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

Shengyuan Luo, William Cassidy, Lennox J Jeffers, K. Rajender Reddy, Christine Bruno, Charles D. Howell

Research output: Contribution to journalArticle

25 Citations (Scopus)

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 ≥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.

Original languageEnglish
Pages (from-to)499-506
Number of pages8
JournalClinical Gastroenterology and Hepatology
Volume3
Issue number5
DOIs
StatePublished - May 1 2005

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Hepatitis C
Orthomyxoviridae
Hepacivirus
Interferons
Gene Expression
eIF-2 Kinase
Genotype
RNA
Therapeutics
Adenosine Deaminase
Ribavirin
Virus Diseases
Ligases
Serum
Genes
Antiviral Agents
Blood Cells
hydroquinone
peginterferon alfa-2a

ASJC Scopus subject areas

  • Gastroenterology

Cite this

Interferon-stimulated gene expression in black and white hepatitis C patients during peginterferon alfa-2a combination therapy. / Luo, Shengyuan; Cassidy, William; Jeffers, Lennox J; Reddy, K. Rajender; Bruno, Christine; Howell, Charles D.

In: Clinical Gastroenterology and Hepatology, Vol. 3, No. 5, 01.05.2005, p. 499-506.

Research output: Contribution to journalArticle

Luo, Shengyuan ; Cassidy, William ; Jeffers, Lennox J ; Reddy, K. Rajender ; Bruno, Christine ; Howell, Charles D. / Interferon-stimulated gene expression in black and white hepatitis C patients during peginterferon alfa-2a combination therapy. In: Clinical Gastroenterology and Hepatology. 2005 ; Vol. 3, No. 5. pp. 499-506.
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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 ≥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.",
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T1 - Interferon-stimulated gene expression in black and white hepatitis C patients during peginterferon alfa-2a combination therapy

AU - Luo, Shengyuan

AU - Cassidy, William

AU - Jeffers, Lennox J

AU - Reddy, K. Rajender

AU - Bruno, Christine

AU - Howell, Charles D.

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AB - 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 ≥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.

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