肿瘤病人感染HBV基因型及耐核苷类似药突变分析

    Analysis of HBV genotypes and nucleoside drug-resistance mutations in tumor patients with HBV infection

    • 摘要:
      目的 分析乙型肝炎病毒(HBV)感染的肿瘤病人HBV基因型及其聚合酶/逆转录酶(RT)区相关耐药突变分布特征,为临床肿瘤病人预防HBV再激活及抗病毒治疗提供依据。
      方法 选取HBV感染的肿瘤病人病毒DNA载量阳性血清130例,首先采用PCR-RFLP法进行HBV基因的分型,然后采用巢式PCR方法扩增RT区基因,PCR产物采用Sanger法测序以分析RT区基因序列耐药相关突变位点和耐药情况。
      结果 130例肿瘤病人中B型16例(12.31%),C型100例(76.92%),B+C型14例(10.77%)。HBV耐药率为26.15%,其中C型30.00%、B+C型14.29%、B型12.50%,3种基因型耐药率差异无统计学意义(P>0.05)。RT区测序共检出11种耐药突变类型和3种突变模式中,以180、181和204位点变异率较高,以拉米夫定耐药率最高(70.59%),恩替卡韦最低(5.88%),且均以C型为主。此外,RT区未检出E164D+I195M对应相关的rtV173L+rtL180M+rtM204V三重突变体。
      结论 HBV感染的肿瘤病人基因型以C型为主,其耐药率为26.15%。不同基因型的耐药突变率、突变模式复杂度以及耐药种类均以C型最高,未发现RT区对应的HBV表面抗原免疫逃逸的突变。建议肿瘤病人使用高耐药屏障的核苷类似物预防HBV再激活。

       

      Abstract:
      Objective To analyze the distribution characteristics of HBV genotypes and polymerase/reverse transcriptase(RT) region-related drug-resistant mutations in tumor patients with HBV infection, and provide evidences for prevention of HBV reactivation and antiviral therapy in clinical tumor patients.
      Methods A total of 130 HBV infection tumor patients with positive viral DNA load were selected. HBV gene typing was performed by PCR-RFLP method, and then nested PCR method was used to amplify RT region genes. The PCR products were sequenced by Sanger method to analyze the mutation sites and drug resistance of RT region gene sequence.
      Results Among the 130 tumor patients, 16 cases of HBV were type B(12.31%), 100 cases were type C (76.92%), and 14 cases were type B+C(10.77%). The drug resistance rate of HBV was 26.15%, including 30.00% for C type, 14.29% for B+C type and 12.50% for B type, and there was no statistical significance in the drug resistance rate among three genotypes(P>0.05). A total of 11 types of drug-resistant mutations and 3 mutation modes in RT region sequencing were detected, and the mutation rate of 180, 181 and 204 sites were higher. Lamivudine resistance rate was the highest (70.59%), Entecavir resistance rate was the lowest (5.88%), and the type C was the main type. In addition, the associated rtV173L+rtL180M+rtM204V triple mutant with E164D+I195M in RT region was not detected.
      Conclusions The genotype of HBV infection tumor patients is mainly type C, and the drug resistance rate is 26.15%. The drug resistance mutation rate, mutation pattern complexity and drug resistance types of different genotypes were the highest in genotype C, and no corresponding HBsAg immune escape mutation in RT region is found. It is recommended that tumor patients use nucleoside analogues with high resistance barrier to prevent HBV reactivation.

       

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