实用肝脏病杂志 ›› 2016, Vol. 19 ›› Issue (1): 60-63.doi: 10.3969/j.issn.1672-5069.2016.01.015

• 肝硬化 • 上一篇    下一篇

耐核苷(酸)类药物慢性乙型肝炎和肝硬化患者血清HBV基因型和P区耐药突变位点分析*

谢巧灵, 丛庆伟, 吴凌虹, 朱英   

  1. 116000 辽宁省大连市大连医科大学附属第一医院感染病科
  • 收稿日期:2015-04-17 出版日期:2016-01-10 发布日期:2016-02-04
  • 通讯作者: 朱英,E-mail:zhuyingsh52@126.com
  • 作者简介:谢巧灵,女,24岁,硕士研究生。E-mail: 13354282583@163.com
  • 基金资助:
    *基金项目:国家自然科学基金资助项目(编号:81273925)

HBV genotypes and P gene resistant mutants in hepatitis B patients during nucleos(t)ide analogues treatment

Xie Qiaoling, Cong Qingwei, Wu Linghong, Zhu Ying   

  1. Department of Infectious Diseases. First Affiliated Hospital,Dalian Medical University,Dalian 116000,Liaoning Province,China
  • Received:2015-04-17 Online:2016-01-10 Published:2016-02-04

摘要: 目的了解慢性乙型肝炎和肝硬化患者HBV基因型分布和P区耐药突变位点的变异模式。方法选择39例经核苷(酸)类似物(NAs)治疗后存在耐药或疑似耐药的慢性乙型肝炎和肝硬化患者为研究对象,采用实时荧光定量PCR法测定血清HBV DNA,将PCR产物经琼脂糖凝胶电泳,鉴定和回收纯化后,交由上海生工生物工程(北京)有限公司进行测序,与HBVseq数据库比对,观察HBV基因型分布和耐药位点变化情况。结果34例(87.2%)患者能检出HBV基因型,其中C基因型有32例(82.1%),B基因型有2例(5.1%);27例(69.2%)患者存在RT区序列突变,其中点变异12例(30.8%),rtM204I/V/S、rtA181V/T、rtI169T突变分别占15.4%、5.1%、10.3%,组合变异15例(38.4%);23例患者存在对NAs耐药,其中8例患者对阿德福韦酯耐药(1例为B基因型,7例为C基因型),耐药位点为rtA181V/T/S、rtV214A/E和rtN236T;11例患者对拉米夫定和替比夫定同时耐药,均为C基因型,其共同耐药位点为rtM204I/V/S和rtL180M;3例患者存在对LAM、LDT和恩替卡韦同时耐药,均为C基因型;1例C基因型患者对LAM、LDT和ADV同时耐药,其变异模式为rtM204I/V/S+rtA181V/T/S+rtL180M。结论多数对NAs耐药患者可在HBV P区检出基因突变,且突变形式多样,其中以rtM204I/V/S突变为主,不同核苷(酸)类似物中存在共同耐药位点。

关键词: 乙型肝炎, HBV基因型, 核苷(酸)类似物, 突变

Abstract: Objective To investigate the distribution characteristics of hepatitis B virus genotypes in patients with CHB or hepatitis B cirrhosis,and to explore the mutants patterns in HBV P gene sequences during nucleos(t)ide analogue(NAs) treatment. Methods 39 patients with CHB or hepatitis B cirrhosis observed drug resistance or suspected drug resistance were enrolled. Serum HBV DNA levels was detected by real time PCR, and then sequenced and compared with standard sequence in HBVseq datebase. Results The genotypes of HBV in 34(87.2%) patients were observed,and the genotype C was found in 32(82.1%),and genotype B in 2 (5.1%). 27(69.2%) of 39 patients were observed carrying mutation in RT gene sequence;point mutations accounted for 30.8%,including 6 harboring rtM204I/V/(15.4%),2 harboring rtA181V/T(5.1%),and 4 harboring rtI169T (10.3%),and combination mutations were 38.4%;there were 23 patients detected to be resistant to NAs. 8 patients were resistant to adefovir dipivoxil(ADV),and among them,one was genotype B,and the other 7 were genotype C,harboring rtA181V/T/S,rtV214A/E or rtN236T;11 patients were resistant to both lamivudine(LAM) and telbivudine (LDT) with genotype C,harboring rtM204I/V/S or rtL180M;3 patients were resistant to LAM,LDT and entecavir(ETV),and they were all with genotype C;1 patient with type C was resistant to LAM, LDT and ADV, and the mutation pattern was rtM204I/V/S+rtA181V/T/S+rtL180M. Conclusion HBV P mutations exist in most patients with chronic hepatitis B;the rtM204I/V/S mutations is the dominate mutation pattern,and different NAs may share the common mutations.

Key words: Hepatitis B, HBV genotypes, Nucleos(t)ide analogues, Mutation