Precore/core promoter mutations and hepatitis B virus genotype in hepatitis B and C dually infected patients treated with interferon-based therapy

We studied the prevalence and distribution of precore/basal core promoter (BCP) mutations and hepatitis B virus (HBV) genotypes in HBV/hepatitis C virus (HCV) dually-infected patients, and evaluated their impact on long-term HBV response of interferon (IFN)-based therapy. The HBV genotypes and sequences of the precore/BCP regions were determined in 180 HBV/HCV dually-infected patients and were compared with 90 age, sex and hepatitis B e antigen-matched chronic hepatitis B controls. Serum HBV DNA and hepatitis B surface antigen (HBsAg) were assessed every 3-6 months after therapy with IFN or pegylated-IFN plus ribavirin in 135 dually-infected patients with active hepatitis C. Dually-infected patients had a higher prevalence of genotype C HBV (P = 0.022) and a lower frequency of G1896A mutation (P = 0.004) as compared with controls. Among dually-infected patients, genotype C was associated with a higher frequency of A1762T/G1764A mutation (P < 0.001), but with lower HBV DNA (P < 0.001) and a lower frequency of A1752T/G (P = 0.008), C1799G (P < 0.001) and G1896A mutation (P < 0.001) than genotype B. Based on Cox proportional hazards model, young age (hazard ratio (HR) = 0.952, P = 0.001), sustained virological response to HCV (HR = 4.638, P = 0.044), C1766T mutation (HR = 5.216, P = 0.003) and A1846T mutation (HR = 2.332, P = 0.031) correlated with HBV DNA reactivation (?2000 IU/ml) after therapy. Age (HR = 1.068, P = 0.020), G1896A mutation (HR = 0.140, P = 0.01) and A1846T mutation (HR = 0.086, P = 0.018) were associated with HBsAg seroclearance independently. In conclusion, specific mutations in the precore/BCP regions could be useful in predicting long-term HBV response in HBV/HCV dually-infected patients treated with IFN-based therapy.