Department of Hepatology, The Third People's Hospital of Kunming City, Kunming, Yunnan, China
| | - Son Do
- Digestive Health Associates of Texas, Dallas, TX, USA
| | | | - Makoto Nakamuta
- Department of Gastroenterology, National Hospital Organization Kyushu Medical Center, Fukuoka, Japan
| | - Hideyuki Nomura
- Department of Internal Medicine, Haradoi Hospital, Fukuoka, Japan
| | - Eiji Kajiwara
- Hepatology Clinic, Kajiwara Clinic, Kitakyushu, Japan
| | - Eileen L Yoon
- Department of Internal Medicine, Hanyang University, College of Medicine, Seoul, Korea
- Hanyang Institute of Bioscience and Biotechnology, Hanyang University, Seoul, Korea
| | - Sang Bong Ahn
- Department of Internal Medicine, Nowon Eulji Medical Center, Eulji University College of Medicine, Seoul, Korea
| | - Koichi Azuma
- Department of Medicine, Kyushu Central Hospital, Fukuoka, Japan
| | - Kazufumi Dohmen
- Department of Internal Medicine, Chihaya Hospital, Fukuoka, Japan
| | - Jihyun An
- Department of Internal Medicine, Hanyang University, College of Medicine, Guri Hospital, Guri, Korea
| | - Do Seon Song
- Division of Hepatology, Department of Internal Medicine, St. Vincent's Hospital, College of Medicine, The Catholic University of Korea, Suwon, Korea
| | - Hyun Chin Cho
- Departments of Internal Medicine, Gyeongsang National University Hospital, Jinju, Korea
| | - Akira Kawano
- Department of Medicine, Kitakyushu Municipal Medical Center, Fukuoka, Japan
| | | | - Aritsune Ooho
- Department of Hepatology, Steel Memorial Yawata Hospital, Kitakyushu, Japan
| | - Takeaki Satoh
- Center for Liver Disease, National Hospital Organization Kokura Medical Center, Kitakyushu, Japan
| | | | - Ming-Lun Yeh
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung
- Hepatitis Research Center, College of Medicine and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung
| | - Pei-Chien Tsai
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung
- Hepatitis Research Center, College of Medicine and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung
| | - Satoshi Yasuda
- Department of Gastroenterology, Ogaki Municipal Hospital, Ogaki, Japan
| | - Yunyu Zhao
- Department of Infectious Diseases, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China
| | - Yishan Liu
- Department of Infectious Diseases, The Second Affiliated Hospital of Xi'an Jiaotong University, Xi'an, Shaanxi, China
| | - Tomomi Okubo
- Division of Gastoroentelorogy, Nippon Medcal School Chiba Hokusoh Hospital, Chiba, Japan
| | - Norio Itokawa
- Division of Gastroenterology and Hepatology, Nippon Medical School, Tokyo, Japan
| | - Mi Jung Jun
- Department of Gastroenterology, Good Gang-An Hospital, Busan, Korea
| | - Toru Ishikawa
- Department of Gastroenterology, Saiseikai Niigata Hospital, Niigata, Japan
| | - Koichi Takaguchi
- Department of Hepatology, Kagawa Prefectural Central Hospital, Kagawa, Japan
| | - Tomonori Senoh
- Department of Hepatology, Kagawa Prefectural Central Hospital, Kagawa, Japan
| | - Mingyuan Zhang
- Department of Hepatology, The First Hospital of Jilin University, Changchun, Jilin, China
| | - Changqing Zhao
- Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China
| | - Raluca Ioana Alecu
- Gastroenterology & Hepatology Department, Clinic Fundeni Institute, Bucharest, Romania
| | - Wei Xuan Tay
- Gastroenterology & Hepatology, Changi General Hospital, Singhealth, Singapore
| | - Pooja Devan
- Gastroenterology & Hepatology, Changi General Hospital, Singhealth, Singapore
| | - Joanne Kimiko Liu
- Division of Gastroenterology and Hepatology, University of Washington, Seattle, WA, USA
| | - Ritsuzo Kozuka
- Department of Hepatology, Osaka Metropolitan University Graduate School of Medicine, Osaka, Japan
| | | | - Ai-Thien Do
- Digestive Health Associates of Texas, Dallas, TX, USA
| | - Mayumi Maeda
- Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University Medical Center, Palo Alto, CA, USA
| | - Wan-Long Chuang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung
| | - Jee-Fu Huang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung
- Hepatitis Research Center, College of Medicine and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung
| | - Chia-Yen Dai
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung
- Hepatitis Research Center, College of Medicine and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung
| | - Ramsey Cheung
- Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University Medical Center, Palo Alto, CA, USA
- Division of Gastroenterology and Hepatology, Veterans Affairs Palo Alto Health Care System, Palo Alto, CA, USA
| | - Maria Buti
- Liver Diseases Group, Vall d'Hebron Research Institute, Barcelona, Spain
- Liver Unit, Department of Internal Medicine, Hospital Universitari Valle d'Hebron and Universitat Autònoma de Barcelona, Barcelona, Spain
| | - Junqi Niu
- Department of Hepatology, The First Hospital of Jilin University, Changchun, Jilin, China
| | - Wen Xie
- Center of liver diseases, Beijing Ditan Hospital Affiliated to Capital Medical University, Beijing, China
| | - Hong Ren
- Department of Infectious Diseases, The Second Affiliated Hospital of Chongqing Medical University, Chongqing, China
| | - Seng Gee Lim
- Division of Gastroenterology and Hepatology, National University Hospital, Singapore
- Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore
| | - Chao Wu
- Department of Infectious Diseases, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, Jiangsu, China
| | - Man-Fung Yuen
- Department of Medicine, The University of Hong Kong, Hong Kong, China
- State Key Laboratory of Liver Research, The University of Hong Kong, Hong Kong, China
| | - Jia Shang
- Department of Infectious Diseases, Henan Provincial People's Hospital Affiliated to Zhengzhou University, Zhengzhou, Henan, China
| | - Qiang Zhu
- Department of Gastroenterology, Shandong Provincial Hospital Affiliated to Shandong University, Ji'nan, Shandong, China
| | - Yoshiyuki Ueno
- Department of Gastroenterology, Yamagata University Faculty of Medicine, Yamagata, Japan
| | - Yasuhito Tanaka
- Department of Gastroenterology and Metabolism, Nagoya City University Graduate School of Medical Sciences, Nagoya, Japan
- Department of Gastroenterology and Hepatology, Faculty of Life Sciences, Kumamoto University, Kumamoto, Japan
| | - Jun Hayashi
- Kyushu General Internal Medicine Center, Haradoi Hospital, Fukuoka, Japan
| | - Ming-Lung Yu
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung
- Hepatitis Research Center, College of Medicine and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung
- School of Medicine and Doctoral Program of Clinical and Experimental Medicine, College of Medicine and Center of Excellence for Metabolic Associated Fatty Liver Disease, National Sun Yat-sen University, Kaohsiung
| | - Mindie H Nguyen
- Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University Medical Center, Palo Alto, CA, USA
- Department of Epidemiology and Population Health, Stanford University, Stanford, CA, USA
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Moschouri E, Salemme G, Baserga A, Cerny A, Deibel A, Müllhaupt B, Meier MA, Bernsmeier C, Ongaro M, Negro F, Grosjean M, Clerc O, Künzler-Heule P, Semela D, Hobi G, Stickel F, Mathieu A, Mdawar-Bailly E, Faouzi M, Moradpour D, Fraga M. Real-life experience of chronic hepatitis C treatment in Switzerland: a retrospective analysis. Swiss Med Wkly 2024; 154:3698. [PMID: 38980176 DOI: 10.57187/s.3698] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/19/2023] [Accepted: 05/27/2024] [Indexed: 07/10/2024] Open
Abstract
BACKGROUND AND AIM Direct-acting antivirals (DAAs) have revolutionised the management of chronic hepatitis C. We analysed the use of different generations of DAAs over time in Switzerland and investigated factors predictive of treatment failure. METHODS This retrospective study was conducted within the framework of the Swiss Association for the Study of the Liver and the Swiss Hepatitis C Cohort Study; it included all patients with chronic hepatitis C treated with DAAs between January 2015 and December 2019 at eight Swiss referral centres. RESULTS A total of 3088 patients were included; 57.3% were male, and the median age was 54 years. Liver cirrhosis was present in 23.9% of the cohort, 87.8% of whom were compensated. The overall sustained virological response (SVR) rate (defined as undetectable HCV RNA at week 12 after the first course of DAA-based treatment) was 96.2%, with an increase over time. The rate of treatment failure dropped from 8.3% in 2015 to 2.5% in 2019. Multivariable analysis revealed that female sex, the use of the latest generation of pangenotypic DAA regimens, Caucasian origin, and genotype (gt) 1 were associated with SVR, whereas the presence of active hepatocellular carcinoma (HCC), gt 3, and increasing liver stiffness were associated with treatment failure. Notably, the presence of active HCC during treatment increased the risk of DAA failure by a factor of almost thirteen. CONCLUSIONS SVR rates increased over time, and the highest success rates were identified after the introduction of the latest generation of pangenotypic DAA regimens. Active HCC, gt 3 and increasing liver stiffness were associated with DAA failure.
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Affiliation(s)
- Eleni Moschouri
- 1Division of Gastroenterology and Hepatology, Lausanne University Hospital and University of Lausanne.
| | | | | | | | - Ansgar Deibel
- Division of Gastroenterology and Hepatology, University Hospital Zurich, Zurich.
| | - Beat Müllhaupt
- Division of Gastroenterology and Hepatology, University Hospital Zurich, Zurich.
| | - Marie-Anne Meier
- University Centre for Gastrointestinal and Liver Diseases (Clarunis), University Hospital Basel.
| | - Christine Bernsmeier
- University Centre for Gastrointestinal and Liver Diseases (Clarunis), University Hospital Basel.
| | - Marie Ongaro
- Division of Gastroenterology and Hepatology, University Hospitals Geneva, Geneva, Switzerland.
| | - Francesco Negro
- Division of Gastroenterology and Hepatology, University Hospitals Geneva, Geneva, Switzerland.
| | - Marielle Grosjean
- Divisions of Internal Medicine and Infectious Diseases, Hôpital Neuchâtelois-Pourtalès, Neuchâtel.
| | - Olivier Clerc
- Divisions of Internal Medicine and Infectious Diseases, Hôpital Neuchâtelois-Pourtalès, Neuchâtel.
| | | | - David Semela
- Division of Gastroenterology and Hepatology, Kantonsspital St. Gallen, St. Gallen.
| | | | - Felix Stickel
- Hirslanden Klinik Beau-Site, Bern, 3Division of Gastroenterology and Hepatology, University Hospital Zurich, Zurich.
| | - Adeline Mathieu
- Division of Gastroenterology and Hepatology, Lausanne University Hospital and University of Lausanne, Lausanne.
| | - Elise Mdawar-Bailly
- Division of Gastroenterology and Hepatology, Lausanne University Hospital and University of Lausanne, Lausanne.
| | - Mohamed Faouzi
- Division of Biostatistics, Center for Primary Care and Public Health (Unisanté), Lausanne;.
| | - Darius Moradpour
- Division of Gastroenterology and Hepatology, Lausanne University Hospital and University of Lausanne, Lausanne.
| | - Montserrat Fraga
- Division of Gastroenterology and Hepatology, Lausanne University Hospital and University of Lausanne, Lausanne.
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Yang CC, Huang CF, Chang TS, Lo CC, Hung CH, Huang CW, Chong LW, Cheng PN, Yeh ML, Peng CY, Cheng CY, Huang JF, Bair MJ, Lin CL, Yang CC, Wang SJ, Hsieh TY, Lee TH, Lee PL, Wu WC, Lin CL, Su WW, Yang SS, Wang CC, Hu JT, Mo LR, Chen CT, Huang YH, Chang CC, Huang CS, Chen GY, Kao CN, Tai CM, Liu CJ, Lee MH, Kuo HT, Tsai PC, Dai CY, Kao JH, Lin HC, Chuang WL, Tseng KC, Chen CY, Yu ML. Real-World Efficacy and Safety of Universal 8-Week Glecaprevir/Pibrentasvir for Treatment-Naïve Patients from a Nationwide HCV Registry in Taiwan. Infect Dis Ther 2024; 13:1199-1213. [PMID: 38679663 PMCID: PMC11128429 DOI: 10.1007/s40121-024-00968-5] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/27/2024] [Accepted: 03/25/2024] [Indexed: 05/01/2024] Open
Abstract
INTRODUCTION Eight-week glecaprevir/pibrentasvir (GLE/PIB) is indicated for treatment-naïve (TN) patients with chronic hepatitis C (CHC), with or without compensated cirrhosis. Given that the Taiwanese government is committed to eliminating hepatitis C virus (HCV) by 2025, this study aimed to measure real-world evidence for TN patients using 8-week GLE/PIB in the Taiwan HCV Registry (TACR). METHODS The data of patients with CHC treated with 8-week GLE/PIB were retrieved from TACR, a nationwide registry program organized by the Taiwan Association for the Study of the Liver (TASL). Treatment efficacy, defined as a sustained virologic response at posttreatment week 12 (SVR12), was assessed in the modified intention-to-treat (mITT) population, which excluded patients who were lost to follow-up or lacked SVR12 data. The safety profile of the ITT population was assessed. RESULTS A total of 7246 (6897 without cirrhosis; 349 with cirrhosis) patients received at least one dose of GLE/PIB (ITT), 7204 of whom had SVR12 data available (mITT). The overall SVR12 rate was 98.9% (7122/7204) among all patients, 98.9% (6780/6856) and 98.3% (342/348) among patients without and with cirrhosis, respectively. For the selected subgroups, which included patients with genotype 3 infection, diabetes, chronic kidney disease, people who injected drugs, and those with human immunodeficiency virus coinfection, the SVR12 rates were 95.1% (272/286), 98.9% (1084/1096), 99.0% (1171/1183), 97.4% (566/581), and 96.1% (248/258), respectively. Overall, 14.1% (1021/7246) of the patients experienced adverse events (AEs). Twenty-two patients (0.3%) experienced serious AEs, and 15 events (0.2%) resulted in permanent drug discontinuation. Only one event was considered treatment drug related. CONCLUSION Eight-week GLE/PIB therapy was effective and well tolerated in all TN patients, regardless of cirrhosis status.
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Affiliation(s)
- Chun-Chi Yang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chi Mei Medical Center, Yongkang District, Tainan, Taiwan
| | - Chung-Feng Huang
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, No. 100, Tzyou 1st Road, Kaohsiung, Taiwan
- Ph.D. Program in Translational Medicine, College of Medicine, Academia Sinica, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Te-Sheng Chang
- Division of Hepatogastroenterology, Department of Internal Medicine, ChiaYi Chang Gung Memorial Hospital, Chiayi, Taiwan
- College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Ching-Chu Lo
- Division of Gastroenterology, Department of Internal Medicine, St. Martin De Porres Hospital, Chiayi, Taiwan
| | - Chao-Hung Hung
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
| | - Chien-Wei Huang
- Division of Gastroenterology, Kaohsiung Armed Forces General Hospital, Kaohsiung, Taiwan
| | - Lee-Won Chong
- Division of Hepatology and Gastroenterology, Department of Internal Medicine, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan
- School of Medicine, Fu-Jen Catholic University, New Taipei City, Taiwan
| | - Pin-Nan Cheng
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Cheng Kung University Hospital, Tainan, Taiwan
- College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Ming-Lun Yeh
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, No. 100, Tzyou 1st Road, Kaohsiung, Taiwan
- Hepatitis Research Center, College of Medicine, Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Cheng-Yuan Peng
- Center for Digestive Medicine, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
- School of Medicine, China Medical University, Taichung, Taiwan
| | - Chien-Yu Cheng
- Division of Infectious Diseases, Department of Internal Medicine, Taoyuan General Hospital, Ministry of Health and Welfare, Taoyuan, Taiwan
| | - Jee-Fu Huang
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, No. 100, Tzyou 1st Road, Kaohsiung, Taiwan
- Hepatitis Research Center, College of Medicine, Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan
- School of Medicine and Doctoral Program of Clinical and Experimental Medicine, College of Medicine and Center of Excellence for Metabolic Associated Fatty Liver Disease, National Sun Yat-Sen University, Kaohsiung, Taiwan
| | - Ming-Jong Bair
- Division of Gastroenterology, Department of Internal Medicine, Taitung Mackay Memorial Hospital, Taitung, Taiwan
- Mackay Medical College, New Taipei City, Taiwan
| | - Chih-Lang Lin
- Liver Research Unit, Department of Hepato-Gastroenterology and Community Medicine Research Center, Chang Gung Memorial Hospital at Keelung, College of Medicine, Chang Gung University, Keelung, Taiwan
| | - Chi-Chieh Yang
- Department of Gastroenterology, Division of Internal Medicine, Show Chwan Memorial Hospital, Changhua, Taiwan
| | - Szu-Jen Wang
- Division of Gastroenterology, Department of Internal Medicine, Yuan's General Hospital, Kaohsiung, Taiwan
| | - Tsai-Yuan Hsieh
- Division of Gastroenterology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
| | - Tzong-Hsi Lee
- Division of Gastroenterology and Hepatology, Far Eastern Memorial Hospital, New Taipei City, Taiwan
| | - Pei-Lun Lee
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chi Mei Medical Center, Liouying, Tainan, Taiwan
| | - Wen-Chih Wu
- Wen-Chih Wu Clinic, Fengshan, Kaohsiung, Taiwan
| | - Chih-Lin Lin
- Department of Gastroenterology, Renai Branch, Taipei City Hospital, Taipei, Taiwan
| | - Wei-Wen Su
- Department of Gastroenterology and Hepatology, Changhua Christian Hospital, Changhua, Taiwan
| | - Sheng-Shun Yang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan
| | - Chia-Chi Wang
- Buddhist Tzu Chi Medical Foundation and School of Medicine, Taipei Tzu Chi Hospital, Tzu Chi University, Taipei, Taiwan
| | - Jui-Ting Hu
- Liver Center, Cathay General Hospital, Taipei, Taiwan
| | - Lein-Ray Mo
- Division of Gastroenterology, Tainan Municipal Hospital (Managed by Show Chwan Medical Care Corporation), Tainan, Taiwan
| | - Chun-Ting Chen
- Division of Gastroenterology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
- Division of Gastroenterology, Department of Internal Medicine Tri-Service, General Hospital Penghu Branch, National Defense Medical Center, Taipei, Taiwan
| | - Yi-Hsiang Huang
- Division of Gastroenterology and Hepatology, Department of Medicine; and Healthcare and Service Center, Taipei Veterans General Hospital, Taipei, Taiwan
- Institute of Clinical Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Chun-Chao Chang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taipei Medical University Hospital, Taipei, Taiwan
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
| | | | - Guei-Ying Chen
- Penghu Hospital, Ministry of Health and Welfare, Penghu, Taiwan
| | - Chien-Neng Kao
- National Taiwan University Hospital Hsin-Chu Branch, Hsinchu, Taiwan
| | - Chi-Ming Tai
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan
- School of Medicine for International Students, College of Medicine, I-Shou University, Kaohsiung, Taiwan
| | - Chun-Jen Liu
- Department of Internal Medicine, Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Mei-Hsuan Lee
- Institute of Clinical Medicine, National Yang-Ming Chiao Tung University, Taipei, Taiwan
| | - Hsing-Tao Kuo
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chi Mei Medical Center, Yongkang District, Tainan, Taiwan
| | - Pei-Chien Tsai
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, No. 100, Tzyou 1st Road, Kaohsiung, Taiwan
- Hepatitis Research Center, College of Medicine, Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chia-Yen Dai
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, No. 100, Tzyou 1st Road, Kaohsiung, Taiwan
- Hepatitis Research Center, College of Medicine, Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Jia-Horng Kao
- Department of Internal Medicine, Hepatitis Research Center, National Taiwan University Hospital, Taipei, Taiwan
| | - Han-Chieh Lin
- Division of Gastroenterology and Hepatology, Department of Medicine; and Healthcare and Service Center, Taipei Veterans General Hospital, Taipei, Taiwan
- Institute of Clinical Medicine, College of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Wang-Long Chuang
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, No. 100, Tzyou 1st Road, Kaohsiung, Taiwan
| | - Kuo-Chih Tseng
- School of Medicine, Tzuchi University, Hualien, Taiwan
- Department of Internal Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi, Taiwan
| | - Chi-Yi Chen
- Division of Gastroenterology and Hepatology, Department of Medicine, Ditmanson Medical Foundation Chiayi Christian Hospital, Chiayi, Taiwan.
| | - Ming-Lung Yu
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, No. 100, Tzyou 1st Road, Kaohsiung, Taiwan.
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan.
- Hepatitis Research Center, College of Medicine, Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan.
