title: Kinetics of serum cytokines reflect changes in the severity of chronic hepatitis C presenting minimal fibrosis.
abstract: Our aims were to measure the kinetics of serum tumour necrosis alpha (TNF-alpha) and transforming growth factor beta (TGF-beta) levels as markers of progression of disease in nontreated chronic hepatitis C virus (HCV)-infected patients with minimal or no fibrosis and minimal histology activity index (HAI) scores. Our study group consisted of 56 patients diagnosed with minimal (1) or no fibrosis (0) and minimal HAI (0-1) on their first biopsy as defined by Knodell and METAVIR scores. We compared their initial (entry of study) cytokine levels with a group of 103 HCV controls with minimal (0-1) to mild fibrosis (0-3) and mild HAI (5.5). Serum TNF-alpha and TGF-beta levels were measured by enzyme-linked-immunosorbent-assay. A significant difference was seen in TNF-alpha levels at baseline in the study group vs. controls. Regardless of their HAI, there was a correlation between TGF-beta and degree of fibrosis. As shown by their biopsies, during the 3 years (from entry to follow up), many of the patients that initially had minimal fibrosis progressed to higher degree of fibrosis. This progression is paralleled by an increase in TGF-beta levels when comparing initial and follow-up levels. In conclusion, serum TNF-alpha reflects the progression of inflammation as seen in liver biopsies and TGF-beta reflects the degree of fibrosis in HCV patients.
authors.affiliation: Division of Clinical Pharmacology, Sunnybrook and Women's College Health Sciences Centre, University of Toronto, 2075 Bayview Avenue, Toronto, Ontario, M4N 3M5, Canada. manuela@sten.sunnybrook.utoronto.ca
authors.forename: Manuela G
authors.initials: MG
authors.lastname: Neuman
authors.forename: J P
authors.initials: JP
authors.lastname: Benhamou
authors.forename: I M
authors.initials: IM
authors.lastname: Malkiewicz
authors.forename: A
authors.initials: A
authors.lastname: Ibrahim
authors.forename: D C
authors.initials: DC
authors.lastname: Valla
authors.forename: M
authors.initials: M
authors.lastname: Martinot-Peignoux
authors.forename: T
authors.initials: T
authors.lastname: Asselah
authors.forename: M
authors.initials: M
authors.lastname: Bourliere
authors.forename: G G
authors.initials: GG
authors.lastname: Katz
authors.forename: N H
authors.initials: NH
authors.lastname: Shear
authors.forename: P
authors.initials: P
authors.lastname: Marcellin
mesh_terms: D000328:Adult; D018450:Disease Progression; D005260:Female; D016174:Hepacivirus / Q000145:classification / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000097:blood / Q000276:immunology / Q000473:pathology*; D006801:Humans; D007700:Kinetics; D008099:Liver / Q000473:pathology*; D008103:Liver Cirrhosis / Q000097:blood / Q000276:immunology / Q000473:pathology*; D008297:Male; D016212:Transforming Growth Factor beta / Q000097:blood*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis*
chemical_list: D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha