Effect of multiple mutations in the core promoter and pre-core/core region of hepatitis B virus genome on the response to interferon in e antigen-positive chronic hepatitis B

Background and Aims: Hepatitis B virus (HBV) genomic mutations may be one of the factors that influence the efficacy of interferon (IFN) therapy. The aim of this study was to investigate the effects of mutations in different parts of the HBV genome on IFN therapy. Methods: We studied the baseline clinical, biochemical, serologic and virologic parameters in 17 patients with e antigen‐positive chronic hepatitis B. The DNA sequence of the X gene and pre‐core/core gene in serum samples of these patients was analyzed before the initiation of IFN therapy. Results: All five patients with the T1762–A1764 mutation were IFN responsive, while among the 12 remaining patients, only two responded to therapy. Among five patients with both a pre‐core A1896 mutation and a mutation in the epitope aa 107–118 of the core region, four were non‐responders whereas the fifth responded to therapy. In three other patients with A1896 mutations, one with simultaneous mutations in five lymphocytic epitopes did not respond to therapy; the two remaining patients with concomitant mutations in one or two epitopes were responsive. Serum HBV‐DNA levels were lower and titers of antibody to hepatitis B virus core antigen‐immunoglobin M (anti‐HBc‐IgM) were higher in the responders than in the non‐responders. Hepatitis B virus genotypes B and C were found to be in all these Chinese patients. Conclusions: These results suggest that HBV genomic mutations, serum viral loads and titers of anti‐HBc‐IgM might be predictive of the efficacy of IFN therapy. These clinical findings should be further investigated by in vivo and in vitro experiments.