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

Background:

Remodeling of extracellular matrix (ECM) is a key factor in progressive liver fibrosis. Recently, we described boost of collagen type III desposition as a new mechanism of acute decompensation. However, ECM is composed by various components. The role of collagen type IV turnover markers in patients with advanced liver cirrhosis and acute decompensation is unclear and investigated in this study.

Methods:

Patients with decompensated liver cirrhosis, who underwent TIPS procedure are included. Clinical and laboratory parameters, as well as P4NP7S and C4 M levels were measured in blood samples from portal and hepatic veins just before TIPS placement.

Results:

Levels of C4 M and P4NP7S are significantly lower in patients with severe ascites and impaired renal sodium excretion. C4 M and P4NP7S show gender-specific profiles with significantly lower levels in females compared to males. Female patients with higher levels of C4 M show higher mortality. Male patients with higher levels of C4 M show better survival. Moreover, in multivariate Cox regression analysis C4 M is an independent predictor of survival in female patients.

Conclusion:

This study shows that the pattern of collagen type IV remodeling, assessed by its markers, is independent of renal function. It is the first to demonstrate a gender-specific profile of C4 M, which can independently predict survival in female patients with decompensated cirrhosis.