• hepatitis B virus;
  • chronic hepatitis B;
  • lamivudine;
  • breakthrough


Drug resistance remains a major problem during lamivudine treatment for patients with hepatitis B virus infection. Continuing or stopping lamivudine in patients with biochemical breakthrough is an issue that has not been investigated extensively. Particularly, HBeAg seroconversion and its durability achieved in these settings have never been studied so far. In this study, we compared the clinical outcomes including HBeAg seroconversion in hepatitis B e antigen (HBeAg)-positive patients who either continued or stopped lamivudine treatment after biochemical breakthrough. This was a retrospective cohort study of 73 consecutive patients with biochemical breakthrough followed up for at least 12 months. Of these, 35 (Group I) stopped and the remaining 38 (Group II) continued lamivudine therapy after breakthrough. During 12 months, there was a tendency towards higher rates of HBeAg seroconversion in Group I compared with Group II (P = 0.078). By multivariate analysis, age ≥45 years and acute exacerbation within 6 months of stopping lamivudine were the two independent predictors of HBeAg seroconversion for Group I (P = 0.034 and P = 0.012, respectively). There was no difference in the overall incidence of acute exacerbation and hepatic decompensation between the two groups (P = 0.333 and P = 0.555, respectively). Six patients (17.1%) in Group I developed hepatic decompensation, for which bilirubin ≥1.2 mg/dl was an independent predictor (P = 0.002). The therapeutic gain in continuing lamivudine for biochemical breakthrough is questionable. This study suggests that discontinuation of lamivudine may be an option in older patients with normal bilirubin level. J. Med. Virol. 77:367–373, 2005. © 2005 Wiley-Liss, Inc.