title: Plasma Pro-C3 (N-terminal type III collagen propeptide) predicts fibrosis progression in patients with chronic hepatitis C.
abstract: OBJECTIVE
  Fibrogenesis results in release of certain extracellular matrix protein fragments into the circulation. We evaluated the diagnostic and prognostic performance of two novel serological markers, the precisely cleaved N-terminal propeptide of type III collagen (Pro-C3) and a peptide of helical collagen type III degradation (C3M), in chronic hepatitis C (CHC) patients.
  
  
  METHODS
  Pro-C3 and C3M were measured by ELISA in plasma from CHC patients (n = 194) from a prior phase II antifibrotic trial (NCT00244751). Plasma samples and paired liver biopsies were obtained at baseline and after 1-year. Patients were stratified according to Ishak stages 2-4. Internal cross-validation was performed by bootstrap analysis.
  
  
  RESULTS
  Pro-C3 levels were significantly higher in CHC patients in Ishak stage 4 compared to stage 2 (P < 0.001) or 3 (P < 0.01). Pro-C3 could significantly distinguish moderate (stage 4) from mild fibrosis (stage 2/3) (AUC = 0.72, P < 0.001). Importantly, an overall significance in Pro-C3 (P = 0.007) levels was observed between the groups of -1, 0, +1 and +2 change in Ishak stage at 12 months. Pro-C3 was significantly increased in group +1 (P = 0.030) and +2 (P = 0.021) compared to group 0. No significant differences were observed for C3M. In multivariate analysis, only baseline Pro-C3, but not FibroTest, had an independent association with fibrosis progression.
  
  
  CONCLUSIONS
  Pro-C3 is a useful test to predict fibrogenesis and monitor disease progression. Moreover, it could differentiate mild from moderate disease. Pro-C3 may become a promising blood parameter be included in future studies for monitoring disease progression and eventually for evaluation of potential antifibrotic therapies.
authors.affiliation: Nordic Bioscience A/S, Herlev, Denmark; Faculty of Health Science, University of Southern Denmark, Odense, Denmark.
authors.forename: Mette J
authors.initials: MJ
authors.lastname: Nielsen
authors.forename: Sanne S
authors.initials: SS
authors.lastname: Veidal
authors.forename: Morten A
authors.initials: MA
authors.lastname: Karsdal
authors.forename: Diana J
authors.initials: DJ
authors.lastname: Ørsnes-Leeming
authors.forename: Ben
authors.initials: B
authors.lastname: Vainer
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Gardner
authors.forename: Robert
authors.initials: R
authors.lastname: Hamatake
authors.forename: Zachary D
authors.initials: ZD
authors.lastname: Goodman
authors.forename: Detlef
authors.initials: D
authors.lastname: Schuppan
authors.forename: Keyur
authors.initials: K
authors.lastname: Patel
mesh_terms: D015415:Biomarkers / Q000097:blood*; D015331:Cohort Studies; D024061:Collagen Type III / Q000097:blood*; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D019698:Hepatitis C, Chronic / Q000097:blood / Q000150:complications / Q000503:physiopathology*; D006801:Humans; D008103:Liver Cirrhosis / Q000175:diagnosis* / Q000209:etiology; D015999:Multivariate Analysis; D011237:Predictive Value of Tests
chemical_list: D015415:Biomarkers; D024061:Collagen Type III
keywords: biomarker; extracellular matrix remodelling; liver fibrosis; prognosis