Fürst Medisinsk Laboratorium, Oslo, Norway.
Hepatology. 2011 Mar;53(3):746-54. doi: 10.1002/hep.24154.
Polymorphisms near the IL28B gene, which code for interferon (IFN)-λ3, predict response to pegylated interferon-α (PEG-IFN) and ribavirin treatment in hepatitis C virus (HCV) genotype 1 infected patients. Follow-up studies of the effect of IL28B gene in HCV non-genotype 1 infected patients have almost always used predominantly HCV genotype 2-infected or mixed genotype 2/3-infected cohorts with results partly conflicting with HCV genotype 1. We performed a retrospective analysis of 281 patients infected with HCV genotype 3 for association of response to therapy with IL28B polymorphisms. We found that the HCV genotype 1 responder genotypes at rs12979860 and rs8099917 did not associate with sustained virological response to PEG-IFN/ribavirin therapy. However, the responder genotypes of both SNPs showed association with rapid viral response measured at 4 weeks (rs12979860, P = 3 × 10(-5) ; rs8099917, P = 3 × 10(-4) ). In multivariate analysis, age (<40 years), baseline viral load (<4 × 10(5) IU/mL) and the responder genotypes of SNPs rs12979860 or rs8099917 remained significant independent predictors of rapid viral response to therapy. Furthermore, we show that IL28B polymorphisms are associated with relapse in patients who achieve rapid viral response to PEG-IFN/ribavirin therapy. The responder genotypes also showed association with markers of stage and activity of liver disease, namely high aspartate aminotransferase platelet ratio index (APRI, rs12979860, P = 0.018; rs8099917, not significant) and high alanine aminotransferase (ALT, rs12979860, P = 0.002; rs8099917, P = 0.001), in addition to a high baseline viral load (rs12979860, P = 1.4 × 10(-5) ; rs8099917, P = 7.3 × 10(-6) ).
Polymorphisms near the IL28B gene show association with rapid viral response but not sustained viral response to PEG-IFN/ribavirin therapy in HCV genotype 3-infected patients.
IL28B 基因附近的多态性可预测聚乙二醇干扰素-α（PEG-IFN）和利巴韦林治疗丙型肝炎病毒（HCV）基因型 1 感染患者的反应。对 HCV 非基因型 1 感染患者 IL28B 基因作用的随访研究几乎都使用了主要为 HCV 基因型 2 感染或混合基因型 2/3 感染的队列，其结果与 HCV 基因型 1 的部分结果相冲突。我们对 281 例 HCV 基因型 3 感染患者进行了一项回顾性分析，以研究治疗反应与 IL28B 多态性的相关性。我们发现，rs12979860 和 rs8099917 上的 HCV 基因型 1 应答基因型与 PEG-IFN/利巴韦林治疗的持续病毒学应答无关。然而，这两个 SNP 的应答基因型均与治疗 4 周时的快速病毒应答相关（rs12979860，P=3×10(-5)；rs8099917，P=3×10(-4)）。在多变量分析中，年龄（<40 岁）、基线病毒载量（<4×10(5)IU/mL）和 SNP rs12979860 或 rs8099917 的应答基因型仍然是治疗快速病毒应答的显著独立预测因子。此外，我们发现 IL28B 多态性与 PEG-IFN/利巴韦林治疗获得快速病毒应答的患者的复发有关。应答基因型也与肝脏疾病的分期和活动的标志物相关，即天门冬氨酸转氨酶血小板比值指数（APRI，rs12979860，P=0.018；rs8099917，无显著性差异）和丙氨酸转氨酶（ALT，rs12979860，P=0.002；rs8099917，P=0.001）升高，以及基线病毒载量升高（rs12979860，P=1.4×10(-5)；rs8099917，P=7.3×10(-6)）。
IL28B 基因附近的多态性与 HCV 基因型 3 感染患者对 PEG-IFN/利巴韦林治疗的快速病毒应答相关，但与持续病毒应答无关。
