AFRICAN AMERICAN RESPONSE TO THERAPY FOR HEPATITIS C

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。干扰素和利巴韦林联合治疗慢性丙型肝炎，白种人和亚洲人的总有效率高达40%。不幸的是，非裔美国人对联合治疗的反应率低得惊人，约为5%。本应用测试了三个相互竞争的假设，以解释丙型肝炎治疗反应的种族差异。准种异质性和选择的差异、干扰素反应的内在差异以及HCV免疫反应的遗传决定差异可能导致非裔美国人和高加索人患者对治疗反应的差异。该研究旨在回答以下问题：(1)丙型肝炎（HCV）准种异质性和/或选择是否解释了非裔美国人对联合治疗的不良反应？(2)非裔美国人对干扰素治疗的不良反应是否存在干扰素敏感性或反应的差异？(3)是否存在由基因决定的HCV免疫反应差异，可以解释种族对治疗反应的差异？(4)丙型肝炎病毒的配体或受体是否存在等位基因差异，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?