乙型肝炎病毒基因分型与耐药突变基因位点的检测分析

Analysis of HBV Genotyping and Drug-Resistance Associated Mutations

目的分析乙型肝炎病毒(HBV)基因型及耐药突变基因位点,为指导临床抗病毒治疗合理用药提供依据.方法回顾分析2014年3月~2016年10月安徽中医药大学第一附属医院114例乙型肝炎患者HBV基因分型和拉米夫定(LAM)、替比夫定(LdT)、阿德福韦酯(ADV)和恩替卡韦(ETV)四种核苷类药物(NAs)耐药及耐药突变位点分布情况、HBV核酸(HBV DNA)定量、HBVE抗原(HBeAg)定量、丙氨酸氨基转移酶(ALT)的浓度、血小板(PLT)的含量.结果114例乙型肝炎患者中检测出HBV基因C型61例,B型45例,D型3例,B+C混合型1例,B+D混合型1例,其他基因型5例.其中C型多于B型(P<0.05).检出39例NAs耐药,耐药率为34.21%;C型与B型耐药无显著差异.C型患者HBeAg定量高于B型患者(P<0.05),PLT计数低于B型患者(P<0.05).耐药突变位点最多见于rt204I;C型多位点突变高于B型(P<0.05).LAM和LdT联合耐药最多见,两种及两种以上多重耐药高于单一耐药(P<0.01).结论本研究中乙型肝炎患者HBV基因型多为C型,其次为B型.C型患者容易发生肝纤维化,更易发生多位点突变.NAs耐药以LAM和LdT联合耐药为主,多为两种以上联合耐药.检测HBV基因型和耐药突变基因位点对评价乙型肝炎临床治疗效果和指导临床抗病毒治疗合理用药具有十分重要的意义.

Objective To analyze the genotypes and mutation sites of hepatitis B virus(HBV)associated with drug resistance.Methods A retrospective analysis was conducted in HBV genotypes,nucleoside drugs(NAs)resistance including lamivudine(LAM),telbivudine(LdT),adefovir dipivoxil(ADV)and entecavir(ETV).Drug resistance mutations,HBV DNA,HBeAg,alanine aminotransferase(ALT)and platelet(PLT)were detected in 114 patients with hepatitis B between 2014 and 2016.Results Sixty-one of 114 patients were found to carrywith HBV genotype C,45 with genotype B,3 with genotype D,one with recombinant B/C,one with recombinant B/D and 5 with other genotypes.Type C had a high frequency(P<0.05).Thirty-nine(3 4.2 1%)cases carried NAs resistance mutations.No significant difference of NAs resistance mutations was seen between types C and B.The patients with type C had significantly decreased HBeAg(P<0.05)and low PLT(P<0.05)compared with type B.The most common drug resistance mutation was found in rt204I.Multilocus mutation of type C was more commonly detectable than that of type B(P<0.05).The combinated resistance of HBV to LAM and LdT,and two or more multiple drug resistance weremost common(P<0.01).Conclusion The genotype C of HBV dominated in this study,followed by genotype B.Patients with genotype C are prone to hepatic fibrosis and multiple site mutations,and the HBV resistance was frequently noted to LAM and LdT.The results indicated that HBV genotyping and drug resistance mutation detectionmay help evaluatethe clinical efficacy of antiviral therapy.