IFNL3 polymorphisms predict response to therapy in chronic hepatitis C genotype 2/3 infection
IFNL3 polymorphisms predict response to therapy in chronic hepatitis C genotype 2/3 infection
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DOI：
10.1016/j.jhep.2014.03.039
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发表时间：
2014-08-01
影响因子：
25.7
通讯作者：
Ahlenstiel, Gobo
中科院分区：
文献类型：
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作者：
Eslam, Mohammed;Leung, Reynold;Ahlenstiel, Gobo
背景和目的：干扰素 lambda 3 (IFNL3，以前称为 IL28B) 区域附近的单核苷酸多态性 (SNP) 是丙型肝炎病毒 (HCV) 基因型 1 感染中聚乙二醇化干扰素和利巴韦林治疗持续病毒学应答 (SVR) 的最强基线预测因子。 IFNL3 SNP 是否影响基因型 2 和 3 (HCV-2/3) 感染的治疗反应仍存在争议。本研究试图在大型队列中阐明 IFNL3 区域的 SNP 是否与 HCV-2/3 患者的治疗反应相关。方法：该队列由 1002 名接受聚乙二醇化干扰素-α 和利巴韦林治疗的 HCV-2/3 白种人患者组成，他们接受了 SNP rs12979860 和 rs8099917 的基因分型。结果：总体而言，736 (73.5%) 患者实现了 SVR（rs12979860 CC、CT 和 TT 分别为 81.9%、67.9% 和 57.8% [p = 0.0001]；rs8099917 TT、TG 和 GG 分别为 78%、68.7% 和 46.3% [p = 0.0001]）。通过逻辑回归，rs12979860 CC 和 rs8099917 TT 都是 SVR 的独立预测因子，优势比 (OR) 分别为 2.39 (1.19-3.81) p = 0.0001 和 OR 1.85 (1.15-2.23) p = 0.0001。 IFNL3 应答者基因型在复发者中比无效者更常见（两个 SNP 的 p = 0.0001）。治疗中快速病毒学应答 (RVR) 仅在那些具有 IFNL3 无应答基因型（rs12979860 CT/TT 和 rs8099917 TG/GG）的个体中预测 SVR。结论：这项针对 HCV 基因型 2 或 3 感染患者的充分有力的研究清楚地表明，IFNL3 基因型是 SVR 的最强基线预测因子，与已知的 SVR 关联一致。基因1型感染。 IFNL3 基因分型可以帮助这些患者做出治疗决策。 (C) 2014 年欧洲肝脏研究协会。由 Elsevier B.V. 出版。保留所有权利。
Background & Aims: Single nucleotide polymorphisms (SNPs) near the interferon lambda 3 (IFNL3, previously known as IL28B) region are the strongest baseline predictors of sustained virologic response (SVR) to pegylated interferon and ribavirin therapy in hepatitis C virus (HCV) genotype 1 infection. Whether IFNL3 SNPs influence treatment response in genotype 2 and 3 (HCV-2/3) infection remains controversial. This study sought to clarify in a large cohort, whether SNPs in the IFNL3 region are associated with treatment response in HCV-2/3 patients.Methods: The cohort comprised 1002 HCV-2/3 Caucasians patients treated with pegylated interferon-alpha and ribavirin who underwent genotyping for the SNPs rs12979860 and rs8099917.Results: Overall, 736 (73.5%) patients achieved SVR (81.9%, 67.9%, and 57.8% for rs12979860 CC, CT, and TT [p = 0.0001]; 78%, 68.7%, and 46.3% for rs8099917 TT, TG, and GG [p = 0.0001]). By logistic regression, both rs12979860 CC and rs8099917 TT were independent predictors of SVR with an odds ratio (OR) of 2.39 (1.19-3.81) p = 0.0001 and OR 1.85 (1.15-2.23) p = 0.0001, respectively. IFNL3 responder genotypes were more frequent in relapsers than null-responders (p = 0.0001 for both SNPs). On-treatment rapid virological response (RVR) was predictive of SVR only in those individuals with IFNL3 non-responder genotypes (rs12979860 CT/TT and rs8099917 TG/GG).Conclusions: This adequately powered study in patients with HCV genotypes 2 or 3 infection clearly demonstrates that IFNL3 genotypes are the strongest baseline predictor of SVR, in keeping with the known association for genotype 1 infection. IFNL3 genotyping can aid in therapeutic decision making for these patients. (C) 2014 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.