Behaviour of occult HBV infection in HCV-infected patients under treatment with direct-acting antivirals

BACKGROUND: There are controversial data on possible occult hepatitis B virus (HBV) reactivation in hepatitis C virus (HCV) patients successfully treated with direct-acting antivirals (DAA). However, diagnosis of occult HBV infection (OBI) was not performed by gold standard procedures in any study. METHODS: By using several highly sensitive assays, we examined serially collected serum samples from 40 HBV-surface-negative DAA-treated HCV patients with OBI identified by testing liver biopsy specimens through nested-PCR technique. Serum samples were obtained at four time points from each patient (at baseline, at 4 weeks after starting, at the end, and 12 weeks after stopping therapy), and tested for HBV-DNA by nested-PCR and real-time PCR techniques. RESULTS: All tested serum samples were negative by both quantitative HBV surface antigen (HBsAg) and HBV-core-related antigen assays. Twenty-six/40 patients were anti-HBs positive and in all of them, the amount of this antibody was stable at the four time points evaluated. Serum HBV-DNA was detected in 10 samples at baseline, in 6 samples 4 weeks after starting therapy, in 11 samples at the end of therapy and in 21 samples 12 weeks after stopping treatment (P=0.001). Aminotransferase values dropped within the normal levels at week four of therapy and persisted normal over time in all cases. CONCLUSIONS: A slight increase in the amount of HBV-DNA three months after stopping DAA therapy was the only parameter showing a possible reappearance of HBV activity in OBI patients cured for a concomitant HCV infection, but it was insufficient to lead toward a virological reactivation capable of inducing liver injury.