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

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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Resumé

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.

OriginalsprogEngelsk
TidsskriftLiver International
Vol/bind39
Udgave nummer5
Sider (fra-til)885-893
ISSN1478-3223
DOI
StatusUdgivet - maj 2019

Fingeraftryk

Collagen Type IV
Transjugular Intrahepatic Portasystemic Shunt
Collagen Type III
Hepatic Veins
Portal Vein
Liver Cirrhosis
Regression Analysis
Kidney
Liver

Citer dette

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. / Collagen type IV remodelling gender-specifically predicts mortality in decompensated cirrhosis. I: Liver International. 2019 ; Bind 39, Nr. 5. s. 885-893.
@article{673a8da9b29f4ed98187a3eb57188ad4,
title = "Collagen type IV remodelling gender-specifically predicts mortality in decompensated cirrhosis",
abstract = "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.",
keywords = "ACLF, acute decompensation, acute-on-chronic liver failure, cirrhosis, collagen type IV, extracellular matrix remodelling, gender, liver, portal hypertension, transjugular intrahepatic portosystemic shunt",
author = "Jennifer Lehmann and Michael Praktiknjo and Nielsen, {Mette Juul} and Robert Schierwagen and Carsten Meyer and Daniel Thomas and Francesco Violi and Strassburg, {Christian P} and Flemming Bendtsen and S{\o}ren M{\o}ller and Aleksander Krag and Karsdal, {Morten Asser} and Leeming, {Diana Julie} and Jonel Trebicka",
note = "{\circledC} 2019 The Authors. Liver International published by John Wiley & Sons Ltd.",
year = "2019",
month = "5",
doi = "10.1111/liv.14070",
language = "English",
volume = "39",
pages = "885--893",
journal = "Liver International",
issn = "1478-3223",
publisher = "Wiley-Blackwell",
number = "5",

}

Lehmann, J, Praktiknjo, M, Nielsen, MJ, Schierwagen, R, Meyer, C, Thomas, D, Violi, F, Strassburg, CP, Bendtsen, F, Møller, S, Krag, A, Karsdal, MA, Leeming, DJ & Trebicka, J 2019, 'Collagen type IV remodelling gender-specifically predicts mortality in decompensated cirrhosis', Liver International, bind 39, nr. 5, s. 885-893. https://doi.org/10.1111/liv.14070

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.

I: Liver International, Bind 39, Nr. 5, 05.2019, s. 885-893.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

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.

KW - ACLF

KW - acute decompensation

KW - acute-on-chronic liver failure

KW - cirrhosis

KW - collagen type IV

KW - extracellular matrix remodelling

KW - gender

KW - liver

KW - portal hypertension

KW - transjugular intrahepatic portosystemic shunt

U2 - 10.1111/liv.14070

DO - 10.1111/liv.14070

M3 - Journal article

VL - 39

SP - 885

EP - 893

JO - Liver International

JF - Liver International

SN - 1478-3223

IS - 5

ER -