Document Detail


Hepatitis C virus load and expression of a unique subset of cellular genes in circulating lymphoid cells differentiate non-responders from responders to pegylated interferon alpha-ribavirin treatment.
MedLine Citation:
PMID:  23280583     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Based on investigations of liver biopsy material, certain cellular genes have been implicated as correlates of success or failure to interferon alpha-ribavirin (IFN/RBV) therapy against hepatitis C. The current study aimed at determining whether expression of host genes thought to be relevant to HCV replication in the liver would be correlated with HCV infection status in peripheral blood mononuclear cells (PBMCs) and also with patient responsiveness to IFN/RBV treatment. Therefore, PBMCs from patients with chronic hepatitis C responding (n = 35) or not (n = 49) to IFN/RBV and from healthy controls (n = 15) were evaluated for HCV RNA load and cellular gene expression. Non-responders had 3- to 10-fold higher basal levels of interleukin (IL)-8, IFN-stimulated gene 15 (ISG15), 2',5'-oligoadenylate synthetase (OAS), and Toll-like receptors (TLR)-4, -5, and -7 compared to responders. Non-responders with similar post-treatment follow-ups as responders persistently expressed 6- to 20-fold greater levels of IL-8, ISG15, and OAS after therapy. Higher expression of IFN-α, IFN-γ, and IFN-λ was found in PBMCs of individuals achieving sustained virological response, either before or after therapy. Pre-treatment HCV RNA loads in PBMCs of non-responders were significantly higher (P = 0.016) than those of responders. In conclusion, the data indicate that immune cells of responders and non-responders to IFN/RBV therapy exhibited significantly different virological and host gene expression profiles. Elevated baseline HCV loads and TLR-4, -5, and -7 levels, and persistently high levels of IL-8, ISG15, and OAS were correlated with IFN non-responsiveness. The results warrant further investigations on the utilization of PBMCs for predicting success or failure to IFN-based therapies. J. Med. Virol. © 2012 Wiley Periodicals, Inc.
Authors:
Tram N Q Pham; Dolly M H Lin; Patricia M Mulrooney-Cousins; Norma D Churchill; Arleta Kowala-Piaskowska; Iwona Mozer-Lisewska; Anna Machaj; Monika Pazgan-Simon; Malgorzata Zalewska; Krzysztof Simon; Dawn King; S Bharati Reddy; Tomasz I Michalak
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-12-21
Journal Detail:
Title:  Journal of medical virology     Volume:  -     ISSN:  1096-9071     ISO Abbreviation:  J. Med. Virol.     Publication Date:  2012 Dec 
Date Detail:
Created Date:  2013-1-2     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7705876     Medline TA:  J Med Virol     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Copyright © 2012 Wiley Periodicals, Inc.
Affiliation:
Molecular Virology and Hepatology Research Group, Faculty of Medicine, Memorial University, St. John's, NL, Canada.
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