Factors involved in transition from the immunotolerant to immunoactive phase in chronic hepatitis B virus (HBV) infection remain unclear We investigated viral mutations occurring during transition and elucidated their virological and immunological significance Full-length HBV DNA sequences were serially determined in a chronic HBV carrier from the immunotolerant to immunoactive phase Viral replicative competence was examined by transfection analysis HBV-specific CD8(+) T cell response was evaluated by coculture of CD8(+) T cells with autologous dendritic cells followed by interferon-gamma Elispot assay Eleven point mutations and two deletions appeared around the onset of the immunoactive phase Viral replicative competence declined significantly after the onset of active hepatitis Examination of the CD8(+) T cell response against two putative T-cell epitopes, which contained substituted amino acids from the immunotolerant to immunoactive phase, showed that mutant HBV epitopes gave a lesser T cell response than wild-type HBV ones In summary, point mutations and deletions may occur prior to or concurrent with the onset of the immunoactive phase during chronic HBV infection These mutations may result in a significant decrease in both viral replicative competence and HBV-specific CD8(+) T cell response, suggesting a possible adaptation for the maintenance of viral persistence (C) 2010 Elsevier Inc All rights reserved