- School of Medicine and Doctoral Program of Clinical and Experimental Medicine, College of Medicine and Center of Excellence for Metabolic Associated Fatty Liver Disease, National Sun Yat-Sen University, Kaohsiung, Taiwan.
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9
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Yu ML, Tai CM, Mo LR, Kuo HT, Huang CF, Tseng KC, Lo CC, Bair MJ, Wang SJ, Huang JF, Yeh ML, Chen CT, Tsai MC, Huang CW, Lee PL, Yang TH, Huang YH, Chong LW, Chen CL, Yang CC, Hung CH, Yang SS, Cheng PN, Hsieh TY, Hu JT, Wu WC, Cheng CY, Chen GY, Zhou GX, Tsai WL, Kao CN, Lin CL, Wang CC, Lin TY, Lin CL, Su WW, Lee TH, Chang TS, Liu CJ, Dai CY, Chen CY, Kao JH, Lin HC, Chuang WL, Peng CY. An algorithm for simplified hepatitis C virus treatment with non-specialist care based on nation-wide data from Taiwan. Hepatol Int 2024; 18:461-475. [PMID: 38246899 PMCID: PMC11014878 DOI: 10.1007/s12072-023-10609-7] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/07/2023] [Accepted: 10/10/2023] [Indexed: 01/23/2024]
Abstract
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 (AASLD-IDSA) guidelines recommend simplified hepatitis C virus (HCV) treatment with pan-genotypic sofosbuvir/velpatasvir or glecaprevir/pibrentasvir for eligible patients. This observational study used real-world data to assess these regimens' safety in eligible patients and develop an algorithm to identify patients suitable for simplified treatment by non-specialists. METHODS 7,677 HCV-infected patients from Taiwan Hepatitis C Registry (TACR) who received at least one dose of sofosbuvir/velpatasvir or glecaprevir/pibrentasvir, and fulfilled the EASL/AASLD-IDSA criteria for simplified treatment were analyzed. Multivariate analysis was conducted on patient characteristics and safety data. RESULTS 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 key liver function parameters (alanine aminotransferase, aspartate aminotransferase, and total bilirubin), with only 18 patients (0.23%) experiencing Grades 3-4 abnormalities. Age > 70 years old, presence of hepatocellular carcinoma, total bilirubin > 1.2 mg/dL, estimated glomerular filtration rate < 60 mL/min/1.73 m2, and Fibrosis-4 > 3.25 were associated with higher risks of Grades 2-4 abnormalities. Patients with any of these had an odds of 4.53 times than that of those without in developing Grades 2-4 abnormalities (p < 0.01). CONCLUSIONS Real-world data from Taiwan confirmed that simplified HCV treatment for eligible patients with pan-genotypic regimens is effective and well tolerated. The TACR algorithm, developed based on this study's results, can further identify patients who can be safely managed by non-specialist care.
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Affiliation(s)
- Ming-Lung Yu
- School of Medicine, College of Medicine and Center of Excellence for Metabolic Associated Fatty Liver Disease, National Sun Yat-Sen University, No. 70, Lianhai Rd, Gushan District, Kaohsiung City, Taiwan, 804
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, No. 100, Shihcyuan 1st Rd, Sanmin District, Kaohsiung City, Taiwan, 807
- Hepatitis Research Center, College of Medicine and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, No. 100, Shihcyuan 1st Rd, Sanmin District, Kaohsiung City, Taiwan, 807
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, No. 123, Dapi Rd, Niaosong District, Kaohsiung City, Taiwan, 833
| | - Chi-Ming Tai
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, E-Da Hospital, I-Shou University, No. 1, Section 1, Xuecheng Rd, Dashu District, Kaohsiung City, Taiwan, 840
- School of Medicine for International Students, College of Medicine, I-Shou University, No. 1, Section 1, Xuecheng Rd, Dashu District, Kaohsiung City, Taiwan, 840
| | - Lein-Ray Mo
- Division of Gastroenterology, Tainan Municipal Hospital (Managed By Show Chwan Medical Care Corporation), No. 670, Chongde Rd, East District, Tainan City, Taiwan, 701
| | - Hsing-Tao Kuo
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chi Mei Medical Center, No. 901, Zhonghua Rd, Yongkang District, Tainan City, Taiwan, 710
- School of Medicine, College of Medicine, National Sun Yat-Sen University, No. 70, Lianhai Rd, Gushan District, Kaohsiung City, Taiwan, 804
| | - Chung-Feng Huang
- School of Medicine, College of Medicine and Center of Excellence for Metabolic Associated Fatty Liver Disease, National Sun Yat-Sen University, No. 70, Lianhai Rd, Gushan District, Kaohsiung City, Taiwan, 804
- Ph.D. Program in Translational Medicine, College of Medicine, Kaohsiung Medical University and Academia Sinica, No. 128, Section 2, Academia Rd, Nangang District, Taipei City, Taiwan, 115
| | - Kuo-Chih Tseng
- Department of Internal Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, No. 2, Minsheng Rd, Dalin Township, Chiayi County, Taiwan, 622
- School of Medicine, Tzuchi University, No. 701, Section 3, Zhongyang Rd, Hualien City, Hualien County, Taiwan, 970
| | - Ching-Chu Lo
- Division of Gastroenterology, Department of Internal Medicine, St. Martin De Porres Hospital, No. 60, Minquan Rd, East District, Chiayi City, Taiwan, 600
| | - Ming-Jong Bair
- Division of Gastroenterology, Department of Internal Medicine, Taitung Mackay Memorial Hospital, No. 1, Lane 303, Zhangsha St, Taitung City, Taitung County, Taiwan, 950
- Mackay Medical College, No. 46, Section 3, Zhongzheng Rd, Sanzhi District, New Taipei City, Taiwan, 252
| | - Szu-Jen Wang
- Division of Gastroenterology, Department of Internal Medicine, Yuan's General Hospital, No. 162, Chenggong 1st Rd, Lingya District, Kaohsiung City, Taiwan, 802
| | - Jee-Fu Huang
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, No. 100, Shihcyuan 1st Rd, Sanmin District, Kaohsiung City, Taiwan, 807
- Hepatitis Research Center, College of Medicine and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, No. 100, Shihcyuan 1st Rd, Sanmin District, Kaohsiung City, Taiwan, 807
| | - Ming-Lun Yeh
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, No. 100, Shihcyuan 1st Rd, Sanmin District, Kaohsiung City, Taiwan, 807
- Hepatitis Research Center, College of Medicine and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, No. 100, Shihcyuan 1st Rd, Sanmin District, Kaohsiung City, Taiwan, 807
| | - Chun-Ting Chen
- Division of Gastroenterology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, No. 325, Section 2, Chenggong Rd, Neihu District, Taipei City, Taiwan, 114
- Division of Gastroenterology, Department of Internal Medicine, Tri-Service General Hospital Penghu Branch, National Defense Medical Center, No. 90, Qianliao, Magong City, Penghu County, Taiwan, 880
| | - Ming-Chang Tsai
- School of Medicine, Chung Shan Medical University, Department of Internal Medicine, Chung Shan Medical University Hospital, No. 110, Section 1, Jianguo N Rd, South District, Taichung City, Taiwan, 402
| | - Chien-Wei Huang
- Division of Gastroenterology, Kaohsiung Armed Forces General Hospital, No. 2, Zhongzheng 1st Rd, Lingya District, Kaohsiung City, Taiwan, 802
| | - Pei-Lun Lee
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chi Mei Medical Center, No. 901, Zhonghua Rd, Yongkang District, Tainan City, Taiwan, 710
| | - Tzeng-Hue Yang
- Lotung Poh-Ai Hospital, No. 83, Nanchang St, Luodong Township, Yilan County, Taiwan, 265
| | - Yi-Hsiang Huang
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, No. 201, Section 2, Shipai Rd, Beitou District, Taipei City, Taiwan, 112
- Institute of Clinical Medicine, School of Medicine, National Yang-Ming Chiao Tung University, No. 155, Section 2, Linong St, Beitou District, Taipei City, Taiwan, 112
| | - Lee-Won Chong
- Division of Hepatology and Gastroenterology, Department of Internal Medicine, Shin Kong Wu Ho-Su Memorial Hospital, Shilin District, Taipei City, Taiwan, 111
- School of Medicine, Fu-Jen Catholic University, No. 510, Zhongzheng Rd, Xinzhuang District, New Taipei City, Taiwan, 242
| | - Chien-Lin Chen
- Department of Medicine, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation and Tzu Chi University, No. 701, Section 3, Zhongyang Rd, Hualien City, Hualien County, Taiwan, 970
| | - Chi-Chieh Yang
- Department of Gastroenterology, Division of Internal Medicine, Show Chwan Memorial Hospital, No. 542, Section 1, Zhongshan Rd, Changhua City, Changhua County, Taiwan, 500
| | - Chao-Hung Hung
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, No. 123, Dapi Rd, Niaosong District, Kaohsiung City, Taiwan, 833
| | - Sheng-Shun Yang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taichung Veterans General Hospital, No. 1650, Section 4, Taiwan Boulevard, Xitun District, Taichung City, Taiwan, 407
| | - Pin-Nan Cheng
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, No. 1, Dasyue Rd, East District, Tainan City, Taiwan, 701
| | - Tsai-Yuan Hsieh
- Division of Gastroenterology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, No. 325, Section 2, Chenggong Rd, Neihu District, Taipei City, Taiwan, 114
| | - Jui-Ting Hu
- Liver Center, Cathay General Hospital, No. 280, Section 4, Ren'ai Rd, Da'an District, Taipei City, Taiwan, 106
| | - Wen-Chih Wu
- Wen-Chih Wu Clinic, Fengshan, Kaohsiung, Taiwan, 830
| | - Chien-Yu Cheng
- Division of Infectious Diseases, Department of Internal Medicine, Taoyuan General Hospital, Ministry of Health and Welfare, No. 1492, Zhongshan Rd, Taoyuan District, Taoyuan City, Taiwan, 330
- Institute of Public Health, School of Medicine, National Yang-Ming Chiao Tung University, No. 155, Section 2, Linong St, Beitou District, Taipei City, Taiwan, 112
| | - Guei-Ying Chen
- Penghu Hospital, Ministry of Health and Welfare, No. 10, Zhongzheng Rd, Magong City, Penghu County, Taiwan, 880
| | | | - Wei-Lun Tsai
- Kaohsiung Veterans General Hospital, No. 386, Dazhong 1st Rd, Zuoying District, Kaohsiung City, Taiwan, 813
| | - Chien-Neng Kao
- National Taiwan University Hospital Hsin-Chu Branch, No. 25, Lane 442, Section 1, Jingguo Rd, North District, Hsinchu City, Taiwan, 300
| | - Chih-Lang Lin
- Liver Research Unit, Department of Hepato-Gastroenterology and Community Medicine Research Center, Chang Gung Memorial Hospital at Keelung, College of Medicine, Chang Gung University, No. 222, Maijin Rd, Anle District, Keelung City, Taiwan, 204
| | - Chia-Chi Wang
- Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation and School of Medicine, Tzu Chi University, No. 289, Jianguo Rd, Xindian District, New Taipei City, Taiwan, 231
| | - Ta-Ya Lin
- Cishan Hospital, Ministry of Health and Welfare, No. 60, Zhongxue Rd, Qishan District, Kaohsiung City, Taiwan, 842
| | - Chih-Lin Lin
- Department of Gastroenterology, Renai Branch, Taipei City Hospital, No. 10, Section 4, Ren'ai Rd, Da'an District, Taipei City, Taiwan, 106
| | - Wei-Wen Su
- Department of Gastroenterology and Hepatology, Changhua Christian Hospital, No. 176, Zhonghua Rd, Changhua City, Changhua County, Taiwan, 500
| | - Tzong-Hsi Lee
- Division of Gastroenterology and Hepatology, Far Eastern Memorial Hospital, No. 21, Section 2, Nanya S Rd, Banqiao District, New Taipei City, Taiwan, 220
| | - Te-Sheng Chang
- Division of Hepatogastroenterology, Department of Internal Medicine, Chang Gung Memorial Hospital, Chiayi, Taiwan and College of Medicine, Chang Gung University, No. 259, Wenhua 1st Rd, Guishan District, Taoyuan City, Taiwan, 333
| | - Chun-Jen Liu
- Hepatitis Research Center and Department of Internal Medicine, National Taiwan University Hospital, No. 1, Section 4, Roosevelt Rd, Da'an District, Taipei City, Taiwan, 106
| | - Chia-Yen Dai
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, No. 100, Shihcyuan 1st Rd, Sanmin District, Kaohsiung City, Taiwan, 807
- Hepatitis Research Center, College of Medicine and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, No. 100, Shihcyuan 1st Rd, Sanmin District, Kaohsiung City, Taiwan, 807
| | - Chi-Yi Chen
- Division of Gastroenterology and Hepatology, Department of Medicine, Ditmanson Medical Foundation Chiayi Christian Hospital, No. 539, Zhongxiao Rd, East District, Chiayi City, Taiwan, 600
| | - Jia-Horng Kao
- Hepatitis Research Center and Department of Internal Medicine, National Taiwan University Hospital, No. 1, Section 4, Roosevelt Rd, Da'an District, Taipei City, Taiwan, 106
| | - Han-Chieh Lin
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, No. 201, Section 2, Shipai Rd, Beitou District, Taipei City, Taiwan, 112
- Institute of Clinical Medicine, School of Medicine, National Yang-Ming Chiao Tung University, No. 155, Section 2, Linong St, Beitou District, Taipei City, Taiwan, 112
| | - Wan-Long Chuang
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, No. 100, Shihcyuan 1st Rd, Sanmin District, Kaohsiung City, Taiwan, 807.
- Hepatitis Research Center, College of Medicine and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, No. 100, Shihcyuan 1st Rd, Sanmin District, Kaohsiung City, Taiwan, 807.
| | - Cheng-Yuan Peng
- Center for Digestive Medicine, Department of Internal Medicine, China Medical University Hospital, No. 2, Yude Rd, North District, Taichung City, Taiwan, 404.
- School of Medicine, China Medical University, No. 91, Xueshi Rd, North District, Taichung City, Taiwan, 404.
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Schiano Moriello N, Pinchera B, Gentile I. Personalized care approaches to hepatitis C therapy: recent advances and future directions. Expert Rev Anti Infect Ther 2024; 22:139-151. [PMID: 38459735 DOI: 10.1080/14787210.2024.2328336] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2023] [Accepted: 03/05/2024] [Indexed: 03/10/2024]
Abstract
INTRODUCTION The introduction of direct-acting antivirals (DAAs) has significantly transformed the therapeutic landscape for chronic C hepatitis virus (HCV) infection. However, there is still room for further improvement in optimizing therapy efficacy and minimizing adverse effects. AREAS COVERED This review is devoted to the rationale for adopting a personalized approach to HCV therapy. Specifically, we explore the role of host-related factors, such as sex or the presence of comorbidities. We thoroughly examine the implications of commonly encountered comorbidities, including HIV infection, chronic renal disease, liver cirrhosis, and other chronic viral hepatitis infections. Additionally, we discuss the prevalent drug-to-drug interactions between DAAs and other medications, while providing guidance on their management. Finally, we investigate viral-related issues that can influence treatment outcomes, such as viral genotype, quasi-species, and the presence of resistance-associated mutations. EXPERT OPINION Despite pivotal trials demonstrating efficacy rates exceeding 90% for currently available DAA regimens, there are still opportunities to optimize therapy outcomes and tailor treatment to each patient. This can be achieved through a meticulous evaluation of the patient's specific clinical conditions and comorbidities, a vigilant approach to manage potential drug interactions, and diligent patient follow-up.
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Affiliation(s)
| | - Biagio Pinchera
- Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy
| | - Ivan Gentile
- Department of Clinical Medicine and Surgery, University of Naples Federico II, Naples, Italy
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11
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Hur MH, Lee JH. Toward hepatitis C virus elimination using artificial intelligence. Clin Mol Hepatol 2024; 30:147-149. [PMID: 38390703 PMCID: PMC11016500 DOI: 10.3350/cmh.2024.0135] [Citation(s) in RCA: 2] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/22/2024] [Accepted: 02/22/2024] [Indexed: 02/24/2024] Open
Affiliation(s)
- Moon Haeng Hur
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
| | - Jeong-Hoon Lee
- Department of Internal Medicine and Liver Research Institute, Seoul National University College of Medicine, Seoul, Korea
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12
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Katiyar H, Kamat M, Mandot AK, Goel A, Singh S, Mishra AK, Singh R, Tiwari P, Dhiman RK, Shah S. Sofosbuvir/Velpatasvir/Voxilaprevir for Hepatitis C Virus Retreatment in Difficult-to-treat Patients: A Real-life Observational Study from India. J Clin Exp Hepatol 2024; 14:101314. [PMID: 38261859 PMCID: PMC10792231 DOI: 10.1016/j.jceh.2023.101314] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/18/2023] [Accepted: 12/03/2023] [Indexed: 01/25/2024] Open
Abstract
Background and aim Hepatitis C virus (HCV) treatment fails to achieve sustained virological response at 12 weeks (SVR12) in 5-10 % and requires retreatment with second-line drugs. We report our experience of sofosbuvir/velpatasvir/voxilaprevir use for HCV retreatment in a small cohort of difficult-to-treat Indian patients. Methods We reviewed our HCV databases to identify the patients who had failed to achieve SVR12 after treatment with sofosbuvir in combination with either daclatasvir, ledipasvir, or velpatasvir with/without ribavirin on one or more occasions. Participants were excluded if they had (i) decompensated cirrhosis, (ii) HIV coinfection or (iii) chronic kidney disease, or (iv) prior organ transplantation. All the participants were treated with sofosbuvir/velpatasvir/voxilaprevir plus ribavirin for 12 weeks. Treatment outcome was categorized as successful or failure if HCV RNA was undetectable or detectable at SVR12, respectively. Results Fifteen patients (male 67 %; genotype-3 80 %) were included in the analysis. Ten (67 %) had cirrhosis. Five, eight, and two participants had previously failed one, two, and three courses of pegylated-interferon free, sofosbuvir containing direct acting antiviral (DAA) regimens respectively. Fourteen participants had failed to at least one course of the sofosbuvir/velpatasvir combination. Fourteen patients achieved SVR12, and one patient was lost to follow-up. Treatment was successful in 100 % and 93.3 % of per-protocol (PP) and intention to treat (ITT) analyses, respectively. Conclusion Sofosbuvir/velpatasvir/voxilaprevir combination is an effective second-line therapy in India for difficult-to-treat HCV patients.
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Affiliation(s)
- Harshita Katiyar
- Department of Hepatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
| | - Mrunal Kamat
- Department of Hepatology, Institute of Liver Diseases, Hepato-Pancreato-Biliary Surgery and Transplant, Global Hospitals, Mumbai, India
| | - Ameet K. Mandot
- Department of Hepatology, Institute of Liver Diseases, Hepato-Pancreato-Biliary Surgery and Transplant, Global Hospitals, Mumbai, India
| | - Amit Goel
- Department of Hepatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
| | - Surender Singh
- Department of Hepatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
| | - Ajay K. Mishra
- Department of Hepatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
| | - Rajani Singh
- Department of Hepatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
| | - Prachi Tiwari
- Department of Hepatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
| | - Radha K. Dhiman
- Department of Hepatology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India
| | - Samir Shah
- Department of Hepatology, Institute of Liver Diseases, Hepato-Pancreato-Biliary Surgery and Transplant, Global Hospitals, Mumbai, India
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13
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Tai CM, Yu ML. Hepatitis C virus micro-elimination in people who inject drugs: Challenges and chance in Taiwan and worldwide. Kaohsiung J Med Sci 2024; 40:112-118. [PMID: 38010851 DOI: 10.1002/kjm2.12788] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/30/2023] [Revised: 11/05/2023] [Accepted: 11/07/2023] [Indexed: 11/29/2023] Open
Abstract
With the introduction of direct-acting antivirals, elimination of hepatitis C virus (HCV) infection is becoming possible. People who inject drugs (PWID) represent a population with a high risk for HCV infection, which has been reported as high as 90% in Taiwanese PWID. To reach the goal of HCV elimination, PWID is a key population deserving special attention. Barriers in HCV care cascade still exist in PWID, and interventions to promote access to HCV diagnosis, link-to-care, treatment, and prevention for PWID are warranted. Although HCV micro-elimination can be achieved in some prisons and opioid substitution therapy (OST) centers by a multidisciplinary team and integrated care in Taiwan, there are still several unmet needs for HCV elimination in PWID. Continuous efforts, such as the participation of OST specialists and the continuum of care for HCV among PWID, are needed to achieve HCV elimination in Taiwan. In addition, the combination of harm reduction services, treatment as prevention and regular posttreatment HCV surveillance is critical to substantially reduce HCV transmission and prevalence in PWID.
