Loss of hepatitis B surface antigen from the serum of patients with chronic hepatitis treated with lamivudine

Although loss of hepatitis B e antigen (HBeAg) from the serum is sought by treatment with lamivudine, clearance of hepatitis B surface antigen (HBsAg) is the eventual goal of any antiviral therapy. In a single hepatology center in the Metropolitan Tokyo, 486 patients with chronic hepatitis B were followed up for longer than 3 years after they started treatment with lamivudine. HBsAg disappeared from the serum in 17 (3.5%). Age > 50 years and low HBsAg levels (hemagglutination titer <= 2(7)) at the start of lamivudine were significantly more frequent in the patients who did than did not lose HBsAg from the serum. Except for these two factors, there were no differences between the two groups of patients in the prevalence of HBeAg and HBV DNA levels at the baseline, as well as the development of YMDD mutants and breakthrough hepatitis during lamivudine treatment. Using multivariate analysis, age >50 years at the start of lamivudine was the only factor predicting the loss of HBsAg (hazard ratio: 2.96 [95% confidence interval: 1.14-7.681, P=0.028). By the method of Kaplan-Meier performed on the 486 patients, the loss of HBsAg was estimated to occur in 3% and 13% of patients, respectively, who had received lamivudine therapy for 5 and 10 years. These results indicate that loss of HBsAg occurs in a minority (3.5%) of patients with chronic hepatitis B who receive lamivudine therapy and more frequently in those with lower HBsAg titers and older ages at the start of treatment.