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

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 (TGF beta 1) 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. (C) 2007 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.