IL28B But Not ITPA Polymorphism Is Predictive of Response to Pegylated Interferon, Ribavirin, and Telaprevir Triple Therapy in Patients With Genotype 1 Hepatitis C
IL28B But Not ITPA Polymorphism Is Predictive of Response to Pegylated Interferon, Ribavirin, and Telaprevir Triple Therapy in Patients With Genotype 1 Hepatitis C
复制标题
DOI：
10.1093/infdis/jir210
复制
发表时间：
2011-07-01
影响因子：
6.4
通讯作者：
Kumada, Hiromitsu
中科院分区：
文献类型：
--
作者：
Chayama, Kazuaki;Hayes, C. Nelson;Kumada, Hiromitsu
背景。聚乙二醇化干扰素、利巴韦林和替拉韦三联疗法有望根除丙型肝炎病毒（HCV），即使感染了难以治疗的基因型1株的患者，尽管不良反应，如贫血和皮疹，是常见的。我们评估了94名日本HCV基因型为1的患者三联治疗的疗效和持续病毒学反应（SVR）的预测因素。我们纳入了最近发现的预测因素，如IL28B和ITPA多态性，以及HCV核心蛋白和NS5A蛋白的替换。接受三联治疗的患者获得了相对较高的SVR率（73%），特别是首次治疗的患者（80%）。然而，值得注意的是，在先前聚乙二醇化干扰素加利巴韦林联合治疗期间复发的患者在接受三联治疗时极有可能达到SVR (93%)；相反，先前无反应者对三联治疗的反应可能性要小得多（32%）。除了先前的治疗反应外，IL28B SNP基因型和快速病毒反应是SVR的重要独立预测因子。伴有贫血易感ITPA SNP rs1127354基因型的患者通常比其他基因型的患者更早需要利巴韦林减量。预测因素分析发现，IL28B SNP、快速病毒反应和对既往治疗的短暂反应是三联治疗后SVR的重要独立预测因素。
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.