核苷（酸）类似物治疗的慢性乙型肝炎患者HBVRT区突变序列分析  

Mutation analysis of the HBV reverse transcriptase in nucleos （t） ide-treated patients with chronicHBV infection

作　　者：焦秀娟[1] 彭勋[1] 焦秀敏[2] 王晋生[1] 孙谢文[1] 赵培丽[1] 王守云[1] 刘加群[1] 李彤[3] 杨静娴[3] 

机构地区：[1]秦皇岛市第三医院,066000 [2]北京军区总医院 [3]北京大学医学部病原生物学系

出　　处：《中华实验和临床病毒学杂志》2012年第6期453-455,共3页Chinese Journal of Experimental and Clinical Virology

基　　金：秦皇岛市科学技术研究与发展计划项目（2010028034）

摘　　要：目的分析使用过核苷（酸）类似物（NA）治疗的慢性乙型肝炎患者体内HBVRT区基因耐药特点。方法收集229例接受过核苷类似物治疗的慢性乙型肝炎患者的血清，应用snPCR法扩增HBV全长RT区，纯化snPCR产物直接测序后分析11个经典耐药位点的氨基酸变异情况。结果229例患者中基因B和C型各占14．41％（33／229）和85．59％（196／229）。且c型患者较B型更易发生耐药变异（X2=2．95，P〈0．05）。共有63例检出HBV耐药变异，在rtll69、rtTl84、rtAl94和rtS202位点上均未检出耐药变异。在63个耐药变异株中rtM204V／l变异株检出率最高（40／63，63．49％），共有11种耐药突变模式。其中rtM204I以与rtL80I／V或rtLl80M联合变异为主，而rtM204V变异常伴有rtLl80M变异。结论使用过核苷（酸）类似物（NA）治疗的慢性乙型肝炎患者体内HBVRT区基因耐药呈现出复杂的变异类型，rtM204V／I突变最为常见。Objective To characterize genotypic resistance within H BV RT region in chronic hepatitis B （CHB） patients with nucleos （t）ide analogue （NA） treatment. Methods Serum samples of 229 CHB patients with NA treatment were obtained. Full-length HBV RT sequences were amplified, sequenced and analyzed, on the following NA resistant （NAr） mutations belonging to different NAr pathways. Results Among 229 HBV isolates, 14.41% （33/229） and 85.59% （196/229） were genotype B and C, respectively;and the patients with HBV genotype C may be more susceptible to develope resistant mutations than patients with HBV genotype B（X2 = 2.95 ,P 〈 0. 05 ）. NAr mutations were detected in 63 CHB patients. Mutations were not found at rtI169, rtT184, rtA194 or rtS202. RtM204 mutations were detected at the highest frequency among 63 mutants （40/63,63.49%） and found to display 11 combination mutation patterns, in which rtM204I were associated with rtL80I/V and rtL180M, and rtM204V were associated with rtL180M, respectively. Conclusions There are complicated mutation patterns in the HBV RT region for chronic hepatitis B （CHB） patients with nucleos（t） ide analogue （NA） treatment. RtM2OgV/I mutation was the highest.

关 键 词：肝炎病毒 乙型 基因型 药物耐受性 苷类 

分 类 号：R512.62[医药卫生—内科学]