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Affiliation(s)
- Chi-Ming Tai
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan
- School of Medicine for International Students, College of Medicine, I-Shou University, Kaohsiung, Taiwan
| | - Ming-Lung Yu
- School of Medicine and Doctoral Program of Clinical and Experimental Medicine, College of Medicine and Center of Excellence for Metabolic Associated Fatty Liver Disease, National Sun Yat-Sen University, Kaohsiung, Taiwan
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- School of Medicine and Hepatitis Research Center, College of Medicine, and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan
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14
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Lopes SS, Pericot-Valverde I, Arnsten J, Lum PJ, Taylor LE, Mehta SH, Tsui JI, Feinberg J, Kim AY, Norton BL, Page K, Murray-Krezan C, Anderson J, Moschella P, Heo M, Litwin AH. Self-reported and measured adherence to hepatitis C direct-acting antiviral therapy and sustained virologic response among people who inject drugs: The HERO study. THE INTERNATIONAL JOURNAL OF DRUG POLICY 2024; 123:104288. [PMID: 38103458 DOI: 10.1016/j.drugpo.2023.104288] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2023] [Revised: 11/30/2023] [Accepted: 12/02/2023] [Indexed: 12/19/2023]
Abstract
BACKGROUND Objective adherence measures, such as electronic blister pack (BP), for direct-acting antivirals (DAAs) for hepatitis C virus (HCV) treatment have high accuracy, but their use is limited in real practice settings. We examined the association of self-reported adherence using a visual analogue scale (VAS) with objective BP adherence and sustained virologic response (SVR) among people who inject drugs. METHODS We conducted secondary analyses using a subset of participants (N = 493) from the per-protocol sample of the HERO study, a pragmatic randomized trial of HCV treatment interventions that used both VAS and BP to measure adherence to a 12-week sofosbuvir/velpatasvir DAA regimen. Multivariable mixed-effects regression models tested the association of self-report adherence level with longitudinal weekly objective adherence. Multivariable logistic regression tested the association of self-report adherence with SVR. RESULTS The average VAS and BP adherences were 95.1 % (SD = 8.9 %) and 76.0 % (16.0 %), respectively, and the proportion of the participants achieving SVR was 92.9 %. The estimated adjusted mean objective adherence was significantly different (-16 %; 95 % CI: -22 %, -11 %, p < .001) between participants with 100 % and <80 % VAS adherence. The likelihood of SVR was significantly lower for those with <80 % VAS adherence [adjusted OR = 0.07; 95 % CI: 0.02, 0.24; p < .001] compared to those with 100 %. CONCLUSION Self-reported adherence overestimated objective adherence. However, higher self-report adherence was significantly associated with higher objective adherence. Also, self-reported adherence ≥80 % was significantly associated with SVR. Thus, the self-report measure has utility as a monitoring tool for adherence during DAA treatment.
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Affiliation(s)
- Snehal S Lopes
- Department of Public Health Sciences, Clemson University, Clemson, SC 29634, USA
| | - Irene Pericot-Valverde
- Department of Psychology, College of Behavioral, Social, and Health Sciences, Clemson University, Clemson, SC 29634, USA
| | - Julia Arnsten
- Albert Einstein College of Medicine, Bronx, NY 10461, USA; Department of Medicine, Montefiore Medical Center, Bronx, NY 10467, USA
| | - Paula J Lum
- Department of Medicine, University of California, 1001 Potrero Ave, San Francisco, CA 94110, USA
| | - Lynn E Taylor
- College of Pharmacy, University of Rhode Island, 7 Greenhouse Road, Kingston, RI 02881, USA
| | - Shruti H Mehta
- Department of Epidemiology, Johns Hopkins Bloomberg School of Public Health, 615N. Wolfe Street, Room E6546, Baltimore, MD 21205, USA
| | - Judith I Tsui
- Department of Medicine, University of Washington, 325 9th Ave., Seattle, WA 98104, USA
| | - Judith Feinberg
- Department of Behavioral Medicine and Psychiatry, West Virginia University School of Medicine, 930 Chestnut Ridge Road, Morgantown, WV 26505, USA; Department of Medicine, Section of Infectious Diseases, West Virginia University School of Medicine, 930 Chestnut Ridge Road, Morgantown, WV 26505, USA
| | - Arthur Y Kim
- Division of Infectious Diseases, Massachusetts General Hospital, 55 Fruit St., Boston, MA 02114, USA; Harvard Medical School, Boston, MA 02115, USA
| | - Brianna L Norton
- Albert Einstein College of Medicine, Bronx, NY 10461, USA; Department of Medicine, Montefiore Medical Center, Bronx, NY 10467, USA
| | - Kimberly Page
- Department of Internal Medicine, University of New Mexico Health Sciences Center, University of New Mexico MSC 10 5550, Albuquerque, NM 87131, USA
| | - Cristina Murray-Krezan
- Division of General Internal Medicine, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA
| | - Jessica Anderson
- Department of Internal Medicine, University of New Mexico Health Sciences Center, University of New Mexico MSC 10 5550, Albuquerque, NM 87131, USA
| | - Phillip Moschella
- Department of Emergency Medicine, Prisma Health, Greenville, SC, USA; School of Health Research, Clemson University, Clemson, SC, USA; Department of Medicine, University of South Carolina School of Medicine, 876W Faris Rd, Greenville, SC 29605, USA
| | - Moonseong Heo
- Department of Public Health Sciences, Clemson University, Clemson, SC 29634, USA
| | - Alain H Litwin
- School of Health Research, Clemson University, Clemson, SC, USA; Department of Medicine, University of South Carolina School of Medicine, 876W Faris Rd, Greenville, SC 29605, USA; Department of Medicine, Prisma Health, Greenville, SC, USA.
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15
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Lu MY, Huang CF, Hung CH, Tai C, Mo LR, Kuo HT, Tseng KC, Lo CC, Bair MJ, Wang SJ, Huang JF, Yeh ML, Chen CT, Tsai MC, Huang CW, Lee PL, Yang TH, Huang YH, Chong LW, Chen CL, Yang CC, Yang S, Cheng PN, Hsieh TY, Hu JT, Wu WC, Cheng CY, Chen GY, Zhou GX, Tsai WL, Kao CN, Lin CL, Wang CC, Lin TY, Lin C, Su WW, Lee TH, Chang TS, Liu CJ, Dai CY, Kao JH, Lin HC, Chuang WL, Peng CY, Tsai CW, Chen CY, Yu ML. Artificial intelligence predicts direct-acting antivirals failure among hepatitis C virus patients: A nationwide hepatitis C virus registry program. Clin Mol Hepatol 2024; 30:64-79. [PMID: 38195113 PMCID: PMC10776298 DOI: 10.3350/cmh.2023.0287] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/02/2023] [Revised: 11/02/2023] [Accepted: 11/20/2023] [Indexed: 01/11/2024] Open
Abstract
BACKGROUND/AIMS Despite the high efficacy of direct-acting antivirals (DAAs), approximately 1-3% of hepatitis C virus (HCV) patients fail to achieve a sustained virological response. We conducted a nationwide study to investigate risk factors associated with DAA treatment failure. Machine-learning algorithms have been applied to discriminate subjects who may fail to respond to DAA therapy. METHODS We analyzed the Taiwan HCV Registry Program database to explore predictors of DAA failure in HCV patients. Fifty-five host and virological features were assessed using multivariate logistic regression, decision tree, random forest, eXtreme Gradient Boosting (XGBoost), and artificial neural network. The primary outcome was undetectable HCV RNA at 12 weeks after the end of treatment. RESULTS The training (n=23,955) and validation (n=10,346) datasets had similar baseline demographics, with an overall DAA failure rate of 1.6% (n=538). Multivariate logistic regression analysis revealed that liver cirrhosis, hepatocellular carcinoma, poor DAA adherence, and higher hemoglobin A1c were significantly associated with virological failure. XGBoost outperformed the other algorithms and logistic regression models, with an area under the receiver operating characteristic curve of 1.000 in the training dataset and 0.803 in the validation dataset. The top five predictors of treatment failure were HCV RNA, body mass index, α-fetoprotein, platelets, and FIB-4 index. The accuracy, sensitivity, specificity, positive predictive value, and negative predictive value of the XGBoost model (cutoff value=0.5) were 99.5%, 69.7%, 99.9%, 97.4%, and 99.5%, respectively, for the entire dataset. CONCLUSION Machine learning algorithms effectively provide risk stratification for DAA failure and additional information on the factors associated with DAA failure.
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Affiliation(s)
- Ming-Ying Lu
- School of Medicine and Doctoral Program of Clinical and Experimental Medicine, College of Medicine and Center of Excellence for Metabolic Associated Fatty Liver Disease, National Sun Yat-sen University, Kaohsiung, Taiwan
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Hepatitis Research Center, College of Medicine and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chung-Feng Huang
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Hepatitis Research Center, College of Medicine and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan
- Ph.D. Program in Translational Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, and Academia Sinica, Taipei, Taiwan
| | - Chao-Hung Hung
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
| | - Chi‐Ming Tai
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan
- School of Medicine for International Students, College of Medicine, I-Shou University, Kaohsiung, Taiwan
| | - Lein-Ray Mo
- Division of Gastroenterology, Tainan Municipal Hospital (Managed By Show Chwan Medical Care Corporation), Tainan, Taiwan
| | - Hsing-Tao Kuo
- School of Medicine and Doctoral Program of Clinical and Experimental Medicine, College of Medicine and Center of Excellence for Metabolic Associated Fatty Liver Disease, National Sun Yat-sen University, Kaohsiung, Taiwan
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chi Mei Medical Center, Yongkang District, Tainan, Taiwan
| | - Kuo-Chih Tseng
- Department of Internal Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi, Taiwan
- School of Medicine, Tzuchi University, Hualien, Taiwan
| | - Ching-Chu Lo
- Division of Gastroenterology, Department of Internal Medicine, St. Martin De Porres Hospital, Chiayi, Taiwan
| | - Ming-Jong Bair
- Division of Gastroenterology, Department of Internal Medicine, Taitung Mackay Memorial Hospital, Taitung, Taiwan
- Mackay Medical College, New Taipei City, Taiwan
| | - Szu-Jen Wang
- Division of Gastroenterology, Department of Internal Medicine, Yuan’s General Hospital, Kaohsiung, Taiwan
| | - Jee-Fu Huang
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Hepatitis Research Center, College of Medicine and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ming-Lun Yeh
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Hepatitis Research Center, College of Medicine and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chun-Ting Chen
- Division of Gastroenterology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
- Division of Gastroenterology, Department of Internal Medicine, Tri-Service General Hospital Penghu Branch, National Defense Medical Center, Taipei, Taiwan
| | - Ming-Chang Tsai
- School of Medicine, Chung Shan Medical University, Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan
| | - Chien-Wei Huang
- Division of Gastroenterology, Kaohsiung Armed Forces General Hospital, Kaohsiung, Taiwan
| | - Pei-Lun Lee
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chi Mei Medical Center, Liouying, Tainan, Taiwan
| | | | - Yi-Hsiang Huang
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
- Institute of Clinical Medicine, School of Medicine, National Yang-Ming Chiao Tung University, Taipei, Taiwan
| | - Lee-Won Chong
- Division of Hepatology and Gastroenterology, Department of Internal Medicine, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan
- School of Medicine, Fu-Jen Catholic University, New Taipei City, Taiwan
| | - Chien-Lin Chen
- Department of Medicine, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation and Tzu Chi University, Hualien, Taiwan
| | - Chi-Chieh Yang
- Department of Gastroenterology, Division of Internal Medicine, Show Chwan Memorial Hospital, Changhua, Taiwan
| | - Sheng‐Shun Yang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan
| | - Pin-Nan Cheng
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Tsai-Yuan Hsieh
- Division of Gastroenterology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
| | - Jui-Ting Hu
- Liver Center, Cathay General Hospital, Taipei, Taiwan
| | - Wen-Chih Wu
- Wen-Chih Wu Clinic, Fengshan, Kaohsiung, Taiwan
| | - Chien-Yu Cheng
- Division of Infectious Diseases, Department of Internal Medicine, Taoyuan General Hospital, Ministry of Health and Welfare, Taoyuan, Taiwan
| | - Guei-Ying Chen
- Penghu Hospital, Ministry of Health and Welfare, Penghu, Taiwan
| | | | - Wei-Lun Tsai
- Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
| | - Chien-Neng Kao
- National Taiwan University Hospital Hsin-Chu Branch, Hsinchu, Taiwan
| | - Chih-Lang Lin
- Liver Research Unit, Department of Hepato-Gastroenterology and Community Medicine Research Center, Chang Gung Memorial Hospital at Keelung, College of Medicine, Chang Gung University, Keelung, Taiwan
| | - Chia-Chi Wang
- Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation and School of Medicine, Tzu Chi University, Taipei, Taiwan
| | - Ta-Ya Lin
- Cishan Hospital, Ministry of Health and Welfare, Kaohsiung, Taiwan
| | - Chih‐Lin Lin
- Department of Gastroenterology, Renai Branch, Taipei City Hospital, Taipei, Taiwan
| | - Wei-Wen Su
- Department of Gastroenterology and Hepatology, Changhua Christian Hospital, Changhua, Taiwan
| | - Tzong-Hsi Lee
- Division of Gastroenterology and Hepatology, Far Eastern Memorial Hospital, New Taipei City, Taiwan
| | - Te-Sheng Chang
- Division of Hepatogastroenterology, Department of Internal Medicine, Chang Gung Memorial Hospital, Chiayi, Taiwan and College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Chun-Jen Liu
- Hepatitis Research Center and Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Chia-Yen Dai
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Hepatitis Research Center, College of Medicine and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Jia-Horng Kao
- Hepatitis Research Center and Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Han-Chieh Lin
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
- Institute of Clinical Medicine, School of Medicine, National Yang-Ming Chiao Tung University, Taipei, Taiwan
| | - Wan-Long Chuang
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Hepatitis Research Center, College of Medicine and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Cheng-Yuan Peng
- Center for Digestive Medicine, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
- School of Medicine, China Medical University, Taichung, Taiwan
| | - Chun-Wei- Tsai
- Department of Computer Science and Engineering, National Sun Yat-sen University, Kaohsiung, Taiwan
| | - Chi-Yi Chen
- Division of Gastroenterology and Hepatology, Department of Medicine, Ditmanson Medical Foundation Chiayi Christian Hospital, Chiayi, Taiwan
| | - Ming-Lung Yu
- School of Medicine and Doctoral Program of Clinical and Experimental Medicine, College of Medicine and Center of Excellence for Metabolic Associated Fatty Liver Disease, National Sun Yat-sen University, Kaohsiung, Taiwan
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Hepatitis Research Center, College of Medicine and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
| | - TACR Study Group
- School of Medicine and Doctoral Program of Clinical and Experimental Medicine, College of Medicine and Center of Excellence for Metabolic Associated Fatty Liver Disease, National Sun Yat-sen University, Kaohsiung, Taiwan
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Hepatitis Research Center, College of Medicine and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan
- Ph.D. Program in Translational Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, and Academia Sinica, Taipei, Taiwan
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan
- School of Medicine for International Students, College of Medicine, I-Shou University, Kaohsiung, Taiwan
- Division of Gastroenterology, Tainan Municipal Hospital (Managed By Show Chwan Medical Care Corporation), Tainan, Taiwan
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chi Mei Medical Center, Yongkang District, Tainan, Taiwan
- Department of Internal Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi, Taiwan
- School of Medicine, Tzuchi University, Hualien, Taiwan
- Division of Gastroenterology, Department of Internal Medicine, St. Martin De Porres Hospital, Chiayi, Taiwan
- Division of Gastroenterology, Department of Internal Medicine, Taitung Mackay Memorial Hospital, Taitung, Taiwan
- Mackay Medical College, New Taipei City, Taiwan
- Division of Gastroenterology, Department of Internal Medicine, Yuan’s General Hospital, Kaohsiung, Taiwan
- Division of Gastroenterology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
- Division of Gastroenterology, Department of Internal Medicine, Tri-Service General Hospital Penghu Branch, National Defense Medical Center, Taipei, Taiwan
- School of Medicine, Chung Shan Medical University, Department of Internal Medicine, Chung Shan Medical University Hospital, Taichung, Taiwan
- Division of Gastroenterology, Kaohsiung Armed Forces General Hospital, Kaohsiung, Taiwan
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chi Mei Medical Center, Liouying, Tainan, Taiwan
- Lotung Poh-Ai Hospital, Yilan, Taiwan
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
- Institute of Clinical Medicine, School of Medicine, National Yang-Ming Chiao Tung University, Taipei, Taiwan
- Division of Hepatology and Gastroenterology, Department of Internal Medicine, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan
- School of Medicine, Fu-Jen Catholic University, New Taipei City, Taiwan
- Department of Medicine, Hualien Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation and Tzu Chi University, Hualien, Taiwan
- Department of Gastroenterology, Division of Internal Medicine, Show Chwan Memorial Hospital, Changhua, Taiwan
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
- Liver Center, Cathay General Hospital, Taipei, Taiwan
- Wen-Chih Wu Clinic, Fengshan, Kaohsiung, Taiwan
- Division of Infectious Diseases, Department of Internal Medicine, Taoyuan General Hospital, Ministry of Health and Welfare, Taoyuan, Taiwan
- Penghu Hospital, Ministry of Health and Welfare, Penghu, Taiwan
- Zhou Guoxiong Clinic, Penghu, Taiwan
- Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
- National Taiwan University Hospital Hsin-Chu Branch, Hsinchu, Taiwan
- Liver Research Unit, Department of Hepato-Gastroenterology and Community Medicine Research Center, Chang Gung Memorial Hospital at Keelung, College of Medicine, Chang Gung University, Keelung, Taiwan
- Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation and School of Medicine, Tzu Chi University, Taipei, Taiwan
- Cishan Hospital, Ministry of Health and Welfare, Kaohsiung, Taiwan
- Department of Gastroenterology, Renai Branch, Taipei City Hospital, Taipei, Taiwan
- Department of Gastroenterology and Hepatology, Changhua Christian Hospital, Changhua, Taiwan
- Division of Gastroenterology and Hepatology, Far Eastern Memorial Hospital, New Taipei City, Taiwan
- Division of Hepatogastroenterology, Department of Internal Medicine, Chang Gung Memorial Hospital, Chiayi, Taiwan and College of Medicine, Chang Gung University, Taoyuan, Taiwan
- Hepatitis Research Center and Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
- Center for Digestive Medicine, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
- School of Medicine, China Medical University, Taichung, Taiwan
- Department of Computer Science and Engineering, National Sun Yat-sen University, Kaohsiung, Taiwan
- Division of Gastroenterology and Hepatology, Department of Medicine, Ditmanson Medical Foundation Chiayi Christian Hospital, Chiayi, Taiwan
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16
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Lo CC, Lei WY, Huang YC, Hwang JJ, Lo CY, Lin CH, Cheng HS, Liao YT, Liang PC, Chiou MJ, Bair MJ, Dai CY, Yu ML. Micro-elimination of hepatitis C virus infection in the rural and remote areas of Taiwan - A multi-center collaborative care model. JOURNAL OF MICROBIOLOGY, IMMUNOLOGY, AND INFECTION = WEI MIAN YU GAN RAN ZA ZHI 2023; 56:680-687. [PMID: 36822945 DOI: 10.1016/j.jmii.2023.01.014] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 09/01/2022] [Revised: 12/05/2022] [Accepted: 01/20/2023] [Indexed: 02/12/2023]
Abstract
INTRODUCTION Taiwan has several hepatitis C virus (HCV) hyper-endemic areas. We aimed to evaluate the effectiveness and safety of a collaborative HCV care system with an outreach decentralized strategy among the resource-constrained rural/remote areas of Taiwan. METHODS The pilot study was conducted in four high HCV-endemic townships in the rural/remote areas of Taoyuan, Alishan, Zhuoxi and Xiulin. Registered residents who worked or lived in the four areas and were aged 30-75 years were invited to participate in this program. Multidisciplinary HCV care teams provided outreach decentralized services of anti-HCV screening, link-to-diagnosis, and link-to-treatment with direct-acting antiviral agents (DAA). The primary end-point was sustained virological response (SVR). RESULTS Of 8291 registered residents who were invited as the target population, 7807 (94.2%) subjects received anti-HCV screening, with the average anti-HCV prevalence rate of 14.2% (1108/7807) (range among four areas: 11.8%-16.7%). The rate of link-to-diagnosis was 94.4% (1046/1108) of anti-HCV-positive subjects (range: 90.9%-100%) with an average HCV-viremic rate of 55.1% (576/1046) (range: 50.0%-64.3%). The link-to-treat rate was 94.4% (544/576) in HCV-viremic subjects (range from 92.7% to 97.2%). Overall, 523 (96.1%) patients achieved an SVR (range: 94.7%-97.6%). Eventually, the overall effectiveness was 80.7% (range: 74.6%-93.1%). The presence of hepatocellular carcinoma at baseline was the only factor associated with DAA failure. The DAA regimens were well-tolerated. CONCLUSION The outreach decentralized community-based care system with DAA therapy was highly effective and safe in the achievement of HCV micro-elimination in the resource-constrained rural and remote regions, which could help us to tackle the disparity.
