Aim: The endpoint of treatment with nucleoside analogs remains unclear for patients with hepatitis B e antigen (HBeAg)-negative chronic hepatitis B. We report the results of a randomized trial to determine the optimal duration of additional therapy after response to lamivudine in HBeAg-negative patients.
Methods: Twenty-two patients with HBeAg-negative chronic hepatitis B who exhibited biochemical and virological responses to lamivudine were enrolled. When patients responded to treatment, they were randomly assigned to receive 12 more months of therapy (Group A, 11 patients) or 24 more months of therapy (Group B, 11 patients).
Results: The baseline characteristics of the patients were similar in the two groups. Biochemical and virological responses were obtained in all patients within 6 months. Drug resistance developed in one patient in Group A during month 7 of additional therapy, and in five patients in Group B from months 13–23 of additional therapy. Ten patients in Group A and six in Group B completed the protocol and were included in analysis. Eight of the 10 patients in Group A experienced relapse between months 2 and 14 after the discontinuation of therapy, while three of the six patients in Group B experienced relapse between months 2 and 24. There was no difference in cumulative relapse rate between the groups (P = 0.275).
Conclusion: Additional therapy with lamivudine for longer than 12 months after biochemical and virological responses in patients with HBeAg-negative chronic hepatitis B could increase the risk of drug resistance, but did not reduce the rate of relapse.