Flow-mediated dilatation (FMD) assessment as a marker of endothelial dysfunction in liver cirrhosis

Background/aims: Portal hypertension (PH) complications are leading causes of death in patients with liver cirrhosis (LC). PH development in chronic liver disease depends on increased vascular intra-hepatic resistance and on hyperdynamic splanchnic circulation. Disturbances in “Endothelium-dependent” vasodilation, a condition known as “endothelial dysfunction” (ED), has been claimed as an important factor responsible for increased vascular hepatic resistance and PH development in LC. Aims of this study were to assess in LC patients: (1) the presence of ED and its correlation with disease stage and (2) correlation between of ED serum markers (MED) and flow-mediated dilatation (FMD), the gold standard test for evaluating ED. Material and methods: 60 consecutive LC patients (mean age 65±10 years, 17 female) without portal thrombosis (40 with compensated and 20 with decompensated disease) underwent a complete clinical, radiological and biochemical evaluation in order to assess the stage of disease and drug history; all subjects were assessed for MED [P-selectin, von Willebrand factor (vWF), endothelin-1 (ET-1), thrombomodulin (TM) and nitric oxide (NO)] serum levels and FMD (measured by ultrasound at brachial artery according to guidelines). MED and FMD were also assessed in 11 healthy subjects (mean age 26±6.6 female; controls). Results: MED plasma levels increased with the degree of liver dysfunction (p for trend <0.001 in all cases); accordingly, FMD values decreased with worsening of the stage of liver cirrhosis [controls (9.9±1.1%), compensated cirrhosis (6.1±1.8%), decompensated cirrhosis (5±1.3%), p for trend <0.01]. In LC patients a statistically significant correlation between MED markers and FMD was observed for ET-1: r= –0.4427 (p=0.0004) and P-selectin: r= –0.477 (p=0.0001), vWF (r= –0.166, p=0.05), but not for TM (r= –0.245, p=0.05951) and NO (p=0.961). At multivariate analysis, ET-1 and P-selectin remained significantly associated to FMD. Conclusions: Our data confirm the presence of ED in LC patients, as indicated by the significant increase in serum MED and by FMD reduction observed in LC patients. All these parameters show also a significant correlation with the severity of liver disease. Significant correlation and association of FMD with serum MED values also suggest that FMD may be a reliable marker of ED in patients with LC.