恩替卡韦耐药位点阳性患者的回顾性分析

目的：探讨ETV变异位点及其相关临床意义。方法对本院临床实验室PCR室2013年1月至2013年7月使用PCR产物直接测序法检测出的18例HBV多聚酶序列ETV耐药位点T184、S202和（或）M250]变异阳性患者的临床状况进行回顾性分析。结果18例患者中有7例（38.9%）肝硬化患者，16例（88.9%）为核苷（酸）类药物经患者，且大多在LAM或LdT治疗失败后采取单药序贯治疗，部分患者的治疗依从性差。12例患者为典型的ETV耐药位点变异，均为（L180M＋M204V）＋T184A/L或S202G变异，其中12例（66.7%）患者检测出T184位点变异，6例患者（33.3%）检测出S202变异，未检测到M250位点的变异。有6例患者为不典型的ETV耐药位点变异，仅检出T184单一位点变异，此6例患者既往均未服用过ETV治疗。结论核苷（酸）类药物经治患者单药序贯治疗及患者的依从性差是ETV耐药发生的主要原因。ETV耐药一般在L180M＋M204V变异的基础上再加上T184、S202和（或）M250位点变异，但M250位点变异少见，而单一T184位点变异阳性并不代表对ETV产生耐药。

Retrospective analysis on the drug resistance of patients with entecavir points mutations positive

Objective To investigate the relationship between the ETV mutation loci and clinical and its clinical signiifcance. Method In our hospital clinical laboratory PCR room in between January 2013 and July 2013, the sequence of 18 cases of HBV polymerase ETV resistance loci （T184, S202 and/or M250） mutations detected by PCR product direct sequencing method in patients with positive clinical condition were analyzed, retrospectively. Results There were 7 （38.9%） cases among 18 cases of patients with cirrhosis, 16 （88.9%） cases were a nucleoside （acid） drugs by patients, and largely in LAM or LdT treatment failure after treated with single-agent sequential, part of the treatment of patients with poor compliance. There were 12 patients for typical ETV resistance loci mutation, who with （L180M ＋M204V） ＋T184A/L or S202G variations, 12 （66.7%） cases were detected T184 locus mutation while 6 （33.3%） cases were detected the S202 variation, and no M250 locus mutation were found. Six patients was not typical of ETV resistance loci mutation, only check out T184 single locus mutation,These 6 cases were treated without ETV. Conclusions Nucleoside （acid） drugs via treated patients with single-agent sequential treatment, and patients with poor compliance is the main cause of ETV resistance occurs. Born in L180M＋ETV resistance in M204V variation on the basis of plus T184, S202 and/or M250 locus mutation, but rare M250 variant, and positive does not represent a single T184 variant of ETV could occasionally result in drug resistance.