BACKGROUND/AIMS: 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.

AT1 receptor antagonist Candesartan in selected cirrhotic patients: effect on portal pressure and liver fibrosis markers

BIASI, Fiorella;VIZIO, Barbara;POLI, Giuseppe;SARACCO, Giorgio Maria;RIZZETTO, Mario;
2007-01-01

Abstract

BACKGROUND/AIMS: 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.
2007
46(6)
6
1026
1033
Hyaluronic acid; Liver fibrosis; Portal hypertension; Portal pressure; Renin-angiotensin system; Adult; Angiotensin II Type 1 Receptor Blockers; Benzimidazoles; Biphenyl Compounds; Female; Fibrosis; Humans; Hyaluronic Acid; Liver; Male; Middle Aged; Portal Pressure; Procollagen; Receptor, Angiotensin, Type 1; Renin-Angiotensin System; Tetrazoles; Transforming Growth Factor beta1; Gastroenterology
DEBERNARDI-VENON W; MARTINI S; BIASI F; VIZIO B; TERMINE A; POLI G; BRUNELLO F; ALESSANDRIA C; BONARDI R; SARACCO G; RIZZETTO M; MARZANO A
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2318/38944
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