Collagen type IV remodeling gender-specifically predicts mortality in decompensated liver cirrhosis.

BACKGROUND: Remodeling of extracellular matrix (ECM) is crucial in progressive liver fibrosis. Collagen type III desposition has been shown in acute decompensation. ECM is compiled of deposition of various components. The role of basement membrane collagen type IV in advanced liver cirrhosis and acute decompensation is unclear and investigated in this study.

METHODS: Patients with decompensated liver cirrhosis from the prospective NEPTUN cohort (ClinicalTrialsgov Identifier: NCT03628807), who underwent TIPS procedure were included. Clinical and laboratory parameters, PRO-C4 and C4M levels were measured in blood samples from portal and hepatic veins just before TIPS 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 remodeling 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. This article is protected by copyright. All rights reserved.