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IL28B 但不是 ITPA 多态性可预测基因型 1 丙型肝炎患者对聚乙二醇干扰素、利巴韦林和替拉瑞韦三联治疗的反应。

IL28B but not ITPA polymorphism is predictive of response to pegylated interferon, ribavirin, and telaprevir triple therapy in patients with genotype 1 hepatitis C.

机构信息

Laboratory for Digestive Diseases, Center for Genomic Medicine, RIKEN, Japan.

出版信息

J Infect Dis. 2011 Jul 1;204(1):84-93. doi: 10.1093/infdis/jir210.

DOI:10.1093/infdis/jir210
PMID:21628662
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3307155/
Abstract

BACKGROUND

Pegylated interferon, ribavirin, and telaprevir triple therapy is a new strategy expected to eradicate the hepatitis C virus (HCV) even in patients infected with difficult-to-treat genotype 1 strains, although adverse effects, such as anemia and rash, are frequent.

METHODS

We assessed efficacy and predictive factors for sustained virological response (SVR) for triple therapy in 94 Japanese patients with HCV genotype 1. We included recently identified predictive factors, such as IL28B and ITPA polymorphism, and substitutions in the HCV core and NS5A proteins.

RESULTS

Patients treated with triple therapy achieved comparatively high SVR rates (73%), especially among treatment-naive patients (80%). Of note, however, patients who experienced relapse during prior pegylated interferon plus ribavirin combination therapy were highly likely to achieve SVR while receiving triple therapy (93%); conversely, prior nonresponders were much less likely to respond to triple therapy (32%). In addition to prior treatment response, IL28B SNP genotype and rapid viral response were significant independent predictors for SVR. Patients with the anemia-susceptible ITPA SNP rs1127354 genotype typically required ribavirin dose reduction earlier than did patients with other genotypes.

CONCLUSIONS

Analysis of predictive factors identified IL28B SNP, rapid viral response, and transient response to previous therapy as significant independent predictors of SVR after triple therapy.

摘要

背景

聚乙二醇干扰素、利巴韦林和特拉匹韦三联疗法是一种新的策略,有望根除丙型肝炎病毒(HCV),即使在感染难治性 1 型基因型的患者中也是如此,尽管经常出现贫血和皮疹等不良反应。

方法

我们评估了聚乙二醇干扰素、利巴韦林和特拉匹韦三联疗法在 94 例日本丙型肝炎 1 型患者中的疗效和持续病毒学应答(SVR)的预测因素。我们包括了最近确定的预测因素,如 IL28B 和 ITPA 多态性,以及 HCV 核心和 NS5A 蛋白的取代。

结果

接受三联疗法的患者达到了相对较高的 SVR 率(73%),尤其是在初治患者中(80%)。然而,值得注意的是,在接受聚乙二醇干扰素联合利巴韦林联合治疗期间复发的患者在接受三联疗法时极有可能达到 SVR(93%);相反,先前无应答者对三联疗法的反应性较低(32%)。除了先前的治疗反应外,IL28B SNP 基因型和快速病毒应答是 SVR 的独立显著预测因素。具有贫血易感 ITPA SNP rs1127354 基因型的患者通常比具有其他基因型的患者更早需要减少利巴韦林剂量。

结论

对预测因素的分析确定了 IL28B SNP、快速病毒应答和先前治疗的短暂应答是三联治疗后 SVR 的独立显著预测因素。

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Hepatic ISG expression is associated with genetic variation in interleukin 28B and the outcome of IFN therapy for chronic hepatitis C.肝组织干扰素刺激基因表达与白细胞介素 28B 基因多态性及慢性丙型肝炎干扰素治疗结局相关。
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