核苷类似物干预下慢性乙型病毒性肝炎患者HBV多聚酶区基因突变检测分析  

Mutation patterns in polymerase gene for chronic hepatitis B patients with nucleotide analogue therapy

作　　者：谭朝霞[1] 汤影子[1] 况雪梅[1] 范熠[1] 丁世涛[1] 

机构地区：[1]第三军医大学西南医院全军感染病研究所,重庆400038

出　　处：《重庆医学》2011年第13期1254-1256,共3页Chongqing medicine

摘　　要：目的研究重庆地区慢性乙型病毒性肝炎(慢乙肝)患者核苷类似物治疗过程中HBV多聚酶区(P)基因变异情况。方法选取350例接受核苷类似物治疗后出现病毒学突破的慢乙肝患者作为研究对象,采用PCR产物直接测序法,分析HBV P区基因变异发生情况。结果 350例患者中有124例检测出基因型耐药,C基因型在基因型耐药患者中所占比例显著高于无基因型耐药患者的比例(P<0.001)。突变类型共计23种,其中以rtM204I突变最多见(41,33.1%),其次为rtL180M/rtM204V联合突变(25,20.1%)。主要核苷类似物耐药所占比例最高为拉米夫定(60.5%),其次为阿德福韦(21.8%)及替比夫定(16.1%)。结论 HBV P区基因耐药的氨基酸突变复杂多变,rtM204V/I突变最为常见。基因C型患者更易出现基因型耐药。Objective To investigate the mutation patterns in the polymerase gene for chronic hepatitis B patients with nucleotide analogue therapy in Chongqing area.Methods Serum samples from 350 chronic hepatitis B patients with virologic breakthrough during nucleotide analogue therapy were studied.Using the PCR-sequencing method,the resistant mutation patterns in the polymerase gene of hepatitis B virus（HBV）were analyzed.Results Resistant mutations were detected in 124 patients.The proportion of HBV genotype C in the patients with resistant mutation was significantly higher than that in the patients without resistant mutation（P0.001,χ2=25.385）.23 types of resistant mutations were detected,in which the ratio of rtM204I mutation was the highest（n=41,33.1%）,and rtL180M/rtM204V combined mutation came to be the next（n=25,20.1%）.For all the patients with genotype resistance,60.5% patients showed lamivudine-resistant mutations,while 21.8% and 16.1% showed adefovir and telbivudine-resistance respectively.Conclusion There are many types of mutation patterns in the polymerase gene for chronic hepatitis B patients receiving nucleotide analogue therapy.The patients with HBV genotype C may be more susceptible to develop resistant mutations.

关 键 词：肝炎 乙型 基因型 药物耐受性 乙型肝炎多聚酶区基因突变 核苷类似物 

分 类 号：R512.62[医药卫生—内科学]