Hepatitis B reactivation in patients receiving direct-acting antiviral therapy or interferon-based therapy for hepatitis C: A systematic review and meta-analysis

World J Gastroenterol. 2018 Jul 28;24(28):3181-3191. doi: 10.3748/wjg.v24.i28.3181.

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: Coinfection; Direct-acting antiviral agents; Hepatitis B virus reactivation; Hepatitis C; Meta-analysis.

Publication types

  • Meta-Analysis
  • Review
  • Systematic Review

MeSH terms

  • Antibiotic Prophylaxis / methods
  • Antiviral Agents / pharmacology
  • Antiviral Agents / therapeutic use*
  • Coinfection / drug therapy*
  • Coinfection / pathology
  • Coinfection / virology
  • Disease Progression
  • Guanine / analogs & derivatives
  • Guanine / therapeutic use
  • Hepatitis B / blood
  • Hepatitis B / epidemiology*
  • Hepatitis B / virology
  • Hepatitis B Surface Antigens / blood
  • Hepatitis B virus / physiology*
  • Hepatitis C / drug therapy*
  • Hepatitis C / pathology
  • Hepatitis C / virology
  • Humans
  • Incidence
  • Interferons / therapeutic use
  • Recurrence
  • Tenofovir
  • Treatment Outcome
  • Virus Activation / drug effects

Substances

  • Antiviral Agents
  • Hepatitis B Surface Antigens
  • entecavir
  • Guanine
  • Interferons
  • Tenofovir