Hepatitis B Reactivation in Hepatitis B and C Coinfected Patients Treated With Antiviral Agents: A Systematic Review and Meta-analysis

There is an increased awareness of hepatitis B (HBV) reactivation in chronic hepatitis C (CHC) patients coinfected with HBV treated with pan-oral direct-acting antiviral agents (DAAs). We performed a systematic review and meta-analysis to compare the rate of HBV reactivation in CHC patients coinfected with overt HBV (hepatitis B surface antigen [HBsAg] positive) and occult HBV (HBsAg negative with positive HBV DNA) infection separately, treated with interferon (IFN)-based therapy to those with pan-oral DAAs. The primary outcome was HBV reactivation, and the secondary outcomes included hepatitis due to HBV reactivation, sustained virologic response (SVR) for CHC, loss of HBV DNA and HBsAg seroclearance. Although the pooled incidence rate of HBV reactivation, among CHC patients with overt HBV (n = 779), was similar among those treated with IFN-based therapy (14.5%, P < 0.001) and DAAs (12.2%, P = 0.03; P = 0.91 for heterogeneity between subgroups), it was reported to occur much earlier in those treated with DAAs (4-12 weeks during treatment) than in those treated with IFN-based therapies (most at the end of treatment and some during follow-up). Also, studies with DAA-based therapies were more likely to report incidence of hepatitis due to HBV reactivation (12.2% in DAAs vs. 0% in IFN; P = 0.009 for heterogeneity between subgroups). HBV reactivation and hepatitis due to HBV reactivation also occurred, though less frequently in CHC patients with occult HBV infection. CHC SVR was not affected by HBV reactivation (P = 0.27). Conclusion: HBV reactivation occurs earlier and is clinically more significant in CHC patients coinfected with overt and occult HBV who are treated with pan-oral DAAs compared with IFN-based therapy. It is therefore important to have all patients screened for evidence of overt or occult HBV infection and managed during pan-oral DAAs therapy.