广东地区100例乙型肝炎患者核苷类似物耐药位点检测及分析  

The detection and analysis of nucleoside analog-resistant loci among 100 hepatitis B patients in the Guangdong area

作　　者：苏荣[1] 杨延斌[2] 黄婉琳[3] 罗娜[1] 何娴[1] 

机构地区：[1]佛山市中医院检验科,广东佛山528000 [2]佛山市中医院统计室,广东佛山528000 [3]广东医学院医学检验学院,广东佛山528000

出　　处：《现代预防医学》2016年第6期1092-1096,共5页Modern Preventive Medicine

基　　金：广东省佛山市医学类科技攻关项目(201208028)<慢性乙型肝炎患者E抗原不同血清学HBV基因分型及耐药位点的研究>

摘　　要：目的对样本血清进行核苷类似物的耐药突变位点检测,分析各耐药位点在人群中的发生率并以此为依据对含不同的耐药突变的患者提出相应的临床用药改进策略。方法采用PCR产物直接测序法,对筛选出的100例符合送检要求的乙肝患者血清标本进行6种核苷类似物共21个耐药突变位点的检测,并对结果进行统计分析。结果 100例标本中21个耐药突变位点均阴性,即表现为6种核苷类似物全敏感者共36例,有1种或2种以上药物敏感性改变者共64例发生率达64%。其中,拉米夫定(LAM)、替比夫定(Ld T)、恩曲他滨(FTC)耐药者均为32例,以rt M204I/V±rt L180M变异最多见。阿德福韦(ADV)耐药者29例,主要变异位点为rt N236T及rt A181T。恩替卡韦(ETV)耐药者7例,暂未发现替诺福韦(TDF)耐药病例。结论广东地区乙肝患者人群中对核苷类似物的耐药发生率较高,提示临床应用HBV耐药变异检测手段对患者进行核苷类似物耐药位点分析,有利于为患者设计合理的有针对性的个体化用药方案。Objective The study detected nucleoside analog- resistant mutation loci in serum specimens and analyzed the incidences of each of the drug- resistant loci in the population,aiming to provide a strategy for improving medication for patients with different drug- resistant mutations. Methods A total of 21 drug- resistant mutation loci corresponding to 6nucleoside analogs were detected in serum specimens of 100 qualifying patients with hepatitis B by direct sequencing of PCR products. The results were statistically analyzed. Results The 100 specimens were tested negative of all of the 21 drug-resistant mutation loci; in other words,a total of 36 cases were sensitive to all of the 6 nucleoside analogs. Changes in drug sensitivity to one drug or more than two drugs were observed in 64 of the cases,with an incidence of 64%. The number of patients resistant to lamivudine（ LAM）,telbivudine（ Ld T）,and emtricitabine（ ETC） were 32,respectively. The most common mutation was rt M204 I / V ± rt L180 M. 29 of the cases were resistant to adefovir（ ADV）,with the main mutation loci being rt N236 T and rt A181 T. 7 of the cases were resistant to entecavir（ ETV）. None was found to be resistant to tenofovir（ TDF）. Conclusion The incidence of nucleoside analog resistance is high among hepatitis B patients in Guangdong area,suggesting that analysis of nucleoside analog- resistant loci in the patients by detection of HBV resistance mutation is critical to designing rational,targeting,and individualized medication regimens for the patients.

关 键 词：乙肝 PCR 耐药突变位点 发生率 

分 类 号：R183[医药卫生—流行病学]