核苷(酸)类似物相关HBV P基因区耐药变异的焦磷酸测序

Pyro-sequencing of nucleoside (acid) analogues-resistance mutation of the P gene of hepatitis B virus

目的分析HBV P基因区核苷(酸)类似物相关10个位点的变异情况。方法采用焦磷酸测序法对NA治疗并发生病毒学突破或不充分病毒学应答的慢性乙型肝炎患者HBV P基因区10个位点(rtI169T、rtV173L、rtL180M、rtA181V/T、rtT184G、rtA194T、rtS202I、rtM204V/I、rtN236T、M205V)进行检测。结果拉米夫定(LAM)耐药48例,4个耐药位点呈8种模式,以rtM204为主;阿德福韦酯(ADV)10例,2个耐药位点呈4种模式,以rtA181为主;替比夫定(LdT)4例,2个耐药位点呈2种模式,均存在rtM204I;恩替卡韦(ETV)6例,7个耐药位点呈4种模式,以rtT184多见。结论应用NA可筛选出HBV P基因区的相关耐药变异,建议病毒突破患者检测耐药并行个体化治疗。

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 virological breakthrough or an inadequate virological response while 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 nucleoside（acid）analogues treatment in CHB patients.We suggest that resistant mutations in CHB patients who developed virological breakthrough be detected and individual therapy be performed.