甘肃地区乙型肝炎病毒分型和耐药突变分析

Genetyping and drug resistance mutation analysis of hepatitis B virus in Gansu area

目的 探讨甘肃地区乙型肝炎病毒(HBV)基因型分布特征及耐药情况,为乙型肝炎患者抗病毒用药提供指导依据。方法 选择2018年1月至2019年8月于该院就诊的131例乙型肝炎患者,通过Sanger测序法分析患者HBV基因型和耐药突变位点分布情况。结果 131例乙型肝炎患者共检出B、C、D 3种基因型。其中B型2例(1.53%),C型126例(96.18%),D型3例(2.29%)。检出51例核苷酸类似物耐药,总耐药率为38.93%,其中B型1例,C型49例,D型1例。耐药突变位点最多见于M204V/I,多位点突变以M204V/I+M204V联合突变多见,常在此基础上发生3位点、4位点甚至5位点突变。与阿德福韦酯相关的A181V/T、N236T、A181V/T+N236T耐单药突变最常见,共15例(29.41%)。耐多药突变36例(70.59%),主要以拉米夫定和替比夫定联合耐药为主,在此基础上多有恩替卡韦联合耐药发生。结论 甘肃地区HBV患者基因型以C型为主,耐药形势严峻,突变组合模式复杂多样,应及时检测患者HBV基因型及耐药突变位点,以评价乙型肝炎患者临床疗效,并指导临床抗病毒治疗合理用药。

Objective To analyze the genotype distribution characteristics and drug resistance situation of hepatitis B virus(HBV)in Gansu area,so as to provide a guidance basis for antiviral medication for the patients with hepatitis B.Methods A total of 131 patients with hepatitis B admitted to this hospital from January 2018 to August 2019 were selected.The distribution situation of HBV genotypes and drug-resistant mutation sites was analyzed by the Sanger sequencing method.Results Among 131 patients with hepatitis B,the genotype B,C and D were detected out,including 2 cases(1.53%)of type B,126 cases(96.18%)of type C and 3 cases(2.29%)of type D.Fifty-one cases of nucleotide drug resistance were detected with a total drug resistance rate of 38.93%,including 1 case of type B,49 cases of type C and 1 case of type D.M204V/I was the most common drug-resistant mutation site,and the M204V/I+M204V combined mutation was more common in multi-stie mutation.The mutations at three sites,four sites and even five sites often occurred on this basis.Adefovir dipivoxil-related A181V/T,N236T,and A181V/T+N236T single-agent mutations were the most common,which had 15 cases(29.41%).There were 36 cases(70.59%)of multi-drug mutations,which was dominated by lamivudine(LAM)and telbivudine(LDT)combined resistance,on this basis more Entecavir(ETV)combined resistance occurred.Conclusion The genotype in the patients with hepatitis B in Gansu area is mainly the genotype C,the drug resistance situation is severe,and its mutation combination forms are complex and diverse.Therefore,the HBV genotype and drug resistance mutation site should be detected in time to evaluate the clinical efficacy of the patients with hepatitis B and guide the drug rational use in clinical antiviral therapy.