Meta-Analysis
Copyright ©The Author(s) 2022. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Hepatol. Jun 27, 2022; 14(6): 1248-1257
Published online Jun 27, 2022. doi: 10.4254/wjh.v14.i6.1248
Efficacy and safety of sofosbuvir/velpatasvir with or without ribavirin in hepatitis C genotype 3 compensated cirrhosis: A meta-analysis
Jing Hong Loo, Wen Xin Flora Xu, Jun Teck Low, Wei Xuan Tay, Le Shaun Ang, Yew Chong Tam, Prem Harichander Thurairajah, Rahul Kumar, Yu Jun Wong
Jing Hong Loo, Wen Xin Flora Xu, Jun Teck Low, Wei Xuan Tay, Le Shaun Ang, Prem Harichander Thurairajah, Yong Loo Lin School of Medicine, National University of Singapore, Singapore 119077, Singapore
Yew Chong Tam, Education Resource Center, Medical Board, Singapore General Hospital, Singapore 100059, Singapore
Prem Harichander Thurairajah, Department of Gastroenterology and Hepatology, National University Hospital, Singapore 119077, Singapore
Rahul Kumar, Yu Jun Wong, Department of Gastroenterology and Hepatology, Changi General Hospital, Singapore 529889, Singapore
Rahul Kumar, Yu Jun Wong, Duke-NUS Medicine Academic Clinical Program, Singapore 100059, Singapore
Author contributions: Loo JH and Xu WXF contributed equally as the first-author; Wong YJ contributed to study concept and design; Loo JH, Tay WX, Low JT, Ang LS, Xu WXF contributed to systematic review of literature; Loo JH, Xu WXF contributed to drafting of manuscript; all authors did critical review of manuscript.
Supported by the Nurturing Clinician Scientist Scheme (NCCS) award by SingHealth Duke-NUS Academic Medical Centre and National Medical Research Council Singapore.
Conflict-of-interest statement: Dr. Wong YJ was an invited speaker for Gilead Science. Other authors have no conflict of interest to declare.
PRISMA 2009 Checklist statement: The authors have read the PRISMA 2009 Checklist, and the manuscript was prepared and revised according to the PRISMA 2009 Checklist.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Yu Jun Wong , FRCP, MD, Consultant Physician-Scientist, Department of Gastroenterology and Hepatology, Changi General Hospital, Singhealth, 2, Simei Street 3, Singapore 529889, Singapore. eugene.wong.y.j@singhealth.com.sg
Received: August 8, 2021
Peer-review started: August 8, 2021
First decision: November 11, 2021
Revised: November 18, 2021
Accepted: May 27, 2022
Article in press: May 27, 2022
Published online: June 27, 2022
Abstract
BACKGROUND

Hepatitis C virus (HCV) is a leading cause of liver cirrhosis and hepatocellular carcinoma globally. Sofosbuvir/velpatasvir (SOF/VEL) is an effective pan-genotypic direct-acting antiviral combination for treatment of chronic HCV infection. While the addition of ribavirin (RBV) to SOF/VEL improved sustained virological response (SVR12) in genotype 3 (GT3) decompensated cirrhosis patients, the benefits of RBV in GT3 compensated cirrhosis patients receiving SOF/VEL remains unclear.

AIM

To evaluate the efficacy and safety of SOF/VEL, with or without RBV in GT3 compensated cirrhosis patients.

METHODS

We searched four electronic databases (PubMed/Medline, Embase, Cochrane Library and Web of Science) from inception up to June 2021 using both free text and MeSH terms. There was no restriction on language, geography, publication dates and publication status (full text or abstracts). All GT3 compensated cirrhosis patients treated with 12 wk of SOF/VEL, with or without RBV, were included, regardless of age, gender or prior treatment experience. The primary outcome was sustained virological response 12-wk post-treatment (SVR12). The secondary outcome was treatment-related adverse events, as defined by symptomatic anemia requiring transfusion or a drop in hemoglobin beyond 2 g/dL. The pooled relative risk (RR), 95%CI and heterogeneity (I2) were estimated using Review Manager version 5.3.

RESULTS

From 1752 citations, a total of seven studies (2 randomized controlled trials, 5 cohort studies) with 1088 subjects were identified. The SVR12 was similar in GT3 compensated cirrhosis patients, regardless of the use of RBV, for both the intention-to-treat RR 1.03, 95%CI: 0.99-1.07; I2 = 0%) and the per-protocol analysis (RR: 1.03, 95%CI: 0.99-1.07; I2 = 48%). The overall pooled rate of treatment-related adverse events was 7.2%. Addition of RBV increased the pooled risk of treatment-related adverse events in GT3 compensated cirrhosis patients receiving SOF/VEL (RR: 4.20, 95%CI: 1.29-13.68; I2 = 0%). Subgroup analysis showed that RBV was associated with a higher SVR12 in GT3 compensated cirrhosis patients with baseline resistance-associated substitutions. However, addition of RBV did not significantly increase the SVR12 among treatment-experienced GT3 compensated cirrhosis patients.

CONCLUSION

Ribavirin was not associated with higher SVR12 in GT3 compensated cirrhosis patients receiving SOF/VEL. Our findings suggest a limited role for RBV as routine add-on therapy to SOF/VEL in GT3 compensated cirrhosis patients.

Keywords: Direct-acting antiviral, Hepatitis C, Cirrhosis, Sofosbuvir/velpatasvir

Core Tip: Ribavirin (RBV) as routine add-on therapy was not associated with higher sustained virological response in genotype 3 (GT3) compensated cirrhosis patients receiving sofosbuvir/velpatasvir (SOF/VEL), except in the subgroup of patients with baseline resistance-associated substitution mutation. As RBV is associated with a higher risk of treatment-related adverse event, RBV as routine add-on therapy to SOF/VEL should be reconsidered among compensated GT3 cirrhosis patients.