Impact of Hepatitis B Virus Integration Into Liver Tissue on the Efficacy of Peginterferon and Ribavirin Therapy in Hepatitis B Virus-negative Chronic Hepatitis C Patients

Abstract

Integration of hepatitis B virus (HBV) DNA into host hepatic DNA is found in patients without HBV surface antigen (HBsAg). We investigated the prevalence of HBV integration and its association with the outcome of peginterferon (PEG-IFN) and ribavirin combination therapy in HBsAg-negative chronic hepatitis C patients. We analyzed 157 patients chronically infected with hepatitis C virus (HCV) with viral load ≥5.0 log10 IU/mL, who underwent PEG-IFN and ribavirin combination therapy. HBV integration was measured by an Alu-PCR assay with liver specimens obtained by needle biopsy before treatment. HBV integration was identified in 54 of the 157 (34.4%) patients. There were no significant differences between patients with and without HBV integration with regard to baseline characteristics including liver histology, pretreatment HCV RNA levels, and genetic polymorphisms near the IL28B gene. In patients with HCV genotype 1b (n=91), a more favorable viral response was observed in patients with HBV integration during therapy, with higher rates of rapid and complete early virologic response. The rate of sustained virologic response (SVR) was significantly higher in patients with HBV integration than those without (P=0.0098). Multivariate analysis identified HBV integration and IL28B polymorphisms as independent factors associated with SVR. HBV integration was associated with favorable viral responses and a higher SVR rate to combination therapy with PEG-IFN and ribavirin in patients infected with HCV genotype 1b. Further studies will be required to confirm this association and elucidate its underlying mechanisms.