Effect of ET-A blockade on portal pressure and hepatic arterial perfusion in patients with cirrhosis: a proof of concept study.

BACKGROUND/AIM Endothelin causes vasoconstriction via the Endothelin-A receptor (ET-A) in the intrahepatic circulation in cirrhosis and its increase leads to portal hypertension. The aim of the study was to investigate the acute effect of a selective ET-A antagonist in patients with portal hypertension and cirrhosis. METHODS Proof-of-concept study with two different substudies: 1) local intrahepatic administration of the ET-A antagonist BQ 123 and 2) systemic oral administration of the ET-A antagonist Ambrisentan. Portal pressure was determined by hepatic venous pressure gradient (HVPG, both substudies) and hepatic arterial blood flow (HABF) by intraarterial Doppler measurements (substudy 1) before and under the ET-A antagonist. Systemic hemodynamic parameters were measured in substudy 2. RESULTS Twelve patients (Child-Pugh [CP] B/C n=7/5) were included in substudy 1 and fourteen patients (CP A/B/C n=4/6/4) in substudy 2. The relative decrease in HVPG was -12.5 % (IQR: -40% - 0%; p=0.05) in substudy 1 and -5.0% (IQR: -11.5% - 0%; p=0.01) in substudy 2. Substudy 1 revealed higher decrease in HVPG in CP B patients. HABF increased significantly and patients without portal pressure decrease showed a higher increase of HABF. Substudy 2 showed a slight decrease in the mean arterial pressure without changes of other systemic hemodynamic parameters. CONCLUSION Administration of a selective ET-A antagonist decreases the portal pressure in cirrhotic patients. This decrease was higher in CP B patients and the non-responders showed a higher increase in hepatic arterial flow. Selective ET-A antagonists might be a future treatment option in patients with portal hypertension.