Influence of Ethnicity in the Outcome of Hepatitis C Virus Infection and Cellular Immune Response

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Abstract
This study was performed to examine the immunologic basis for the apparent ethnic difference in clinical outcome of hepatitis C virus (HCV) infection between African Americans (AA) and Caucasian Americans (CA). To this end, we recruited 99 chronically HCV–infected and 31 spontaneously HCV–cleared subjects for clinical, virologic, and immunologic analysis. In particular, CD4–proliferative T–cell response to genotype 1-derived HCV antigens (core, NS3–NS5) was examined in 82 patients chronically infected with genotype 1 (54 AA, 28 CA) and in all HCV–cleared subjects (14 AA, 17 CA). HCV–specific Th1 response also was examined in 52 chronic and 13 recovered subjects. Our results showed that HCV clearance was associated with a vigorous HCV–specific Th1 response irrespective of ethnic origin. Although the HCV–specific CD4 T–cell response clearly was weaker during chronic infection, AA ethnicity in this setting was associated with a significantly greater CD4–proliferative T–cell response to HCV, particularly to the nonstructural antigens (22% AA vs. 0% CA, P = .007) as well as better clinical parameters of liver disease. Interestingly, most HCV–specific CD4 T–cell proliferative responses in AA patients were unaccompanied by concurrent interferon γ (IFN–γ) production, suggesting a dysregulated virus–specific, CD4 T–cell effector function during chronic HCV infection. In conclusion, our results suggest that host ethnicity does influence the clinical outcome and antiviral T–cell response during HCV infection. AA ethnicity is associated with a more robust antiviral CD4 T–cell response than CA ethnicity, although these T cells are limited in direct virus or disease control due to their dysfunctional nature.

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