The pathogenesis of hepatitis C (HCV) associated liver injury is poorly understood. Studies of HCV pathogenesis have been impeded by the lack of an animal model, the inability to maintain HCV in cell culture systems, and the slow progression of disease, which hinders natural history studies. However, though host and viral factors likely play a role in liver injury, neither has been rigorously analyzed. Early studies suggest that viral clearance with acute infection as well as with treatment is markedly decreased iin patients of African American heritage. The reasons for this poor response are not understood, but possibly relate to differences in demographics (e.g socioeconomic status), comorbid conditions (e.g., obesity), genotype distribution or virulence, viral kinetics, immune response, and compliance with therapy. Previous studies have been limited by small sample size and referral bias. Over the last 2 years, The Columbia-Cornell Liver Clinical Trials Network has established an extended network of care that has performed clinical trials including a large number of African Americans. This Network includes the Columbia Presbyterian and Harlem Hospital Centers both within the Harlem section of Manhattan and The New York-Cornell Center in central Manhattan. Within this ethnically diverse population, we will answer several questions. The primary hypothesis is that treatment response to PEGylated interferon and ribavirin is decreased in African Americans. However, we postulate that most of this decrease can be explained by differences in baseline characteristics and non-biologic parameters, including body mass index, comorbid medical conditions, socioeconomic status and the ability to complete therapy. Additionally we will search for clinical predictors of response to therapy including differences in immunogenetics and early viral kinetics. The secondary hypothesis is that the progression of liver disease in African Americans is comparable to that in a Caucasian American population after controlling for potential confounders including the variables mentioned above and alcohol consumption.
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