Racial Difference in HCV-Host Interactions and Response

描述（由申请人提供）：丙型肝炎病毒（HCV）是非甲、非乙型肝炎的病原。HCV目前是美国慢性肝病最常见的病因，并已超过酒精性肝病，成为北美最常见的肝移植指征。估计1.8%的美国人被感染，非洲裔美国人（AA）的比例更高。该病的一个特点是慢性，接触者中高达85%患有慢性感染。UTHSC孟菲斯丙型肝炎合作研究中心的成立是为了支持临床和基础研究，以了解丙型肝炎感染慢性疾病的基础和临床感染患者对治疗的反应。大孟菲斯地区55%的人口是AA型肝炎，其中慢性丙型肝炎病毒感染是一个重大问题。有充分证据表明，AA对联合治疗的低应答率加剧了该地区慢性HCV的明显健康问题。孟菲斯丙型肝炎合作研究中心和本项目的主要研究目标是了解为什么AA患者更容易发生慢性感染，以及为什么他们对联合治疗的反应率只有非AA患者的50%或更少。该项目以该中心的成功和成就为基础，实施了一种真正的多学科方法，进行假设驱动的研究，以了解为什么对慢性病的易感性和对治疗的反应存在种族差异。此外，该项目将寻求识别新的小分子抑制剂，抑制病毒配体或其受体之间的相互作用，以开发新一代的治疗方式。该中心拟议的研究计划包括两个项目，一个是行政核心，一个是临床核心。项目1将确定HLA II类依赖的免疫调节和T细胞特异性如何影响AA患者与非AA患者对HCV免疫反应和治疗反应的差异。项目2将确定对治疗有反应的患者和对治疗无反应的患者之间干扰素诱导的信号传导是否存在差异。每个项目都需要优秀临床核心提供的患者资源。

DESCRIPTION (provided by applicant): Hepatitis C virus (HCV) is the etiologic agent of non-A, non-B hepatitis. HCV is now the most common cause of chronic liver disease in the United States and has surpassed alcoholic liver disease as the most common indication for liver transplantation in North America. An estimated 1.8% of all Americans are infected with a higher percentage among African Americans (AA). A hallmark of the disease is its chronicity with up to 85% of those exposed having chronic infection. The UTHSC Memphis Hepatitis C Cooperative Research Center was established to support clinical and basic research to understand the basis for chronic disease in HCV infection and response to therapy in clinically infected patients. The population of the greater Memphis area is 55% AA within which there is a significant problem with chronic HCV infection. The well documented poor response rate of AA to combination therapy exacerbates the obvious health problem of chronic HCV in this region. The primary research goal of the Memphis Hepatitis C Cooperative Research Center and this project is to understand why AA are more susceptible to chronic infection and why then response rate to combination therapy is only 50% or less of that for non AA patients. The project builds upon the success and achievements of the Center to implement a truly multidisciplinary approach for hypothesis-driven research to understand why there are racial differences in susceptibility to chronic disease and response to therapy. In addition, the program will seek to identify novel small molecule inhibitors that inhibit interaction between viral ligands or their receptors for development of a new generation of therapeutic modalities. The proposed research program for the Center includes two projects, an administrative core, and a clinical core. Project 1 will determine how HLA class II- dependent immune regulation and T cell specificities affect differences in immune responses to HCV and response to therapy in AA compared to non AA patients. Project 2 will determine if there is a difference in interferon-induced signaling between patients that respond to therapy and those that do not. Each project will require the patient resources provided by the outstanding clinical core.