HBV准种变异预测核苷(酸)类似物治疗HBeAg阳性慢性乙型肝炎持续疗效的初步研究  

Primary research of HBV P gene quasispecies as an predictor for nucleos (t) ide analog (ue) treatment of chronic hepatitis B patients with HBeAg positive

作　　者：罗志雄[1] 刘映霞[1,2] 彭忠田[1] 李红梅[1] 

机构地区：[1]南华大学附属第一医院感染科,湖南衡阳421001 [2]深圳市第三人民医院

出　　处：《中华实验和临床感染病杂志（电子版）》2009年第2期16-20,共5页Chinese Journal of Experimental and Clinical Infectious Diseases(Electronic Edition)

基　　金：国家教委留学回国人员基金;湖南省自然科学基金(06jj4106);深圳市科技计划重点项目基金

摘　　要：目的观察核苷(酸)类似物治疗HBeAg阳性的慢性乙型肝炎患者的HBV聚合酶(HBV-P)基因序列的准种组成及其变异特点,探讨其与抗病毒疗效的关系。方法巢式PCR法扩增HBV-P基因中覆盖B区～E区序列的基因片段,PCR产物纯化后直接测序以评估HBV准种的复杂性。观察拉米夫定治疗完全应答组、部分应答组和无应答组患者治疗前、治疗12周和24周的准种组成并分析其与疗效的关系。疗效评估包括血清学、病毒学、血液生物化学和综合应答。结果拉米夫定治疗2年,完全应答者36例,部分应答者59例,无应答者32例。HBV DNA转阴率81.2%(103/127),HBeAg/HBeAb血清转换率37.9%(48/127)),ALT复常率86.4%(109/127)。治疗前、治疗后24周、48周、96周时YMDD变异率分别为0、2.4%(4/165)、11.2%(18/161)和25.9%(38/147)。所有患者HBV准种变异在治疗前、治疗12周和24周时均有不同程度的改变,无应答组12周与24周时HBV准种复杂性显著高于完全应答组(P<0.001)。结论HBV P区准种变异的复杂性与慢性乙型肝炎患者拉米夫定抗病毒治疗的持续疗效存在相关性,治疗12周与24周时的HBV准种变异可能作为核苷(酸)类似物抗病毒持续疗效的预测指标之一。Objective To investigate the relationship between hepatitis B virus P gene （HBV-P） quasispecies mutants and nucleos （t）ide analogues treatment effect in chronic hepatitis B patients with HBeAg positive. Methods HBV quasispecies were determined by nested polymerase chain reaction （NT- PCR） and DNA sequence analysis. One hundred and sixty five patients were treated with lamivudine 100 mg once daily for 9 to 24 months. Therapeutic effect evaluation involved serum HBV DNA level, HBeAg/HBe- Ab seroconversion and biochemical response. According to the therapeutic effect, patients were divided into three groups including the long term complete responders （ CRL）, partial responders （PR） and non respond- ers （NR）. Analysis of the relationship between HBV-P quasispecies and nucleos（t） ide analogues treatment effect was carried out. Results Of the 165 patients received lamivudine for two years, thirty six reached CRL, fifty nine reached PR and 32 were NR. The ratios of HBV DNA negative, HBeAg/HBeAb seroconvero sion and normal alanine aminotransferas （ALT） were 81.2% （ 103/127 ）, 37.9% （48/127） and 86.4 % （109/127）, respectively. YMDD mutants was not discovered before therapy, but were found in 2.4% （4/165） patients on the 6th month, 11.2% （18/161） on the 12th month and 25.9% （38/147） on the 24th month. All the quasispecies were different among the three groups during treatment of lamivudine. The quasispecies mutation was distinctly different between the group CRL and NR on the 12th,24th week of treat- ment （P 〈 0. 001 ） . Conclusions The complexity of HBV quasispecies was correlated with therapy effect. HBV quasispecies mutations on the 12th week and the 24th week was an important predictor for nucleos（t） ide analog（ue） treatment of chronic hepatitis B patients with HBeAg positive.

关 键 词：乙型肝炎病毒 准种 疗效 拉米夫定 

分 类 号：R512.62[医药卫生—内科学] R512.620.3[医药卫生—临床医学]