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目的分析瑞安地区慢性乙型肝炎核苷(酸)类药物治疗不应答患者血清中HBV P区变异情况和核苷(酸)类药物耐药情况。方法检测逆转录酶11个位点上的碱基突变情况,分析耐药基因耐药位点相关突变情况及不同核苷(酸)类药物的突变形式,根据位点变异情况,计算敏感性下降和耐药情况。结果检测202例乙型肝炎患者11个基因位点,其中54.46%发生1个或1个以上位点突变。突变的基因位点有173V、180L、181A、184T、202S、204M、236N,构成比分别为5.21%、25.52%、17.71%、3.13%、2.08%、39.06%、7.29%。另外P区耐药突变形式分析中,110例患者的样本在11个分析位点上共有17种突变模式。核苷(酸)类药物敏感性下降或耐药情况,202例乙型肝炎DNA中拉米夫定的耐药率最高,为45.05%,恩曲他滨、替比夫定、恩替卡韦、阿德福韦的耐药率分别为43.56%、34.65%、31.68%、10.89%,未发现替诺福韦的耐药株。结论阿德福韦和替诺福韦可作为核苷(酸)类药物治疗出现反弹的首选药物。
Objective To analyze the variation of serum HBV P region and nucleotide (acid) drug resistance in patients with unresponsive chronic hepatitis B nucleoside (acid) drugs in Ruian area. Methods Mutations of 11 bases of reverse transcriptase were detected. Mutations of drug-resistant gene-resistant sites and mutations of different nucleoside (acid) drugs were analyzed. According to the site variation, the sensitivity was decreased And resistance situation. Results A total of 11 gene loci were detected in 202 cases of hepatitis B patients, of which 54.46% had one or more loci mutations. The mutated gene loci were 173V, 180L, 181A, 184T, 202S, 204M and 236N, respectively, with the proportions of 5.21%, 25.52%, 17.71%, 3.13%, 2.08%, 39.06% and 7.29%, respectively. In addition, in the analysis of drug resistance mutations in P region, a total of 17 mutation patterns were found in 110 samples in 11 analysis sites. The sensitivity of nucleoside (acid) drugs decreased or drug resistance, the highest resistance rate of lamivudine in 202 cases of hepatitis B DNA was 45.05%. Emtricitabine, telbivudine, entecavir, Fu Wei resistance rates were 43.56%, 34.65%, 31.68%, 10.89%, no resistant strains of tenofovir were found. Conclusion Adefovir and tenofovir may be the drug of choice for the rebound of nucleoside (acid) drugs.