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Affiliation(s)
- Ching-Chu Lo
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, St. Martin De Porres Hospital, Chung-Jen Junior College of Nursing, Health Sciences and Management, Chiayi, Taiwan
| | - Wei-Yi Lei
- Department of Medicine, Hualien Tzu Chi Hospital, Buddihist Tzu Chi Medical Foundation, Tzu Chi University, Hualien, Taiwan
| | - Ying-Che Huang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taipei Veterans General Hospital Yuli Branch, Taipei, Taiwan
| | - Jow-Jyh Hwang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, St. Martin De Porres Hospital, Chung-Jen Junior College of Nursing, Health Sciences and Management, Chiayi, Taiwan
| | - Chen-Yu Lo
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, St. Martin De Porres Hospital, Chung-Jen Junior College of Nursing, Health Sciences and Management, Chiayi, Taiwan; Eberly College of Science, Department of Biology, Schreyer Honors College, Pennsylvania State University, United States
| | - Chien-Hung Lin
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, St. Martin De Porres Hospital, Chung-Jen Junior College of Nursing, Health Sciences and Management, Chiayi, Taiwan
| | - Hsu-Sheng Cheng
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, St. Martin De Porres Hospital, Chung-Jen Junior College of Nursing, Health Sciences and Management, Chiayi, Taiwan
| | - Yee-Tam Liao
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, St. Martin De Porres Hospital, Chung-Jen Junior College of Nursing, Health Sciences and Management, Chiayi, Taiwan
| | - Po-Cheng Liang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Hepatitis Research Center, College of Medicine and Center for Liquid Biopsy and Cohort Research, Kaohsiung, Taiwan
| | - Meng-Jau Chiou
- Taoyuan District Public Health Center, Kaohsiung, Taiwan
| | - Ming-Jong Bair
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taitung Mackay Memorial Hospital, Taitung, Taiwan; Department of Medicine, Mackay Medical College, New Taipei, Taiwan.
| | - Chia-Yen Dai
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Hepatitis Research Center, College of Medicine and Center for Liquid Biopsy and Cohort Research, Kaohsiung, Taiwan; School of Medicine, College of Medicine and Center of Excellence for Metabolic Associated Fatty Liver Disease, National Sun Yat-sen University, Kaohsiung, Taiwan.
| | - Ming-Lung Yu
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Hepatitis Research Center, College of Medicine and Center for Liquid Biopsy and Cohort Research, Kaohsiung, Taiwan; School of Medicine, College of Medicine and Center of Excellence for Metabolic Associated Fatty Liver Disease, National Sun Yat-sen University, Kaohsiung, Taiwan; Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan
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17
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Chang TS, Huang CF, Kuo HT, Lo CC, Huang CW, Chong LW, Cheng PN, Yeh ML, Peng CY, Cheng CY, Huang JF, Bair MJ, Lin CL, Yang CC, Wang SJ, Hsieh TY, Lee TH, Lee PL, Wu WC, Lin CL, Su WW, Yang SS, Wang CC, Hu JT, Mo LR, Chen CT, Huang YH, Chang CC, Huang CS, Chen GY, Kao CN, Tai CM, Liu CJ, Lee MH, Tsai PC, Dai CY, Kao JH, Lin HC, Chuang WL, Chen CY, Tseng KC, Hung CH, Yu ML. Effectiveness and safety of 8-week glecaprevir/pibrentasvir in HCV treatment-naïve patients with compensated cirrhosis: real-world experience from Taiwan nationwide HCV registry. Hepatol Int 2023; 17:550-561. [PMID: 36973633 PMCID: PMC10042416 DOI: 10.1007/s12072-023-10506-z] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/28/2022] [Accepted: 02/22/2023] [Indexed: 03/29/2023]
Abstract
BACKGROUND Large-scale real-world data of the 8-week glecaprevir/pibrentasvir (GLE/PIB) therapy for treatment-naïve patients of chronic hepatitis C virus (HCV) infection with compensated cirrhosis is scarce. METHODS The TASL HCV Registry (TACR) is an ongoing nationwide registry program that aims to set up a database and biobank of patients with chronic HCV infection in Taiwan. In this study, data were analyzed as of 31 October 2021 for treatment-naïve HCV patients with compensated cirrhosis receiving 8-week GLE/PIB therapy. Effectiveness reported as sustained virologic response at off-therapy week 12 (SVR12) and safety profiles were assessed. Patient characteristics potentially related to SVR12 were also evaluated. RESULTS Of the 301 patients enrolled, 275 had available SVR12 data. The SVR12 rate was 98.2% (270/275) in the modified intention-to-treat (mITT) population and 89.7% (270/301) in the ITT population. For those mITT patients with genotype 3, FibroScan > 20 kPa, platelet < 150,000/µl, and FibroScan > 20 kPa and platelet < 150,000/µl, the SVR12 rates were 100% (6/6), 100% (12/12), 98.0% (144/147), 100% (7/7), respectively. Overall, 24.9% (75/301) patients experienced adverse events (AEs). The most frequent AEs (> 5%) included fatigue (9.0%) and pruritus (7.0%). Seven (2.3%) patients experienced serious AEs and two (0.7%) resulted in permanent drug discontinuation. None of them were considered as GLE/PIB-related. CONCLUSIONS In this large-scale real-world Taiwanese cohort, 8-week GLE/PIB therapy was efficacious and well tolerated for treatment-naïve compensated cirrhosis patients. SVR12 rates were similarly high as in the clinical trials, including those with characteristics of advanced liver disease.
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Affiliation(s)
- Te-Sheng Chang
- Division of Hepatogastroenterology, Department of Internal Medicine, Chang Gung Memorial Hospital, Chiayi, Taiwan
- College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Chung-Feng Huang
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Ph.D. Program in Translational Medicine, College of Medicine, Kaohsiung Medical University, Academia Sinica, Kaohsiung, Taiwan
| | - Hsing-Tao Kuo
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chi Mei Medical Center, Yongkang District, Tainan, Taiwan
| | - Ching-Chu Lo
- Division of Gastroenterology, Department of Internal Medicine, St. Martin De Porres Hospital, Chiayi, Taiwan
| | - Chien-Wei Huang
- Division of Gastroenterology, Kaohsiung Armed Forces General Hospital, Kaohsiung, Taiwan
| | - Lee-Won Chong
- Division of Hepatology and Gastroenterology, Department of Internal Medicine, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan
- School of Medicine, Fu-Jen Catholic University, New Taipei City, Taiwan
| | - Pin-Nan Cheng
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Ming-Lun Yeh
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Cheng-Yuan Peng
- Center for Digestive Medicine, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
- School of Medicine, China Medical University, Taichung, Taiwan
| | - Chien-Yu Cheng
- Division of Infectious Diseases, Department of Internal Medicine, Taoyuan General Hospital, Ministry of Health and Welfare, Taoyuan, Taiwan
| | - Jee-Fu Huang
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Hepatitis Research Center, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ming-Jong Bair
- Division of Gastroenterology, Department of Internal Medicine, Taitung Mackay Memorial Hospital, Taitung, Taiwan
- Mackay Medical College, New Taipei City, Taiwan
| | - Chih-Lang Lin
- Liver Research Unit, Department of Hepato-Gastroenterology and Community Medicine Research Center, Chang Gung Memorial Hospital at Keelung, College of Medicine, Chang Gung University, Keelung, Taiwan
| | - Chi-Chieh Yang
- Department of Gastroenterology, Division of Internal Medicine, Show Chwan Memorial Hospital, Changhua, Taiwan
| | - Szu-Jen Wang
- Division of Gastroenterology, Department of Internal Medicine, Yuan's General Hospital, Kaohsiung, Taiwan
| | - Tsai-Yuan Hsieh
- Division of Gastroenterology, Department of Internal Medicine, Tri‑Service General Hospital, National Defense Medical Center, Taipei, Taiwan
| | - Tzong-Hsi Lee
- Division of Gastroenterology and Hepatology, Far Eastern Memorial Hospital, New Taipei City, Taiwan
| | - Pei-Lun Lee
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chi Mei Medical Center, Liouying, Tainan, Taiwan
| | - Wen-Chih Wu
- Wen-Chih Wu Clinic, Fengshan, Kaohsiung, Taiwan
| | - Chih-Lin Lin
- Department of Gastroenterology, Renai Branch, Taipei City Hospital, Taipei, Taiwan
| | - Wei-Wen Su
- Department of Gastroenterology and Hepatology, Changhua Christian Hospital, Changhua, Taiwan
| | - Sheng-Shun Yang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan
- Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan
- Department of Post-Baccalaureate Medicine, College of Medicine, National Chung Hsing University, Taichung, Taiwan
| | - Chia-Chi Wang
- Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation and School of Medicine, Tzu Chi University, Taipei, Taiwan
| | - Jui-Ting Hu
- Liver Center, Cathay General Hospital, Taipei, Taiwan
| | - Lein-Ray Mo
- Division of Gastroenterology, Tainan Municipal Hospital (Managed By Show Chwan Medical Care Corporation), Tainan, Taiwan
| | - Chun-Ting Chen
- Division of Gastroenterology, Department of Internal Medicine, Tri‑Service General Hospital, National Defense Medical Center, Taipei, Taiwan
- Division of Gastroenterology, Department of Internal Medicine, Tri‑Service General Hospital Penghu Branch, National Defense Medical Center, Taipei, Taiwan
| | - Yi-Hsiang Huang
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
- Institute of Clinical Medicine, School of Medicine, National Yang-Ming Chiao Tung University, Taipei, Taiwan
| | - Chun-Chao Chang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taipei Medical University Hospital, Taipei, Taiwan
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
| | | | - Guei-Ying Chen
- Penghu Hospital, Ministry of Health and Welfare, Penghu, Taiwan
| | - Chien-Neng Kao
- National Taiwan University Hospital Hsin-Chu Branch, Hsinchu, Taiwan
| | - Chi-Ming Tai
- Department of Internal Medicine, E-Da Hospital, Kaohsiung, Taiwan
- School of Medicine, College of Medicine, I-Shou University, Kaohsiung, Taiwan
| | - Chun-Jen Liu
- Hepatitis Research Center and Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Mei-Hsuan Lee
- Institute of Clinical Medicine, National Yang-Ming Chiao Tung University, Taipei, Taiwan
| | - Pei-Chien Tsai
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chia-Yen Dai
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Jia-Horng Kao
- Hepatitis Research Center and Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Han-Chieh Lin
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
- Institute of Clinical Medicine, School of Medicine, National Yang-Ming Chiao Tung University, Taipei, Taiwan
| | - Wang-Long Chuang
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chi-Yi Chen
- Division of Gastroenterology and Hepatology, Department of Medicine, Ditmanson Medical Foundation Chiayi Christian Hospital, Chiayi, Taiwan
| | - Kuo-Chih Tseng
- Department of Internal Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi, Taiwan
- School of Medicine, Tzuchi University, Hualien, Taiwan
| | - Chao-Hung Hung
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan.
| | - Ming-Lung Yu
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
- Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan.
- Hepatitis Research Center, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan.
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung, Taiwan.
- School of Medicine, College of Medicine, Center of Excellence for Metabolic Associated Fatty Liver Disease, National Sun Yat-Sen University, Kaohsiung, Taiwan.
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18
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Brzdęk M, Zarębska-Michaluk D, Rzymski P, Lorenc B, Kazek A, Tudrujek-Zdunek M, Janocha-Litwin J, Mazur W, Dybowska D, Berak H, Parfieniuk-Kowerda A, Klapaczyński J, Sitko M, Sobala-Szczygieł B, Piekarska A, Flisiak R. Changes in characteristics of patients with hepatitis C virus-related cirrhosis from the beginning of the interferon-free era. World J Gastroenterol 2023; 29:2015-2033. [PMID: 37155527 PMCID: PMC10122793 DOI: 10.3748/wjg.v29.i13.2015] [Citation(s) in RCA: 8] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/21/2022] [Revised: 01/16/2023] [Accepted: 03/20/2023] [Indexed: 04/06/2023] Open
Abstract
BACKGROUND Nearly 290000 patients with chronic hepatitis C die annually from the most severe complications of the disease. One of them is liver cirrhosis, which occurs in about 20% of patients chronically infected with the hepatitis C virus (HCV). Direct-acting antivirals (DAAs), which replaced interferon (IFN)-based regimens, significantly improved the prognosis of this group of patients, increasing HCV eradication rates and tolerability of therapy. Our study is the first to assess changes in patient profile, effectiveness, and safety in the HCV-infected cirrhotic population in the IFN-free era.
AIM To document changes in patient characteristics and treatment regimens along with their effectiveness and safety profile over the years.
METHODS The studied patients were selected from 14801 chronically HCV-infected individuals who started IFN-free therapy between July 2015 and December 2021 in 22 Polish hepatology centers. The retrospective analysis was conducted in real-world clinical practice based on the EpiTer-2 multicenter database. The measure of treatment effectiveness was the percentage of sustained virologic response (SVR) calculated after excluding patients lost to follow-up. Safety data collected during therapy and the 12-wk post-treatment period included information on adverse events, including serious ones, deaths, and treatment course.
RESULTS The studied population (n = 3577) was balanced in terms of gender in 2015-2017, while the following years showed the dominance of men. The decline in the median age from 60 in 2015-2016 to 57 years in 2021 was accompanied by a decrease in the percentage of patients with comorbidities and comedications. Treatment-experienced patients dominated in 2015-2016, while treatment-naive individuals gained an advantage in 2017 and reached 93.2% in 2021. Genotype (GT)-specific options were more prevalent in treatment in 2015-2018 and were supplanted by pangenotypic combinations in subsequent years. The effectiveness of the therapy was comparable regardless of the period analyzed, and patients achieved an overall response rate of 95%, with an SVR range of 72.9%-100% for the different therapeutic regimens. Male gender, GT3 infection, and prior treatment failure were identified as independent negative predictors of therapeutic success.
CONCLUSION We have documented changes in the profile of HCV-infected cirrhotic patients over the years of accessibility to changing DAA regimens, confirming the high effectiveness of IFN-free therapy in all analyzed periods.
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Affiliation(s)
- Michał Brzdęk
- Department of Infectious Diseases, Jan Kochanowski University, Kielce 25-317, Poland
| | | | - Piotr Rzymski
- Department of Environmental Medicine, Poznan University of Medical Sciences, Poznań 60-806, Poland
- Integrated Science Association, Universal Scientific Education and Research Network, Poznań 60-806, Poland
| | - Beata Lorenc
- Pomeranian Center of Infectious Diseases, Medical University Gdańsk, Gdańsk 80-214, Poland
| | | | | | - Justyna Janocha-Litwin
- Department of Infectious Diseases and Hepatology, Medical University Wrocław, Wrocław 50-367, Poland
| | - Włodzimierz Mazur
- Clinical Department of Infectious Diseases, Clinical University of Silesia in Katowice, Chorzów 41-500, Poland
| | - Dorota Dybowska
- Department of Infectious Diseases and Hepatology, Faculty of Medicine, Nicolaus Copernicus University, Bydgoszcz 85-030, Poland
| | - Hanna Berak
- Daily Department, Hospital for Infectious Diseases in Warsaw, Warszawa 01-201, Poland
| | - Anna Parfieniuk-Kowerda
- Department of Infectious Diseases and Hepatology, Medical University of Białystok, Białystok 15-089, Poland
| | - Jakub Klapaczyński
- Department of Internal Medicine and Hepatology, Central Clinical Hospital of the Ministry of Internal Affairs and Administration, Warszawa 00-241, Poland
| | - Marek Sitko
- Department of Infectious and Tropical Diseases, Jagiellonian University, Kraków 31-088, Poland
| | - Barbara Sobala-Szczygieł
- Department of Infectious Diseases, Medical University of Silesia in Katowice, Bytom 41-902, Poland
| | - Anna Piekarska
- Department of Infectious Diseases and Hepatology, Medical University of Łódź, Łódź 90-419, Poland
| | - Robert Flisiak
- Department of Infectious Diseases and Hepatology, Medical University of Białystok, Białystok 15-089, Poland
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Yu ML, Wang CY, Lee MH, Ou HY, Cheng PN, Tu ST, Huang JF, Chen JF, Hu TH, Hsu CC, Kao JH, Chen CJ, Lin HC, Huang CN. TASL, TADE, and DAROC consensus for the screening and management of hepatitis C in patients with diabetes. J Formos Med Assoc 2023; 122:202-220. [PMID: 36750398 DOI: 10.1016/j.jfma.2023.01.011] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/08/2022] [Revised: 01/19/2023] [Accepted: 01/21/2023] [Indexed: 02/09/2023] Open
Abstract
Diabetes mellitus (DM) and hepatitis C virus (HCV) infection are prevalent diseases globally and emerging evidence demonstrates the bidirectional association between the two diseases. Direct-acting antivirals (DAAs) for HCV have a high treatment success rate and can significantly reduce the risks of short and long-term complications of HCV infection. However, despite the evidence of the association between diabetes and HCV and the benefits of anti-HCV treatment, previously published guidelines did not focus on the universal HCV screening for patients with diabetes and their subsequent management once confirmed as having HCV viremia. Nonetheless, screening for HCV among patients with diabetes will contribute to the eradication of HCV infection. Thus, the three major Taiwan medical associations of diabetes and liver diseases endorsed a total of 14 experts in the fields of gastroenterology, hepatology, diabetology, and epidemiology to convene and formulate a consensus statement on HCV screening and management among patients with diabetes. Based on recent studies and guidelines as well as from real-world clinical experiences, the Taiwan experts reached a consensus that provides a straightforward approach to HCV screening, treatment, and monitoring of patients with diabetes.
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Affiliation(s)
- Ming-Lung Yu
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; School of Medicine, College of Medicine and Center of Excellence for Metabolic Associated Fatty Liver Disease, National Sun Yat-sen University, Kaohsiung, Taiwan
| | - Chih-Yuan Wang
- Division of Endocrinology and Metabolism, Department of Internal Medicine, National Taiwan University Hospital, College of Medicine, National Taiwan University, Taipei, Taiwan
| | - Mei-Hsuan Lee
- Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Horng-Yih Ou
- Division of Endocrinology and Metabolism, Department of Internal Medicine, National Cheng-Kung University Medical College and Hospital, Tainan, Taiwan
| | - Pin-Nan Cheng
- Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Shih-Te Tu
- Department of Endocrinology and Metabolism, Changhua Christian Hospital, Changhua, Taiwan
| | - Jee-Fu Huang
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; Center for Cancer Research, Center for Liquid Biopsy, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Jung-Fu Chen
- Division of Endocrinology and Metabolism, Department of Internal Medicine, Kaohsiung Chang Gung Hospital, Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Tsung-Hui Hu
- Department of Internal Medicine, Kaohsiung, Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Chih-Cheng Hsu
- Institute of Population Health Sciences, National Health Research Institutes, Zhunan, Miaoli, Taiwan
| | - Jia-Horng Kao
- Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Chien-Jen Chen
- Genomics Research Center, Academia Sinica, Taipei, Taiwan
| | - Han-Chieh Lin
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
| | - Chien-Ning Huang
- Department of Internal Medicine, Chung Shan Medical University Hospital, Institute of Medicine, Chung Shan Medical University, Taichung, Taiwan.
