title: AT1 receptor antagonist Candesartan in selected cirrhotic patients: effect on portal pressure and liver fibrosis markers.
abstract: 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.
authors.affiliation: Division of Gastroenterology and Hepatology, S Giovanni Battista Hospital, Turin, Italy. wilmadebernardi@yahoo.it
authors.forename: Wilma
authors.initials: W
authors.lastname: Debernardi-Venon
authors.forename: Silvia
authors.initials: S
authors.lastname: Martini
authors.forename: Fiorella
authors.initials: F
authors.lastname: Biasi
authors.forename: Barbara
authors.initials: B
authors.lastname: Vizio
authors.forename: Angela
authors.initials: A
authors.lastname: Termine
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Poli
authors.forename: Franco
authors.initials: F
authors.lastname: Brunello
authors.forename: Carlo
authors.initials: C
authors.lastname: Alessandria
authors.forename: Renato
authors.initials: R
authors.lastname: Bonardi
authors.forename: Giorgio
authors.initials: G
authors.lastname: Saracco
authors.forename: Mario
authors.initials: M
authors.lastname: Rizzetto
authors.forename: Alfredo
authors.initials: A
authors.lastname: Marzano
mesh_terms: 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
chemical_list: 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