title: Circulating matrix metalloproteinases 1, 2, 9 and their inhibitors TIMP-1 and TIMP-2 as serum markers of liver fibrosis in patients with chronic hepatitis C: comparison with PIIINP and hyaluronic acid.
abstract: OBJECTIVE
  Histological examination of liver biopsy is currently required in the management of patients with chronic hepatitis C. Our aim was to evaluate the diagnostic utility of a panel of circulating markers in detecting the stage of fibrosis.
  
  
  METHODS
  One hundred and ninety four-patients who had undergone a percutaneous liver biopsy before antiviral treatment, and 194 age- and sex-matched healthy subjects were studied. Serum levels of hyaluronate, procollagen type III N-terminal peptide (PIIINP), matrix metalloproteinases (MMP)-1, MMP-2, MMP-9 and their tissue inhibitors of metalloproteinases (TIMP)-1 and TIMP-2 were determined by RIA and ELISA. Histological lesions were staged according to the METAVIR score.
  
  
  RESULTS
  Hyaluronate, PIIINP, TIMP-1, and TIMP-2 serum levels were significantly higher in patients than in controls. Six markers were significantly correlated with fibrosis: MMP-2 (r = 0.28; p < 0.01), TIMP-1 (r = 0.42; p < 0.001), HA (r = 0.50; p < 0.001), PIIINP (r = 0.62; p < 0.0001), MMP-1 (r = -0.32; p < 0.01), and MMP-9 (r = -0.22; p < 0.05). By multivariate analysis, only PIIINP and MMP-1 were independently associated with fibrosis, and were combined using the equation of the logistic regression model. Using receiver-operating characteristics analysis, the area under the curve of the score to discriminate mild (FO/F1) from significant fibrosis (F2/F3/F4) was 0.82, with a sensitivity of 60% for a specificity of 92%.
  
  
  CONCLUSIONS
  Our results suggest that combining two serum markers reflecting fibrogenesis (PIIINP) and fibrolysis (MMP-1) may provide a useful tool for evaluating liver fibrosis.
authors.affiliation: Département d 'Hépato-Gastroentérologie, CHU de Grenoble, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Leroy
authors.forename: Frederique
authors.initials: F
authors.lastname: Monier
authors.forename: Serge
authors.initials: S
authors.lastname: Bottari
authors.forename: Candice
authors.initials: C
authors.lastname: Trocme
authors.forename: Nathalie
authors.initials: N
authors.lastname: Sturm
authors.forename: Marie-Noëlle
authors.initials: MN
authors.lastname: Hilleret
authors.forename: Francoise
authors.initials: F
authors.lastname: Morel
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Zarski
mesh_terms: D000328:Adult; D015415:Biomarkers / Q000097:blood; D017364:Collagenases / Q000097:blood*; D005260:Female; D019698:Hepatitis C, Chronic / Q000097:blood* / Q000150:complications / Q000473:pathology; D006801:Humans; D006820:Hyaluronic Acid / Q000097:blood; D008103:Liver Cirrhosis / Q000097:blood* / Q000473:pathology; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000097:blood; D020778:Matrix Metalloproteinase 2 / Q000097:blood; D020780:Matrix Metalloproteinase 9 / Q000097:blood; D008875:Middle Aged; D010446:Peptide Fragments / Q000097:blood; D011347:Procollagen / Q000097:blood; D012720:Severity of Illness Index; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000097:blood; D019714:Tissue Inhibitor of Metalloproteinases / Q000097:blood*
chemical_list: D015415:Biomarkers; D010446:Peptide Fragments; D011347:Procollagen; D019715:Tissue Inhibitor of Metalloproteinase-1; D019714:Tissue Inhibitor of Metalloproteinases; C041876:procollagen Type III-N-terminal peptide; D019716:Tissue Inhibitor of Metalloproteinase-2; D006820:Hyaluronic Acid; D017364:Collagenases; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9; D020781:Matrix Metalloproteinase 1