昆明地区乙型肝炎患者基因型和耐药情况分析

Analysis of Genotype and Drug Resistance of Patients with Hepatitis B in Kunming

目的分析昆明地区乙型肝炎患者基因型和HBV核苷(酸)类似物耐药相关的10个位点的突变情况及其临床意义。方法选取昆明市第三人民医院2017年5月至2019年3月期间,住院及门诊就医的2707例慢性乙肝患者,采用Sanger测序法进行常见的核苷(酸)类治疗乙肝病毒的相关耐药基因突变位点检测,并分析不同耐药的突变模式。结果昆明地区HBV基因型以C型为主占62.4%,B型次之占37.3%,D型也有发现占3.4%,2707例患者中,共有274例(10.1%)患者检测到发生耐药基因突变,变异率为10.12%。其中,168例患者发生拉米夫定耐药突变,突变比例为6.20%。耐药突变位点主要集中于rt M204V/I和rt L180M,替比夫定5.68%和恩曲他滨(5.91%)次之,阿德福韦1.07%和恩替卡韦2.10%耐药率较低。替诺福韦尚未发现耐药株,敏感度最高为99.66%。结论昆明地区的HBV基因型分布状况有独立特征。一线核苷(酸)类治疗药是高耐药屏障的替诺福韦或恩替卡韦,在乙型肝炎治疗上具有广阔的应用前景。使用基因测序法进行慢性乙型肝炎患者基因型和耐药突变位点检测,准确有效,可以更好地指导临床用药,为临床进行精准医疗提供有力的客观依据。

Objective To analyze the mutations and clinical significance of 10 genotypes associated with genotypes of HBV patients and HBV nucleoside(acid)analogues in Kunming.Me thods A total of 2707 patients with chronic hepatitis B who were admitted to the Third People’s Hospital of Kunming from May 2017 to March 2019 were enrolled.The Sanger sequencing method was used to treat the common nucleoside(acid)treatment of hepatitis B virus.Gene mutation sites were detected and analyzed for mutation patterns of different resistance.Re s ults Type C accounted for 62.4%of The HBV genotypes in Kunming,fwllowed by 37.3%of type B,and 3.4%of type D.In the 2707 cases,drug resistance mutations were found in a total of 274 patients(10.1%),with a mutation rate of10.12%.Among them,168 patients developed lamivudine-resistant mutations,and the mutation rate was(6.20%).Drug-resistant mutation sites were mainly concentrated in rtM204 V/I and rtL180 M,telbivudine(5.68%)and emtricitabine(5.91%)followed by adefovir(1.07%)and entecavir(2.10%).No drug-resistant strains were found in tenofovir,which had the highest sensitivity(99.66%).Conclus ion The distribution of HBV genotypes in this region has independent characteristics.As the first-line nucleoside(acid)therapeutic drugs,tenofovir or entecavir,with its highly resistant barrier,has broad application prospects in the treatment of hepatitis B.The use of gene sequencing for the detection of genotypes and drug-resistant mutation sites in patients with chronic hepatitis B is accurate and effective,and can better guide the clinical drug use,providing a powerful objective basis for a precise clinic practice.