Racial Difference in HCV/Host Interactions

The University of Tennessee Health Science Center (UTHSC) Memphis Hepatitis C Cooperative Research Center was established in 2000 to support clinical and basic research in understanding the basis for chronic disease in hepatitis C (HCV) infection and response to therapy in clinically infected patients. The primary research goal is to understand why African American (AA) patients with chronic hepatitis C are more susceptible to chronic infection and why their response rate to combination therapy is only 50 percent or less of that for non AA patients. The present study will support this ongoing work by continuing to provide clinical samples from patients with chronic hepatitis C who are undergoing treatment. The specific aims for the 2005-2010 Hepatitis C Cooperative Research Center are: to determine how human leukocyte antigen (HLA) class II-dependent immune regulation and T cell specificities affect differences in immune responses to HCV and response to therapy in AA patients compared to non AA patients; to determine if there is a difference in interferon-induced signaling between patients that respond to therapy and those that do not; and to measure and compare the sustained virologic response to standard treatment for hepatitis C between AA and non AA patients. Researchers plan to continue enrollment of patients to the "African American Response to Therapy for Hepatitis C" study (112 African American patients and 20 Caucasian patients) in order to meet the current specific aims. Participants will include adult African American and Caucasian patients with compensated chronic hepatitis C who have not been previously treated with interferon and/or ribavirin. Patients meeting the entry criteria will be enrolled. The total number of patients to be enrolled is 260 over a 10-year period. In the next 5 years 132 subjects (112 African American, 20 Caucasian) will be studied locally. Patients will be recruited primarily from the clinical practices of the hepatologists at UTHSC. Patients will also be selected from referrals at local Gastroenterology Hepatology clinics and the Memphis Department of Veterans Affairs (VA) Hospital. Patients will be treated with weight based pegylated interferon alfa-2b once weekly and weight based ribavirin twice a day. Duration of treatment with both pegylated interferon alfa-2b and ribavirin will be for up to 72 weeks. Treatment will be discontinued at 24 weeks if there is persistent viremia and the patient wishes to discontinue therapy. Ribavirin will be administered orally at a dose of 13 +/- 2 mg/kg per day twice daily, with 200 mg capsules. Pegylated interferon alpha-2b will be administered by the subcutaneous route.