鄂西北地区慢性乙型肝炎患者HBV基因型与耐药突变的研究

摘要

目的:分析鄂西北地区慢性乙型肝炎患者乙型肝炎病毒(HBV)基因分型与耐药突变的分布及其临床特点.方法:回顾性研究2011.1-2016.11太和医院感染科病房及门诊基因测序法和基因芯片法检测的324例慢性乙型肝炎患者的HBV基因型、常见核苷(酸)类似物(NAs)耐药突变位点、肝功能指标、HBV DNA定量及临床特点等,并分析其相关性.结果:基因测序法检测238例,芯片法86例,其基因分型均以B型为主,基因芯片法中可以检测到少量D型及混合基因型.共132例患者检测出NAs耐药,耐药突变位点以204位点最多见,B、C基因型耐药率及临床表现的差异无统计学意义,耐药位点整体分布存在差异,但NAs耐药分布一致,均以拉米夫定耐药为主.结论:鄂西北地区慢性乙型肝炎患者的HBV基因分型以B型为主,C型次之,B、C基因型患者耐药突变位点的分布存在一定差异,但其耐药率、临床表现及NAs耐药分布差异无统计学意义. B型患者无NAs抗病毒治疗史患者NAs耐药率高于C型患者.%Objective:To investigate the distribution and clinical characteristics of hepatitis B virus (HBV) genotypes and drug resistance mutations in patients with chronic HBV infection in northwest of Hubei Province.Methods:From Jan 2011 to Nov 2016,a total of 324 patients with Hepatitis B who were admitted to the department of infectious diseases of Taihe Hospital,Hubei University of Medicine received HBV genotyping and drug resistance mutations analysis by gene sequencing or gene chipassay.HBV genotypes,common mutation sitesrelated tonucleoside (acid) analogues (NAs),liver function index,HBV DNA viral loads and clinical characteristics of patients were extracted from clinical databases of Taihe Hospital,Hubei University of Medicine.The relationships among these parameters were statistically analyzed.Results:HBV genotypes of 238 samples were detected by gene sequencing,and the other 86 cases by gene chip assay.Genotype B was the most common genotype,and a few of type D and mixed genotypes could be detected by gene chip assay.A total of 132 patients were found to have NAs related resistant mutant,and the most common mutation was M204I/V.There were no significant difference between genotype B and C in the rate of NAs related resistance and clinical manifestations.The profiles of the NAs-related mutations were different,while the distribution of NAs-related resistance were consistent,with lamivudine resistance primarily.Conclusion:Genotype B was the most common HBV genotype in northwest of Hubei province,followed by genotype C.There were some differences between the genotype B and C in the distribution of NAs-related resistant mutation sites,but nostatistical difference was found in the rate of NAs-related resistant,clinical manifestations,or the distribution of NAs-related resistance.NAs-related resistance rate in patients without NAs antiviral treatment history was much higher in genotype B than that ingenotype C patients.