Analysis on the mutation patterns of HBV polymerase gene in patients with Lamivudine resistant chronic hepatitis B / 解放军医学杂志

ABSTRACT

Objective To analyze the clinical features and mutation patterns of HBV polymerase gene in patients with chronic hepatitis B(CHB) after the emergence of drug-resistance during Lamivudine(LAM) therapy.Methods LAM-resistant mutations were detected by direct sequencing of the HBV polymerase gene in hospitalized patients and outpatients of CHB with LAM-resistance in Changhai Hospital from Dec.2005 to Dec.2007.Clinical features after the emergence of LAM-resistant mutations were retrospectively analyzed.Results Two hundred and fifteen patients with CHB were diagnosed as LAM-resistant.Among them 192 patients were found to have LAM-resistant-associated mutations in the HBV polymerase gene.The mean value of serum HBV DNA was 6.25?1.31(log10copies/ml),the mean value of alanine aminotransferase(ALT) was 75U/L(ranged 19-821 U/L).ALT elevation and hepatitis recrudescence were found in 139 among 192(72.4%) patients.99.0%(190/192) patients had YMDD mutations.Four major mutation patterns of LAM-resistant HBV were identified as rtM204I(33.9%),rtL180M+rtM204V(26.0%),rtL180M+rtM204I(21.9%) and rtV173L+rtL180M+rtM204V(11.5%).The rtM204V mutation was accompanied more frequently by the rtL180M mutation compared with the rtM204I mutation(P0.05).Conclusions YMDD is the major mutation pattern of HBV polymerase gene after emergence of LAM-resistance.The mutation patterns of HBV polymerase gene are possibly not related to the clinical severity of CHB patients during LAM therapy.