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目的对我国南方184例无抗病毒治疗史的慢性丙型肝炎患者进行NS3/4A蛋白酶抑制剂相关耐药位点检测。方法 NS3/4A蛋白酶抑制剂相关的耐药位点分析采用自行设计型别特异性引物行巢式PCR,PCR产物经纯化后采用直接测序法鉴定。结果 184例样本中有162例扩增成功,其中125例(77.16%)患者共检出266个变异位点。HCV1b型A156S变异率为18.33%,V170I为16.67%;HCV2a型V36L、Q80G、V170I变异率为100%,A156S为64.29%;HCV6a型Q80K变异率为95.45%,V170I为98.86%。结论未使用抗病毒药的慢性丙型肝炎患者对NS3/4A蛋白酶抑制剂也存在预存耐药,变异率因HCV基因型而不同。1b型发生变异较少,HCV2a型及6a型普遍发生变异。
Objective To detect NS3 / 4A protease inhibitor-related drug resistant sites in 184 patients with chronic hepatitis C without anti-virus therapy in southern China. Methods NS3 / 4A protease inhibitors related to drug-resistant loci were analyzed by nested-PCR using self-designed type-specific primers. The PCR products were purified and identified by direct sequencing. Results A total of 162 cases of 184 cases were successfully amplified, of which 266 cases were detected in 125 cases (77.16%). The mutation rate of HCV1b A156S was 18.33% and V170I was 16.67%. The mutation rates of V36L, Q80G and V170I of HCV2a were 100% and A156S was 64.29%. The variation rate of HCV6a Q80K was 95.45% and V170I was 98.86%. Conclusions Patients with chronic hepatitis C who did not use antiviral drugs also had pre-existing resistance to NS3 / 4A protease inhibitors, with variability varying with HCV genotype. 1b variant occurred less, HCV2a and 6a-type mutation occurred.