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20
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Tsai PC, Kuo HT, Hung CH, Tseng KC, Lai HC, Peng CY, Wang JH, Chen JJ, Lee PL, Chien RN, Yang CC, Lo GH, Kao JH, Liu CJ, Liu CH, Yan SL, Bair MJ, Lin CY, Su WW, Chu CH, Chen CJ, Tung SY, Tai CM, Lin CW, Lo CC, Cheng PN, Chiu YC, Wang CC, Cheng JS, Tsai WL, Lin HC, Huang YH, Yeh ML, Huang CF, Hsieh MH, Huang JF, Dai CY, Chung WL, Chen CY, Yu ML. Metformin reduces hepatocellular carcinoma incidence after successful antiviral therapy in patients with diabetes and chronic hepatitis C in Taiwan. J Hepatol 2023; 78:281-292. [PMID: 36208843 DOI: 10.1016/j.jhep.2022.09.019] [Citation(s) in RCA: 21] [Impact Index Per Article: 10.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/31/2021] [Revised: 08/10/2022] [Accepted: 09/14/2022] [Indexed: 01/24/2023]
Abstract
BACKGROUND & AIMS Diabetes mellitus (DM) is known to increase the risk of hepatocellular carcinoma (HCC) among individuals with chronic hepatitis C (CHC). We aimed to evaluate whether metformin reduces HCC risk among individuals with DM and CHC after successful antiviral therapy. METHODS Individuals with CHC who achieved a sustained virological response (SVR) after interferon-based therapy were enrolled in a large-scale, multicenter cohort in Taiwan (T-COACH). Cases of HCC at least 1 year after SVR were identified through linkage to the catastrophic illness and cancer registry databases. RESULTS Of 7,249 individuals with CHC enrolled in the study, 781 (10.8%) had diabetes and 647 (82.8%) were metformin users. During a median follow-up of 4.4 years, 227 patients developed new-onset HCC. The 5-year cumulative HCC incidence was 10.9% in non-metformin users and 2.6% in metformin users, compared to 3.0% in individuals without DM (adjusted hazard ratio [aHR] 2.83; 95% CI 1.57-5.08 and aHR 1.46; 95% CI 0.98-2.19, respectively). Cirrhosis was the most important factor significantly associated with higher HCC risk in Cox regression analysis, followed by DM non-metformin use, older age, male sex, and obesity; whereas hyperlipidemia with statin use was associated with a lower HCC risk. Using the two most crucial risk factors, cirrhosis and DM non-metformin use, we constructed a simple risk model that could predict HCC risk among individuals with CHC after SVR. Metformin use was shown to reduce the risk of all liver-related complications. CONCLUSIONS Metformin use greatly reduced HCC risk after successful antiviral therapy in individuals with diabetes and CHC. A simple risk stratification model comprising cirrhosis and DM non-metformin use could predict long-term outcomes in individuals with CHC after SVR. IMPACT AND IMPLICATIONS The current study provides evidence that metformin could reduce hepatocellular carcinoma (HCC) incidence after successful antiviral therapy among those with diabetes and chronic hepatitis C in a large-scale nationwide cohort study. Although successful antiviral therapy greatly reduces HCC risk in individuals with chronic hepatitis C, those with cirrhosis, diabetes, obesity, and the elderly remain at high risk of HCC development. We demonstrated that a simple risk model composed of two crucial unfavorable factors, cirrhosis and diabetes without metformin use, predicts the risk of HCC and major liver-related complications after successful antiviral therapy in individuals with chronic hepatitis C. Metformin use is highly recommended for individuals with diabetes and chronic hepatitis C after viral eradication to reduce the risk of HCC.
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Affiliation(s)
- Pei-Chien Tsai
- Hepatobiliary Section, Department of Internal Medicine, and Hepatitis Center, Kaohsiung Medical University Hospital; Hepatitis Research Center, School of Medicine and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan; Health Management Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Hsing-Tao Kuo
- Division of Hepatogastroenterology, Department of Internal Medicine, Chi Mei Medical Center, Tainan, Taiwan; School of Medicine, College of Medicine, National Sun Yat-sen University, Kaohsiung, Taiwan
| | - Chao-Hung Hung
- Division of Hepatogastroenterology, Department of Internal Medicine, Chiayi Chang Gung Memorial Hospital, Chiayi, Taiwan
| | - Kuo-Chih Tseng
- Department of Gastroenterology, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi, Taiwan
| | - Hsueh-Chou Lai
- Division of Hepatogastroenterology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
| | - Cheng-Yuan Peng
- Division of Hepatogastroenterology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
| | - Jing-Houng Wang
- Division of Hepatogastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, Taiwan
| | - Jyh-Jou Chen
- Division of Gastroenterology and Hepatology, Chi-Mei Medical Center, Liouying, Tainan, Taiwan
| | - Pei-Lun Lee
- Division of Gastroenterology and Hepatology, Chi-Mei Medical Center, Liouying, Tainan, Taiwan
| | - Rong-Nan Chien
- Division of Hepatology, Department of Gastroenterology and Hepatology, Linkou Medical Center, Chang Gung Memorial Hospital, Keelung, Taiwan
| | - Chi-Chieh Yang
- Division of Gastroenterology, Department of Internal Medicine, Show Chwan Memorial Hospital, Changhua, Taiwan
| | - Gin-Ho Lo
- Division of Gastroenterology and Hepatology, Department of Medicine, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan
| | - Jia-Horng Kao
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan; Division of Gastroenterology and Hepatology, National Taiwan University Hospital, Taipei, Taiwan
| | - Chun-Jen Liu
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan; Division of Gastroenterology and Hepatology, National Taiwan University Hospital, Taipei, Taiwan
| | - Chen-Hua Liu
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei, Taiwan; Division of Gastroenterology and Hepatology, National Taiwan University Hospital, Taipei, Taiwan
| | - Sheng-Lei Yan
- Division of Gastroenterology, Department of Internal Medicine, Chang Bing Show-Chwan Memorial Hospital, Changhua, Taiwan
| | - Ming-Jong Bair
- Division of Gastroenterology, Department of Internal Medicine, Taitung Mackay Memorial Hospital, Taitung, Taiwan
| | - Chun-Yen Lin
- Division of Hepatology, Department of Gastroenterology and Hepatology, Linkou Medical Center, Chang Gung Memorial Hospital, Keelung, Taiwan
| | - Wei-Wen Su
- Division of Gastroenterology, Department of Internal Medicine, Changhua Christian Hospital, Changhua, Taiwan
| | - Cheng-Hsin Chu
- Division of Gastroenterology, Department of Internal Medicine, MacKay Memorial Hospital, Taipei, Taiwan
| | - Chih-Jen Chen
- Division of Gastroenterology, Department of Internal Medicine, MacKay Memorial Hospital, Taipei, Taiwan
| | - Shui-Yi Tung
- Division of Hepatogastroenterology, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
| | - Chi-Ming Tai
- Division of Gastroenterology and Hepatology, Department of Medicine, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan
| | - Chih-Wen Lin
- Division of Gastroenterology and Hepatology, Department of Medicine, E-Da Hospital, I-Shou University, Kaohsiung, Taiwan
| | - Ching-Chu Lo
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, St. Martin De Porres Hospital-Daya, Chiayi, Taiwan
| | - Pin-Nan Cheng
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Yen-Cheng Chiu
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Chia-Chi Wang
- Division of Gastroenterology, Department of Internal Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation and School of Medicine, Tzu Chi University, New Taipei, Taiwan
| | - Jin-Shiung Cheng
- Division of Gastroenterology and Hepatology, Department of Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
| | - Wei-Lun Tsai
- Division of Gastroenterology and Hepatology, Department of Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
| | - Han-Chieh Lin
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
| | - Yi-Hsiang Huang
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan; Institute of Clinical Medicine, Faculty of Medicine, National Yang Ming, Chiao Tung University, Taipei, Taiwan
| | - Ming-Lun Yeh
- Hepatobiliary Section, Department of Internal Medicine, and Hepatitis Center, Kaohsiung Medical University Hospital; Hepatitis Research Center, School of Medicine and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chung-Feng Huang
- Hepatobiliary Section, Department of Internal Medicine, and Hepatitis Center, Kaohsiung Medical University Hospital; Hepatitis Research Center, School of Medicine and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Meng-Hsuan Hsieh
- Hepatobiliary Section, Department of Internal Medicine, and Hepatitis Center, Kaohsiung Medical University Hospital; Hepatitis Research Center, School of Medicine and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan; Health Management Center, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan
| | - Jee-Fu Huang
- Hepatobiliary Section, Department of Internal Medicine, and Hepatitis Center, Kaohsiung Medical University Hospital; Hepatitis Research Center, School of Medicine and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chia-Yen Dai
- Hepatobiliary Section, Department of Internal Medicine, and Hepatitis Center, Kaohsiung Medical University Hospital; Hepatitis Research Center, School of Medicine and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Wan-Long Chung
- Hepatobiliary Section, Department of Internal Medicine, and Hepatitis Center, Kaohsiung Medical University Hospital; Hepatitis Research Center, School of Medicine and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chi-Yi Chen
- Department of Internal Medicine, Chiayi Christian Hospital, Chiayi, Taiwan.
| | - Ming-Lung Yu
- Hepatobiliary Section, Department of Internal Medicine, and Hepatitis Center, Kaohsiung Medical University Hospital; Hepatitis Research Center, School of Medicine and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan; School of Medicine, College of Medicine, National Sun Yat-sen University, Kaohsiung, Taiwan; School of Medicine, College of Medicine and Center of Excellence for Metabolic Associated Fatty Liver Disease, National Sun Yat-sen University, Kaohsiung, Taiwan.
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Ito T, Nguyen MH. Perspectives on the Underlying Etiology of HCC and Its Effects on Treatment Outcomes. J Hepatocell Carcinoma 2023; 10:413-428. [PMID: 36926055 PMCID: PMC10013586 DOI: 10.2147/jhc.s347959] [Citation(s) in RCA: 29] [Impact Index Per Article: 14.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/17/2023] [Accepted: 02/25/2023] [Indexed: 03/11/2023] Open
Abstract
Hepatocellular carcinoma (HCC) continues to be a serious medical problem with poor prognosis worldwide. The distribution of the major etiologies of HCC is changing due to the progress of anti-viral treatments, including hepatitis B virus (HBV) suppression by nucleoside/nucleotide analogues (NAs) and increased sustained virologic response (SVR) rates by direct-acting antivirals (DAAs) for hepatitis C virus (HCV), as well as the rising trend of nonviral liver disease. Although viral hepatitis remains the most common cause of HCC, non-alcoholic liver disease (NAFLD) with metabolic syndrome and alcohol-associated liver disease (ALD) are increasing. Effective and well-tolerated NAs treatment can slow the disease progression of chronic HBV infection to cirrhosis, end-stage liver disease, and reduce HCC risk. Treatment with NAs is also associated with significant improvement in the long-term survival of patients with HBV infection who already have HCC. DAAs have achieved viral elimination in almost all patients with HCV without significant adverse events, even in patients with decompensated liver cirrhosis and HCC. Similarly, DAA therapy can reduce disease progression, liver and non-liver complications, and improve the long-term survival of patients with chronic HCV infection with or without HCC. Meanwhile, NAFLD is a rapidly increasing cause of HCC along with the epidemics of obesity and type 2 diabetes globally. NAFLD-related HCC can occur in patients without cirrhosis and is known to have a lower survival rate than viral hepatitis-related HCC. Since there is currently no specific pharmacotherapy effective for NAFLD, lifestyle modification and prevention of complications are important to improve prognosis. Additionally, ALD is the second fastest-growing cause of HCC-related deaths, especially with an accelerated trend since the COVID-19 pandemic. This review provides an overview of the epidemiologic trends in the etiologies of HCC, and the progress of treatments for each etiology and the impact on outcome in the patients with HCC.
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Affiliation(s)
- Takanori Ito
- Department of Gastroenterology and Hepatology, Nagoya University Graduate School of Medicine, Nagoya, Japan
| | - Mindie H Nguyen
- Division of Gastroenterology and Hepatology, Department of Medicine, Stanford University Medical Center, Palo Alto, CA, USA.,Department of Epidemiology and Population Health, Stanford University Medical Center, Palo Alto, CA, USA
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22
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Clark PJ, Valery PC, Strasser SI, Weltman M, Thompson AJ, Levy M, Leggett B, Zekry A, Rong J, Angus P, George J, Bollipo S, McGarity B, Sievert W, Macquillan G, Tse E, Nicoll A, Wade A, Chu G, Harding D, Cheng W, Farrell G, Roberts SK. Liver Disease and Poor Adherence Limit Hepatitis C Cure: A Real-World Australian Treatment Cohort. Dig Dis Sci 2023; 68:291-303. [PMID: 35552941 PMCID: PMC9883319 DOI: 10.1007/s10620-022-07483-y] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/03/2022] [Accepted: 03/07/2022] [Indexed: 02/01/2023]
Abstract
BACKGROUND AND AIMS In 2016, direct-acting antiviral (DAA) treatment for hepatitis C (HCV) became available through Australia's universal health care system, with the aim of HCV elimination. We report real-world effectiveness of DAA HCV treatment in Australia from a clinically well-informed cohort, enriched for cirrhosis and prior HCV treatment. METHODS 3413 patients were recruited from 26 hospital liver clinics across Australia from February 2016 to June 2020. Clinical history and sustained viral response (SVR) were obtained from medical records and data linkage to the Australian Pharmaceutical Benefits Scheme. Factors associated with SVR were assessed by multivariable logistic regression (MVR). RESULTS At recruitment, 32.2% had cirrhosis (72.9% Child Pugh class B/C), and 19.9% were treatment experienced. Of the 2,939 with data, 93.3% confirmed SVR. 137 patients received second-line therapy. Patients with cirrhosis had lower SVR rate (88.4 vs. 95.8%; p < 0.001). On MVR, failure to achieve SVR was associated with Genotype 3 (adj-OR = 0.42, 95%CI 0.29-0.61), male gender (adj-OR = 0.49, 95%CI 0.31-0.77), fair/poor adherence (adj-OR = 0.52, 95%CI 0.28-0.94), cirrhosis (adj-OR = 0.57, 95%CI 0.36-0.88), FIB-4 > 3.25 (adj-OR = 0.52, 95%CI 0.33-0.83) and MELD score ≥ 20 (adj-OR = 0.25, 95%CI 0.08-0.80). Consistent results were seen in cirrhotic sub-analysis. CONCLUSIONS Excellent SVR rates were achieved with DAAs in this real-world cohort of patients with chronic HCV infection. More advanced liver disease and clinician impression of poor adherence were associated with HCV treatment failure. Supports to improve liver fibrosis assessment skills for non-specialist DAA prescribers in the community and to optimize patient adherence are likely to enable more effective pursuit of HCV elimination in Australia.
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Affiliation(s)
- Paul J Clark
- Department of Gastroenterology, Princess Alexandra and Mater Hospitals, and Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia.
| | - Patricia C Valery
- QIMR Berghofer Medical Research Institute, and Faculty of Medicine, The University of Queensland, Brisbane, QLD, Australia
| | - Simone I Strasser
- AW Morrow Gastroenterology and Liver Centre Royal Prince Alfred Hospital, Sydney, NSW, Australia
| | - Martin Weltman
- Hepatology Services, Nepean Hospital, Penrith, NSW, Australia
| | - Alexander J Thompson
- Department of Gastroenterology, St Vincent's Hospital, Melbourne, VIC, Australia
| | - Miriam Levy
- Department of Gastroenterology and Liver, Liverpool Hospital, Sydney, NSW, Australia
| | - Barbara Leggett
- Department of Gastroenterology and Hepatology, Royal Brisbane and Women's Hospital, Brisbane, QLD, Australia
| | - Amany Zekry
- Department of Gastroenterology and Hepatology, St George Hospital, Sydney, NSW, Australia
| | - Julian Rong
- Gippsland Gastroenterology, Latrobe Regional Hospital, Traralgon, VIC, 3844, Australia
| | - Peter Angus
- Department of Gastroenterology and Hepatology, Austin Hospital, Melbourne, VIC, Australia
| | - Jacob George
- Storr Liver Unit, Westmead Hospital, Westmead, NSW, Australia
| | - Steven Bollipo
- Gastroenterology Department, John Hunter Hospital, New Lambton, NSW, Australia
| | - Bruce McGarity
- Bathurst Liver Clinic Bathurst Hospital, Bathurst, NSW, Australia
| | - William Sievert
- Gastrointestinal and Liver Unit, Monash Health, Melbourne, VIC, Australia
| | - Gerry Macquillan
- Liver Transplant Unit Sir Charles Gairdner Hospital, Nedlands Perth, WA, Australia
| | - Edmund Tse
- Department of Hepatology, Royal Adelaide Hospital, Adelaide, SA, Australia
| | | | - Amanda Wade
- Barwon Health Liver Clinic University Hospital, Geelong, VIC, Australia
| | - Geoff Chu
- Orange Liver Clinic, Orange Hospital, Orange, NSW, Australia
| | - Damian Harding
- Department of Gastroenterology & Hepatology, Lyell McEwin Hospital, Vale, SA, Australia
| | - Wendy Cheng
- Department of Gastroenterology & Hepatology, Royal Perth Hospital, Perth, WA, Australia
| | - Geoff Farrell
- Gastroenterology & Hepatology Unit Canberra Hospital, Canberra, ACT, Australia
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23
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Lo CC, Huang CF, Cheng PN, Tseng KC, Chen CY, Kuo HT, Huang YH, Tai CM, Peng CY, Bair MJ, Chen CH, Yeh ML, Lin CL, Lin CY, Lee PL, Chong LW, Hung CH, Chang TS, Huang JF, Yang CC, Hu JT, Lin CW, Chen CT, Wang CC, Su WW, Hsieh TY, Lin CL, Tsai WL, Lee TH, Chen GY, Wang SJ, Chang CC, Mo LR, Yang SS, Wu WC, Huang CS, Hsiung CK, Kao CN, Tsai PC, Liu CH, Lee MH, Liu CJ, Dai CY, Chuang WL, Lin HC, Kao JH, Yu ML. Ledipasvir/sofosbuvir for HCV genotype 1, 2, 4-6 infection: Real-world evidence from a nationwide registry in Taiwan. J Formos Med Assoc 2022; 121:1567-1578. [PMID: 35123849 DOI: 10.1016/j.jfma.2022.01.012] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/20/2021] [Revised: 12/08/2021] [Accepted: 01/11/2022] [Indexed: 11/19/2022] Open
Abstract
BACKGROUND/PURPOSE The Taiwan Association for the Study of the Liver (TASL) HCV Registry (TACR) is a nationwide registry of chronic hepatitis C patients in Taiwan. This study evaluated antiviral effectiveness of ledipasvir (LDV)/sofosbuvir (SOF) in patients in the TACR. METHODS Patients enrolled in TACR from 2017-2020 treated with LDV/SOF were eligible. The primary outcome was the proportion of patients with sustained virologic response 12 weeks after end of treatment (SVR12). RESULTS 5644 LDV/SOF ± ribavirin-treated patients were included (mean age: 61.4 years; 54.4% female). Dominant viral genotypes were GT1 (50.8%) and GT2 (39.3%). 1529 (27.1%) patients had liver cirrhosis, including 201 (3.6%) with liver decompensation; 686 (12.2%) had chronic kidney disease. SVR12 was achieved in 98.6% of the overall population and in 98.2% and 98.7% of patients with and without cirrhosis, respectively. SVR12 rates in patients with compensated cirrhosis treated with LDV/SOF without RBV were >98%, regardless of prior treatment experience. SVR12 was 98.6%, 98.4%, 100%, 100%, and 98.7% among those with GT1, GT2, GT4, GT5, and GT6 infections, respectively. Although patient numbers were relatively small, SVR12 rates of 100% were reported in patients infected with HCV GT2, GT5, and GT6 with decompensated cirrhosis and 98% in patients with severely compromised renal function. LDV/SOF adherence ≤60% (P < 0.001) was the most important factor associated with treatment failure. Incidence of adverse events was 15.8%, with fatigue being the most common. CONCLUSION LDV/SOF is effective and well tolerated in routine clinical practice in Taiwan. Cure rates were high across patient populations.
