Systemic and splanchnic endothelin-1 plasma levels in liver cirrhosis before and after transjugular intrahepatic portosystemic shunt (TIPS)

Aims/Background: Endothelin-1 (ET-1) may be a mediator for portal hypertens ion in liver cirrhosis. The aim of the present study was to determine the c oncentrations of ET-1 in the systemic and splanchnic circulation before and after reduction of portal hypertension by transjugular intrahepatic portos ystemic shunt implantation (TIPS), Methods: Plasma concentrations of immuno reactive ET-1 were measured ill peripheral venous blood samples from 25 pat ients with liver cirrhosis before and at 1, 3, 9 and 15 months after TIPS. Furthermore, acute effects of TIPS on ET-1 were studied in plasma samples f rom the hepatic vein, the portal vein 30 minutes before and after TIPS and in the femoral artery (only after TIPS) in a subgroup of 15 patients. Tn ad dition, the portocaval pressure gradient was determined before and after TI PS. Results: Before TIPS peripheral venous plasma ET-1 concentrations (n=25 ; median 4.2 pg/ml; range 1.9-14.7) were significantly increased in patient s with refractory ascites (n=7; median 7.8, range 3.5-14.7) compared to pat ients with repetitive bleeding (n=18, median 3.4; range 1.9-7.1) (p=0.003). Furthermore, peripheral ET-1 concentrations correlated with the degree of liver dysfunction according to the Child-Pugh classification (Spearman's r= 0.46; p=0.02). Following TIPS, peripheral ET-1 concentrations remained unch anged during a follow-up of 15 months. Before TIPS, a positive gradient of ET-1 concentrations from portalvenous to hepatovenous and peripheral venous levels was found (p<0.03), Immediately after TIPS, arterial ET-1 concentra tions reached markedly increased levels in individual patients (88, 92 and 103 pg/ml). Severe systemic reactions to these high levels were not observe d. Peripheral venous, hepatovenous and portalvenous ET-1 concentrations did not correlate with portocaval pressure gradients. Conclusion: Cirrhotic pa tients demonstrated unchanged peripheral venous ET-1 concentrations up to 1 5 months after TIPS. Portal congestion was associated with increased ET-1 l evels in the prehepatic splanchnic area. The effect of portal decompression on splanchnic and systemic ET-1 levels deserves further investigation.