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Plasma Pro-C3 (N-terminal type III collagen propeptide) predicts fibrosis progression in patients with chronic hepatitis C.

Publication ,  Journal Article
Nielsen, MJ; Veidal, SS; Karsdal, MA; Ørsnes-Leeming, DJ; Vainer, B; Gardner, SD; Hamatake, R; Goodman, ZD; Schuppan, D; Patel, K
Published in: Liver Int
February 2015

BACKGROUND & AIMS: 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. METHOD: 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.

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Published In

Liver Int

DOI

EISSN

1478-3231

Publication Date

February 2015

Volume

35

Issue

2

Start / End Page

429 / 437

Location

United States

Related Subject Headings

  • Predictive Value of Tests
  • Multivariate Analysis
  • Liver Cirrhosis
  • Humans
  • Hepatitis C, Chronic
  • Gastroenterology & Hepatology
  • Enzyme-Linked Immunosorbent Assay
  • Disease Progression
  • Collagen Type III
  • Cohort Studies
 

Citation

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Nielsen, M. J., Veidal, S. S., Karsdal, M. A., Ørsnes-Leeming, D. J., Vainer, B., Gardner, S. D., … Patel, K. (2015). Plasma Pro-C3 (N-terminal type III collagen propeptide) predicts fibrosis progression in patients with chronic hepatitis C. Liver Int, 35(2), 429–437. https://doi.org/10.1111/liv.12700
Nielsen, Mette J., Sanne S. Veidal, Morten A. Karsdal, Diana J. Ørsnes-Leeming, Ben Vainer, Stephen D. Gardner, Robert Hamatake, Zachary D. Goodman, Detlef Schuppan, and Keyur Patel. “Plasma Pro-C3 (N-terminal type III collagen propeptide) predicts fibrosis progression in patients with chronic hepatitis C.Liver Int 35, no. 2 (February 2015): 429–37. https://doi.org/10.1111/liv.12700.
Nielsen MJ, Veidal SS, Karsdal MA, Ørsnes-Leeming DJ, Vainer B, Gardner SD, et al. Plasma Pro-C3 (N-terminal type III collagen propeptide) predicts fibrosis progression in patients with chronic hepatitis C. Liver Int. 2015 Feb;35(2):429–37.
Nielsen, Mette J., et al. “Plasma Pro-C3 (N-terminal type III collagen propeptide) predicts fibrosis progression in patients with chronic hepatitis C.Liver Int, vol. 35, no. 2, Feb. 2015, pp. 429–37. Pubmed, doi:10.1111/liv.12700.
Nielsen MJ, Veidal SS, Karsdal MA, Ørsnes-Leeming DJ, Vainer B, Gardner SD, Hamatake R, Goodman ZD, Schuppan D, Patel K. Plasma Pro-C3 (N-terminal type III collagen propeptide) predicts fibrosis progression in patients with chronic hepatitis C. Liver Int. 2015 Feb;35(2):429–437.
Journal cover image

Published In

Liver Int

DOI

EISSN

1478-3231

Publication Date

February 2015

Volume

35

Issue

2

Start / End Page

429 / 437

Location

United States

Related Subject Headings

  • Predictive Value of Tests
  • Multivariate Analysis
  • Liver Cirrhosis
  • Humans
  • Hepatitis C, Chronic
  • Gastroenterology & Hepatology
  • Enzyme-Linked Immunosorbent Assay
  • Disease Progression
  • Collagen Type III
  • Cohort Studies