HBV基因型及服药依从性与NAs耐药突变位点的相关性  

The correlation of hepatitis B virus genotypes and medication compliance with the occurrence of nucleos(t)ide analogues drug-resistance mutations

作　　者：杨国绘 窦琳琳[1] 汪敏[1] 刘军[1] 夏大静 YANG Guo-hui;DOU Lin-lin;WANG Min;LIU Jun;XIA Da-jing(Zhejiang Xiaoshan Hospital,Xiaoshan,Zhejiang 311201,China)

机构地区：[1]浙江萧山医院临床医学检验中心,浙江萧山311201 [2]浙江大学医学院感染与免疫研究中心,浙江杭州310058 [3]浙江大学公共卫生学院,浙江杭州310058

出　　处：《中华医院感染学杂志》2018年第19期2964-2968,共5页Chinese Journal of Nosocomiology

基　　金：国家自然科学基金资助项目(31471297);杭州市萧山区重大科技公关基金资助项目(2015208)

摘　　要：目的分析本地区核苷(酸)类似物[Nucleos(t)ide analogues,NAs]相关耐药位点的突变特征,进一步探讨乙型肝炎病毒(HBV)基因型及服药依从性与其之间的相关性。方法收集2015年1月-2016年12月医院肝炎门诊具有明确服用一种或两种以上NAs抗病毒治疗的慢性乙型肝炎(CHB)患者血清标本186例。采用聚合酶链锁反应(PCR)反向点杂交法检测血清HBV基因型及与NAs耐药相关的DNA聚合酶P区8个位点(rt180、rt181、rt184、rt202、rt204、rt207、rt236、rt250)的突变状况,采用调查问卷法了解患者服用NAs依从性。结果186例CHB患者,检出HBV基因B、C、B+C混合型及未分型分别为68、106、5、7例。检出耐药突变基因共72例,其中HBV基因C型患者耐药突变率为48.11%(51/106)高于HBV基因B型患者30.88%(21/68)(P=0.028),B+C混合型5例及未分型7例均未检出耐药突变基因。在72例基因位点变异的患者中,HBV基因B型患者以rt204I/rt236T单位点突变为主,占76.19%(16/21),HBV基因C型患者以双位点(rt204I/V+rt180 M、rt250V/L+rt181T)和多位点突变为主,分别占54.90%(28/51)和29.41%(15/51),不同突变位点在HBV基因B、C型患者中差异有统计学意义(P=0.001)。186份调查问卷结果显示,依从性良患者耐药突变率为29.21%(26/89)低于依从性差患者耐药突变率47.42%(46/97)(P=0.016)。结论萧山区服用NAs抗病毒治疗的CHB患者HBV基因型以B、C型为主,C型较高,感染HBV基因C型患者的耐药突变率高于HBV基因B型患者且突变模式较为复杂。依从性是引起核苷(酸)类药物耐药的重要原因,提高患者服药依从性,可减少耐药突变基因的产生。OBJECTIVE To investigate the characteristics of the nucleos（t）ide analogues（NAs）related drug-resistance mutations in Xiaoshan area,and further analyze the correlation of the occurrence of NAs related drug-resistance mutations with medication compliance and hepatitis B virus genotypes.METHODS A total of 186 patients infected with chronic hepatitis B virus（CHB）which were treated with NAs from Jan.2015 to Dec.2016 were enrolled and the serum samples were collected.PCR reverse dot hybridization technology was performed to detect the HBV genotype（HBV-B/C/D）and the drug-resistance mutations related with NAs in the 8 sites of hepatitis B virus DNA polymerase P area（rt180,rt181,rt184,rt202,rt204,rt207,rt236,rt250）.Questionnaire was used to understand the patient＇s medication adherence.RESULTS Among the 186 CHB patients,68,106,5 and 7 cases of HBV gene B,C,B ＋ C mixed and undivided type were detected respectively.A total of 72 cases of drug-resistance mutations were detected.The drug-resistance mutation rate of HBV-C genotype was 48.11%（51/106）,which was higher than that in HBV-B genotype patients（30.88%,21/68）（P=0.028）,whereas drug-resistance mutation was not found in B＋ C mixed nor undivided type patients.The dominant drug-resistance mutation was single site（rt204I/rt236T）in patients with HBV genotype B,and genotype C patients were dominated by double-loci（rt204I/V＋rt180M,rt250V/L ＋rt181T）and multiple-sites（more than 3 sites,such as：rt204I/V ＋rt250V/L＋rt180M）mutations,which accounted for 54.90%（28/51）and 29.41%（15/51）respectively,the difference was significant（P=0.001）.The results of 186 questionnaires showed that the drug-resistance mutation rate in poor adherence group was 47.42%（46/97）,which was significantly higher than that in good adherence group（29.21%,26/89）（P=0.016）.CONCLUSIONThe main genotypes were HBV-B and C of CHB patients with NAs treatment in Xiaoshan area,and the dominant genotype was HBV-C.The NAs drug-resistance rate of

关 键 词：乙型肝炎病毒 基因型 依从性 耐药基因 核苷(酸)类似物 

分 类 号：R512.62[医药卫生—内科学]