Race & Viral Resistance in Chronic Hepatitis C (VIRAHEP*

种族

• 批准号: 6647205
• 负责人: ROBERT S BROWN
• 金额: $ 35万
• 依托单位: COLUMBIA UNIVERSITY HEALTH SCIENCES
• 依托单位国家: 美国
• 财政年份: 2001
• 资助国家: 美国
• 起止时间: 2001-09-01 至 2006-04-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6647205
• 关键词: African American; caucasian American; chronic disease /disorder; clinical trials; combination chemotherapy; fibrosis; genotype; hepatitis C; hepatitis C virus; human subject; human therapy evaluation; immunogenetics; interferons; liver disorder; microorganism disease chemotherapy; obesity; pathologic process; patient oriented research; quality of life; racial /ethnic difference; ribavirin; socioeconomics; therapy compliance; urban area; virulence; virus genetics

DESCRIPTION (provided by applicant): The pathogenesis of hepatitis C (HCV) associated liver injury is poorly understood. Studies of HCV pathogenesis have been impeded by the lack of an animal model, the inability to maintain HCV in cell culture systems, and the slow progression of disease, which hinders natural history studies. However, though host and viral factors likely play a role in liver injury, neither has been rigorously analyzed. Early studies suggest that viral clearance with acute infection as well as with treatment is markedly decreased iin patients of African American heritage. The reasons for this poor response are not understood, but possibly relate to differences in demographics (e.g socioeconomic status), comorbid conditions (e.g., obesity), genotype distribution or virulence, viral kinetics, immune response, and compliance with therapy. Previous studies have been limited by small sample size and referral bias. Over the last 2 years, The Columbia-Cornell Liver Clinical Trials Network has established an extended network of care that has performed clinical trials including a large number of African Americans. This Network includes the Columbia Presbyterian and Harlem Hospital Centers both within the Harlem section of Manhattan and The New York-Cornell Center in central Manhattan. Within this ethnically diverse population, we will answer several questions. The primary hypothesis is that treatment response to PEGylated interferon and ribavirin is decreased in African Americans. However, we postulate that most of this decrease can be explained by differences in baseline characteristics and non-biologic parameters, including body mass index, comorbid medical conditions, socioeconomic status and the ability to complete therapy. Additionally we will search for clinical predictors of response to therapy including differences in immunogenetics and early viral kinetics. The secondary hypothesis is that the progression of liver disease in African Americans is comparable to that in a Caucasian American population after controlling for potential confounders including the variables mentioned above and alcohol consumption.

描述（由申请人提供）： 丙型肝炎（HCV）相关肝损伤的发病机制尚不清楚 明白了。由于缺乏证据，HCV 发病机制的研究受到阻碍。 动物模型、无法在细胞培养系统中维持 HCV 以及 疾病进展缓慢，阻碍了自然史研究。然而， 尽管宿主和病毒因素可能在肝损伤中发挥作用，但两者都没有 进行了严格的分析。早期研究表明，急性病毒清除 在以下患者中，感染以及治疗均显着减少 非裔美国人的遗产。造成这种不良反应的原因并非 理解，但可能与人口统计差异有关（例如 社会经济地位）、合并症（例如肥胖）、基因型 分布或毒力、病毒动力学、免疫反应和依从性 治疗。先前的研究受到样本量小和转诊的限制 偏见。在过去的两年里，哥伦比亚-康奈尔大学肝脏临床试验网络 已建立了广泛的护理网络并进行了临床试验 其中包括大量非裔美国人。该网络包括 哥伦比亚长老会医院和哈莱姆区医院中心均位于哈莱姆区 曼哈顿部分地区和曼哈顿市中心的纽约康奈尔中心。 在这个种族多元化的人群中，我们将回答几个问题。 主要假设是对聚乙二醇化干扰素的治疗反应和 利巴韦林在非裔美国人中的水平下降。然而，我们假设大多数 这种下降可以用基线特征的差异来解释 非生物参数，包括体重指数、合并症医疗 条件、社会经济地位和完成治疗的能力。 此外，我们将寻找治疗反应的临床预测因子 包括免疫遗传学和早期病毒动力学的差异。二级 假设非裔美国人肝病的进展是 控制后与美国白人人口的情况相当 潜在的混杂因素，包括上述变量和酒精 消耗。