AT1 receptor antagonist Candesartan in selected cirrhotic patients: effect on portal pressure and liver fibrosis markers.
OBJECTIVE
The renin-angiotensin system plays an important role in hepatic fibrogenesis and in portal hypertension. To examine the long-term effects of Candesartan cilexetil, an angiotensin type 1 (AT1) receptor blocker, on portal-systemic haemodynamics and on liver fibrosis.


METHODS
Forty-seven compensated Child A and Child B (8) cirrhotic patients were randomly assigned to receive Candesartan cilexetil, 8 mg/d (N.24) and no treatment (N.23) for 1 year. Portal-systemic haemodynamic parameters, serological levels of procollagen (PIIINP), hyaluronic acid (HA) and transforming growth factor beta 1 (TGFbeta1) were assessed at baseline and after 12 months.


RESULTS
No patients discontinued or decreased the drug. The hepatic venous pressure gradient (HVPG) decreased significantly in treated patients (-8.4%+/-2.4) with a reduction >20% in 25% of cases vs+5.6%+/-2.9 in the untreated group. HA plasma levels decreased significantly in Candesartan treated patients in whom HVPG diminished and rose in untreated patients in whom HVPG increased.


CONCLUSIONS
In selected cirrhotic patients, pharmacological inhibition of the AT1 receptor is well tolerated and induced a mild reduction of portal pressure. This haemodynamic effect might be related to liver fibrogenesis activity.
Debernardi-Venon
Wilma
W
Division of Gastroenterology and Hepatology, S Giovanni Battista Hospital, Turin, Italy. wilmadebernardi@yahoo.it
Martini
Silvia
S
Biasi
Fiorella
F
Vizio
Barbara
B
Termine
Angela
A
Poli
Giuseppe
G
Brunello
Franco
F
Alessandria
Carlo
C
Bonardi
Renato
R
Saracco
Giorgio
G
Rizzetto
Mario
M
Marzano
Alfredo
A
D000328:Adult; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D001562:Benzimidazoles / Q000737:chemistry*; D001713:Biphenyl Compounds / Q000737:chemistry*; D005260:Female; D005355:Fibrosis / Q000188:drug therapy*; D006801:Humans; D006820:Hyaluronic Acid / Q000097:blood / Q000494:pharmacology; D008099:Liver / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D017082:Portal Pressure; D011347:Procollagen / Q000378:metabolism; D044140:Receptor, Angiotensin, Type 1 / Q000737:chemistry*; D012084:Renin-Angiotensin System / Q000187:drug effects; D013777:Tetrazoles / Q000737:chemistry*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism
D047228:Angiotensin II Type 1 Receptor Blockers; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D011347:Procollagen; D044140:Receptor, Angiotensin, Type 1; D013777:Tetrazoles; D053773:Transforming Growth Factor beta1; D006820:Hyaluronic Acid; C077793:candesartan cilexetil