Association of a single nucleotide polymorphism near the interleukin-28B gene with response to hepatitis C therapy in HIV/hepatitis C virus-coinfected patients.
Association of a single nucleotide polymorphism near the interleukin-28B gene with response to hepatitis C therapy in HIV/hepatitis C virus-coinfected patients.
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DOI：
10.1097/qad.0b013e3283391d6d
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发表时间：
2010-05-15
期刊：
影响因子：
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通讯作者：
Soriano V
中科院分区：
文献类型：
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作者：
Rallón NI;Naggie S;Benito JM;Medrano J;Restrepo C;Goldstein D;Shianna KV;Vispo E;Thompson A;McHutchison J;Soriano V
鉴于聚乙二醇干扰素-利巴韦林治疗的耐受性差，有兴趣在确定的预测反应，特别是在HIV/丙型肝炎病毒（HCV）的合并感染的患者，响应小于HCV单感染的个人。IL 28 B基因（rs 12979860）附近的单核苷酸多态性（SNP）已被证明可以预测携带基因型1的HCV单感染患者的治疗反应。缺乏关于HIV/HCV合并感染个体和/或其他HCV基因型的信息。从650例HIV/HCV合并感染患者中，我们确定了那些完成了聚乙二醇干扰素-利巴韦林治疗过程的患者，这些患者具有经验证的结果和可用的储存库DNA。以盲法检查rs 12979860 SNP。最终的IL 28 B基因分型分析共纳入164例患者，其中90例（55%）获得持续病毒学应答（SVR）。HCV基因型分布：HCV-1型占58%，HCV-3型占31%，HCV-4型占11%。总的来说，CC基因型患者的SVR率高于CT/TT基因型患者：75例中有56例（75%），89例中有34例（38%）（P <0.0001）。在HCV基因型1和4中观察到SNP的作用，但在HCV基因型3携带者中未观察到。在多变量分析中（比值比; 95%置信区间; P值），rs 12979860 CC基因型是SVR的强预测因子（3.7; 1.6-8.5; 0.002），与HCV基因型3无关（8.0; 3.1-21.0; <0.001）、血清HCV-RNA低于60万IU/ml（11.9; 3.8-37.4; <0.001）和无晚期肝纤维化（3.5; 1.4-8.9; 0.009）。位于IL 28 B基因附近的rs 12979860 SNP与因基因型1或4导致的慢性丙型肝炎HIV感染患者的HCV治疗反应相关因此，IL 28 B基因分型应被视为该难治性人群治疗决策算法的一部分。
Given that peginterferon–ribavirin treatment is poorly tolerated, there is interest in the identification of predictors of response, particularly in HIV/hepatitis C virus (HCV)-coinfected patients that respond less than HCV-monoinfected individuals. A single nucleotide polymorphism (SNP) near the IL28B gene (rs12979860) has been shown to predict treatment response in HCV-monoinfected patients carrying genotype 1. Information is lacking for HIV/HCV-coinfected individuals and/or other HCV genotypes. From 650 HIV/HCV-coinfected patients, we identified those who had completed a course of peginterferon–ribavirin therapy with a validated outcome and available repository DNA. The rs12979860 SNP was examined in a blinded fashion. A total of 164 patients were included in the final IL28B genotyping analysis, 90 (55%) of whom achieved sustained virological response (SVR). HCV genotype distribution was as follows: HCV-1 58%, HCV-3 31% and HCV-4 11%. Overall, the SVR rate was higher in patients with CC than in those CT/TT genotypes: 56 of 75 (75%) versus 34 of 89 (38%) (P <0.0001). The effect of the SNP was seen in HCV genotypes 1 and 4 but not in HCV genotype 3 carriers. In the multivariable analysis (odds ratio; 95% confidence interval; P value), the rs12979860 CC genotype was a strong predictor of SVR (3.7; 1.6–8.5; 0.002), independent of HCV genotype 3 (8.0; 3.1–21.0; <0.001), serum HCV-RNA less than 600 000 IU/ml (11.9; 3.8–37.4; <0.001) and lack of advanced liver fibrosis (3.5; 1.4–8.9; 0.009). The rs12979860 SNP located near the IL28B gene is associated with HCV treatment response in HIV-infected patients with chronic hepatitis C due to genotypes 1 or 4. Thus, IL28B genotyping should be considered as part of the treatment decision algorithm in this difficult-to-treat population.