Direct-Acting Antivirals and the Risk of Hepatitis B Reactivation in Hepatitis B and C Co-Infected Patients: A Systematic Review and Meta-Analysis

Abstract

Hepatitis B (HBV) reactivation was observed to be more than 10% in patients receiving interferon-based therapy for hepatitis C (HCV) co-infection. At present, when direct-acting antiviral (DAA) has become the main treatment for HCV, there are few large-scale studies on the reactivation of HBV in these population. We studied HBV reactivation risk and prophylactic HBV treatment efficacy in HBV/HCV co-infected patients receiving DAA therapy. Relevant studies were selected from the Ovid-Medline, Ovid-EMBASE, Cochrane Central Register of Controlled Trials, KoreaMed, KMbase, and RISS databases through 4 September 2020. Data pooling was carried out using the random-effects method. We identified 39 articles with 119,484 patients with chronic (n = 1673) or resolved (n = 13,497) HBV infection under DAA therapy. When the studies were pooled, the HBV reactivation rate was 12% (95% confidence interval (CI) 6–19, I2 = 87%), indicating that this population needs careful attention. When stratified by baseline HBV DNA, the undetectable HBV DNA group showed a significantly lower risk of reactivation than the detectable HBV DNA group (odds ratio (OR) 0.30, 95% CI 0.11–0.86, I2 = 0%). Prophylactic HBV therapy reduced HBV reactivation risk (OR 0.25, 95% CI 0.07–0.92, I2 = 0%). Patients with a resolved HBV infection showed a negligible rate (0.4%) of HBV reactivation. In conclusion, patients with detectable HBV DNA levels warrant careful monitoring for HBV reactivation and may benefit from preventive anti-HBV treatment.

Management of HBV reactivation: Challenges and opportunities

“…Treatment of HCV infection with direct-acting antivirals (DAAs) is associated with HBVr, and is hypothesized to be triggered by a loss of immune break of HCV infection with DAA-associated viral suppression in patients with active chronic HBV or resolved HBV. [8,9] Outcomes from HBVr can be very serious: in a case series of 29 adverse event reports of HBVr associated with DAA treatment for HCV, 2 affected individuals died and 1 underwent liver transplantation. [10]…”