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Assessment of liver fibrosis progression and regression by a serological collagen turnover profile.

Publication ,  Journal Article
Karsdal, MA; Hjuler, ST; Luo, Y; Rasmussen, DGK; Nielsen, MJ; Holm Nielsen, S; Leeming, DJ; Goodman, Z; Arch, RH; Patel, K; Schuppan, D
Published in: Am J Physiol Gastrointest Liver Physiol
January 1, 2019

There is a need for noninvasive biomarkers that can identify patients with progressive liver fibrosis and monitor response to antifibrotic therapy. An equally important need is identification of patients with spontaneous fibrosis regression, since they may not need treatment nor be included in clinical studies with fibrosis as end point. Circulating biomarkers, originating from defined fragments of the scar tissue itself, may serve as valuable tools for this aspect of precision medicine. We investigated a panel of serological collagen formation and degradation markers to identify patients likely to regress or progress in absence of a therapeutic intervention. Plasma samples from patients with moderate-stage hepatitis C receiving placebo treatment in a phase II trial of the peroxisome proliferator-activated receptor agonist farglitazar were included. The patients had matched liver biopsies at baseline and 52 wk of follow-up. Serological biomarkers of collagen formation (PRO-C3, PRO-C4, PRO-C5) and collagen degradation (C3M, C4M, and C6M) were analyzed. Logistic regression analysis including PRO-C3 and C6M identified subjects with progressive liver fibrosis with an AUROC of 0.91 ( P < 0.0001) and positive and negative predictive values (PPV/NPV) of 75.0%/88.6%. Low levels of PRO-C5 predicted a spontaneous regression phenotype, with an odds ratio of 33.8 times higher compared with patients with high levels ( P < 0.0025) with an AUROC of 0.78 ( P < 0.0001) and PPV/NPV of 60.0%/95.7%. Two collagen fragments (PRO-C3 and C6M) identified liver fibrosis progressors, and one collagen fragment (PRO-C5) identified liver fibrosis regressors. These biomarkers may improve patient stratification and monitor treatment efficacy in studies with fibrosis as clinical end point. NEW & NOTEWORTHY In this study we report two biomarkers of collagen fragments (PRO-C3 and C6M) that are able to identify liver fibrosis progressors while one biomarker (PRO-C5) identified liver fibrosis regressors. In particular, we present three noninvasive biomarkers that can be used to identify patients with progressive liver fibrosis, monitor response to antifibrotic therapy, and also identify the spontaneous liver fibrosis regression phenotype.

Duke Scholars

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Published In

Am J Physiol Gastrointest Liver Physiol

DOI

EISSN

1522-1547

Publication Date

January 1, 2019

Volume

316

Issue

1

Start / End Page

G25 / G31

Location

United States

Related Subject Headings

  • Phenotype
  • Middle Aged
  • Male
  • Liver Cirrhosis
  • Humans
  • Gastroenterology & Hepatology
  • Fibrosis
  • Female
  • Disease Progression
  • Collagen
 

Citation

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Chicago
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Karsdal, M. A., Hjuler, S. T., Luo, Y., Rasmussen, D. G. K., Nielsen, M. J., Holm Nielsen, S., … Schuppan, D. (2019). Assessment of liver fibrosis progression and regression by a serological collagen turnover profile. Am J Physiol Gastrointest Liver Physiol, 316(1), G25–G31. https://doi.org/10.1152/ajpgi.00158.2018
Karsdal, Morten A., Sara T. Hjuler, Yi Luo, Daniel G. K. Rasmussen, Mette J. Nielsen, Signe Holm Nielsen, Diana J. Leeming, et al. “Assessment of liver fibrosis progression and regression by a serological collagen turnover profile.Am J Physiol Gastrointest Liver Physiol 316, no. 1 (January 1, 2019): G25–31. https://doi.org/10.1152/ajpgi.00158.2018.
Karsdal MA, Hjuler ST, Luo Y, Rasmussen DGK, Nielsen MJ, Holm Nielsen S, et al. Assessment of liver fibrosis progression and regression by a serological collagen turnover profile. Am J Physiol Gastrointest Liver Physiol. 2019 Jan 1;316(1):G25–31.
Karsdal, Morten A., et al. “Assessment of liver fibrosis progression and regression by a serological collagen turnover profile.Am J Physiol Gastrointest Liver Physiol, vol. 316, no. 1, Jan. 2019, pp. G25–31. Pubmed, doi:10.1152/ajpgi.00158.2018.
Karsdal MA, Hjuler ST, Luo Y, Rasmussen DGK, Nielsen MJ, Holm Nielsen S, Leeming DJ, Goodman Z, Arch RH, Patel K, Schuppan D. Assessment of liver fibrosis progression and regression by a serological collagen turnover profile. Am J Physiol Gastrointest Liver Physiol. 2019 Jan 1;316(1):G25–G31.

Published In

Am J Physiol Gastrointest Liver Physiol

DOI

EISSN

1522-1547

Publication Date

January 1, 2019

Volume

316

Issue

1

Start / End Page

G25 / G31

Location

United States

Related Subject Headings

  • Phenotype
  • Middle Aged
  • Male
  • Liver Cirrhosis
  • Humans
  • Gastroenterology & Hepatology
  • Fibrosis
  • Female
  • Disease Progression
  • Collagen