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Article type: Research Article
Authors: Lee, Silvia; | Varano, Julius | Flexman, James P. | Cheng, Wendy | Watson, Mark W. | Rossi, Enrico | Adams, Leon A. | Bulsara, Max | Price, Patricia;
Affiliations: Department of Microbiology and Infectious Disease, Royal Perth Hospital, Perth, Australia | School of Pathology and Laboratory Medicine, University of Western Australia, Perth, Australia | Department of Gastroenterology and Hepatology, Royal Perth Hospital, Perth, Australia | Clinical Immunology and Immunogenetics, Royal Perth Hospital, Perth, Australia | PathWest, Queen Elizabeth II Medical Centre, Nedlands, Australia | School of Medicine and Pharmacology, University of Western Australia, Perth, Australia | School of Population Health, University of Western Australia, Perth, Australia
Note: [] Corresponding author: Prof. Patricia Price, Level 2, MRF Building, Rear 50 Murray Street, Near Royal Perth Hospital, Perth, Western Australia 6000. Tel.: +61 8 9224 0223; Fax: +61 8 9224 0204; E-mail: patricia.price@uwa.edu.au
Abstract: The role of pro-fibrogenic cytokines in the outcome of infections with hepatitis C virus (HCV) and the response to treatment with pegylated interferon-alpha (pegIFNα) and ribavirin remains unclear. To address this issue, we assessed hepatic fibrosis and plasma markers pertinent to T-cell mediated fibrogenesis and inflammation at the start of treatment. Levels of soluble (s)CD30, interleukin-13 receptor alpha 2 (IL-13Rα2), total and active transforming growth factor-beta 1 (TGFβ1), interleukin-18 (IL-18) and interferon-gamma inducible protein-10 (IP-10, CXCL10) were correlated with the severity of fibrosis and with treatment outcome using multiple logistic regression modelling. The Hepascore algorithm was confirmed as a marker of fibrosis, but was a poor predictor of treatment outcome. Inclusion of all immunological markers improved prediction based on Hepascore alone (p=0.045), but optimal prediction was achieved with an algorithm ("TIPscore") based on TGFβ1 (total), IP-10, age, sex and HCV genotype (p=0.003 relative to Hepascore). Whilst this was only marginally more effective than predictions based on HCV genotype age and sex (p=0.07), it associates high TGFβ1 and low IP-10 levels with a failure of therapy.
Keywords: Hepatitis C virus, interferon-based therapy, chemokines, fibrosis
DOI: 10.3233/DMA-2010-0699
Journal: Disease Markers, vol. 28, no. 5, pp. 273-280, 2010
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