Skip to main content
Journal cover image

An MMP-degraded and cross-linked fragment of type III collagen as a non-invasive biomarker of hepatic fibrosis resolution.

Publication ,  Journal Article
Pehrsson, M; Manon-Jensen, T; Sun, S; Villesen, IF; Castañé, H; Joven, J; Patel, K; Goodman, Z; Nielsen, MJ; Bay-Jensen, A-C; Leeming, DJ ...
Published in: Liver Int
July 2022

BACKGROUND AND AIMS: Liver fibrosis results from a prolonged wound healing response to continued injury with excessive production of extracellular proteins. In patients with chronic liver disease, the monitoring of liver fibrosis dynamics is of high interest. Whilst markers of fibrogenesis exist, markers of hepatic fibrosis resolution remain an unmet clinical need. Thus, we sought to develop an assay quantifying a circulating proteolytic fragment of cross-linked type III collagen as a biomarker of fibrolysis, testing its utility in two clinical cohorts of liver fibrosis of distinct aetiology and regressing endotype METHODS: We used a monoclonal antibody targeting the C-telopeptide of type III collagen following C-proteinase cleavage to develop and validate a neo-epitope-specific enzyme-linked immunosorbent assay (CTX-III). A potential fibrosis resolution marker, CTX-III, was measured in two clinical cohorts of patients with obesity-associated non-alcoholic fatty liver disease undergoing bariatric surgery or hepatitis C virus infection from a clinical trial study evaluating the anti-fibrotic effect of farglitazar. RESULTS: CTX-III was robust and specific for the targeted neo-epitope with good reproducibility in EDTA plasma. We assessed type III collagen remodelling using a panel of biomarkers, including a type III collagen formation marker (PRO-C3), degradation (C3M), and CTX-III (fibrolysis). Net fibrolysis was increased in patients with non-alcoholic fatty liver disease following bariatric surgery (p < .001). Moreover, net fibrolysis identified spontaneous fibrotic regressors from stable and progressors (p < .05 and p < .001) among hepatitis C virus infection patients. CONCLUSION: Circulating CTX-III as a marker of fibrolysis indicates the biomarker's beneficial use in assessing hepatic fibrosis resolution.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

Liver Int

DOI

EISSN

1478-3231

Publication Date

July 2022

Volume

42

Issue

7

Start / End Page

1605 / 1617

Location

United States

Related Subject Headings

  • Reproducibility of Results
  • Non-alcoholic Fatty Liver Disease
  • Matrix Metalloproteinases
  • Liver Cirrhosis
  • Humans
  • Gastroenterology & Hepatology
  • Fibrosis
  • Epitopes
  • Collagen Type III
  • Biomarkers
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Pehrsson, M., Manon-Jensen, T., Sun, S., Villesen, I. F., Castañé, H., Joven, J., … Karsdal, M. A. (2022). An MMP-degraded and cross-linked fragment of type III collagen as a non-invasive biomarker of hepatic fibrosis resolution. Liver Int, 42(7), 1605–1617. https://doi.org/10.1111/liv.15270
Pehrsson, Martin, Tina Manon-Jensen, Shu Sun, Ida F. Villesen, Helena Castañé, Jorge Joven, Keyur Patel, et al. “An MMP-degraded and cross-linked fragment of type III collagen as a non-invasive biomarker of hepatic fibrosis resolution.Liver Int 42, no. 7 (July 2022): 1605–17. https://doi.org/10.1111/liv.15270.
Pehrsson M, Manon-Jensen T, Sun S, Villesen IF, Castañé H, Joven J, et al. An MMP-degraded and cross-linked fragment of type III collagen as a non-invasive biomarker of hepatic fibrosis resolution. Liver Int. 2022 Jul;42(7):1605–17.
Pehrsson, Martin, et al. “An MMP-degraded and cross-linked fragment of type III collagen as a non-invasive biomarker of hepatic fibrosis resolution.Liver Int, vol. 42, no. 7, July 2022, pp. 1605–17. Pubmed, doi:10.1111/liv.15270.
Pehrsson M, Manon-Jensen T, Sun S, Villesen IF, Castañé H, Joven J, Patel K, Goodman Z, Nielsen MJ, Bay-Jensen A-C, Leeming DJ, Mortensen JH, Karsdal MA. An MMP-degraded and cross-linked fragment of type III collagen as a non-invasive biomarker of hepatic fibrosis resolution. Liver Int. 2022 Jul;42(7):1605–1617.
Journal cover image

Published In

Liver Int

DOI

EISSN

1478-3231

Publication Date

July 2022

Volume

42

Issue

7

Start / End Page

1605 / 1617

Location

United States

Related Subject Headings

  • Reproducibility of Results
  • Non-alcoholic Fatty Liver Disease
  • Matrix Metalloproteinases
  • Liver Cirrhosis
  • Humans
  • Gastroenterology & Hepatology
  • Fibrosis
  • Epitopes
  • Collagen Type III
  • Biomarkers