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IL-28B 多态性对儿童和青少年感染 HCV 基因型 1 和 4 接受聚乙二醇干扰素加利巴韦林治疗反应的影响。

Impact of IL-28B polymorphisms on pegylated interferon plus ribavirin treatment response in children and adolescents infected with HCV genotypes 1 and 4.

机构信息

Department of Infectious Diseases and Hepatology, Collegium Medicum, Nicolaus Copernicus University, Floriana 12 Str., 85-030, Bydgoszcz, Poland.

出版信息

Eur J Clin Microbiol Infect Dis. 2013 Jun;32(6):745-54. doi: 10.1007/s10096-012-1799-z. Epub 2013 Jan 13.

Abstract

IL-28B polymorphisms are predictors of response to therapy in adults infected with hepatitis C. We do not know whether they are markers of response to therapy in children and adolescents. The aim of this study was to determine whether single-nucleotide polymorphisms (SNPs) in the IL-28B gene could influence the probability of response to therapy compared with other known baseline prognostic factors and correlate with clinical findings in pediatric patients infected with hepatitis C virus (HCV) genotypes 1 or 4. We determined three SNPs of IL-28B (rs12979860, rs12980275, and rs8099917) in 82 patients with chronic HCV infection treated with pegylated interferon alpha and ribavirin (peg-IFNα/RBV). Treatment response and clinical data were analyzed. Overall, sustained virological response (SVR) was achieved by 45 % of patients infected with difficult-to-treat HCV genotypes 1 and 4. Except for IL-28B polymorphisms, there was no association of SVR with any other clinical data. IL-28B rs12979860 CC [odds ratio (OR), 6.81; p = 0.001] and rs8099917 TT (OR, 3.14; p = 0.013) genotypes were associated with higher SVR rates. IL-28B rs12980275 was not significantly associated with SVR (p = 0.058). Only the distribution between CC and CT-TT genotypes of rs12979860 significantly differentiated patients achieving early virological response (EVR) (OR, 10.0; p = 0.011). Children with the rs12979860 CC genotype had significantly higher baseline viral load compared with CT-TT patients (p = 0.010). In children and adolescents chronically infected with HCV genotypes 1 and 4, IL-28B rs12979860 and rs8099917 polymorphisms were the only predictors of response to peg-IFN/RBV.

摘要

IL-28B 多态性是丙型肝炎感染者治疗反应的预测因子。我们不知道它们是否是儿童和青少年治疗反应的标志物。本研究的目的是确定 IL-28B 基因中的单核苷酸多态性(SNP)是否可以影响治疗反应的概率,与其他已知的基线预后因素进行比较,并与感染丙型肝炎病毒(HCV)基因型 1 或 4 的儿科患者的临床发现相关。我们在 82 例接受聚乙二醇干扰素α和利巴韦林(peg-IFNα/RBV)治疗的慢性 HCV 感染患者中确定了 IL-28B 的三个 SNP(rs12979860、rs12980275 和 rs8099917)。分析了治疗反应和临床数据。总体而言,45%的难治性 HCV 基因型 1 和 4 感染者获得持续病毒学应答(SVR)。除了 IL-28B 多态性外,SVR 与任何其他临床数据均无关联。IL-28B rs12979860 CC [比值比(OR),6.81;p=0.001]和 rs8099917 TT(OR,3.14;p=0.013)基因型与更高的 SVR 率相关。IL-28B rs12980275 与 SVR 无显著相关性(p=0.058)。只有 rs12979860 的 CC 和 CT-TT 基因型分布显著区分了达到早期病毒学应答(EVR)的患者(OR,10.0;p=0.011)。携带 rs12979860 CC 基因型的儿童基线病毒载量明显高于 CT-TT 患者(p=0.010)。在慢性感染 HCV 基因型 1 和 4 的儿童和青少年中,IL-28B rs12979860 和 rs8099917 多态性是 peg-IFN/RBV 反应的唯一预测因子。

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