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Decreased HCV-specific Immunity in African-Americans May Help Explain Poorer Response to Antiviral Therapy

Baseline HCV It is well known that African-American patients with chronic hepatitis C virus (HCV) infection do not respond as well as whites to interferon-based therapy, but the reasons for this difference are not well understood.

In a study reported in the August 2007 issue of Hepatology, researchers from the University of Colorado in Denver performed a study to shed further light on this issue.

They examined type 1 T-helper cell (Th1) responses to HCV proteins and cytomegalovirus (CMV) antigens in 187 Caucasian-American and 187 African-American patients with chronic genotype 1 HCV infection, using a sensitive interferon-gamma enzyme-linked immunospot (ELISPOT) assay.

ELISPOT responses were examined relative to human leukocyte antigen (HLA) class II alleles and outcome of therapy with pegylated interferon plus ribavirin.

bullet Th1 responses specific to hepatitis C core protein and combined HCV antigens were significantly lower in African-Americans compared with Caucasian-Americans.

bullet Responses to CMV antigens, however, were comparable in the 2 racial groups.

bullet The difference in HCV-specific immunity remained after adjusting for sex, serum alanine aminotransferase (ALT), liver histology severity, and HCV viral load.

bullet Differential prevalence of HLA class II alleles in black and white patients did not account for the differences in anti-HCV immune responses.

bullet Pre-treatment total HCV-specific CD4 T-cell response was associated with sustained virological response (SVR) to pegylated interferon plus ribavirin.

bullet 43% of patients who had more than 168 ELISPOTs per 106 peripheral blood mononuclear cells (above background) achieved SVR, compared to 28% of subjects with ELISPOT tests showing less responsiveness (P = 0.007).

bullet ELISPOT response was independently associated with SVR in a multivariable analysis.


"Compared to Caucasian-Americans, African-Americans have weaker HCV-specific immunity," the authors concluded. "Pretreatment HCV-specific immunity is associated with response to combination antiviral therapy."

HR Rosen, SJ Weston, K Im, and others. Selective decrease in hepatitis C virus-specific immunity among African Americans and outcome of antiviral therapy.
Hepatology 46(2): 350-358. August 2007.

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