Serum endothelin-1 as predictor of ascitic decompensation in patients with liver cirrhosis

Background and aims: Intra- and extrahepatic endothelial dysfunction (ED) is considered to have a pivotal role in the development of portal hypertension (PH) in liver cirrhosis (LC). Serum levels of markers of ED (MED) are increased in LC patients; they correlate with the stage of liver disease. Aims of the present study were to assess 1) differences between MED in patients with compensated and decompensated LC; 2) possible prognostic role of MED in ascites development in compensated LC patients. Methods: 90 consecutive LC patients (mean age 65±9 years, 24 female) underwent a complete clinical, radiological and biochemical evaluation in order to assess stage and characteritics of disease; all subjects were assessed for MED [P-selectin, von Willebrand factor (vWF), endothelin-1 (ET-1), thrombomodulin (TM) and nitric oxide (NO)]. The 70 patients (mean age 65±9 years,19 female) with compensated LC (no ascites, cLC) underwent a 2 years-follow-up; their data were also compared with those of 20 (mean age 63±10 years, 5 female) LC patients with decompensated LC (presence of ascites, dLC) and those of 11 healthy controls (mean age 26±6.6 female). Results: ET-1, P-selectin and TM serum levels were significantly higher in LC and in dLC patients with respect to controls. NO and vWF serum levels were higher in dLC patients, whereas no difference was observed in cLC with respect to controls. 33/70 (47.1%) of cLC patients developed ascites at follow-up. At univariate analysis, predictors of ascites development in cLC patients were serum concentrations of ET-1 (OR=3.56, p=0.000), TM (OR=1.95, p=0.000) and P-selectin (OR=1.033, p=0.004) and Child-Pugh score (OR=1.05, p=0.041). At multivariate analysis (Cox regression), serum ET-1 and diabetes were independent predictors of early development of ascites during the follow-up (HR=2.631, p=0.004) in cLC patients. Efficiency (ROC method) of high levels (cut-off value=6 pg/ml) of ET-1 in predicting ascites development was good (AUC=0.803).