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

• Published in: Liver international 2019-05, Vol.39 (5), p.885-893
• Main Authors: 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
• Format: Article
• Language: English
• Subjects: ACLF; acute decompensation; acute‐on‐chronic liver failure; Adult; Aged; Aged, 80 and over; Ascites; Ascites - etiology; Biomarkers - blood; Cirrhosis; Cirrhosis and Liver Failure; Collagen; Collagen (type III); collagen type IV; Collagen Type IV - blood; Excretion; Extracellular matrix; extracellular matrix remodelling; Female; Females; Fibrosis; Gender; Humans; Hypertension, Portal - blood; Hypertension, Portal - diagnosis; Liver; Liver cirrhosis; Liver Cirrhosis - mortality; Liver Cirrhosis - surgery; Male; Males; Markers; Middle Aged; Mortality; Multivariate Analysis; portal hypertension; Portasystemic Shunt, Transjugular Intrahepatic; Prospective Studies; Regression analysis; Renal function; Sex Factors; Sodium; Survival; Survival Analysis; transjugular intrahepatic portosystemic shunt
• ISSN: 1478-3223; 1478-3231
• DOI: 10.1111/liv.14070

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.