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?
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