Objective: To study the efficacy of lamivudine treatment in chronic hepatitis B patients affected by structures of HBV P-genes.
Methods: P genes of HBV isolated from sera were amplified by means of one-step PCR and then sequenced. The sequences of the P-genes from responders, primary non-responders and rebounders were compared before and after their lamivudine treatments.
Results: (1) Among the primary non-responders and rebounders, commixture genotype B and C was found in 2 patients with genotype B and in 1 patient with genotype C; genotype shift from B into C was also observed in one patient after lamivudine therapy. (2) During the course of the therapy YMDD mutation emerged in all 8 primary non-responders and rebounders, which existed in some patients of the 3 groups before their lamivudine treatment. (3) An rtL164V mutation in the reverse transcriptase region was observed in all primary non-responders before and after lamivudine therapy and also in rebounders when viral breakthrough occurred, which was not seen in the responders. (4) Four amino acid substitutions at rt91, rt168, rt234 and rt256 in the reverse transcriptase region were seen in the rebounders and primary non-responders.
Conclusion: YMDD mutation was not the only key point closely linked to HBV resistant to lamivudine therapy. RtL164V may be a novel mutation correlated with lamivudine-resistance.