Selection of precore mutants during lamivudine treatment in patients with chronic hepatitis B.

Abstract

BACKGROUND/AIMS: Evolution of precore genes can occur during lamivudine therapy in HBV infection. This study investigated the changes in precore regions in patients treated with lamivudine and the pattern during relapse.

METHODOLOGY: The sequences of codon 28 in precore region in serial samples of 16 patients with HBV (11 HBeAg-positive and 5 HBeAg-negative) treated with lamivudine were analyzed by restriction fragment mass polymorphism.

RESULTS: Among 9 patients who had wild-type virus, the wild-type virus was replaced by A1896 during relapse after initial treatment in 2 patients, and a pure population with A1896 selected during relapse in all 4 patients with mixed infection. In 5 patients with A1896 during relapse, 3 patients initially reverted to wild-type and later selected A1896, and 2 patients maintained A1896 during lamivudine retreatment. In 8 patients showing HBeAg negative reactivation, 3 patients showed A1896 and 5 patients showed wildtype virus.

CONCLUSIONS: Lamivudine therapy induced initial reversion from precore mutants to wild-type virus, but precore mutants reappeared in patients infected with precore mutants. In some patients infected by wildtype HBV, wild-type HBV was replaced by precore mutants, resulting in a flare-up of hepatitis after cessation of lamivudine administration, and HBeAg negativity did not always correspond to the presence of precore mutants.