Conflict of interest: nothing to declare.
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†
Article first published online: 21 DEC 2012
Copyright © 2012 Wiley Periodicals, Inc.
Journal of Medical Virology
Volume 85, Issue 3, pages 441–448, March 2013
How to Cite
Pham, T. N.Q., Lin, D. M.H., Mulrooney-Cousins, P. M., Churchill, N. D., Kowala-Piaskowska, A., Mozer-Lisewska, I., Machaj, A., Pazgan-Simon, M., Zalewska, M., Simon, K., King, D., Reddy, S. B. and Michalak, T. I. (2013), 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. J. Med. Virol., 85: 441–448. doi: 10.1002/jmv.23481
- Issue published online: 22 JAN 2013
- Article first published online: 21 DEC 2012
- Manuscript Accepted: 5 NOV 2012
- Canadian Institutes of Health Research (CIHR) (to T.I.M.). Grant Number: MOP-77544
- Partially supported by Polish National Science Center (to I.M.-L.). Grant Number: NN401 535 740
- chronic HCV infection;
- HCV RNA in PBMCs;
- gene expression profiles
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. 85:441–448, 2013. © 2012 Wiley Periodicals, Inc.