Potential role for interleukin-28B genotype in treatment decision-making in recent hepatitis C virus infection.
Potential role for interleukin-28B genotype in treatment decision-making in recent hepatitis C virus infection.
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DOI：
10.1002/hep.23850
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发表时间：
2010-10
期刊：
影响因子：
13.5
通讯作者：
Dore, Gregory J.
中科院分区：
文献类型：
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作者：
Grebely, Jason;Petoumenos, Kathy;Hellard, Margaret;Matthews, Gail V.;Suppiah, Vijayaprakash;Applegate, Tanya;Yeung, Barbara;Marks, Phillipa;Rawlinson, William;Lloyd, Andrew R.;Booth, David;Kaldor, John M.;George, Jacob;Dore, Gregory J.
IL 28 B基因多态性在预测慢性丙型肝炎病毒（HCV）感染治疗后的结果方面很重要。我们评估了IL 28 B在近期HCV感染后自发和治疗诱导清除中的作用。澳大利亚急性丙型肝炎试验是一项对近期HCV的自然史和治疗的研究，定义为抗HCV抗体阳性，之前12个月内有急性临床HCV感染或之前24个月内有血清转换。评估了与自发和治疗诱导的HCV清除相关的因素，包括IL 28 B的变化。在163例受试者中，132例未接受治疗（n=52）或在治疗开始时存在持续感染（感染持续时间≥26周）（n=80）。在23%（30/132）中观察到自发清除。在考克斯比例风险分析（无IL 28 B）中，HCV血清转换疾病伴黄疸是预测自发清除的唯一因素（AHR 2.86，95% CI，1.24，6.59，P=0.014）。在IL 28 B基因分型的参与者中（总体n=102/163，自发清除人群n = 79/132），rs 8099917 TT纯合性（vs GT/GG）是独立预测自发清除时间的唯一因素（AHR 3.78，95% CI，1.04，13.76，P=0.044）。血清转换疾病伴黄疸的参与者rs 8099917 TT纯合子的频率高于其他（GG/GT）基因型（32%对5%，P=0.047）。在坚持治疗并具有IL 28 B基因型的参与者中（n=54），TT纯合子（18/29，62%）和GG/GT基因型（16/25，64%，P=0.884）的SVR相似。在最近的HCV中，IL 28 B区域的遗传变异与自发清除相关，但与治疗诱导的清除无关。对于IL 28 B基因型不利的个体，建议早期治疗干预。
Polymorphisms in the IL28B gene region are important in predicting outcome following therapy for chronic hepatitis C virus (HCV) infection. We evaluated the role of IL28B in spontaneous and treatment-induced clearance following recent HCV infection. The Australian Trial in Acute Hepatitis C was a study of the natural history and treatment of recent HCV, as defined by positive anti-HCV antibody, preceded by either acute clinical HCV infection within the prior 12 months or seroconversion within the prior 24 months. Factors associated with spontaneous and treatment-induced HCV clearance, including variations in IL28B, were assessed. Among 163 participants, 132 were untreated (n=52) or had persistent infection (infection duration ≥26 weeks) at treatment initiation (n=80). Spontaneous clearance was observed in 23% (30 of 132). In Cox proportional hazards analysis (without IL28B), HCV seroconversion illness with jaundice was the only factor predicting spontaneous clearance (AHR 2.86, 95% CI, 1.24, 6.59, P=0.014). Among participants with IL28B genotyping (n=102/163 overall and 79/132 for spontaneous clearance population), rs8099917 TT homozygosity (vs GT/GG) was the only factor independently predicting time to spontaneous clearance (AHR 3.78, 95% CI, 1.04, 13.76, P=0.044). Participants with seroconversion illness with jaundice were more frequently rs8099917 TT homozygotes than other (GG/GT) genotypes (32% versus 5%, P=0.047). Among participants adherent to treatment and had IL28B genotyping (n=54), SVR was similar among TT homozygotes (18/29, 62%) and those with GG/GT genotype (16/25, 64%, P=0.884). During recent HCV, genetic variations in IL28B region were associated with spontaneous but not treatment-induced clearance. Early therapeutic intervention could be recommended for individuals with unfavorable IL28B genotypes.
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