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Clin Gastroenterol Hepatol. 2005 May;3(5):499-506.

Interferon-stimulated gene expression in black and white hepatitis C patients during peginterferon alfa-2a combination therapy.

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  • 1University of Maryland School of Medicine, USA,

Abstract

BACKGROUND & AIMS:

Black American patients are less likely to eradicate hepatitis C virus (HCV) infections during treatment with peginterferon (PEG-IFN) and ribavirin. We hypothesized that racial differences in IFN-stimulated antiviral gene induction during treatment might be responsible.

METHODS:

We examined myxovirus resistance-A (MxA), RNA-dependent protein kinase (PKR), 2'-5' oligoadenylate synthetase (2,5-OAS), and adenosine deaminase-1 (ADAR1) gene expression in the peripheral blood mononuclear cells (PBMCs) of 31 black and 11 white HCV genotype 1 patients at baseline and at weeks 4-12 during PEG-IFN alfa-2a combination treatment. The primary study end point was the early virologic response (EVR)-either an undetectable serum HCV-RNA level or a > or =2-log decrease in serum HCV-RNA level at week 12 compared with week 0.

RESULTS:

The EVR rate was 67.7% in blacks and 63.6% in whites. Both blacks and whites experienced a significant (200%-500%) increase in 2,5-OAS, MxA, PKR, and ADAR1 expression at treatment weeks 4-12 compared with baseline (P < .01). However, the relationship between IFN-stimulated gene expression and the EVR differed by race. White responders exhibited higher 2,5-OAS and MxA levels at week 4 than white nonresponders (P < .05). IFN-stimulated gene levels did not correlate with EVR in blacks. Black responders had much lower MxA and PKR levels at week 4 than black nonresponders (P < .05). However, black responders maintained increased 2,5-OAS, MxA, and PKR levels from weeks 4-12, whereas the levels decreased to baseline at weeks 8-12 in black nonresponders.

CONCLUSIONS:

The mechanisms of resistance to PEG-IFN combination therapy may be different in black and white HCV genotype 1 patients.

PMID:
15880320
[PubMed - indexed for MEDLINE]
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