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Affiliation(s)
- Ching-Chu Lo
- Division of Gastroenterology, Department of Internal Medicine, St. Martin De Porres Hospital, Chiayi, Taiwan; Chung-Jen Junior College of Nursing, Health Sciences and Management, Chiayi, Taiwan
| | - Chung-Feng Huang
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; School of Medicine and Hepatitis Research Center, College of Medicine, Center for Cancer Research and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Pin-Nan Cheng
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Kuo-Chih Tseng
- Department of Internal Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi; School of Medicine, Tzuchi University, Hualien, Taiwan
| | - Chi-Yi Chen
- Division of Gastroenterology and Hepatology, Department of Medicine, Ditmanson Medical Foundation Chiayi Christian Hospital, Taiwan
| | - Hsing-Tao Kuo
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chi Mei Medical Center, Yongkang District, Tainan, 710, Taiwan
| | - Yi-Hsiang Huang
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taiwan; Institute of Clinical Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Chi-Ming Tai
- Department of Internal Medicine, E-Da Hospital, Kaohsiung, Taiwan; School of Medicine, College of Medicine, I-Shou University, Kaohsiung, Taiwan
| | - Cheng-Yuan Peng
- Center for Digestive Medicine, Department of Internal Medicine, China Medical University Hospital, School of Medicine, China Medical University, Taichung, Taiwan
| | - Ming-Jong Bair
- Division of Gastroenterology, Department of Internal Medicine, Taitung Mackay Memorial Hospital, Taiwan; Mackay Medical College, New Taipei City, Taiwan
| | - Chien-Hung Chen
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Taiwan
| | - Ming-Lun Yeh
- School of Medicine and Hepatitis Research Center, College of Medicine, Center for Cancer Research and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Internal Medicine, Kaohsiung Municipal Siaogang Hospital, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chih-Lang Lin
- Department of Gastroenterology and Hepatology, Keelung Chang Gung Memorial Hospital, Taiwan
| | - Chun-Yen Lin
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou Branch, Taiwan; Graduate Institute of Biomedical Science, College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Pei-Lun Lee
- Chi Mei Medical Center, Liouying Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taiwan
| | - Lee-Won Chong
- Division of Hepatology and Gastroenterology, Department of Internal Medicine, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan; School of Medicine, Fu-Jen Catholic University, New Taipei City, Taiwan
| | - Chao-Hung Hung
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Taiwan; Division of Hepatogastroenterology, Department of Internal Medicine, ChiaYi Chang Gung Memorial Hospital and College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Te Sheng Chang
- Division of Hepatogastroenterology, Department of Internal Medicine, ChiaYi Chang Gung Memorial Hospital and College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Jee-Fu Huang
- School of Medicine and Hepatitis Research Center, College of Medicine, Center for Cancer Research and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Internal Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chi-Chieh Yang
- Department of Gastroenterology, Division of Internal Medicine, Show Chwan Memorial Hospital, Taiwan
| | - Jui-Ting Hu
- Liver Center, Cathay General Hospital, Taiwan
| | - Chih-Wen Lin
- Division of Gastroenterology and Hepatology, E-Da Dachang Hospital, School of Medicine, College of Medicine, I-Shou University, Kaohsiung, Taiwan
| | - Chun-Ting Chen
- Division of Gastroenterology, Department of Internal Medicine Tri-Service General Hospital Penghu Branch, National Defense Medical Center, Taipei, Taiwan; Division of Gastroenterology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
| | - Chia-Chi Wang
- Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation and School of Medicine, Tzu Chi University, Taiwan
| | - Wei-Wen Su
- Department of Gastroenterology and Hepatology, Changhua Christian Hospital, Taiwan
| | - Tsai-Yuan Hsieh
- Division of Gastroenterology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
| | - Chih-Lin Lin
- Department of Gastroenterology, Renai Branch, Taipei City Hospital, Taipei, Taiwan
| | - Wei-Lun Tsai
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Taiwan
| | - Tzong-Hsi Lee
- Division of Gastroenterology and Hepatology, Far Eastern Memorial Hospital, Taiwan
| | | | - Szu-Jen Wang
- Division of Gastroenterology, Department of Internal Medicine, Yuan's General Hospital, Taiwan
| | - Chun-Chao Chang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taipei Medical University Hospital, Taiwan; Division of Gastroenterology and Hepatology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taiwan
| | - Lein-Ray Mo
- Division of Gastroenterology, Tainan Municipal Hospital, Taiwan
| | - Sheng-Shun Yang
- Division of Gastroenterology & Hepatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan
| | | | | | | | - Chien-Neng Kao
- National Taiwan University Hospital Hsin-Chu Branch, Taiwan
| | - Pei-Chien Tsai
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chen-Hua Liu
- Hepatitis Research Center and Department of Internal Medicine, National Taiwan University Hospital, Taiwan
| | - Mei-Hsuan Lee
- Institute of Clinical Medicine, National Yang Ming Chiao Tung University, Taiwan
| | - Chun-Jen Liu
- Hepatitis Research Center and Department of Internal Medicine, National Taiwan University Hospital, Taiwan
| | - Chia-Yen Dai
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; School of Medicine and Hepatitis Research Center, College of Medicine, Center for Cancer Research and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Wan-Long Chuang
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; School of Medicine and Hepatitis Research Center, College of Medicine, Center for Cancer Research and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Han-Chieh Lin
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taiwan
| | - Jia-Horng Kao
- Hepatitis Research Center and Department of Internal Medicine, National Taiwan University Hospital, Taiwan.
| | - Ming-Lung Yu
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; School of Medicine and Hepatitis Research Center, College of Medicine, Center for Cancer Research and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan.
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Dai CY, Huang CF, Huang JF, Chuang WL, Yu ML. High efficacy of glecaprevir/pibrentasvir for HCV-infected individuals with active drug use: Some issues. J Infect 2022; 85:e94-e95. [PMID: 35810942 DOI: 10.1016/j.jinf.2022.07.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/30/2022] [Accepted: 07/03/2022] [Indexed: 11/18/2022]
Affiliation(s)
- Chia-Yen Dai
- Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Biological Science and Technology, College of Biological Science and Technology, National Yang Ming Chiao Tung University, Hsinchu, Taiwan
| | - Chung-Feng Huang
- Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Jee-Fu Huang
- Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Wan-Long Chuang
- Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ming-Lung Yu
- Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Biological Science and Technology, College of Biological Science and Technology, National Yang Ming Chiao Tung University, Hsinchu, Taiwan.
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Determination of Risk Factors Associated with the Failure of 12 Weeks of Direct-Acting Antiviral Therapy in Patients with Hepatitis C: A Prospective Study. BIOMED RESEARCH INTERNATIONAL 2022; 2022:6054677. [PMID: 35572735 PMCID: PMC9106452 DOI: 10.1155/2022/6054677] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 10/15/2021] [Revised: 04/04/2022] [Accepted: 04/07/2022] [Indexed: 11/21/2022]
Abstract
Introduction Direct-acting antivirals (DAAs) have significantly improved the efficacy and tolerability of the treatment of hepatitis C virus (HCV). However, studies conducted on actual patients with the aim of predicting the risk associated with treatment failure are lacking. Methods Our study enrolled 334 new HCV patients and assessed the effectiveness of treatment and predicted the risk of failure to achieve sustained virological response (SVR) by developing a multiple logistic model. Our study compared the variables between the two groups, those who did (group 0, n = 239) and did not achieve SVR (group 1, n = 95). Results The cure rate of HCV at 12th week in our study was 71.56%. We found that advanced cirrhosis, HCV genotype, HBV coinfection, rapid virological response (RVR), fibrosis index (FIB-4) score, serum levels of AST, ALP, hemoglobin, and viral load before treatment were prognostic factors associated with rate of failure to achieve SVR at week 12 of DAA therapy. In the multiple logistic model, eight significant predictors including advanced cirrhosis status, HCV genotype, RVR, AST/ALP levels, FIB-4 score, and viral load before treatment predicted the risk of failure with excellent model performance (area under the receiver operating characteristic curve (AUCROC) [95% CI] =0.986 (0.971-0.999)). RVR and advanced cirrhosis were the two strongest predictors with odd ratios (95% CI) =9.72 (2.8, 39.28) and 51.54 (6.39, 139.82), respectively. Conclusion The multiple logistic regression model included significant factors to estimate the probability of failure to achieve SVR, which could improve HCV treatment strategy.
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Huang CF, Tseng KC, Cheng PN, Hung CH, Lo CC, Peng CY, Bair MJ, Yeh ML, Chen CH, Lee PL, Lin CY, Kuo HT, Chen CT, Yang CC, Huang JF, Tai CM, Hu JT, Lin CL, Su WW, Tsai WL, Huang YH, Cheng CY, Lin CL, Wang CC, Yang SS, Mo LR, Chen GY, Chang CC, Wang SJ, Huang CS, Hsieh TY, Lin CW, Lee TH, Chong LW, Huang CW, Chang SN, Tsai MC, Hsu SJ, Kao JH, Liu CJ, Liu CH, Lin HC, Lee MH, Tsai PC, Dai CY, Chuang WL, Chen CY, Yu ML. Impact of Sofosbuvir-Based Direct-Acting Antivirals on Renal Function in Chronic Hepatitis C Patients With Impaired Renal Function: A Large Cohort Study From the Nationwide HCV Registry Program (TACR). Clin Gastroenterol Hepatol 2022; 20:1151-1162.e6. [PMID: 34333150 DOI: 10.1016/j.cgh.2021.07.037] [Citation(s) in RCA: 20] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 04/08/2021] [Revised: 07/16/2021] [Accepted: 07/21/2021] [Indexed: 12/13/2022]
Abstract
BACKGROUND & AIMS Sofosbuvir is approved for chronic hepatitis C (CHC) patients with severe chronic kidney disease (CKD). The impact of sofosbuvir-based therapy on renal function augmentation on a real-world nationwide basis is elusive. METHODS The 12,995 CHC patients treated with sofosbuvir-based (n = 6802) or non-sofosbuvir-based (n = 6193) regimens were retrieved from the Taiwan nationwide real-world HCV Registry Program. Serial estimated glomerular filtration rate (eGFR) levels were measured at baseline, end of treatment (EOT), and end of follow-up (EOF) (3 months after EOT). RESULTS The eGFR decreased from baseline (91.4 mL/min/1.73 m2) to EOT (88.4 mL/min/1.73 m2; P < .001) and substantially recovered at EOF (88.8 mL/min/1.73 m2) but did not return to pretreatment levels (P < .001). Notably, a significant decrease in eGFR was observed only in patients with baseline eGFR ≥90 mL/min/1.73 m2 (from 112.9 to 106.4 mL/min/1.73 m2; P < .001). In contrast, eGFR increased progressively in patients whose baseline eGFR was <90 mL/min/1.73 m2 (from 70.0 to 71.5 mL/min/1.73 m2; P < .001), and this increase was generalized across different stages of CKD. The trend of eGFR amelioration was consistent irrespective of sofosbuvir usage. Multivariate adjusted analysis demonstrated that baseline eGFR >90 mL/min/1.73 m2 was the only factor independently associated with significant slope coefficient differences of eGFR (-1.98 mL/min/1.73 m2; 95% confidence interval, -2.24 to -1.72; P < .001). The use of sofosbuvir was not an independent factor associated with eGFR change. CONCLUSIONS Both sofosbuvir and non-sofosbuvir-based regimens restored renal function in CHC patients with CKD, especially in those with significant renal function impairment.
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Affiliation(s)
- Chung-Feng Huang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Kuo-Chih Tseng
- Department of Internal Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi; School of Medicine, Tzu Chi University, Hualien, Taiwan
| | - Pin-Nan Cheng
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Chao-Hung Hung
- Division of Hepatogastroenterology, Department of Internal Medicine, ChiaYi Chang Gung Memorial Hospital, Taiwan; Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Taiwan
| | - Ching-Chu Lo
- Division of Gastroenterology, Department of Internal Medicine, St Martin De Porres Hospital, Chiayi, Taiwan
| | - Cheng-Yuan Peng
- Center for Digestive Medicine, Department of Internal Medicine, China Medical University Hospital; School of Medicine, China Medical University, Taichung, Taiwan
| | - Ming-Jong Bair
- Division of Gastroenterology, Department of Internal Medicine, Taitung Mackay Memorial Hospital, Taiwan; Mackay Medical College, New Taipei City, Taiwan
| | - Ming-Lun Yeh
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Internal Medicine, Kaohsiung Municipal Siaogang Hospital, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chien-Hung Chen
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Taiwan
| | - Pei-Lun Lee
- Chi Mei Medical Center, Liouying Division of Gastroenterology and Hepatology, Department of Internal Medicine, Tainan, Taiwan
| | - Chun-Yen Lin
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou Branch, Taiwan; Graduate Institute of Biomedical Science, College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Hsing-Tao Kuo
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chi Mei Medical Center, Taiwan
| | - Chun-Ting Chen
- Division of Gastroenterology, Department of Internal Medicine, Tri-Service General Hospital Penghu Branch, National Defense Medical Center, Taipei, Taiwan; Division of Gastroenterology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
| | - Chi-Chieh Yang
- Department of Gastroenterology, Division of Internal Medicine, Show Chwan Memorial Hospital, Taiwan
| | - Jee-Fu Huang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan; Department of Internal Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chi-Ming Tai
- Department of Internal Medicine, E-Da Hospital, Kaohsiung, Taiwan; School of Medicine, College of Medicine, I-Shou University, Kaohsiung, Taiwan
| | - Jui-Ting Hu
- Liver Center, Cathay General Hospital, Taiwan
| | - Chih-Lang Lin
- Liver Research Unit, Department of Hepato-Gastroenterology and Community Medicine Research Center, Chang Gung Memorial Hospital at Keelung, Chang Gung University, College of Medicine, Taiwan
| | - Wei-Wen Su
- Department of Gastroenterology and Hepatology, Changhua Christian Hospital, Taiwan
| | - Wei-Lun Tsai
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Taiwan
| | - Yi-Hsiang Huang
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital; Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Chien-Yu Cheng
- Division of Infectious Diseases, Department of Internal Medicine, Taoyuan General Hospital, Ministry of Health and Welfare, Taoyuan, Taiwan
| | - Chih-Lin Lin
- Department of Gastroenterology, Renai Branch, Taipei City Hospital, Taipei, Taiwan
| | - Chia-Chi Wang
- Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation and School of Medicine, Tzu Chi University, Taiwan
| | - Sheng-Shun Yang
- Division of Gastroenterology & Hepatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan
| | - Lein-Ray Mo
- Division of Gastroenterology, Tainan Municipal Hospital (Managed by Show Chwan Medical Care Corporation), Taiwan
| | | | - Chun-Chao Chang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taipei Medical University Hospital, Taiwan; Division of Gastroenterology and Hepatology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taiwan
| | - Szu-Jen Wang
- Division of Gastroenterology, Department of Internal Medicine, Yuan's General Hospital, Taiwan
| | | | - Tsai-Yuan Hsieh
- Division of Gastroenterology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
| | - Chih-Wen Lin
- Department of Internal Medicine, E-Da Hospital, Kaohsiung, Taiwan; School of Medicine, College of Medicine, I-Shou University, Kaohsiung, Taiwan
| | - Tzong-Hsi Lee
- Division of Gastroenterology and Hepatology, Far Eastern Memorial Hospital, Taiwan
| | - Lee-Won Chong
- Division of Hepatology and Gastroenterology, Department of Internal Medicine, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan; School of Medicine, Fu-Jen Catholic University, New Taipei City, Taiwan
| | - Chien-Wei Huang
- Division of Gastroenterology, Kaohsiung Armed Forces General Hospital, Kaohsiung City, Taiwan
| | | | - Ming-Chang Tsai
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chung Shan Medical University Hospital, Institute of Medicine, School of Medicine, Chung Shan Medical University, Taichung, Taiwan
| | - Shih-Jer Hsu
- Hepatitis Research Center and Department of Internal Medicine, National Taiwan University Hospital. Taiwan
| | - Jia-Horng Kao
- Hepatitis Research Center and Department of Internal Medicine, National Taiwan University Hospital. Taiwan
| | - Chun-Jen Liu
- Hepatitis Research Center and Department of Internal Medicine, National Taiwan University Hospital. Taiwan
| | - Chen-Hua Liu
- Hepatitis Research Center and Department of Internal Medicine, National Taiwan University Hospital. Taiwan
| | - Han-Chieh Lin
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital; Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei, Taiwan
| | - Mei-Hsuan Lee
- Institute of Clinical Medicine, National Yang-Ming University, Taiwan
| | - Pei-Chien Tsai
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chia-Yen Dai
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Wan-Long Chuang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chi-Yi Chen
- Division of Gastroenterology and Hepatology, Department of Medicine, Ditmanson Medical Foundation Chiayi Christian Hospital, Taiwan
| | - Ming-Lung Yu
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
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Factors Associated with the Refusal of Direct-Acting Antiviral Agents for the Treatment of Hepatitis C in Taiwan. Medicina (B Aires) 2022; 58:medicina58040521. [PMID: 35454360 PMCID: PMC9031294 DOI: 10.3390/medicina58040521] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/01/2022] [Revised: 03/29/2022] [Accepted: 04/01/2022] [Indexed: 12/12/2022] Open
Abstract
Background and Objectives: Direct-acting antiviral agents (DAA) are a safe and highly effective treatment for hepatitis C virus (HCV) infection. However, the uptake of DAA treatment remains a challenge. This study aims to examine the reasons for DAA refusal among HCV patients covered by the Taiwan National Health Insurance system. Materials and Methods: This retrospective observational study covered the period from January 2009 to December 2019 and was conducted at a single hepatitis treatment center in Taiwan. This study involved chart reviews and phone-based surveys to confirm treatment status and refusal causes. To confirm treatment status, subjects with HCV without treatment records were phone-contacted to confirm treatment status. Patients who did not receive treatment were invited back for treatment. If the patient refused, the reason for refusal was discussed. Results: A total of 3566 patients were confirmed with DAA treatment; 418 patients (179 patients who were lost to contact or refused the survey and 239 patients who completed the survey of DAA refusal) were included in the no-DAA-therapy group. Factors associated with receiving DAAs were hemoglobin levels, hepatitis B virus co-infection, and regular gastroenterology visits. Meanwhile, male sex, platelet levels, and primary care physician visits were associated with DAA refusal. The leading causes of treatment refusal were multiple comorbidities, low health literacy, restricted access to hospitals, nursing home residence, and old age. The rate of DAA refusal remains high (10%). Conclusions: The reasons for treatment refusal are multifactorial, and addressing them requires complex interventions.
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Chen YC, Chang TS, Chen CH, Cheng PN, Lo CC, Mo LR, Chen CT, Huang CF, Kuo HT, Huang YH, Tai CM, Peng CY, Bair MJ, Yeh ML, Lin CL, Lin CY, Lee PL, Chong LW, Hung CH, Huang JF, Yang CC, Hu JT, Lin CW, Wang CC, Su WW, Hsieh TY, Lin CL, Tsai WL, Lee TH, Chen GY, Wang SJ, Chang CC, Yang SS, Wu WC, Huang CS, Hsiung CK, Kao CN, Tsai PC, Liu CH, Lee MH, Dai CY, Kao JH, Chuang WL, Lin HC, Chen CY, Tseng KC, Yu ML. Factors Associated with Significant Platelet Count Improvement in Thrombocytopenic Chronic Hepatitis C Patients Receiving Direct-Acting Antivirals. Viruses 2022; 14:333. [PMID: 35215926 PMCID: PMC8879038 DOI: 10.3390/v14020333] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/26/2021] [Revised: 01/25/2022] [Accepted: 02/02/2022] [Indexed: 11/17/2022] Open
Abstract
To clarify the predictive factors of significant platelet count improvement in thrombocytopenic chronic hepatitis C (CHC) patients. CHC patients with baseline platelet counts of <150 × 103/μL receiving direct-acting antiviral (DAA) therapy with at least 12-weeks post-treatment follow-up (PTW12) were enrolled. Significant platelet count improvement was defined as a ≥10% increase in platelet counts at PTW12 from baseline. Platelet count evolution at treatment week 4, end-of-treatment, PTW12, and PTW48 was evaluated. This study included 4922 patients. Sustained virologic response after 12 weeks post-treatment was achieved in 98.7% of patients. Platelet counts from baseline, treatment week 4, and end-of-treatment to PTW12 were 108.8 ± 30.2, 121.9 ± 41.1, 123.1 ± 43.0, and 121.1 ± 40.8 × 103/μL, respectively. Overall, 2230 patients (45.3%) showed significant platelet count improvement. Multivariable analysis revealed that age (odds ratio (OR) = 0.99, 95% confidence interval (CI): 0.99-1.00, p = 0.01), diabetes mellitus (DM) (OR = 1.20, 95% CI: 1.06-1.38, p = 0.007), cirrhosis (OR = 0.66, 95% CI: 0.58-0.75, p < 0.0001), baseline platelet counts (OR = 0.99, 95% CI: 0.98-0.99, p < 0.0001), and baseline total bilirubin level (OR = 0.80, 95% CI: 0.71-0.91, p = 0.0003) were independent predictive factors of significant platelet count improvement. Subgroup analyses showed that patients with significant platelet count improvement and sustained virologic responses, regardless of advanced fibrosis, had a significant increase in platelet counts from baseline to treatment week 4, end-of-treatment, PTW12, and PTW48. Young age, presence of DM, absence of cirrhosis, reduced baseline platelet counts, and reduced baseline total bilirubin levels were associated with significant platelet count improvement after DAA therapy in thrombocytopenic CHC patients.
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Affiliation(s)
- Yen-Chun Chen
- Department of Internal Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi School of Medicine, Tzuchi University, Hualien 970, Taiwan;
| | - Te-Sheng Chang
- Division of Hepatogastroenterology, Department of Internal Medicine, Chiayi Chang Gung Memorial Hospital and College of Medicine, Chang Gung University, Taoyuan 333, Taiwan; (T.-S.C.); (C.-H.H.)
| | - Chien-Hung Chen
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Taoyuan 333, Taiwan;
| | - Pin-Nan Cheng
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 701, Taiwan;
| | - Ching-Chu Lo
- Division of Gastroenterology, Department of Internal Medicine, St. Martin De Porres Hospital, Chiayi 600, Taiwan;
| | - Lein-Ray Mo
- Division of Gastroenterology, Tainan Municipal Hospital, Tainan 701, Taiwan;
| | - Chun-Ting Chen
- Division of Gastroenterology, Department of Internal Medicine Tri-Service General Hospital Penghu Branch, National Defense Medical Center, Taipei 114, Taiwan;
- Division of Gastroenterology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan;
| | - Chung-Feng Huang
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan; (C.-F.H.); (P.-C.T.); (C.-Y.D.); (W.-L.C.)
