AFRICAN AMERICAN RESPONSE TO THERAPY FOR HEPATITIS C

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。干扰素和利巴韦林联合治疗慢性丙型肝炎在高加索人和亚洲人中的总应答率高达40%。不幸的是，非洲裔美国人对联合治疗的反应率低得惊人，约为5%。本申请测试了三种竞争性假设，以解释对丙型肝炎治疗的反应的种族差异。准种异质性和选择的差异，干扰素反应的固有差异，以及基因决定的HCV免疫反应的差异可能导致非洲裔美国人和高加索人之间的治疗反应的差异。该研究旨在回答以下问题：（1）丙型肝炎（HCV）准种异质性和/或选择性是否解释了非洲裔美国人对联合治疗的不良反应？(2)干扰素敏感性或反应是否存在差异，从而导致非裔美国人对基于干扰素的治疗反应较差？(3)是否存在基因决定的对HCV的免疫反应差异，可以解释治疗反应的种族差异？(4)丙型肝炎病毒配体或受体的等位基因差异是否可以解释疾病进展或治疗反应的种族差异？

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Combination therapy with interferon and ribavirin for chronic hepatitis C leads to a general response rate of up to 40% in Caucasians and Asians. Unfortunately, African Americans have a surprisingly low response rate of approximately 5% to combination therapy. The present application tests three competing hypotheses to explain the racial differences in response to therapy for hepatitis C. Differences in quasispecies heterogeneity and selection, inherent differences in the interferon response, and genetically determined differences in the HCV immune response may contribute to the difference in response to therapy between African American and Caucasin patients. The study intends to answer the following questions: (1) Does hepatitis C (HCV) quasispecies heterogeneity and/or selection explain the poor response of African Americans to combination therapy? (2) Are there differences in interferon sensitivity or response that account for the poor response of African Americans to interferon-based therapy? (3) Are there genetically determined differences in immune responses to HCV that could explain the racial differences in response to therapy? (4) Are there allelic differences in the ligands or receptors for hepatitis C virus that may explain racial differences in disease progression or response to therapy?