Published online Jul 28, 2018. doi: 10.3748/wjg.v24.i28.3181
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
Hepatitis B virus/hepatitis C virus (HBV/HCV) dual infection is common in regions with high HBV prevalence, as HBV and HCV share a similar mode of transmission. HBV/HCV-coinfected patients tend to have more severe liver fibrosis and a higher risk of hepatocellular carcinoma than those without coinfection. HBV reactivation may occur after patients receive direct-acting antiviral agent (DAA)-based therapy or interferon (IFN)-based therapy for hepatitis C. Several studies have reported HBV reactivation but a meta-analysis to determine the proportion of HBV reactivation is still lacking.
Although previous studies reported HBV reactivation in patients undergoing DAA-based therapy or IFN-based therapy, the results indicate contradictory HBV reactivation rates. Moreover, the need for preemptive anti-HBV therapy remains controversial.
The main objectives of the systematic review and meta-analysis were to evaluate the incidence of HBV reactivation in patients receiving DAA-based therapy or IFN-based therapy for hepatitis C and the effectiveness of preemptive anti-HBV therapy for preventing HBV reactivation.
Relevant publications were searched in the PubMed, MEDLINE and EMBASE databases with the indicated key words and subject terms. The data were extracted, and statistical analysis was conducted in Stata to assess the incidence of HBV reactivation and reactivation-related hepatitis. Significant heterogeneity was investigated using meta-regression and subgroup analyses for treatment regimen, HBV DNA level, study sample size, and race. Publication bias was tested using Egger’s test and was assessed by funnel plots.
The systematic review identified 7092 articles and enrolled 39 full articles that met the inclusion criteria. The pooled random effects overall HBV reactivation rate was 15.7% (95%CI: 10.6-21.5) in hepatitis B surface antigen (HBsAg)-positive patients. The HBV reactivation rate was higher in the DAA-treated group (21.1%, 95%CI: 15.8-26.9) than in the IFN-treated group (11.9%, 95%CI: 6.3-18.6). The incidence of hepatitis related to HBV reactivation was 0.7% (95%CI: 0-2.6) in HBsAg-positive patients and patients receiving DAA therapy (3.8%, 95%CI: 0.3-9.5) had a higher rate of HBV reactivation-related hepatitis than those receiving IFN-based therapy (0, 95%CI: 0-0.9). Preemptive anti-HBV therapy with entecavir or tenofovir significantly reduced the risk of HBV reactivation in patients receiving DAA-based treatment (RR = 0.31, 95%CI: 0.1-0.96).
Our study found that HBV reactivation and hepatitis flare occurred more frequently in HBsAg-positive patients receiving DAA-based anti-HCV treatment than in patients receiving IFN-based therapy. HBV reactivation was rare in patients with previous HBV infection. Preemptive anti-HBV therapy with NUCs was effective in HBsAg-positive patients to prevent HBV reactivation, especially in those with detectable serum HBV DNA.
Our study found the high risk of HBV reactivation in patients receiving DAA-based therapy for hepatitis C. Preemptive anti-HBV treatment proved to be effective in preventing HBV reactivation during DAA therapy. However, more high quality randomized controlled trials are needed to assess the risk of HBV reactivation in patients with HBV/HCV coinfection. Further investigation is required to assess the cost effectiveness of treating HBV/HCV-coinfected patients with NUCs prior to initiating DAA therapy.