慢性丙型肝炎和丙型肝炎肝硬化患者HCV NS5A和NS5B抑制剂天然耐药变异分析  

HCV NS5A and NS5B inhibitor natural resistance mutations in patients with chronic hepatitis C and hepatitis C cirrhosis

作　　者：邓浩辉 许敏 刘惠媛 高洪波 卓丽 DENG Hao-hui;XU Min;LIU Hui-yuan;GAO Hong-bo;ZHUO Li(Department of Liver Disease,Guangzhou Eighth People's Hospital,Guangzhou Medical University,Guangzhou,Guangdong 510060,China)

机构地区：[1]广州医科大学附属市八人民医院重症肝病科,广东广州510060

出　　处：《热带医学杂志》2020年第4期484-488,共5页Journal of Tropical Medicine

基　　金：广东省医学科学技术研究基金(A2017142);广州市卫生健康科技项目(20191A011037)。

摘　　要：目的探讨慢性丙型肝炎和丙型肝炎肝硬化患者丙型肝炎病毒(HCV)NS5A和NS5B抑制剂天然耐药变异的差异。方法收集158例广州医科大学附属市八人民医院住院或门诊的慢性丙型肝炎和丙型肝炎肝硬化患者的血清标本,使用Illumina二代测序平台进行测序,比较两组患者不同基因型HCV NS5A和NS5B抑制剂相关天然耐药变异的差异。结果共纳入72例慢性丙型肝炎和86例丙型肝炎肝硬化患者,除HCV1b基因型外,其他基线资料差异无统计学意义(P>0.05)。慢性丙型肝炎患者存在A30K、L31M、P58S和Y93H等HCV NS5A抑制剂耐药相关变异,丙型肝炎肝硬化患者存在Q24R、A30K、L31M、P/T58S/A和Y93H等HCV NS5A抑制剂耐药相关变异,各基因型两组患者的HCV NS5A抑制剂耐药相关变异差异无统计学意义(P>0.05)。慢性丙型肝炎患者存在L159F、T179A、I293L和C316N等HCV NS5B抑制剂耐药相关变异,丙型肝炎肝硬化者存在L159F、T179A、S282T、I293L、C316N和L320F等HCV NS5B抑制剂耐药相关变异,各基因型两组患者HCV NS5B抑制剂耐药相关变异差异亦无统计学意义(P>0.05)。结论慢性丙型肝炎和丙型肝炎肝硬化患者的HCV NS5A和NS5B抑制剂相关天然耐药变异差异无统计学意义,丙型肝炎肝硬化患者较低的持续病毒学应答率可能与丙型肝炎肝硬化患者天然耐药变异无关。Objective To detect the mutations in hepatitis C virus(HCV)NS5 A and NS5 B genes in chronic hepatitis C and hepatitis C cirrhosis patients.Methods A total of 158 HCV infected patients were enrolled in this study.Next-generation sequencing(Illumina platform,PE300)was used to detect the drug resistance mutations.DAAs resistant associated variants of HCV NS5 A and NS5 B genes were compared in chronic HCV patients and HCV related liver cirrhosis patients within different HCV genotypes.Results 72 cases of chronic HCV patients and 86 cases of HCV related liver cirrhosis patients were enrolled.The baseline characteristics between chronic HCV and HCV related liver cirrhosis patients(P>0.05)did not differ except the HCV genotype.A30 K,L31 M,P58 S and Y93 H mutations in NS5 A gene of chronic HCV patients while Q24 R,A30 K,L31 M,P/T58 S/A and Y93 H mutations in NS5 A gene were found in HCV related liver cirrhosis patients;the naturally occurring DAAs resistance mutations of HCV NS5 A did not differ between chronic HCV patients and HCV related liver cirrhosis patients in different HCV genotypes(P>0.05).L159 F,T179 A,I293 L and C316 N mutations in NS5 B gene were found in chronic HCV patients while L159 F,T179 A,S282 T,I293 L,C316 N and L320 F mutations in NS5 B gene were found in HCV related liver cirrhosis patients;the naturally occurring DAAs resistance mutations of HCV NS5 B gene also did not differ between chronic HCV patients and HCV related liver cirrhosis patients in different HCV genotypes(P>0.05).Conclusion The naturally occurring DAAs resistant associated variants of HCV NS5 A and NS5 B genes between chronic HCV patients and HCV related liver cirrhosis patients did not differ,and the lower SVR in HCV related liver cirrhosis patients treated by DAAs might not be associated with drug resistance mutations.

关 键 词：慢性丙型肝炎 肝硬化 丙型肝炎病毒 耐药变异 

分 类 号：R512.63[医药卫生—内科学] R575.2[医药卫生—临床医学]