Collagen type IV remodelling gender-specifically predicts mortality in decompensated cirrhosis
Research output: Contribution to journal › Journal article › Research › peer-review
Standard
Collagen type IV remodelling gender-specifically predicts mortality in decompensated cirrhosis. / Lehmann, Jennifer; Praktiknjo, Michael; Nielsen, Mette Juul; Schierwagen, Robert; Meyer, Carsten; Thomas, Daniel; Violi, Francesco; Strassburg, Christian P; Bendtsen, Flemming; Møller, Søren; Krag, Aleksander; Karsdal, Morten Asser; Leeming, Diana Julie; Trebicka, Jonel.
In: Liver International, Vol. 39, No. 5, 05.2019, p. 885-893.Research output: Contribution to journal › Journal article › Research › peer-review
Harvard
APA
Vancouver
Author
Bibtex
}
RIS
TY - JOUR
T1 - Collagen type IV remodelling gender-specifically predicts mortality in decompensated cirrhosis
AU - Lehmann, Jennifer
AU - Praktiknjo, Michael
AU - Nielsen, Mette Juul
AU - Schierwagen, Robert
AU - Meyer, Carsten
AU - Thomas, Daniel
AU - Violi, Francesco
AU - Strassburg, Christian P
AU - Bendtsen, Flemming
AU - Møller, Søren
AU - Krag, Aleksander
AU - Karsdal, Morten Asser
AU - Leeming, Diana Julie
AU - Trebicka, Jonel
N1 - © 2019 The Authors. Liver International published by John Wiley & Sons Ltd.
PY - 2019/5
Y1 - 2019/5
N2 - 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.
AB - 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.
U2 - 10.1111/liv.14070
DO - 10.1111/liv.14070
M3 - Journal article
C2 - 30739387
VL - 39
SP - 885
EP - 893
JO - Liver International
JF - Liver International
SN - 1478-3223
IS - 5
ER -
ID: 235916092