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Selective decrease in hepatitis C virus–specific immunity among African Americans and outcome of antiviral therapy
Author(s) -
Rosen Hugo R.,
Weston Scott J.,
Im KyungAh,
Yang Huiying,
Burton James R.,
Erlich Henry,
Klarquist Jared,
Belle Steven H.
Publication year - 2007
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.21714
Subject(s) - elispot , immunology , ribavirin , medicine , hepatitis c virus , pegylated interferon , hepatitis c , immunity , antigen , viral load , immune system , virology , virus , t cell
Hepatitis C virus (HCV) infection is a leading cause of chronic hepatitis, end‐stage liver disease, and hepatocellular carcinoma throughout the world. Considerable evidence indicates that the risk of viral persistence, natural history, and response to antiviral therapy varies among racial groups, but limited data exist on potential mechanisms to account for these differences. Type 1 helper (Th1) responses to HCV proteins and cytomegalovirus (CMV) antigens were examined using a sensitive interferon (IFN)‐γ enzyme‐linked immunospot (ELISPOT) assay in 187 Caucasian American (CA) and 187 African American (AA) patients with chronic genotype 1 infection. ELISPOT responses were examined relative to human leukocyte antigen (HLA) class II alleles and outcome of therapy with pegylated IFN and ribavirin. Th1 responses specific to hepatitis C core protein and combined HCV antigens were significantly lower in AAs compared to CAs, but CMV responses were comparable in the 2 races. The HCV difference in immunity remained after adjusting for gender, serum alanine aminotransferase, histologic severity, and viral level, and was not accounted for by the differential prevalence of human leukocyte antigen class II alleles. Pretreatment total HCV‐specific CD4+ T cell response was associated with sustained virologic response (SVR) to pegylated IFN and ribavirin; 43% of patients who had more than 168 ELISPOTs/10 6 peripheral blood mononuclear cells (above background) experienced SVR compared to 28% of those who did not ( P = 0.007). ELISPOT response was independently associated with SVR by multivariable analysis. Conclusion: Compared to CAs, AAs have weaker HCV‐specific immunity. Pretreatment HCV‐specific immunity is associated with response to combination antiviral therapy. (H EPATOLOGY 2007.)