VIRAHEP-C

这个子项目是利用由NIH/NCRR资助的中心拨款提供的资源的许多研究子项目之一。子项目和调查员(PI)可能从另一个NIH来源获得了主要资金，因此可能会出现在其他CRISE条目中。列出的机构是针对中心的，而不一定是针对调查员的机构。在过去十年中，慢性丙型肝炎的治疗领域取得了重大进展。两种药物，即干扰素和利巴韦林的联合治疗将根治率(持续的病毒学应答/治疗完成24周后血清中无法检测到的丙型肝炎病毒/丙型肝炎病毒RNA)的机会提高到近40%，而单独使用干扰素的患者只有10%-15%。不幸的是，对治疗的反应并不是一致有利的。以前的试验结果表明，对丙型肝炎的治疗反应可能存在种族差异。非裔美国人患者的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了研究种族作为治疗反应的一个因素而设计的，而且很少有非洲裔美国人被纳入研究对象，尽管这一人群中丙型肝炎的发病率很高。VIRAHEP-C是一项由美国国立卫生研究院(NIH)赞助的多中心协作临床试验，旨在测试非裔美国人对治疗的反应是否不如白人患者。总共有400名患者，平均分配给非裔美国人和高加索人，将在全美的八个临床中心登记。所有参与者都将患有丙型肝炎病毒(丙型肝炎病毒)1。参与者将接受为期48周的新干扰素(聚乙二醇化干扰素α-2a)治疗，每周一次，剂量为180微克，外加利巴韦林胶囊，剂量为1000-1200毫克/天。在停止治疗后，参与者将再接受48周的跟踪。将比较两组之间的SVR(治疗24周后血清中检测不到丙型肝炎病毒RNA)和持久持续病毒学应答率(治疗48周后血清中检测不到丙型肝炎病毒RNA)，以确定两个种族组之间治疗反应的差异。将研究两个种族群体之间预测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(外周单核细胞)。这些研究将被用来研究病毒如何抵抗体内免疫系统的潜在机制，以及这些药物的作用(抗病毒耐药性)。它们包括病毒动力学(治疗期间丙型肝炎病毒RNA从血清中清除的速率)、免疫学反应、干扰素作用的测量，以及宿主和病毒遗传学将根据治疗反应进行评估。这项全面的研究包括治疗以及对抗病毒耐药机制的更多研究，对于回答有关慢性丙型肝炎治疗的重要临床问题将是重要的。

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.