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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HCV1b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,MEGA4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)。ISDRaa突变数目与SVR关系密切(P=0.000),ISDRaa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HCV1b亚型ISDR突变型(氨基酸变异≥4)极少。ISDRaa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ISDRaa突变数可由4个减少为2个。
Objective To investigate the effect of variant sequence of HCV interferon sensitive region (aDR) on the treatment of chronic hepatitis C (CHC) in type 1b subtypes with peginterferon (PEG-IFN) and ribavirin (RBV) Impact. Methods Fifty-eight chronic HCV1b infected patients were treated with PEG-IFN / RBV regimen for 48 weeks and were followed up for 24 weeks. HCV RNA was amplified by reverse transcription polymerase chain reaction (RT-PCR) and sequenced. MEGA4 was used to analyze the amino acid sequence variation. Logistic regression analysis was used to analyze the relationship between variables and sustained virologic response (SVR) Relationship. Results The ISDR amino acid sequence of serum HCV before treatment was 15 (wild type), 42 as intermediate (1-3) and 1 as mutant (≥ 4) compared with HCVJ. Among them, the point mutation of 2218 locus was the most, about 60.3% (35/58). The number of ISDRaa mutations was closely related to SVR (P = 0.000). The EVR and SVR of CHC group with ISDRaa mutation ≥2 were significantly higher than those of CHC group with mutation of aa <2 (P = 0.041 / P = 0.012). Conclusions There is very few ISDR mutant (amino acid mutation≥4) in southern China. The ISDRaa mutation predicted SVR; the number of ISDRaa mutations predictive of SVR was reduced from 4 to 2 with PEG-IFN / RBV regimen.