Background: The lamivudine dosage used for treatment of patients with hepatitis B virus (HBV) chronic liver disease is one-third of the dose used in patients infected with human immunodeficiency virus. Moreover, lamivudine therapy is hampered by the early and high rate of drug-resistance. Aim: To assess the effect of an initial high dose of lamivudine on the rate and temporal incidence of the development of resistance to treatment.

Methods: We retrospectively studied 62 patients (49 males; median age 54 years) with chronic HBV-related liver disease who were treated with lamivudine and who had at least 1-year on-treatment follow-up. Patients were subdivided according to the lamivudine dosage: 25 patients were treated with lamivudine 300mg qd for two weeks, then shifted to 100mg qd (high-dose group) and 37 patients were treated with the standard dose of 100mg qd (standard-dose group).

Results: Median treatment duration was 45 months. As far as baseline HBV-DNA, HBeAg status, stage of disease, and previous interferon treatment are concerned there were no differences between groups. Viral resistance was detected in 43 patients (69%) after a median of 27 months (range: 6-72) with no significant difference between groups (high-dose, 60% versus standard-dose, 76%). Appearance of viral resistance was significantly delayed in the high-dose group (p=0.0274).

Conclusions: This study has shown that an initial high dose of lamivudine is able to delay the appearance of viral resistance in patients with chronic HBV infection, thus suggesting that the genetic barrier of lamivudine could be dose-dependent.


Lamivudine, chronic hepatitis B, resistance