IFNL3 多态性可预测慢性丙型肝炎基因型 2/3 感染的治疗反应。
IFNL3 polymorphisms predict response to therapy in chronic hepatitis C genotype 2/3 infection.
机构信息
Storr Liver Unit, Westmead Millennium Institute and Westmead Hospital, University of Sydney, NSW, Australia.
Storr Liver Unit, Westmead Millennium Institute and Westmead Hospital, University of Sydney, NSW, Australia; Institute of Immunology and Allergy Research, Westmead Hospital and Westmead Millennium Institute, University of Sydney, NSW, Australia.
出版信息
J Hepatol. 2014 Aug;61(2):235-41. doi: 10.1016/j.jhep.2014.03.039. Epub 2014 Apr 24.
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.
背景与目的
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 感染患者对聚乙二醇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。本研究旨在通过对大量队列进行研究，阐明 IFNL3 区域的 SNP 是否与 HCV-2/3 患者的治疗反应相关。
方法
该队列包括 1002 名接受聚乙二醇干扰素-α和利巴韦林治疗的 HCV-2/3 高加索患者，他们接受了 rs12979860 和 rs8099917 的 SNP 基因分型。
结果
总体而言，736 名（73.5%）患者达到 SVR（rs12979860 CC、CT 和 TT 的 SVR 率分别为 81.9%、67.9%和 57.8%[p=0.0001]；rs8099917 TT、TG 和 GG 的 SVR 率分别为 78%、68.7%和 46.3%[p=0.0001]）。通过逻辑回归，rs12979860 CC 和 rs8099917 TT 均为 SVR 的独立预测因子，比值比（OR）分别为 2.39（1.19-3.81）p=0.0001 和 1.85（1.15-2.23）p=0.0001。在复发患者中，IFNL3 应答基因型比无应答基因型更常见（两个 SNP 均为 p=0.0001）。在治疗过程中快速病毒学应答（RVR）仅在 IFNL3 非应答基因型（rs12979860 CT/TT 和 rs8099917 TG/GG）的个体中预测 SVR。
结论
本研究对 HCV 基因型 2 或 3 感染患者进行了充分的研究，清楚地表明 IFNL3 基因型是 SVR 的最强基线预测因子，与已知的基因型 1 感染相关。IFNL3 基因分型可辅助这些患者的治疗决策。
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