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Collagen type IV remodelling gender-specifically predicts mortality in decompensated cirrhosis

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  • Jennifer Lehmann
  • Michael Praktiknjo
  • Mette Juul Nielsen
  • Robert Schierwagen
  • Carsten Meyer
  • Daniel Thomas
  • Francesco Violi
  • Christian P Strassburg
  • Flemming Bendtsen
  • Søren Møller
  • Aleksander Krag
  • Morten Asser Karsdal
  • Diana Julie Leeming
  • Jonel Trebicka
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Background & Aims: Remodelling of extracellular matrix is crucial in progressive liver fibrosis. Collagen type III desposition has been shown in acute decompensation. Extratracellular matrix is compiled of deposition of various components. The role of basement membrane collagen type IV in advanced cirrhosis and acute decompensation is unclear and investigated in this study. Methods: Patients with decompensated cirrhosis from the prospective NEPTUN cohort (ClinicalTrials.gov Identifier: NCT03628807), who underwent transjugular intrahepatic portosystemic shunt procedure were included. Clinical and laboratory parameters, PRO-C4 and C4M levels were measured in blood samples from portal and hepatic veins just before transjugular intrahepatic portosystemic shunt placement. Results: Levels of C4M and PRO-C4 are significantly lower in patients with massive ascites and impaired renal sodium excretion. C4M and PRO-C4 show gender-specific profiles with significantly lower levels in females compared to males. Females with higher C4M levels show higher mortality. By contrast, males with higher C4M levels show lower mortality. In multivariate Cox regression analysis, C4M is an independent predictor of survival in female patients. Conclusion: This study shows that markers of collagen type IV remodelling do not accumulate in severe renal dysfunction. Although collagen type IV degradation markers derive from the liver, portal venous C4M levels are relevant for survival. Moreover, it demonstrates that circulating C4M shows gender-specific profiles, which can independently predict survival in female patients with decompensated cirrhosis.

Original languageEnglish
JournalLiver international : official journal of the International Association for the Study of the Liver
Volume39
Issue number5
Pages (from-to)885-893
Number of pages9
ISSN1478-3223
DOIs
Publication statusPublished - May 2019

Bibliographical note

© 2019 The Authors. Liver International published by John Wiley & Sons Ltd.

    Research areas

  • ACLF, acute decompensation, acute-on-chronic liver failure, cirrhosis, collagen type IV, extracellular matrix remodelling, gender, liver, portal hypertension, transjugular intrahepatic portosystemic shunt

ID: 56499189