HCV is 2 times more prevalent in African Americans than in Caucasian Americans. In addition, African Americans appear to have worse outcomes from chronic HCV with both a higher incidence of primary HCC and higher death rate from cirrhosis 3, 4. Paradoxically, African Americans exhibit significantly lower rates of HCV clearance following treatment with pegylated interferon alpha plus ribavirin combination therapy relative to Caucasian Americans. The lower efficacy of lFN treatment in African-Americans is due, partly, to a higher prevalence of infection with HCV genotype 1. However, the efficacy of peginterferon plus ribavirin was lower in African Americans in a recent clinical trial limited to HCV genotype 1 patients. These results point to an important role for non-viral host factors. The basis for the racial disparities treatment efficacy has not been defined. There is compelling evidence that the host immune responses to HCV is crucial to the clearance of HCV infection during treatment. Thus, we hypothesize that differential expression of host immune genes in the livers based on race determines the racial disparity in HCV treatment outcomes. If so, we predict that measuring the antiviral, immune, and inflammatory gene expression profiles in liver biopsies might be able to predict the efficacy of antiviral therapy for chronic HCV in genotype 1. To test this hypothesis, the current project will utilize cDNA gene expression microarray technology to pursue the following 2 aims: 1) Define the alterations in host intrahepatic gene expression in vivo related to chronic HCV genotype 1 infection in previously untreated patients; 2) Determine the capacity of differentially expressed HCV-related gene in the liver biopsies taken from previously untreated patients to predict the efficacy of initial therapy with peginterferon plus ribavirin in African American and Caucasian HCV genotype 1 patients (NIDDK VIRAHEP-C cohort). These studies will provide new insights into the biological basis for the racial disparity in HCV treatment outcomes, and facilitate development of more effective treatments for HCV genotype 1.
| Howell, Charles D; Gorden, Alexis; Ryan, Kathleen A et al. (2012) Single nucleotide polymorphism upstream of interleukin 28B associated with phase 1 and phase 2 of early viral kinetics in patients infected with HCV genotype 1. J Hepatol 56:557-63 |
| Jin, Runyan; Cai, Ling; Tan, Ming et al. (2012) Optimum ribavirin exposure overcomes racial disparity in efficacy of peginterferon and ribavirin treatment for hepatitis C genotype 1. Am J Gastroenterol 107:1675-83 |
| Huang, Chao; Chen, Hegang; Cassidy, William et al. (2008) Peripheral blood gene expression profile associated with sustained virologic response after peginterferon plus ribavirin therapy for chronic hepatitis-C genotype 1. J Natl Med Assoc 100:1425-33 |
