Race & Viral Resistance in Chronic Hepatitis C (VIRAHEP*

描述（由申请人提供）： 丙型肝炎（HCV）相关性肝损伤的发病机制尚不清楚， 明白HCV致病机制的研究一直受到缺乏一种有效的方法的阻碍。 动物模型，不能在细胞培养系统中维持HCV， 疾病进展缓慢，阻碍了自然史研究。然而，在这方面， 尽管宿主和病毒因素可能在肝损伤中起作用， 经过严格分析。早期的研究表明，病毒清除与急性 感染以及治疗显著减少， 非裔美国人的遗产。这种反应不佳的原因不是 可以理解，但可能与人口统计学差异有关（例如 社会经济状况），共病状况（例如，肥胖），基因型 分布或毒力、病毒动力学、免疫应答和依从性 疗法以前的研究受到样本量小和转诊的限制 bias.在过去的2年里，哥伦比亚-康奈尔肝脏临床试验网络 已经建立了一个扩展的护理网络， 包括大量的非洲裔美国人。该网络包括 哈莱姆内的哥伦比亚长老会和哈莱姆医院中心 位于曼哈顿的一部分和位于曼哈顿中心的纽约-康奈尔中心。 在这个种族多样的人群中，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减少。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， 非生物学参数，包括体重指数、共病医学 条件，社会经济地位和完成治疗的能力。 此外，我们还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。次级 假设是，非裔美国人的肝病进展是 在控制了以下因素后， 潜在混杂因素，包括上述变量和酒精 消费

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.