Systemic and splanchnic endothelin-1 plasma levels in liver cirrhosis before and after transjugular intrahepatic portosystemic shunt (TIPS).
OBJECTIVE
Endothelin-1 (ET-1) may be a mediator for portal hypertension in liver cirrhosis. The aim of the present study was to determine the concentrations of ET-1 in the systemic and splanchnic circulation before and after reduction of portal hypertension by transjugular intrahepatic portosystemic shunt implantation (TIPS).


METHODS
Plasma concentrations of immunoreactive ET-1 were measured in peripheral venous blood samples from 25 patients 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 from 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. In addition, the portocaval pressure gradient was determined before and after TIPS.


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 patients with refractory ascites (n=7; median 7.8, range 3.5 14.7) compared to patients 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 unchanged 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 concentrations reached markedly increased levels in individual patients (88, 92 and 103 pg/ml). Severe systemic reactions to these high levels were not observed. Peripheral venous, hepatovenous and portalvenous ET-1 concentrations did not correlate with portocaval pressure gradients.


CONCLUSIONS
Cirrhotic patients demonstrated unchanged peripheral venous ET-1 concentrations up to 15 months after TIPS. Portal congestion was associated with increased ET-1 levels in the prehepatic splanchnic area. The effect of portal decompression on splanchnic and systemic ET-1 levels deserves further investigation.
Nolte
W
W
Department of Internal Medicine, Georg-August-Universität, Göttingen, Germany.
Ehrenreich
H
H
Wiltfang
J
J
Pahl
K
K
Unterberg
K
K
Kamrowski-Kruck
H
H
Schindler
C G
CG
Figulla
H R
HR
Buchwald
A B
AB
Hartmann
H
H
Ramadori
G
G
D000328:Adult; D000368:Aged; D019332:Endothelin-1 / Q000097:blood*; D005260:Female; D006801:Humans; D006975:Hypertension, Portal / Q000601:surgery; D008103:Liver Cirrhosis / Q000097:blood* / Q000601:surgery; D008297:Male; D008875:Middle Aged; D019168:Portasystemic Shunt, Transjugular Intrahepatic; D011446:Prospective Studies; D011863:Radioimmunoassay; D013152:Splanchnic Circulation / Q000502:physiology*
D019332:Endothelin-1