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

American Journal of Physiology. Gastrointestinal and Liver Physiology
Morten A KarsdalDetlef Schuppan

Abstract

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 ...Continue Reading

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Citations

Jun 12, 2020·Alimentary Pharmacology & Therapeutics·Signe WieseFlemming Bendtsen
Feb 13, 2020·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·Shuya ZhangZheng Gen Jin
May 19, 2020·Alimentary Pharmacology & Therapeutics·Ida Falk VillesenMette Juul Nielsen
Apr 17, 2019·International Journal of Molecular Sciences·Angela PuenteJavier Crespo
Feb 27, 2020·International Journal of Molecular Sciences·Zhi HeMingyao Yang
Oct 9, 2019·Nature Medicine·Francesca MoroniStuart J Forbes
Nov 24, 2020·JHEP Reports : Innovation in Hepatology·Mette VesterhusDouglas Thorburn
Feb 3, 2021·Gastroenterology·Don C Rockey, Scott L Friedman
Jun 11, 2021·The FEBS Journal·Lynn WilliamsJagdeep Nanchahal
Jul 13, 2021·Alimentary Pharmacology & Therapeutics·Bjørn S MadsenUNKNOWN GALAXY consortium
Aug 5, 2021·Expert Review of Molecular Diagnostics·Saleh A Alqahtani, Jörn M Schattenberg
Aug 25, 2021·Alimentary Pharmacology & Therapeutics·Maja ThieleUNKNOWN GALAXY Consortium
Nov 7, 2021·Alimentary Pharmacology & Therapeutics·Stine JohansenMaja Thiele
Nov 7, 2021·Alimentary Pharmacology & Therapeutics·Shilpa Chokshi, Gautam Mehta

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Methods Mentioned

BETA
biopsy
biopsies
ELISA

Clinical Trials Mentioned

NCT00244751

Software Mentioned

LOOCV
R
MedCalc

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