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:
[email protected]
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
