HCV1b亚型ISDR变异影响PEG-IFN/RBV抗病毒疗效的新特点分析

目的 探讨HCV干扰素敏感决定区(ISDR)氨基酸(aa)序列变异度对聚乙二醇干扰素(PEG-IFN)联合利巴韦林(RBV)治疗1b亚型慢性丙型肝炎(CHC)疗效的影响.方法 58例HCV 1b亚型慢性感染者采用PEG-IFN/RBV联合方案治疗48周,并随访24周.定量检测血清HCV RNA,逆转录-聚合酶链反应扩增治疗前血标本中HCV ISDR片段并测序,MEGA 4分析氨基酸序列变异度；二分类Logistic回归分析各变量与持续病毒学应答(SVR)之间的关系.结果 治疗前血清HCV的ISDR氨基酸序列与HCVJ株比较,15例为野生型(未突变),42例为中间型(1-3个突变),1例为突变型(≥4个突变).其中2218位点突变最多,约为60.3％(35/58).dSDR aa突变数目与SVR关系密切(P=0.000),ISDR aa突变数≥2的CHC组所获得的EVR和SVR明显高于aa突变数＜2的CHC组(P=0.041/P=0.012).结论 华南HCV 1b亚型ISDR突变型(氨基酸变异≥4)极少.ISDR aa变异能够预测SVR；采用PEG-IFN/RBV联合方案治疗,对SVR有预测价值的ISDR aa突变数可由4个减少为2个.

Impact of mutation in HCV ISDR on the efficacy of the combined pegylated interferon/ribavirin therapy in Chinese patients with chronic hepatitis C virus genotype 1b infection

Objective To elucidate the impact of amino acid (aa) substitutions of interferon sensitivity determining region (ISDR) of HCV on the outcome of combined pegylated interferon/ribavirin therapy in the patients with chronic hepatitits C virus genotype 1b infection. Methods A total of 58 patients with chronic HCV 1b infection received 48 weeks of the combination therapy and 24-week follow up.The HCV RNA in patients’ serum samples was isolated and quantified.The fragments of HCV ISDR were amplified by RT-PCR and directly sequenced. Alignment and analysis of amino acids sequences were carried out with MEGA4 software..Binary logistic regression was performed to analyze the correlations between variables and sustained virological response.(SVR)..Results Among 58 samples,there were 15 wild type(no aa mutation),42 intermediate type (1～3 aa substitutions) and only 1 mutant type (4 or more aa substitutions) when compared with HCV J strain. Mutations occurred most frequently about 60.3%.(35/58).at aa position 2218..A statistically significant association was observed between the aa substitutions in ISDR and SVR (P=0.000). The SVR and EVR were significantly higher in the group with 2 or more aa mutations in ISDR than that in the group with less 2 aa mutations (P=0.012/P=0.041) by logistic regression analysis. Conclusion The mutant type of ISDR (≥4) was rare in south China. Identification of ISDR mutation (more than 2 amino acids substitutions)can be used to predict SVR and consider PEG-IFN plus RBV combination therapy for CHC patients.