- School of Medicine and Hepatitis Research Center, College of Medicine, Center for Cancer Research, Center for Liquid Biopsy, Cohort Research, Kaohsiung Medical University, Kaohsiung 807, Taiwan; (M.-L.Y.); (J.-F.H.)
| | - Hsing-Tao Kuo
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chi Mei Medical Center, Yongkang District, Tainan 710, Taiwan;
| | - Yi-Hsiang Huang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taipei Veterans General Hospital, Taipei 11217, Taiwan; (Y.-H.H.); (H.-C.L.)
- Institute of Clinical Medicine, School of Medicine, National Yang-Ming Chiao Tung University, Taipei 112, Taiwan
| | - Chi-Ming Tai
- Department of Internal Medicine, E-Da Hospital, Kaohsiung 824, Taiwan;
- School of Medicine, College of Medicine, I-Shou University, Kaohsiung 824, Taiwan
| | - Cheng-Yuan Peng
- Center for Digestive Medicine, Department of Internal Medicine, China Medical University Hospital, School of Medicine, China Medical University, Taichung 406, Taiwan;
| | - Ming-Jong Bair
- Division of Gastroenterology, Department of Internal Medicine, Taitung Mackay Memorial Hospital, Taitung 950, Taiwan;
- Mackay Medical College, New Taipei City 252, Taiwan
| | - Ming-Lun Yeh
- School of Medicine and Hepatitis Research Center, College of Medicine, Center for Cancer Research, Center for Liquid Biopsy, Cohort Research, Kaohsiung Medical University, Kaohsiung 807, Taiwan; (M.-L.Y.); (J.-F.H.)
- Department of Internal Medicine, Kaohsiung Municipal Siaogang Hospital, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan
| | - Chih-Lang Lin
- Department of Gastroenterology and Hepatology, Keelung Chang Gung Memorial Hospital, Keelung 204, Taiwan;
| | - Chun-Yen Lin
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou Branch, Linkou 333, Taiwan;
- Graduate Institute of Biomedical Science, College of Medicine, Chang Gung University, Taoyuan 333, Taiwan
| | - Pei-Lun Lee
- Chi Mei Medical Center, Liouying Division of Gastroenterology and Hepatology, Department of Internal Medicine, Tainan 736, Taiwan;
| | - Lee-Won Chong
- Division of Hepatology and Gastroenterology, Department of Internal Medicine, Shin Kong Wu Ho-Su Memorial Hospital, Taipei 111, Taiwan;
- School of Medicine, Fu-Jen Catholic University, New Taipei City 242, Taiwan
| | - Chao-Hung Hung
- Division of Hepatogastroenterology, Department of Internal Medicine, Chiayi Chang Gung Memorial Hospital and College of Medicine, Chang Gung University, Taoyuan 333, Taiwan; (T.-S.C.); (C.-H.H.)
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Taoyuan 333, Taiwan;
| | - Jee-Fu Huang
- School of Medicine and Hepatitis Research Center, College of Medicine, Center for Cancer Research, Center for Liquid Biopsy, Cohort Research, Kaohsiung Medical University, Kaohsiung 807, Taiwan; (M.-L.Y.); (J.-F.H.)
- Department of Internal Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan
| | - Chi-Chieh Yang
- Department of Gastroenterology, Division of Internal Medicine, Show Chwan Memorial Hospital, Changhua 500, Taiwan;
| | - Jui-Ting Hu
- Liver Center, Cathay General Hospital, Taipei 106, Taiwan;
| | - Chih-Wen Lin
- Division of Gastroenterology and Hepatology, E-Da Dachang Hospital, School of Medicine, College of Medicine, I-Shou University, Kaohsiung 824, Taiwan;
| | - Chia-Chi Wang
- Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation and School of Medicine, Tzu Chi University, New Taipei City 231, Taiwan;
| | - Wei-Wen Su
- Department of Gastroenterology and Hepatology, Changhua Christian Hospital, Changhua 500, Taiwan;
| | - Tsai-Yuan Hsieh
- Division of Gastroenterology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei 114, Taiwan;
| | - Chih-Lin Lin
- Department of Gastroenterology, Renai Branch, Taipei City Hospital, Taipei 106, Taiwan;
| | - Wei-Lun Tsai
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung 813, Taiwan;
| | - Tzong-Hsi Lee
- Division of Gastroenterology and Hepatology, Far Eastern Memorial Hospital, New Taipei City 220, Taiwan;
| | - Guei-Ying Chen
- Penghu Hospital, Ministry of Health and Welfare, Penghu 880, Taiwan;
| | - Szu-Jen Wang
- Division of Gastroenterology, Department of Internal Medicine, Yuan’s General Hospital, Kaohsiung 802, Taiwan;
| | - Chun-Chao Chang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taipei Medical University Hospital, Taipei 110, Taiwan;
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei 110, Taiwan
| | - Sheng-Shun Yang
- Division of Gastroenterology & Hepatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung 407, Taiwan;
| | | | | | | | - Chien-Neng Kao
- National Taiwan University Hospital Hsin-Chu Branch, Hsinchu 300, Taiwan;
| | - Pei-Chien Tsai
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan; (C.-F.H.); (P.-C.T.); (C.-Y.D.); (W.-L.C.)
| | - Chen-Hua Liu
- Hepatitis Research Center, Department of Internal Medicine, National Taiwan University Hospital, Taipei 106, Taiwan; (C.-H.L.); (J.-H.K.)
| | - Mei-Hsuan Lee
- Institute of Clinical Medicine, National Yang-Ming Chiao-Tung University, Taipei 112, Taiwan;
| | - Chia-Yen Dai
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan; (C.-F.H.); (P.-C.T.); (C.-Y.D.); (W.-L.C.)
- School of Medicine and Hepatitis Research Center, College of Medicine, Center for Cancer Research, Center for Liquid Biopsy, Cohort Research, Kaohsiung Medical University, Kaohsiung 807, Taiwan; (M.-L.Y.); (J.-F.H.)
| | - Jia-Horng Kao
- Hepatitis Research Center, Department of Internal Medicine, National Taiwan University Hospital, Taipei 106, Taiwan; (C.-H.L.); (J.-H.K.)
| | - Wan-Long Chuang
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan; (C.-F.H.); (P.-C.T.); (C.-Y.D.); (W.-L.C.)
- School of Medicine and Hepatitis Research Center, College of Medicine, Center for Cancer Research, Center for Liquid Biopsy, Cohort Research, Kaohsiung Medical University, Kaohsiung 807, Taiwan; (M.-L.Y.); (J.-F.H.)
| | - Han-Chieh Lin
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taipei Veterans General Hospital, Taipei 11217, Taiwan; (Y.-H.H.); (H.-C.L.)
- Institute of Clinical Medicine, School of Medicine, National Yang-Ming Chiao Tung University, Taipei 112, Taiwan
| | - Chi-Yi Chen
- Division of Gastroenterology and Hepatology, Department of Medicine, Ditmanson Medical Foundation Chiayi Christian Hospital, Chiayi 600, Taiwan;
| | - Kuo-Chih Tseng
- Department of Internal Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi School of Medicine, Tzuchi University, Hualien 970, Taiwan;
| | - Ming-Lung Yu
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 807, Taiwan; (C.-F.H.); (P.-C.T.); (C.-Y.D.); (W.-L.C.)
- School of Medicine and Hepatitis Research Center, College of Medicine, Center for Cancer Research, Center for Liquid Biopsy, Cohort Research, Kaohsiung Medical University, Kaohsiung 807, Taiwan; (M.-L.Y.); (J.-F.H.)
- Institute of Biomedical Sciences, National Sun Yat-sen University, Kaohsiung 804, Taiwan
- National Pingtung University of Science and Technology, Pingtung 912, Taiwan
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29
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Cheng PN, Mo LR, Chen CT, Chen CY, Huang CF, Kuo HT, Lo CC, Tseng KC, Huang YH, Tai CM, Peng CY, Bair MJ, Chen CH, Yeh ML, Lin CL, Lin CY, Lee PL, Chong LW, Hung CH, Chang TS, Huang JF, Yang CC, Hu JT, Lin CW, Wang CC, Su WW, Hsieh TY, Lin CL, Tsai WL, Lee TH, Chen GY, Wang SJ, Chang CC, Yang SS, Wu WC, Huang CS, Chou KH, Kao CN, Tsai PC, Liu CH, Lee MH, Cheng CY, Tsai MC, Liu CJ, Dai CY, Lin HC, Kao JH, Chuang WL, Yu ML. Sofosbuvir/Velpatasvir for Hepatitis C Virus Infection: Real-World Effectiveness and Safety from a Nationwide Registry in Taiwan. Infect Dis Ther 2022; 11:485-500. [PMID: 34967920 PMCID: PMC8847492 DOI: 10.1007/s40121-021-00576-7] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2021] [Accepted: 11/29/2021] [Indexed: 12/13/2022] Open
Abstract
INTRODUCTION Pangenotypic direct-acting antivirals are expected to cure hepatitis C virus (HCV) in more than 95% of treated patients. However, data on the effectiveness and safety of sofosbuvir/velpatasvir (SOF/VEL) in Taiwan are limited. This study aims to characterize the patient population in the nationwide Taiwan Association for the Study of the Liver (TASL) HCV Registry and evaluate treatment outcome in Taiwanese patients receiving SOF/VEL. METHODS This study was a retrospective-prospective, observational, multicenter, real-world analysis. Adults with chronic hepatitis C were treated with SOF/VEL 400/100 mg ± ribavirin for 12 weeks. The primary outcome was sustained virologic response 12 weeks after end of therapy (SVR12). Factors associated with not achieving SVR12 were evaluated using logistic regression and covariate analysis. Safety was also assessed. RESULTS In total, 3480 patients were included: 86.8% genotype 1/2, 2.8% genotype 3, 0.1% genotype 4/5, 9.6% genotype 6; unclassified, 0.8%; 12.2% compensated cirrhosis; 3.3% decompensated cirrhosis; and 15.8% chronic kidney disease. Overall SVR12 rate was 99.4% (genotype 1, 99.5%; genotype 2, 99.4%; genotype 3, 96.9%; genotype 4, 100%; genotype 6, 99.7%). SVR12 rates among patients with compensated cirrhosis, decompensated cirrhosis, and chronic kidney disease stages 4-5 were 99.5%, 100%, and 100%, respectively. There were 21 patients (0.6%) who did not achieve SVR12. Factors associated with failure were treatment adherence below 60%, high viral load, and genotype 3 (p < 0.001, p = 0.028, and p = 0.001, respectively). Adverse events occurred in 10% of patients; 0.6% were serious and one was related to treatment. Treatment discontinuation occurred in 0.3% of patients; none were treatment related. The estimated glomerular filtration rate remained stable throughout treatment and follow-up, regardless of baseline values and cirrhosis status. CONCLUSION SOF/VEL was highly effective and well tolerated in Taiwanese patients, irrespective of viral genotype, liver disease severity, and comorbidities.
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Affiliation(s)
- Pin-Nan Cheng
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Lein-Ray Mo
- Division of Gastroenterology, Tainan Municipal Hospital, Tainan, Taiwan
| | - Chun-Ting Chen
- Division of Gastroenterology, Department of Internal Medicine, Tri-Service General Hospital Penghu Branch, National Defense Medical Center, Taipei, Taiwan
- Division of Gastroenterology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
| | - Chi-Yi Chen
- Division of Gastroenterology and Hepatology, Department of Medicine, Ditmanson Medical Foundation Chiayi Christian Hospital, Chiayi, Taiwan
| | - Chung-Feng Huang
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- School of Medicine and Hepatitis Research Center, College of Medicine, and Center for Cancer Research and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Hsing-Tao Kuo
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chi Mei Medical Center, Yongkang District, Tainan, Taiwan
| | - Ching-Chu Lo
- Division of Gastroenterology, Department of Internal Medicine, St. Martin De Porres Hospital, Chiayi, Taiwan
| | - Kuo-Chih Tseng
- Department of Internal Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi, Taiwan
- School of Medicine, Tzuchi University, Hualien, Taiwan
| | - Yi-Hsiang Huang
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
- Institute of Clinical Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Chi-Ming Tai
- Department of Internal Medicine, E-Da Hospital, Kaohsiung, Taiwan
- School of Medicine, College of Medicine, I-Shou University, Kaohsiung, Taiwan
| | - Cheng-Yuan Peng
- Center for Digestive Medicine, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
- School of Medicine, China Medical University, Taichung, Taiwan
| | - Ming-Jong Bair
- Division of Gastroenterology, Department of Internal Medicine, Taitung Mackay Memorial Hospital, Taitung, Taiwan
- Mackay Medical College, New Taipei City, Taiwan
| | - Chien-Hung Chen
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Taoyuan City, Taiwan
| | - Ming-Lun Yeh
- School of Medicine and Hepatitis Research Center, College of Medicine, and Center for Cancer Research and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Internal Medicine, Kaohsiung Municipal Siaogang Hospital, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chih-Lang Lin
- Department of Gastroenterology and Hepatology, Keelung Chang Gung Memorial Hospital, Keelung, Taiwan
| | - Chun-Yen Lin
- Department of Gastroenterology and Hepatology, Chang Gung Memorial Hospital, Linkou Branch, Taiwan
- Graduate Institute of Biomedical Science, College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Pei-Lun Lee
- Liouying Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chi Mei Medical Center, Tainan, Taiwan
| | - Lee-Won Chong
- Division of Hepatology and Gastroenterology, Department of Internal Medicine, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan
- School of Medicine, Fu-Jen Catholic University, New Taipei City, Taiwan
| | - Chao-Hung Hung
- Division of Hepato-Gastroenterology, Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Taoyuan City, Taiwan
- Division of Hepatogastroenterology, Department of Internal Medicine, ChiaYi Chang Gung Memorial Hospital and College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Te Sheng Chang
- Division of Hepatogastroenterology, Department of Internal Medicine, ChiaYi Chang Gung Memorial Hospital and College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Jee-Fu Huang
- School of Medicine and Hepatitis Research Center, College of Medicine, and Center for Cancer Research and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Internal Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chi-Chieh Yang
- Department of Gastroenterology, Division of Internal Medicine, Show Chwan Memorial Hospital, Changhua, Taiwan
| | - Jui-Ting Hu
- Liver Center, Cathay General Hospital, Taipei, Taiwan
| | - Chih-Wen Lin
- Division of Gastroenterology and Hepatology, E-Da Dachang Hospital, and School of Medicine, College of Medicine, I-Shou University, Kaohsiung, Taiwan
| | - Chia-Chi Wang
- Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation and School of Medicine, Tzu Chi University, Hualien, Taiwan
| | - Wei-Wen Su
- Department of Gastroenterology and Hepatology, Changhua Christian Hospital, Changhua, Taiwan
| | - Tsai-Yuan Hsieh
- Division of Gastroenterology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
| | - Chih-Lin Lin
- Department of Gastroenterology, Taipei City Hospital, Renai Branch, Taipei, Taiwan
| | - Wei-Lun Tsai
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan
| | - Tzong-Hsi Lee
- Division of Gastroenterology and Hepatology, Far Eastern Memorial Hospital, New Taipei, Taiwan
| | - Guei-Ying Chen
- Penghu Hospital, Ministry of Health and Welfare, Penghu, Taiwan
| | - Szu-Jen Wang
- Division of Gastroenterology, Department of Internal Medicine, Yuan's General Hospital, Kaohsiung, Taiwan
| | - Chun-Chao Chang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taipei Medical University Hospital, Taipei, Taiwan
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
| | - Sheng-Shun Yang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan
| | - Wen-Chih Wu
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | | | - Kwok-Hsiung Chou
- Division of Gastroenterology, Department of Internal Medicine, Tri-Service General Hospital Penghu Branch, National Defense Medical Center, Taipei, Taiwan
- Division of Gastroenterology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
| | - Chien-Neng Kao
- National Taiwan University Hospital Hsin-Chu Branch, Hsin-Chu, Taiwan
| | - Pei-Chien Tsai
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chen-Hua Liu
- Hepatitis Research Center and Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University, Taipei, Taiwan
| | - Mei-Hsuan Lee
- Institute of Clinical Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
- Institute of Public Health, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
| | - Chien-Yu Cheng
- Institute of Public Health, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
- Department of Infectious Diseases, Taoyuan General Hospital, Ministry of Health and Welfare, Taoyuan, Taiwan
| | - Ming-Chang Tsai
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chung Shan Medical University Hospital, Institute of Medicine, School of Medicine, Chung Shan Medical University, Taichung, Taiwan
| | - Chun-Jen Liu
- Hepatitis Research Center and Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University, Taipei, Taiwan
| | - Chia-Yen Dai
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- School of Medicine and Hepatitis Research Center, College of Medicine, and Center for Cancer Research and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Han-Chieh Lin
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan.
- Institute of Clinical Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
| | - Jia-Horng Kao
- Hepatitis Research Center and Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University, Taipei, Taiwan
| | - Wan-Long Chuang
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- School of Medicine and Hepatitis Research Center, College of Medicine, and Center for Cancer Research and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ming-Lung Yu
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
- School of Medicine and Hepatitis Research Center, College of Medicine, and Center for Cancer Research and Center for Liquid Biopsy and Cohort Research, Kaohsiung Medical University, Kaohsiung, Taiwan.
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Ogawa E, Nakamuta M, Furusyo N, Kajiwara E, Dohmen K, Kawano A, Ooho A, Azuma K, Takahashi K, Satoh T, Koyanagi T, Yamashita N, Ichiki Y, Yamashita N, Kuniyoshi M, Yanagita K, Amagase H, Morita C, Sugimoto R, Kato M, Shimoda S, Nomura H, Hayashi J. Long-term assessment of recurrence of hepatocellular carcinoma in patients with chronic hepatitis C after viral cure by direct-acting antivirals. J Gastroenterol Hepatol 2022; 37:190-199. [PMID: 34374128 PMCID: PMC9291903 DOI: 10.1111/jgh.15659] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/16/2021] [Revised: 07/15/2021] [Accepted: 08/04/2021] [Indexed: 12/09/2022]
Abstract
BACKGROUND AND AIM Early hepatocellular carcinoma (HCC) recurrence is common, even after achieving hepatitis C virus (HCV) cure. This study was carried out to assess the long-term trends and predictors of recurrence after HCV cure by direct-acting antivirals (DAAs). METHODS This retrospective, multicenter cohort study enrolled 365 consecutive patients with chronic hepatitis C who required HCC treatment following sustained viral response (SVR) by DAA administration. Patients with HCC recurrence before SVR were excluded. Late HCC recurrence and its predictors beyond the post-treatment early phase (24 weeks after SVR) were evaluated. RESULTS The data of 326 patients were available for the final analysis. The median follow-up duration from SVR determination was 2.7 years. Median age was 74, and 220 (67.5%) were 70 or over. The corresponding 5-year cumulative HCC recurrence rates of previous curative and palliative treatment groups were 45.4% and 65.7%, respectively (log-rank test: P < 0.001). Cox regression multivariable analysis revealed that cirrhosis (hazard ratio [HR] 1.85, P = 0.021), the number of HCC nodules (≥ 2) (HR 1.52, P = 0.031), and previous palliative HCC treatment (HR 1.71, P = 0.012) were independent predictors of late recurrence, in addition to the predictors of early recurrence; AFP > 7 ng/mL at 12 weeks after DAA administration, time from HCC complete response (CR) to DAA initiation (< 1 year), and the number of HCC treatments necessary to achieve CR (≥ 2). CONCLUSIONS The evaluation of fibrosis and characteristics of the previous HCC would allow for better HCC recurrence stratification, which would be helpful for developing long-term surveillance strategies.
