Meta-Analysis
Copyright ©The Author(s) 2018. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Jul 28, 2018; 24(28): 3181-3191
Published online Jul 28, 2018. doi: 10.3748/wjg.v24.i28.3181
Hepatitis B reactivation in patients receiving direct-acting antiviral therapy or interferon-based therapy for hepatitis C: A systematic review and meta-analysis
Xian-Wan Jiang, Jian-Zhong Ye, Ya-Ting Li, Lan-Juan Li
Xian-Wan Jiang, Jian-Zhong Ye, Ya-Ting Li, Lan-Juan Li, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, Hangzhou 310003, Zhejiang Province, China
Xian-Wan Jiang, Jian-Zhong Ye, Ya-Ting Li, Lan-Juan Li, Collaborative Innovation Center for Diagnosis and Treatment of Infectious Diseases, Hangzhou 310003, Zhejiang Province, China
Author contributions: Jiang XW, Ye JZ, Li YT and Li LJ contributed the data extraction and statistical analysis; Jiang XW wrote the manuscript; Ye JZ, Li YT and Li LJ reviewed the manuscript; all authors have approved the final version of the manuscript.
Supported by the National Natural Science Foundation of China, No. 81330011; and the Science Fund for Creative Research Groups of the National Natural Science Foundation of China, No. 81721091.
Conflict-of-interest statement: There is no conflict of interest in this study.
PRISMA 2009 Checklist statement: The PRISMA checklist has been adopted.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (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: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Lan-Juan Li, MD, PhD, Professor, State Key Laboratory for Diagnosis and Treatment of Infectious Diseases, The First Affiliated Hospital, School of Medicine, Zhejiang University, No. 79 Qingchun Road, Hangzhou 310003, Zhejiang Province, China. ljli@zju.edu.cn
Telephone: +86-571-87236759 Fax: +86-571-87236459
Received: March 28, 2018
Peer-review started: March 28, 2018
First decision: May 9, 2018
Revised: June 2, 2018
Accepted: June 22, 2018
Article in press: June 22, 2018
Published online: July 28, 2018
Abstract
AIM

To assess the incidence of hepatitis B virus (HBV) reactivation in patients receiving direct-acting antiviral agent (DAA)-based therapy or interferon (IFN)-based therapy for hepatitis C and the effectiveness of preemptive anti-HBV therapy for preventing HBV reactivation.

METHODS

The PubMed, MEDLINE and EMBASE databases were searched, and 39 studies that reported HBV reactivation in HBV/hepatitis C virus coinfected patients receiving DAA-based therapy or IFN-based therapy were included. The primary outcome was the rate of HBV reactivation. The secondary outcomes included HBV reactivation-related hepatitis and the effectiveness of preemptive anti-HBV treatment with nucleos(t)ide analogues. The pooled effects were assessed using a random effects model.

RESULTS

The rate of HBV reactivation was 21.1% in hepatitis B surface antigen (HBsAg)-positive patients receiving DAA-based therapy and 11.9% in those receiving IFN-based therapy. The incidence of hepatitis was lower in HBsAg-positive patients with undetectable HBV DNA compared to patients with detectable HBV DNA receiving DAA therapy (RR = 0.20, 95%CI: 0.06-0.64, P = 0.007). The pooled HBV reactivation rate in patients with previous HBV infection was 0.6% for those receiving DAA-based therapy and 0 for those receiving IFN-based therapy, and none of the patients experienced a hepatitis flare related to HBV reactivation. Preemptive anti-HBV treatment significantly reduced the potential risk of HBV reactivation in HBsAg-positive patients undergoing DAA-based therapy (RR = 0.31, 95%CI: 0.1-0.96, P = 0.042).

CONCLUSION

The rate of HBV reactivation and hepatitis flare occurrence is higher in HBsAg-positive patients receiving DAA-based therapy than in those receiving IFN-based therapy, but these events occur less frequently in patients with previous HBV infection. Preemptive anti-HBV treatment is effective in preventing HBV reactivation.

Keywords: Hepatitis C, Hepatitis B virus reactivation, Coinfection, Direct-acting antiviral agents, Meta-analysis

Core tip: We assessed the potential risk of hepatitis B virus (HBV) reactivation in patients receiving direct-acting antiviral agent (DAA)-based therapy or interferon-based therapy for hepatitis C. Preemptive anti-HBV treatment proved to be effective in preventing HBV reactivation during DAA therapy. These findings support the use of entecavir or tenofovir in hepatitis B surface antigen-positive patients prior to the initiation of DAA therapy.