Race & Viral Resistance in Chronic Hepatitis C (VIRAHEP*

种族

• 批准号: 6407013
• 负责人: ROBERT S BROWN
• 金额: $ 24.01万
• 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 2006-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6407013
• 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）： 肝炎（HCV）相关的肝损伤的发病机理不良 理解。缺乏HCV发病机理的研究阻碍了 动物模型，无法维持细胞培养系统中的HCV，以及 疾病的进展缓慢，这阻碍了自然历史研究。然而， 尽管宿主和病毒因素可能在肝损伤中起作用，但也没有 经过严格分析。早期研究表明，急性呼吸率 感染以及治疗的IIN患者明显降低 非裔美国人的遗产。这种反应不佳的原因不是 理解，但可能与人口统计学的差异有关（例如 社会经济地位），合并状况（例如肥胖），基因型 分布或毒力，病毒动力学，免疫反应以及遵守 治疗。先前的研究受到样本量和推荐小的限制 偏见。在过去的两年中，哥伦比亚 - 哥伦比亚肝癌临床试验网络 已经建立了一个扩展的护理网络，该网络已进行了临床试验 包括大量非裔美国人。该网络包括 哥伦比亚长老会和哈林医院都在哈林中心 曼哈顿地区和曼哈顿中部的纽约 - 康奈尔中心。 在这个种族多样化的人群中，我们将回答几个问题。 主要的假设是治疗反应对类乙二醇干扰素的反应和 非洲裔美国人的利巴韦林有所减少。但是，我们假设大多数 这种减少可以通过基线特征的差异和 非生物学参数，包括体重指数，合并医学 条件，社会经济状况和完成治疗的能力。 此外，我们将搜索对治疗反应的临床预测指标 包括免疫遗传学和早期病毒动力学的差异。次要 假设是，非裔美国人肝病的进展是 在控制之后，与高加索的美国人口相当 潜在的混杂因素，包括上述变量和酒精 消耗。