Von Willebrand factor levels predict clinical outcome in patients with cirrhosis and portal hypertension

Background and aims: Endothelial dysfunction is a major determinant of the increased hepatic vascular tone of cirrhotic livers. Von Willebrand factor (vWF), P-selectin and 8-iso-PGF2α (isoprostanes), surrogate markers of endothelial dysfunction, are increased in patients with cirrhosis. This study was aimed at exploring in patients with cirrhosis and portal hypertension the relation of these endothelial factors with systemic and hepatic haemodynamics and their possible clinical prognostic value. Methods: 42 consecutive patients with cirrhosis and portal hypertension had measurement of the hepatic venous pressure gradient (HVPG), cardiopulmonary pressures and vWF, P-selectin and isoprostane levels in blood samples from hepatic and peripheral veins. Patients were followed up to 2 years, death or liver transplantation and any clinical event were recorded. Results: vWF, P-selectin and isoprostanes were increased in patients with cirrhosis compared with controls (p<0.001). vWF levels significantly correlated with HVPG, Child-Pugh score and MELD. Cox model analysis disclosed an independent indirect association of peripheral vWF with survival free of portal hypertension-related events and of transplantation. The vWF cut-off value of 216 U/dl (Youden index) disclosed two different populations of patients with cirrhosis with a highly different probability of survival free of portal hypertension-related events and transplantation (87% vs 22%, p=0.001). The prognostic role of vWF persisted after adjusting for parameters of liver dysfunction and for HVPG. Conclusions: In patients with cirrhosis and portal hypertension vWF levels correlate with liver function and HVPG and independently predict clinical outcome.