VIRAHEP-C

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。在过去十年中，慢性丙型肝炎治疗领域取得了重大进展，干扰素和利巴韦林两种药物联合治疗将根除率（持续病毒学反应/SVR -完成治疗后24周血清中检测不到丙型肝炎病毒/HCV RNA）的机会提高到近40%，而单独使用干扰素治疗的患者只有10-15%。不幸的是，对治疗的反应并不都是有利的。先前的试验结果表明，对丙型肝炎治疗的反应可能存在种族差异，非洲裔美国患者的SVR似乎明显低于使用相同方案治疗的高加索患者。然而，这些试验并不是专门为研究种族作为治疗反应因素而设计的，而且很少有非洲裔美国人被纳入研究对象，尽管该人群中丙型肝炎的患病率很高。VIRAHEP-C是一项由美国国立卫生研究院（NIH）赞助的多中心合作临床试验，旨在测试非裔美国人对治疗的反应是否不如白人患者。共有400名患者，平均分为非裔美国人和白种人，将在美国各地的8个临床中心登记。所有参与者将携带丙型肝炎病毒（HCV基因型）1。参与者将使用新配方的干扰素（聚乙二醇化干扰素α -2a）治疗48周，剂量为180微克，每周一次（mcg/周），外加剂量为1000-1200mg/天的利巴韦林胶囊。在停止治疗后，参与者将被随访48周。将比较两组之间的SVR（治疗后24周血清中检测不到HCV RNA）和持久的持续病毒学反应率（治疗后48周血清中检测不到HCV RNA），以确定两个种族组之间治疗反应的差异。将研究预测两种种族对治疗反应的患者相关因素和病毒相关因素。其他研究（辅助研究），使用本研究中不同时间点患者的血清和白细胞（外周单个核细胞）。这些研究将用于调查病毒如何抵抗体内免疫系统和这些药物的作用（抗病毒耐药性）的潜在机制。它们包括病毒动力学（治疗期间HCV RNA从血清中清除的速率）、免疫反应、干扰素作用的测量以及与治疗反应相关的宿主和病毒遗传学将被评估。这项全面的研究包括治疗以及抗病毒药物耐药性机制的额外研究，对于回答有关慢性丙型肝炎治疗的重要临床问题非常重要。

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Major advances have been made over the last decade in the field of therapy for chronic hepatitis C. Combination therapy with two medication namely interferon and ribavirin has improved chances of eradication rates (sustained virological response/SVR - undetectable hepatitis C virus/HCV RNA in serum 24 weeks after completing treatment) to nearly 40% compared to only 10-15% for patients treated with interferon alone. Unfortunately, response to therapy is not uniformly favorable. Results from previous trials have suggested that there may be racial disparities in response to therapy for hepatitis C. SVR in African American patients appear to be significantly less than in Caucasian patients treated with the same regimens. However, these trials were not designed specifically to study race as a factor in response to treatment and very few African Americans have been included as study subjects, despite the high prevalence of hepatitis C in this population. VIRAHEP-C is a multicenter, collaborative clinical trial, sponsored by the National Institutes of Health (NIH), designed to test whether African Americans respond less well to therapy than Caucasian patients. A total of 400 patients, equally divided between African American and Caucasians, will be enrolled at eight clinical centers throughout the United States. All participants will have hepatitis C virus type (HCV genotype) 1. Participants will be treated for 48 weeks with a new formulation of interferon (pegylated interferon alfa-2a) at a dose of 180 micrograms once a week (mcg/week) plus ribavirin capsules given at a dose of 1000-1200mg/day. Participants will be followed for an additional 48 weeks after stopping therapy. SVR (undetectable HCV RNA in serum 24 weeks post-treatment) and durable sustained virological response rates (undetectable HCV RNA in serum 48 weeks post-treatment) between the two groups will be compared to determine differences in treatment response between the two racial groups. Patient-related and virus-related factors that predict responses to treatment between the two racial groups will be studied. Additional studies (Ancillary studies), using serum and white blood cells (peripheral mononuclear cells) obtained from patients at various time points in this study. These studies will be performed to investigate potential mechanisms of how the virus is resistant to the immune system in the body and to the actions of these medications (antiviral resistance). They include viral kinetics (the rate at which HCV RNA is cleared from serum during therapy), immunological responses, measures of interferon actions, and host and viral genetics will be evaluated in relationship to treatment response. This comprehensive study that includes treatment along with additional studies of mechanisms of antiviral resistance will be important to answer important clinical questions about the treatment of chronic hepatitis C.