Different impact of IL28B polymorphisms on response to peginterferon-α plus ribavirin in HIV-positive patients infected with HCV subtypes 1a or 1b
Different impact of IL28B polymorphisms on response to peginterferon-α plus ribavirin in HIV-positive patients infected with HCV subtypes 1a or 1b
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DOI：
10.1016/j.jcv.2012.05.012
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发表时间：
2012-09-01
影响因子：
8.8
通讯作者：
Soriano, Vincent
中科院分区：
文献类型：
--
作者：
Vispo, Eugenia;Rallon, Norma I.;Soriano, Vincent
背景：HCV亚型1a已成为丙型肝炎三联治疗（包括boceprevir或telaprevir）不良反应的预测因子，这主要归因于HCV-1a与-1b相比具有较低的耐药屏障。目的：我们研究pegIFN/RBV对HCV-1a的疗效是否低于HCV-1b可能有助于解释这一现象。研究设计：对所有在我院完成pegIFN/RBV治疗疗程的慢性丙型肝炎患者进行检查。在这项研究中，我们选择了ifn幼稚的个体，并成功地分型为1a或1b。此外，仅纳入艾滋病毒合并感染患者，因为他们在我们机构的人口统计和治疗暴露方面代表了更统一的人群。采用5′核酸酶法对IL28B rs12979860等位基因进行分型。结果：共检查96例，其中58例携带HCV-1a， 38例携带HCV-1b。IL28B等位基因分布如下：33 CC和63 CT/TT。CC患者的SVR为64%，CT/TT患者为30% （p = 0.001）。另一方面，HCV-1b的SVR为53%，而HCV-1a为34% （p = 0.08）。有趣的是，IL28B变异对SVR的影响主要体现在HCV-1a中（CC为63%，CT/TT为20%，p = 0.001），对HCV-1b的影响微乎其微（CC为64%，CT/TT为46%，p = 0.27）。结论：HCV-1a型感染的慢性丙型肝炎患者对pegIFN/RBV治疗的SVR率倾向于低于HCV-1b型；IL28B变异对HCV-1a的影响明显强于HCV-1b。(C) 2012 Elsevier b.v.版权所有
Background: HCV subtype 1a has emerged as a predictor of poor response to triple hepatitis C therapy including boceprevir or telaprevir, which largely has been attributed to a lower resistance barrier in HCV-1a compared to -1b.Objectives: We examined whether a lower efficacy of pegIFN/RBV on HCV-1a than HCV-1b could alternatively contribute to explain it.Study design: All chronic hepatitis C patients who had completed a course of pegIFN/RBV therapy at our institution were examined. For this study we selected individuals that were IFN-naive and had been successfully subtyped as 1a or 1b. Moreover, only HIV-coinfected patients were included as they represented a more uniform population in terms of demographics and treatment exposure at our institution. The IL28B rs12979860 alleles were typed using the 5' nuclease assay.Results: A total of 96 individuals were examined, 58 of whom harbored HCV-1a and 38 HCV-1b. IL28B allele distribution was as follows: 33 CC and 63 CT/TT. SVR was achieved by 64% of CC vs 30% of CT/TT patients (p = 0.001). On the other hand, SVR was 53% in HCV-1b vs 34% in HCV-1a (p = 0.08). Interestingly, the effect of IL28B variants on SVR was mainly recognized in HCV-1a (63% in CC vs 20% in CT/TT; p = 0.001), being marginal on HCV-1b (64% in CC vs 46% in CT/TT; p = 0.27).Conclusions: The rate of SVR to pegIFN/RBV therapy tends to be lower in HIV-infected patients with chronic hepatitis C due to HCV-1a than HCV-1b; being the impact of IL28B variants significantly stronger on HCV-1a than HCV-1b. (C) 2012 Elsevier B. V. All rights reserved.