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Affiliation(s)
- Eiichi Ogawa
- Department of General Internal MedicineKyushu University HospitalFukuokaJapan
| | - Makoto Nakamuta
- Department of Gastroenterology, Kyushu Medical CenterNational Hospital OrganizationFukuokaJapan
| | | | | | | | - Akira Kawano
- Department of MedicineKitakyushu Municipal Medical CenterKitakyushuJapan
| | - Aritsune Ooho
- Department of HepatologySteel Memorial Yawata HospitalKitakyushuJapan
| | - Koichi Azuma
- Department of MedicineKyushu Central HospitalFukuokaJapan
| | | | - Takeaki Satoh
- Center for Liver Disease, Kokura Medical CenterNational Hospital OrganizationKitakyushuJapan
| | | | | | - Yasunori Ichiki
- Department of Internal MedicineJCHO Kyushu HospitalKitakyushuJapan
| | - Naoki Yamashita
- Department of Gastroenterology, Kyushu Medical CenterNational Hospital OrganizationFukuokaJapan
| | - Masami Kuniyoshi
- Department of GastroenterologyKyushu Rosai HospitalKitakyushuJapan
| | - Kimihiko Yanagita
- Department of Internal MedicineSaiseikai Karatsu HospitalKaratsuJapan
| | | | - Chie Morita
- Department of Internal MedicineKyushu Railway Memorial HospitalKitakyushuJapan
| | - Rie Sugimoto
- Department of GastroenterologyKyushu Cancer CenterFukuokaJapan
| | - Masaki Kato
- Department of Medicine and Bioregulatory Science, Graduate School of Medical SciencesKyushu UniversityFukuokaJapan,Graduate School of Nutritional SciencesNakamura Gakuen UniversityFukuokaJapan
| | - Shinji Shimoda
- Department of Medicine and Biosystemic Science, Graduate School of Medical SciencesKyushu UniversityFukuokaJapan
| | | | - Jun Hayashi
- Kyushu General Internal Medicine CenterHaradoi HospitalFukuokaJapan
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31
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Santos APDT, Silva VCM, Mendes-Corrêa MC, Lemos MF, Malta FDM, Santana RAF, Dastoli GTF, Castro VFDD, Pinho JRR, Moreira RC. Characterization of primary direct-acting antiviral (DAA) drugs resistance mutations in NS5A/NS5B regions of hepatitis C virus with genotype 1a and 1b from patients with chronic hepatitis. Rev Inst Med Trop Sao Paulo 2022; 64:e61. [PMID: 36197422 PMCID: PMC9528309 DOI: 10.1590/s1678-9946202264061] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/02/2022] [Accepted: 07/18/2022] [Indexed: 11/21/2022] Open
Affiliation(s)
| | | | | | | | | | | | | | | | - João Renato Rebello Pinho
- Universidade de São Paulo, Brazil; Universidade de São Paulo, Brazil; Hospital Israelita Albert Einstein, Brazil
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32
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Huang CF, Kuo HT, Chang TS, Lo CC, Hung CH, Huang CW, Chong LW, Cheng PN, Yeh ML, Peng CY, Cheng CY, Huang JF, Bair MJ, Lin CL, Yang CC, Wang SJ, Hsieh TY, Lee TH, Lee PL, Wu WC, Lin CL, Su WW, Yang SS, Wang CC, Hu JT, Mo LR, Chen CT, Huang YH, Chang CC, Huang CS, Chen GY, Kao CN, Tai CM, Liu CJ, Lee MH, Tsai PC, Dai CY, Kao JH, Lin HC, Chuang WL, Chen CY, Tseng KC, Yu ML. Nationwide registry of glecaprevir plus pibrentasvir in the treatment of HCV in Taiwan. Sci Rep 2021; 11:23473. [PMID: 34873250 PMCID: PMC8648748 DOI: 10.1038/s41598-021-03006-3] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/07/2021] [Accepted: 11/03/2021] [Indexed: 12/25/2022] Open
Abstract
The study evaluated the real-world treatment outcomes of Glecaprevir/pibrentasvir (GLE/PIB) including effectiveness, safety and healthcare resource utilization based on a nation-wide registry in Taiwan. The Taiwan HCV Registry (TACR) is a nation-wide platform organized and supervised by the Taiwan Association for the Study of the Liver. Data were analyzed for patients treated with GLE/PIB, including 3144 patients who had treatment outcome available. The primary endpoint was sustained virological response (SVR12, undetectable HCV RNA throughout 12 weeks of end-of-treatment). The overall SVR12 rate was 98.9% (3110/3144), with 98.8%, 99.4% and 100% in patients receiving 8 weeks, 12 weeks, and 16 weeks of GLE/PIB respectively. The SVR12 rate in the treatment-naïve cirrhotic patients receiving 8 weeks of GLE/PIB was 98.2% (108/110). The most common AEs were fatigue (7.5%), pruritus (6.7%) and dizziness (1.5%). The mean number of outpatient visits during the GLE/PIB was 5.94 visits for patients treated with 8 weeks, significantly different from the patients treated with 12 weeks of GLE/PIB (6.90 visits). The results support the effectiveness and safety of GLE/PIB treatment in real-world clinical practice, and provide further evidence that the shorter, 8-week GLE/PIB regimen is effective and cost-saving.
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Affiliation(s)
- Chung-Feng Huang
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Hsing-Tao Kuo
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chi Mei Medical Center, Yongkang District, Tainan, Taiwan
| | - Te-Sheng Chang
- Division of Hepatogastroenterology, Department of Internal Medicine, ChiaYi Chang Gung Memorial Hospital and College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Ching-Chu Lo
- Division of Gastroenterology, Department of Internal Medicine, St. Martin De Porres Hospital, Chiayi, Taiwan
| | - Chao-Hung Hung
- Division of Hepatogastroenterology, Department of Internal Medicine, ChiaYi Chang Gung Memorial Hospital and College of Medicine, Chang Gung University, Taoyuan, Taiwan
| | - Chien-Wei Huang
- Division of Gastroenterology, Kaohsiung Armed Forces General Hospital, Kaohsiung, Taiwan
| | - Lee-Won Chong
- Division of Hepatology and Gastroenterology, Department of Internal Medicine, Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan
- School of Medicine, Fu-Jen Catholic University, New Taipei City, Taiwan
| | - Pin-Nan Cheng
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan, Taiwan
| | - Ming-Lun Yeh
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Internal Medicine, Kaohsiung Municipal Siaogang Hospital, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Cheng-Yuan Peng
- Center for Digestive Medicine, Department of Internal Medicine, China Medical University Hospital, Taichung, Taiwan
- School of Medicine, China Medical University, Taichung, Taiwan
| | - Chien-Yu Cheng
- Division of Infectious Diseases, Department of Internal Medicine, Taoyuan General Hospital, Ministry of Health and Welfare, Taoyuan, Taiwan
| | - Jee-Fu Huang
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Deppartment of Internal Medicine, Kaohsiung Municipal Ta-Tung Hospital, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ming-Jong Bair
- Division of Gastroenterology, Department of Internal Medicine, Taitung Mackay Memorial Hospital, Taitung, Taiwan
- Mackay Medical College, New Taipei City, Taiwan
| | - Chih-Lang Lin
- Liver Research Unit, Department of Hepato-Gastroenterology and Community Medicine Research Center, Chang Gung Memorial Hospital at Keelung, College of Medicine, Chang Gung University, Keelung, Taiwan
| | - Chi-Chieh Yang
- Department of Gastroenterology, Division of Internal Medicine, Show Chwan Memorial Hospital, Changhua, Taiwan
| | - Szu-Jen Wang
- Division of Gastroenterology, Department of Internal Medicine, Yuan's General Hospital, Kaohsiung, Taiwan
| | - Tsai-Yuan Hsieh
- Division of Gastroenterology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
| | - Tzong-Hsi Lee
- Division of Gastroenterology and Hepatology, Far Eastern Memorial Hospital, New Taipei City, Taiwan
| | - Pei-Lun Lee
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Chi Mei Medical Center, Liouying, Tainan, Taiwan
| | - Wen-Chih Wu
- Wen-Chih Wu Clinic, Fengshan, Kaohsiung, Taiwan
| | - Chih-Lin Lin
- Department of Gastroenterology, Renai Branch, Taipei City Hospital, Taipei, Taiwan
| | - Wei-Wen Su
- Department of Gastroenterology and Hepatology, Changhua Christian Hospital, Changhua, Taiwan
| | - Sheng-Shun Yang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan
| | - Chia-Chi Wang
- Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation and School of Medicine, Tzu Chi University, Taipei, Taiwan
| | - Jui-Ting Hu
- Liver Center, Cathay General Hospital, Taipei, Taiwan
| | - Lein-Ray Mo
- Division of Gastroenterology, Tainan Municipal Hospital (Managed By Show Chwan Medical Care Corporation), Tainan, Taiwan
| | - Chun-Ting Chen
- Division of Gastroenterology, Department of Internal Medicine, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan
- Division of Gastroenterology, Department of Internal Medicine Tri-Service General Hospital Penghu Branch, National Defense Medical Center, Taipei, Taiwan
| | - Yi-Hsiang Huang
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
- Institute of Clinical Medicine, School of Medicine, National Yang-Ming Chiao Tung University, Taipei, Taiwan
| | - Chun-Chao Chang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taipei Medical University Hospital, Taipei, Taiwan
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan
| | | | - Guei-Ying Chen
- Penghu Hospital, Ministry of Health and Welfare, Penghu, Taiwan
| | - Chien-Neng Kao
- National Taiwan University Hospital Hsin-Chu Branch, Hsinchu, Taiwan
| | - Chi-Ming Tai
- Department of Internal Medicine, E-Da Hospital, Kaohsiung, Taiwan
- School of Medicine, College of Medicine, I-Shou University, Kaohsiung, Taiwan
| | - Chun-Jen Liu
- Hepatitis Research Center and Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Mei-Hsuan Lee
- Institute of Clinical Medicine, National Yang-Ming Chiao Tung University, Taipei, Taiwan
| | - Pei-Chien Tsai
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chia-Yen Dai
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Jia-Horng Kao
- Hepatitis Research Center and Department of Internal Medicine, National Taiwan University Hospital, Taipei, Taiwan
| | - Han-Chieh Lin
- Division of Gastroenterology and Hepatology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan
- Institute of Clinical Medicine, School of Medicine, National Yang-Ming Chiao Tung University, Taipei, Taiwan
| | - Wang-Long Chuang
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chi-Yi Chen
- Division of Gastroenterology and Hepatology, Department of Medicine, Ditmanson Medical Foundation Chiayi Christian Hospital, Chiayi, Taiwan
| | - Kuo-Chih Tseng
- Department of Internal Medicine, Dalin Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Chiayi, Taiwan.
- School of Medicine, Tzuchi University, Hualien, Taiwan.
| | - Ming-Lung Yu
- Hepatobiliary Division, Department of Internal Medicine and Hepatitis Center, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan.
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Hong CM, Lin YY, Liu CJ, Lai YY, Yeh SH, Yang HC, Kao JH, Hsu SJ, Huang YH, Yang SS, Kuo HT, Cheng PN, Yu ML, Chen PJ. Drug Resistance Profile and Clinical Features for Hepatitis C Patients Experiencing DAA Failure in Taiwan. Viruses 2021; 13:2294. [PMID: 34835100 PMCID: PMC8621340 DOI: 10.3390/v13112294] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2021] [Revised: 11/12/2021] [Accepted: 11/14/2021] [Indexed: 11/17/2022] Open
Abstract
About 4% of the population in Taiwan are seropositive for anti-HCV Ab and 70% with HCV RNA. To address this high chronic hepatitis C disease load, Taiwan National Health Insurance started reimbursing genotype-specific DAAs in 2017 and pangenotype DAAs in mid-2018. With a 97% SVR12 rate, there were still 2-3% of patients that failed to clear HCV. To understand the causes of DAA failure in Taiwan, we conducted a multi-center, clinical, and virologic study. A total of 147 DAA-failure patients were recruited, and we searched HCV NS3/4A, NS5A and NS5B for known resistance-associated substitutions (RASs) by population sequencing, and conducted whole genome sequencing (WGS) for those without known RASs. A total of 107 patients received genotype-specific DAAs while 40 had pangenotype DAAs. Clinically, the important cause of failure is poor adherence. Virologically, common RASs in genotype-specific DAAs were NS5A-L31, NS5A-Y93, and NS5B-C316, while common RASs in pangenotype DAAs were NS5A-L31, NS5A-A/Q/R30, and NS5A-Y93. Additionally, new amino acid changes were found by WGS. Finally, we identified 12 cases with inconsistent baseline and post-treatment HCV genotypes, which is suggestive of re-infection rather than treatment failure. Our study described the drug resistance profile for DAA failure in Taiwan, showing differences from other countries.
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Affiliation(s)
- Chun-Ming Hong
- Division of Hospital Medicine, Department of Internal Medicine, National Taiwan University Hospital, Taipei 10022, Taiwan;
| | - You-Yu Lin
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei 10002, Taiwan; (Y.-Y.L.); (C.-J.L.); (J.-H.K.)
| | - Chun-Jen Liu
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei 10002, Taiwan; (Y.-Y.L.); (C.-J.L.); (J.-H.K.)
- Division of Gastroenterology, Department of Internal Medicine, National Taiwan University Hospital, Taipei 10022, Taiwan; (H.-C.Y.); (S.-J.H.)
| | - Ya-Yun Lai
- Center of Precision Medicine, National Taiwan University, Taipei 10055, Taiwan; (Y.-Y.L.); (S.-H.Y.)
| | - Shiou-Hwei Yeh
- Center of Precision Medicine, National Taiwan University, Taipei 10055, Taiwan; (Y.-Y.L.); (S.-H.Y.)
- Graduate Institute of Microbiology, National Taiwan University College of Medicine, National Taiwan University, Taipei 10051, Taiwan
| | - Hung-Chih Yang
- Division of Gastroenterology, Department of Internal Medicine, National Taiwan University Hospital, Taipei 10022, Taiwan; (H.-C.Y.); (S.-J.H.)
| | - Jia-Horng Kao
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei 10002, Taiwan; (Y.-Y.L.); (C.-J.L.); (J.-H.K.)
- Division of Gastroenterology, Department of Internal Medicine, National Taiwan University Hospital, Taipei 10022, Taiwan; (H.-C.Y.); (S.-J.H.)
| | - Shih-Jer Hsu
- Division of Gastroenterology, Department of Internal Medicine, National Taiwan University Hospital, Taipei 10022, Taiwan; (H.-C.Y.); (S.-J.H.)
- Department of Internal Medicine, National Taiwan University Hospital Yunlin Branch, Yunlin 64000, Taiwan
| | - Yi-Hsiang Huang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taipei Veterans General Hospital, Taipei 11217, Taiwan;
- Institute of Clinical Medicine, National Yang Ming Chiao Tung University School of Medicine, Taipei 11230, Taiwan
| | - Sheng-Shun Yang
- Division of Gastroenterology and Hepatology, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung 40705, Taiwan;
| | - Hsing-Tao Kuo
- Chi Mei Medical Center, Department of Internal Medicine, Tainan 71004, Taiwan;
| | - Pin-Nan Cheng
- Department of Internal Medicine, National Cheng Kung University Hospital, Tainan 70403, Taiwan;
| | - Ming-Lung Yu
- Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung 80756, Taiwan
| | - Pei-Jer Chen
- Graduate Institute of Clinical Medicine, National Taiwan University College of Medicine, Taipei 10002, Taiwan; (Y.-Y.L.); (C.-J.L.); (J.-H.K.)
- Division of Gastroenterology, Department of Internal Medicine, National Taiwan University Hospital, Taipei 10022, Taiwan; (H.-C.Y.); (S.-J.H.)
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Strategies for hepatitis C virus treatment failure. J Formos Med Assoc 2021; 121:876-878. [PMID: 34538553 DOI: 10.1016/j.jfma.2021.09.004] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2021] [Accepted: 09/05/2021] [Indexed: 11/20/2022] Open
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Smirne C, D'Avolio A, Bellan M, Gualerzi A, Crobu MG, Pirisi M. Sofosbuvir-based therapies in genotype 2 hepatitis C virus cirrhosis: A real-life experience with focus on ribavirin dose. Pharmacol Res Perspect 2021; 9:e00811. [PMID: 34152088 PMCID: PMC8214994 DOI: 10.1002/prp2.811] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2021] [Accepted: 05/14/2021] [Indexed: 12/05/2022] Open
Abstract
This study aimed to investigate the efficacy and safety of sofosbuvir-based therapies for the treatment of cirrhosis from hepatitis C virus (HCV) genotype 2 infection. Data of all consecutive HCV genotype 2 cirrhotic patients who started sofosbuvir-based treatments between January 2015 and March 2017 in eight Italian tertiary hospitals were collected retrospectively. Overall, 273 patients (Child A: 94.5%) were enrolled. In the 194 subjects treated with sofosbuvir/ribavirin, median initial ribavirin dosage was 13.9 mg/kg/day, and therapy duration was 16 weeks. Sustained virological response (SVR) rates were 93.8% in intention-to-treat (ITT) and 95.3% in per-protocol (PP) analyses for the 129 treatment-naïve patients, and 96.9% (ITT) and 98.4% (PP) for the 65 treatment-experienced subjects. Adverse events were reported in 142 patients (73.2%), but only 1.5% discontinued treatment. Eighty-eight subjects with treatment-induced anemia (mild: 34.5%, moderate: 7.7%, severe: 3.1%) had to reduce ribavirin dosage, but SVR rates were comparable to the weight-based dose group, both in ITT (95.4% and 94.3%) and PP (97.7% and 95.2%) analyses, respectively. Moreover, ITT and PP SVR rates were similar between shorter (<20 weeks) (94.1% and 96.0%, respectively) and prolonged (≥20 weeks) regimens (95.7% and 96.7%, respectively). SVR rates in the 79 subjects treated with sofosbuvir/daclatasvir (without ribavirin) were similar (ITT: 96.2%; PP: 97.4%, respectively), without de novo/worsening anemia. In conclusion, in a real-life study centered on genotype 2 patients with well-compensated cirrhosis, sofosbuvir-based regimens were associated with good SVR and tolerability rates, regardless of previous antiviral treatments, without a significant impact of on treatment ribavirin dose reductions.
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Affiliation(s)
- Carlo Smirne
- Internal Medicine DivisionDepartment of Translational MedicineUniversità del Piemonte OrientaleNovaraItaly
| | - Antonio D'Avolio
- Infectious Diseases UnitDepartment of Medical SciencesUniversity of TorinoTurinItaly
| | - Mattia Bellan
- Internal Medicine DivisionDepartment of Translational MedicineUniversità del Piemonte OrientaleNovaraItaly
| | | | - Maria G. Crobu
- Laboratory of Molecular VirologyMaggiore della Carità HospitalNovaraItaly
| | - Mario Pirisi
- Internal Medicine DivisionDepartment of Translational MedicineUniversità del Piemonte OrientaleNovaraItaly
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Liu HY, Lin YH, Lin PJ, Tsai PC, Liu SF, Huang YC, Tsai JJ, Huang CI, Yeh ML, Liang PC, Lin ZY, Dai CY, Huang JF, Chuang WL, Huang CF, Yu ML. Anti-HCV antibody titer highly predicts HCV viremia in patients with hepatitis B virus dual-infection. PLoS One 2021; 16:e0254028. [PMID: 34197557 PMCID: PMC8248640 DOI: 10.1371/journal.pone.0254028] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/29/2021] [Accepted: 06/17/2021] [Indexed: 11/18/2022] Open
Abstract
BACKGROUND/AIMS Hepatitis C Virus (HCV) infection is diagnosed by the presence of antibody to HCV and/or HCV RNA. This study aimed to evaluate the accuracy of anti-HCV titer (S/CO ratio) in predicting HCV viremia in patients with or without hepatitis B virus (HBV) dual infection. METHODS Anti-HCV seropositive patients who were treatment-naïve consecutively enrolled. Anti-HCV antibodies were detected using a commercially chemiluminescent microparticle immunoassay. HCV RNA was detected by real-time PCR method. RESULTS A total of 1321 including1196 mono-infected and 125 HBV dually infected patients were analyzed. The best cut-off value of anti-HCV titer in predicting HCV viremia was 9.95 (AUROC 0.99, P<0.0001). Of the entire cohort, the anti-HCV cut-off value of 10 provided the best accuracy, 96.8%, with the sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) of 96.3%, 98.9%, 99.7% and 87.3% respectively. The best cut-off value of anti-HCV titer in predicting HCV viremia was 9.95 (AUROC 0.99, P<0.0001) and 9.36 (AUROC 1.00, P<0.0001) in patients with HCV mono-infection and HBV dual-infection respectively. Among the HBV dually infected patients, the accuracy of anti-HCV titer in predicting HCV viremia reached up to 100% with the cut-off value of 9. All the patients were HCV-viremic if their anti-HCV titer was greater than 9 (PPV 100%). On the other hand, all the patients were HCV non-viremic if their anti-HCV titer was less than 9 (NPV 100%). CONCLUSIONS Anti-HCV titer strongly predicted HCV viremia. This excellent performance could be generalized to either HCV mono-infected or HBV dually infected patients.
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Affiliation(s)
- Hung-Yin Liu
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Yi-Hung Lin
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Pei-Ju Lin
- Department of Nursing, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Pei-Chien Tsai
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Shu-Fen Liu
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ying-Chou Huang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Jia-Jiun Tsai
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ching-I Huang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Faculty of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Ming-Lun Yeh
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Faculty of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Po-Cheng Liang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Zu-Yau Lin
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Department of Nursing, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chia-Yen Dai
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Faculty of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Jee-Fu Huang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Faculty of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Wan-Long Chuang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Faculty of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
| | - Chung-Feng Huang
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Faculty of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- * E-mail:
| | - Ming-Lung Yu
- Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung Medical University, Kaohsiung, Taiwan
- Faculty of Internal Medicine, School of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung, Taiwan
- Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung, Taiwan
- College of Biological Science and Technology, National Chiao Tung University, Hsin-Chu, Taiwan
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