SELECTIVE ENDOTHELIN-A BLOCKADE DECREASES PORTAL PRESSURE IN PATIENTS WITH CIRRHOSIS. A PILOT STUDY COMBINING A LOCAL INTRAARTERIAL AND SYSTEMIC ADMINISTRATION.
Author(s): ,
Alexander Zipprich
Affiliations:
First Department of Internal Medicine,Martin-Luther-University Halle-Wittenberg,Halle (Saale),Germany
,
Enno Schenkel
Affiliations:
First Department of Internal Medicine,Martin-Luther-University Halle-Wittenberg,Halle (Saale),Germany
,
Fleur Gittinger
Affiliations:
First Department of Internal Medicine,Martin-Luther-University Halle-Wittenberg,Halle (Saale),Germany
,
Matthias Winkler
Affiliations:
First Department of Internal Medicine,Martin-Luther-University Halle-Wittenberg,Halle (Saale),Germany
,
Patrick Michl
Affiliations:
First Department of Internal Medicine,Martin-Luther-University Halle-Wittenberg,Halle (Saale),Germany
Cristina Ripoll
Affiliations:
First Department of Internal Medicine,Martin-Luther-University Halle-Wittenberg,Halle (Saale),Germany
EASL LiverTree™. Zipprich A. Apr 14, 2016; 126344
Topic: Experimental
Dr. Alexander Zipprich
Dr. Alexander Zipprich

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Abstract
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THU-006

Topic: Clinical aspects

Background and aims
Increased intrahepatic resistance is one of the main mechanisms in the development of portal hypertension.  Increased levels of the vasoconstrictor Endothelin-1 (ET) are involved in this increased resistance, by acting through the ET A receptor. A previous study using a non selective ET inhibitor, showed no effect of endothelin blockade in portal hypertension (Eur J Clin Pharmacol (2012) 68:533–541). BQ123 and Ambrisentan are selective ET-A receptor blockers. The aim was to evaluate the effect of selective ET A blockade on portal pressure and hepatic arterial blood flow in patients with cirrhosis.

Methods
A total of 26 patients with cirrhosis were included (Child Pugh A 4/ B 11/ C 9) were included. In a first group (n=12) hepatic arterial (HA) catheterization using a 5-F-catheter was performed and a Doppler flow wire introduced for continuous measurement of HA blood flow (HABF) (Hepatology 2003;37:385). BQ 123 (Clinalfa, Switzerland) was continuously infused selectively in the hepatic artery with a progressive increase in dosis (300, 500,1000, 2000 nmol/l). HABF and hepatic venous pressure gradient (HVPG) were measured before and during the infusion of BQ 123. In the second group (n=14); oral administration of ET-A blocker (Ambrisentan; Volibris, GlaxoSmithKline, Germany, 5 mg or 10 mg) was given. HVPG and Doppler hepatic arterial resistance index (PI and RI) were measured before and 90 minutes after administration. ANOVA for repeat measurements and Wilcoxon test was used as statistical test.

Results
BQ 123 caused vasodilatation in the hepatic artery (∆%HABF±SD: +176±359%, p=0.029). There was a trend towards a higher hepatic arterial vasodilatation in Child B (n=7) (+238±473 %) compared to Child C (n=5) (+88±47 %) patients. Infusion of BQ 123 lead to a decrease in HVPG (∆%: -18±26 %, p=0.048). Ambrisentan caused significant decrease of HVPG (-5.4±6.8%, p=0.001). The decrease of HVPG was higher (-7.0±6.0%) with 10 mg Ambrisentan compared to 5 mg (-4.8±7.6%). Hepatic arterial PI and RI were unchanged due to Ambrisentan administration.

Conclusions
Selective intrahepatic arterial infusion of an Endothelin-A-Blocker increases hepatic arterial flow and decreases portal pressure. Both, the selective intrahepatic as well as the systemic administration of ET-A blocker decreased portal pressure. Selective inhibition of the Endothelin-A receptor might be beneficial in the treatment of portal hypertension.

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