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

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.

Results

  • Th1 responses specific to hepatitis C core protein and combined HCV antigens were significantly lower in African-Americans compared with Caucasian-Americans.
  • Responses to CMV antigens, however, were comparable in the 2 racial groups.
  • The difference in HCV-specific immunity remained after adjusting for sex, serum alanine aminotransferase (ALT), liver histology severity, and HCV viral load.
  • Differential prevalence of HLA class II alleles in black and white patients did not account for the differences in anti-HCV immune responses.
  • Pre-treatment total HCV-specific CD4 T-cell response was associated with sustained virological response (SVR) to pegylated interferon plus ribavirin.
  • 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).
  • ELISPOT response was independently associated with SVR in a multivariable analysis.

Conclusion

"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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