关键词: 肝炎,乙型,慢性；变异；核苷（酸）类似物；焦磷酸测序

Abstract:

Objective  To analyze the nucleoside(acid) analogues-resistant mutations at 10 sites of the P gene of hepatitis B virus(HBV). Methods  The 10 sites（rtI169T, rtV173L, rtL180M, rtA181V/T, rtT184G, rtA194T, rtS202I, rtM204V/I, rtN236T and M205V）of the HBV P gene were detected by Pyrosequencing in chronic hepatitis B (CHB) patients who had virologic breakthrough or inadequate virologic response during taking nucleoside(acid) analogues. Results  Lamivudine (LAM)  resistance of 8 modes at 4 sites was detected in 48 cases, in which rtM204 was the commonest. Adefovir dipivoxil ADV)resistance of 4 modes at 2 sites was detected in 10 cases, in which rtA181 was the commonest. Telbivudine (LdT)resistance of 2 modes at 2 sites was detected in 4 cases, and rtM204I existed in all of them. Entacavir (ETV) - resistance of 4 modes at 7 sites was detected in 6 cases, in which rtT184 was the commonest. Conclusions  Mutations in the HBV P gene can be detected during the nucleoside(acid) analogues treatment in CHB patients. We suggest that resistant mutations in CHB patients who developed virologic breakthrough be detected and individual therapy be performed.

Key words: Hepatitis B, chronic; Mutation; Nucleoside (acid) analogues; Pyrosequencing