We experienced a case of a 36-year-old married man who was found to be hepatitis B virus (HBV) positive at 23 years of age. His liver function was repeatedly abnormal in the past 13 years. In November 2007 he presented with fatigue. Laboratory tests showed serum alanine aminotransferase concentration 255.3 U/l, positive for hepatitis B surface antigen (HBsAg) and hepatitis B e antibody, HBV DNA 3.01 × 10(7) copies/ml; liver biopsy showed necroinflammatory scores 11 and fibrosis scores 4. After 20 weeks of treatment with Peg-IFN α-2b, laboratory tests showed HBV DNA <500 copies/ml and normal liver function. By week 52 of the treatment, HBsAg became negative. By week 92 of continuing treatment, HBsAb became weakly positive and Peg-IFN α-2b treatment was stopped. On follow-up, both HBsAg and HBsAb were negative 28 weeks after discontinuation of Peg-IFN α-2b. We then performed a second liver biopsy and histological examination revealed necroinflammtary scores 2 and fibrosis scores 2. We administered hepatitis B vaccine intramuscularly every 4 weeks combined with IFN α-1b 30 μg intramuscularly every other day. HBsAb was 244.8 IU/l at week 32 of this combined treatment. Follow-up showed that after discontinuation of the combined treatment HBsAb concentration declined rapidly but could be maintained above 100 IU/l by intermittent injections of hepatitis B vaccine. Findings from this case reveal that HBsAg loss may be not sufficient; however, HBsAg seroconversion together with maintenance of certain concentrations of HBsAb may be a better endpoint to HBV treatment.