昆明地区慢性乙型肝炎患者替诺福韦酯耐药突变位点情况调查

Tenofovir Resistance and Related Gene Mutations Characteristics in Patients with Chronic Hepatitis B in Kunming

目的分析昆明地区慢性乙型肝炎患者,不同HBV基因型和替诺福韦酯耐药相关位点的突变情况,并分析替诺福韦酯耐药位点突变与HBV-DNA量和HBe Ag之间的关系。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,分析不同HBV基因型和替诺福韦酯耐药相关位点的突变情况,并分析替诺福韦酯耐药位点突变与HBV-DNA量和HBe Ag之间的关系。结果 2707例患者中,共有52例(1.92%,52/2707)患者检测到替诺福韦酯耐药相关位点的突变,变异率为1.92%。52例患者中HBV基因型以C型为主65.38%(34/52),B型次之占34.62%(18/52)。检出与替诺福韦酯(TDF)耐药相关位点突变(A194T、N236T、A181T/V),耐药不敏感性I (1.92%,52/2707)。其中A181T/V位点单独突变率最高(19.23%),N236T位点单独突变率次之(15.38%);检出与替诺福韦酯耐药相关位点单独变异情况,在HBV-DNA中、低水平两组的各耐药位点的突变检出率较高。替诺福韦酯耐药相关位点A181T/V变异在HBe Ag阳性组的突变检出率较高。结论本研究使用基因测序法,进行慢性乙型肝炎患者不同HBV基因型和替诺福韦酯耐药相关位点的突变情况检测,准确有效,以期更好地明确替诺福韦酯疗效,为临床进行精准医疗提供有力的客观依据。

Objective To analyze tenofovir resistance and related gene mutations characteristics with different genotypes of chronic hepatitis B patients,and to analyze their relationship between HBV-DNA and HBeAg in patients with chronic hepatitis Bin Kunming.Methods 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 test the resistance and related gene mutations of the common nucleoside(acid)treatment of hepatitis B virus.The mutations of different HBV genotypes and tenofovir dipivoxil resistance loci were analyzed,and the relationship between the mutations of tenofovir dipivoxil resistance loci and HBV-DNA amount and HBeAg was analyzed.Results A total of 52 patients(1.92%,52/2707)were found with Tenofovir resistance mutation,with a mutation rate of 1.92%.Type C HBV genotype in the 52 patients accounted for 65.38%(34/52),and type Baccounted for34.62%(18/52).Tenofovir resistance mutation sites were mainly concentrated in A194T,N236T and A181T/V.The rate of drug insensitivity was 1.92%(52/2707).Single tenofovir resistance mutation sites were deceted.Among them,A181T/V site had the highest mutation rate(19.23%),N236T site had the second highest mutation rate(15.38%).Tenofovir resistance mutation sites were mainly concentrated in group with low and medium level of HBV-DNA.The most common tenofovir resistance mutation was found in A181T/V in HBeAg positive group.Conclusion The distribution of HBV genotypes and tenofovir resistance mutation in this region has independent characteristics.The difference of tenofovir resistance mutation rate was statistically significant in different HBV-DNA and HBeAg levels(P<0.05).The use of gene sequencing for the detection of genotypes and tenofovir resistance mutation sites in patients with chronic hepatitis B is accurate and effective,and can better guide the clinical use oftenofovir,providing a powerful objective basis for clinical precision medicine.