Baltimore VIRAHEP-C Clinical Center

巴尔的摩 VIRAHEP-C 临床中心

• 批准号: 6517971
• 负责人: CHARLES D HOWELL
• 金额: $ 37万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-08-21 至 2006-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6517971
• 关键词: African American; caucasian American; chronic disease /disorder; combination chemotherapy; cooperative study; drug resistance; genetic susceptibility; hepatitis C; human subject; human therapy evaluation; immunotherapy; interferon alpha; liver disorder chemotherapy; patient oriented research; pharmacogenetics; prognosis; racial /ethnic difference; ribavirin; virus genetics; virus load

DESCRIPTION (provided by applicant): Hepatitis C (HCV) is the most common cause for chronic liver disease and cirrhosis in the United States, affecting three million U.S residents and causing 8-10 thousand deaths annually. The number of deaths per year due to chronic HCV is projected to triple by 2010-2015, as individual infected during the peak incidence of infection develop end-stage liver cirrhosis. HCV infection is two times mores prevalent in African Americans than White Americans. Furthermore, African Americans appear to have worse outcome, with a higher incidence of primary hepatocellular carcinoma (HCC) and higher death rates due to cirrhosis and HCC. Few African Americans have beer enrolled in clinical trials of HCV therapies. Yet the available data shows significantly lower rates of HCV clearance long-term following interferon alfa (IFN) therapies alone and IFN combined with ribavirin (RBV), compared to White Americans. The lower efficacy of antiviral therapies in African Americans is due, in part, to a higher prevalence of infection with HCV genotype 1 (HCV-1). Yet-the long term clearance of HCV adjusted for HCV genotype is still lower in African American patients, suggesting a potentially important role for host factors in determining the lower treatment response rates. There is a critical need for multicenter clinical trials with adequate numbers of African Americans to conclusively determine the efficacy of combination antiviral therapy for chronic HCV in African Americans and to define the host and viral mechanisms that form the basis for the racial differences in treatment outcomes. Thus, we propose the Baltimore Clinical Center to participate in a multicenter clinical study of resistance to antiviral therapies for chronic HCV-1(VIRAHEP-C). The long-term objective of this award is to identify effective antiviral treatment(s) for African Americans infected with HCV-1. The projects has four Specific Aims: I) Determine the rates of sustained virological response to a 48 week course of combination antiviral therapy, among non-Hispanic, African American and non-Hispanic, White American chronic HCV-1 patients; 2) Determine which host and viral factors predict a sustained virological response to combination antiviral therapy in non-Hispanic, African American and non-Hispanic, White American chronic HCV-I patients; 3) Determine the patterns of HCV (RNA) kinetics in African American and Caucasian chronic. HCV-1 patients during antiviral therapy; 4) Determine whether early HCV (RNA) kinetics accurately predicts the end of treatment and sustained virological responses in African-American and Caucasian chronic HCV-I patients following antiviral therapy. In collaboration with ancillary studies, this project will investigate the influence of selected viral and host factors on the efficacy of treatment for chronic HCV. These studies may provide important new insights into the pathogenesis of HCV and lead to novel therapies for chronic HCV.

描述（由申请人提供）： 丙型肝炎（HCV）是慢性肝病最常见的原因， 肝硬化在美国，影响了300万美国居民， 每年造成8- 1万人死亡。每年死于 预计到2010-2015年，慢性HCV感染者将增加两倍， 感染发生高峰期发展为终末期肝硬化。HCV 非裔美国人感染率是白色人的两倍 美国人此外，非洲裔美国人似乎有更糟糕的结果， 原发性肝细胞癌（HCC）的发病率和死亡率较高 肝硬化和肝癌的发病率。很少有非洲裔美国人有啤酒登记在 HCV治疗的临床试验。然而，现有数据显示， α-干扰素（IFN）治疗后长期HCV清除率较低 单独治疗和IFN联合利巴韦林（RBV）治疗，与白色相比 美国人抗病毒治疗在非裔美国人中的疗效较低， 部分原因是HCV基因型1（HCV-1）感染的流行率较高。 然而，根据HCV基因型调整的HCV长期清除率仍然较低， 非裔美国人患者，这表明宿主可能发挥重要作用 决定较低治疗反应率的因素。存在一个临界 需要有足够数量的非裔美国人参加多中心临床试验 以最终确定联合抗病毒治疗的疗效， 非裔美国人中的慢性HCV，并确定宿主和病毒机制 这是治疗结果中种族差异的基础。因此我们 建议巴尔的摩临床中心参加多中心临床试验 慢性HCV-1（VIRAHEP-C）抗病毒治疗耐药性研究。的 该奖项的长期目标是确定有效的抗病毒药物， 治疗感染HCV-1的非裔美国人。该项目有四个 具体目的：I）确定对48例感染者持续病毒学应答的比率。 在非西班牙裔、非洲裔和非裔美国人中， 美国和非西班牙裔、白色美国慢性HCV-1患者; 2）确定 哪些宿主和病毒因素预测了持续的病毒学应答， 非西班牙裔、非裔美国人和 非西班牙裔、白色美国慢性HCV-I患者; 3）确定模式 非裔美国人和高加索人慢性丙型肝炎病毒（RNA）的动力学。HCV-1患者 在抗病毒治疗期间; 4）确定早期HCV（RNA）动力学是否 准确预测治疗结束和持续的病毒学应答， 接受抗病毒治疗的非裔美国人和白人慢性HCV-I患者 疗法与辅助研究合作，本项目将调查 选定的病毒和宿主因素对治疗效果的影响 治疗慢性丙型肝炎这些研究可能会提供重要的新见解， HCV的发病机制，并导致慢性HCV的新疗法。