Service of Infectious Diseases, Department of Medicine, University Hospital and University of Lausanne, Switzerland.
J Hepatol. 2011 Nov;55(5):980-8. doi: 10.1016/j.jhep.2011.01.050. Epub 2011 Feb 25.
BACKGROUND & AIMS: Single nucleotide polymorphisms (SNPs) associated with IL28B influence the outcome of peginterferon-α/ribavirin therapy of chronic hepatitis C virus (HCV) infection. We analyzed the kinetics of HCV RNA during therapy as a function of IL28B SNPs.
IL28B SNPs rs8099917, rs12979860, and rs12980275 were genotyped in 242 HCV treatment-naïve Caucasian patients (67% genotype 1, 28% genotype 2 or 3) receiving peginterferon-α2a (180 μg weekly) and ribavirin (1000-1200 mg daily) with serial HCV-RNA quantifications. Associations between IL28B polymorphisms and early viral kinetics were assessed, accounting for relevant covariates.
In the multivariate analyses for genotype 1 patients, the T allele of rs12979860 (T(rs12979860)) was an independent risk factor for a less pronounced first phase HCV RNA decline (log(10) 0.89IU/ml among T carriers vs. 2.06 among others, adjusted p < 0.001) and lower rapid (15% vs. 38%, adjusted p = 0.007) and sustained viral response rates (48% vs. 66%, adjusted p < 0.001). In univariate analyses, T(rs12979860) was also associated with a reduced second phase decline (p = 0.002), but this association was no longer significant after adjustment for the first phase decline (adjusted p = 0.8). In genotype 2/3 patients, T(rs12979860) was associated with a reduced first phase decline (adjusted p = 0.04), but not with a second phase decline.
Polymorphisms in IL28B are strongly associated with the first phase viral decline during peginterferon-α/ribavirin therapy of chronic HCV infection, irrespective of HCV genotype.
与 IL28B 相关的单核苷酸多态性（SNPs）影响聚乙二醇干扰素-α/利巴韦林治疗慢性丙型肝炎病毒（HCV）感染的效果。我们分析了 IL28B SNPs 对治疗期间 HCV RNA 动力学的影响。
在 242 例初治的白种人丙型肝炎患者（67%基因型 1，28%基因型 2 或 3）中，检测 IL28B SNPs rs8099917、rs12979860 和 rs12980275，这些患者接受聚乙二醇干扰素-α2a（每周 180μg）和利巴韦林（每日 1000-1200mg）治疗，并进行连续的 HCV-RNA 定量检测。评估了 IL28B 多态性与早期病毒动力学之间的关联，并考虑了相关的协变量。
在基因型 1 患者的多变量分析中，rs12979860 的 T 等位基因（T(rs12979860)）是第一阶段 HCV RNA 下降幅度较小的独立危险因素（T 携带者的对数 10 下降 0.89IU/ml，而其他患者为 2.06，调整后 p<0.001），快速（15% vs. 38%，调整后 p=0.007）和持续病毒应答率（48% vs. 66%，调整后 p<0.001）较低。在单变量分析中，T(rs12979860)也与第二阶段下降幅度减小相关（p=0.002），但在调整第一阶段下降幅度后，这种相关性不再显著（调整后 p=0.8）。在基因型 2/3 患者中，T(rs12979860)与第一阶段下降幅度减小相关（调整后 p=0.04），但与第二阶段下降幅度无关。
IL28B 多态性与聚乙二醇干扰素-α/利巴韦林治疗慢性 HCV 感染期间的第一阶段病毒下降密切相关，与 HCV 基因型无关。
