恩替卡韦初治患者早期乙型肝炎病毒准种多样性变化与疗效关系的研究  被引量:3

Diversity evolution of hepatitis B virus quasispecies during the primary stage: correlation with longterm Entecavir antiviral efficacy

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作  者:刘斐[1] 武静[2] 黄潇潇[2] 刘寿荣[2] 

机构地区:[1]浙江中医药大学第二临床医学院,杭州310053 [2]杭州市西溪医院原杭州市第六人民医院

出  处:《中华实验和临床病毒学杂志》2014年第1期35-37,共3页Chinese Journal of Experimental and Clinical Virology

基  金:浙江省自然科学基金项目(Y2091061);杭州市卫生科技计划(一般)项目(2011A040)

摘  要:目的 观察恩替卡韦(Entecavir,ETV)初治慢性乙型肝炎(CHB)患者治疗前后乙型肝炎病毒逆转录区(HBV RT)准种多样性的变化,探讨治疗4周时准种多样性的变化与抗病毒持续病毒学应答的关系.方法 收集64例初始ETV治疗(0.5 mg/d)的慢性乙型肝炎患者资料,并留取各患者用药0、4、12、24、36和48周血清标本,其中有22例患者在治疗4周时HBV DNA> 1E +3 IU/ml,其余均发生了快速病毒学应答.根据治疗12周时HBV DNA是否转阴,将这22例患者分为完全应答组(对照组11例)和应答不佳组(实验组11例).对两组患者基线和4周的血清标本进行HBV RT区基因扩增,对目的片段进行T-A克隆,每个标本挑取20 ~ 30个克隆并测序.结果 治疗前两组患者的HBV准种多样性差异无统计学意义(P>0.05),但完全应答组患者在治疗第4周时的准种多样性较应答不佳组明显增加,差异具有统计学意义(P<0.05).结论 在抗病毒药物的压力下,CHB患者HBV RT区准种发生不同的变化,治疗4周准种多样性的变化与ETV抗病毒治疗持续病毒学应答密切相关.Objective To investigate the diversity evolution of hepatitis B virus(HBV) quasispecies during the long-term entecavir therapy and its impact on the virological reponse.Methods Sixty-four chronic hepatitis B patients were received Entecavir therapy for the first time.Serum samples were collected at six different time points during Entecavir therapy (0,4,12,24,36,48weeks,respectively).Twenty-two patients could be detected HBV DNA at week 4,which were divided into two groups according to the therapeutic effect at week 12:complete response group (ll cases) and partial response group (11 cases).The sequence of HBV RT region was amplified by polymerase chain reaction(PCR) and cloned into T-vector for these serum samples at baseline and week 4.Twenty to thirty clones per sample were selected,sequenced and analyzed.Results Despite comparable at baseline,the diversity change of HBV quasispecies in complete responders were statistically higher than those of partial reponders in week 4 (P 〈 0.05).Conclusion The HBV quasispecies changed during the primary stage of Entecavir treament.And the heterogeneity of HBV quasispecies during the first 4 weeks was significant association with the long term therapeutic outcome of Entecavir.

关 键 词:肝炎 乙型 慢性 恩替卡韦 

分 类 号:R512.62[医药卫生—内科学]

 

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