Aim : To evaluate the efficacy of a long-term course of lamivudine monotherapy in patients with anti-HBe-positive chronic hepatitis B who relapsed after the first course of either lamivudine/interferon (n = 16; Group 1) or lamivudine (n = 20; Group 2).

Methods : Biochemical and virological tests were performed every 3 months. At baseline and breakthrough, the region coding for the YMDD amino acid motif was sequenced.

Results : The length of re-treatment averaged 24 months. The virological response peaked at 6 months (94.4%), and declined to 66.7% and 50% at 12 and 24 months, respectively. The rates of breakthrough were 2.9%, 31.4% and 48.6% at 6, 12 and 24 months, respectively. By the second year, responders amounted to 62.5% and 40% in Groups 1 and 2, respectively (P = 0.10). The 18 responders at month 24 are still on therapy after 25–51 months of treatment: 14 still maintain a response, nine from Group 1 and five from Group 2.

Conclusions : Re-treatment with lamivudine can control viral replication. This effect is maintained for the initial 12 months in two-thirds of patients, but afterwards the duration of response lessens due to the development of viral resistance.