An MMP-degraded and cross-linked fragment of type III collagen as a non-invasive biomarker of hepatic fibrosis resolution
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An MMP-degraded and cross-linked fragment of type III collagen as a non-invasive biomarker of hepatic fibrosis resolution. / Pehrsson, Martin; Manon-Jensen, Tina; Sun, Shu; Villesen, Ida F.; Castañé, Helena; Joven, Jorge; Patel, Keyur; Goodman, Zachary; Nielsen, Mette J.; Bay-Jensen, Anne Christine; Leeming, Diana J.; Mortensen, Joachim H.; Karsdal, Morten A.
In: Liver International, Vol. 42, No. 7, 2022, p. 1605-1617.Research output: Contribution to journal › Journal article › Research › peer-review
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T1 - An MMP-degraded and cross-linked fragment of type III collagen as a non-invasive biomarker of hepatic fibrosis resolution
AU - Pehrsson, Martin
AU - Manon-Jensen, Tina
AU - Sun, Shu
AU - Villesen, Ida F.
AU - Castañé, Helena
AU - Joven, Jorge
AU - Patel, Keyur
AU - Goodman, Zachary
AU - Nielsen, Mette J.
AU - Bay-Jensen, Anne Christine
AU - Leeming, Diana J.
AU - Mortensen, Joachim H.
AU - Karsdal, Morten A.
N1 - Publisher Copyright: © 2022 Nordic Bioscience. Liver International published by John Wiley & Sons Ltd.
PY - 2022
Y1 - 2022
N2 - 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.
AB - 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.
KW - collagen cross-linking
KW - fibrosis resolution
KW - hepatic fibrosis
KW - non-invasive biomarkers
UR - http://www.scopus.com/inward/record.url?scp=85127977989&partnerID=8YFLogxK
U2 - 10.1111/liv.15270
DO - 10.1111/liv.15270
M3 - Journal article
C2 - 35384259
AN - SCOPUS:85127977989
VL - 42
SP - 1605
EP - 1617
JO - Liver International
JF - Liver International
SN - 1478-3223
IS - 7
ER -
ID: 313873163