title: Decreased IP-10 and elevated TGFbeta1 levels are associated with viral clearance following therapy in patients with hepatitis C virus.
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 (pegIFNalpha) 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-13Ralpha2), total and active transforming growth factor-beta 1 (TGFbeta1), 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 TGFbeta1 (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 TGFbeta1 and low IP-10 levels with a failure of therapy.
authors.affiliation: Department of Microbiology and Infectious Disease, Royal Perth Hospital, University of Western Australia, Perth, Australia.
authors.forename: Silvia
authors.initials: S
authors.lastname: Lee
authors.forename: Julius
authors.initials: J
authors.lastname: Varano
authors.forename: James P
authors.initials: JP
authors.lastname: Flexman
authors.forename: Wendy
authors.initials: W
authors.lastname: Cheng
authors.forename: Mark W
authors.initials: MW
authors.lastname: Watson
authors.forename: Enrico
authors.initials: E
authors.lastname: Rossi
authors.forename: Leon A
authors.initials: LA
authors.lastname: Adams
authors.forename: Max
authors.initials: M
authors.lastname: Bulsara
authors.forename: Patricia
authors.initials: P
authors.lastname: Price
mesh_terms: D000328:Adult; D000368:Aged; D000465:Algorithms; D000998:Antiviral Agents / Q000627:therapeutic use*; D019540:Area Under Curve; D054357:Chemokine CXCL10 / Q000097:blood*; D016326:Extracellular Matrix Proteins / Q000097:blood*; D005260:Female; D016174:Hepacivirus / Q000502:physiology*; D006526:Hepatitis C / Q000097:blood / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use; D008103:Liver Cirrhosis / Q000175:diagnosis / Q000188:drug therapy; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000627:therapeutic use; D011994:Recombinant Proteins; D012254:Ribavirin / Q000627:therapeutic use; D012680:Sensitivity and Specificity; D016212:Transforming Growth Factor beta / Q000097:blood*; D016896:Treatment Outcome; D019562:Viral Load; D000099222:betaIG-H3 Protein
chemical_list: D000998:Antiviral Agents; D054357:Chemokine CXCL10; D016326:Extracellular Matrix Proteins; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011092:Polyethylene Glycols; D011994:Recombinant Proteins; D012254:Ribavirin; D016212:Transforming Growth Factor beta; D000099222:betaIG-H3 Protein; C114753:CXCL10 protein, human; C100416:peginterferon alfa-2a