Baltimore VIRAHEP-C Clinical Center

巴尔的摩 VIRAHEP-C 临床中心

• 批准号: 6765823
• 负责人: CHARLES D HOWELL
• 金额: $ 17.5万
• 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 2006-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6765823
• 关键词: African American; caucasian American; chronic disease /disorder; clinical research; clinical trials; 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) 是慢性肝病的最常见原因， 美国肝硬化影响了三百万美国居民 每年造成8-1万人死亡。每年因以下原因死亡的人数 预计到 2010 年至 2015 年，慢性丙型肝炎病毒感染人数将增加两倍，因为在 感染发展为终末期肝硬化的高峰发生率。丙型肝炎病毒 非裔美国人的感染率是白人的两倍 美国人。此外，非裔美国人的结果似乎更糟， 原发性肝细胞癌 (HCC) 的发病率较高，死亡率较高 肝硬化和肝癌的发生率。很少有非裔美国人参加啤酒比赛 HCV 疗法的临床试验。然而现有数据显着表明 干扰素α (IFN) 后长期 HCV 清除率较低 与 White 相比，单独治疗和 IFN 联合利巴韦林 (RBV) 治疗 美国人。非裔美国人的抗病毒治疗效果较低 部分原因是 HCV 基因型 1 (HCV-1) 感染率较高。 然而，根据 HCV 基因型调整后的 HCV 长期清除率在 非裔美国患者表明宿主具有潜在的重要作用 决定较低治疗反应率的因素。有一个关键的 需要有足够数量的非裔美国人进行多中心临床试验 最终确定联合抗病毒治疗的疗效 非裔美国人的慢性丙型肝炎并确定宿主和病毒机制 这构成了治疗结果中种族差异的基础。因此，我们 提议巴尔的摩临床中心参与多中心临床 慢性 HCV-1（VIRAHEP-C）抗病毒治疗耐药性研究。这 该奖项的长期目标是确定有效的抗病毒药物 针对感染 HCV-1 的非裔美国人的治疗。该项目有四个 具体目标： I) 确定对 48 的持续病毒学反应率 非西班牙裔、非洲裔联合抗病毒治疗的周疗程 美国和非西班牙裔美国白人慢性 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反应 非西班牙裔、非裔美国人和非裔美国人的联合抗病毒治疗 非西班牙裔美国白人慢性 HCV-I 患者； 3）确定模式 非裔美国人和白种人慢性丙型肝炎病毒 (RNA) 动力学的研究。 HCV-1患者 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反应 接受抗病毒治疗后的非裔美国人和白种人慢性 HCV-I 患者 治疗。该项目将与辅助研究合作，调查 选定的病毒和宿主因素对治疗效果的影响 对于慢性丙肝病毒。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。