title: Effects of 1-year administration of olmesartan on portal pressure and TGF-beta1 in selected patients with cirrhosis: a randomized controlled trial.
abstract: BACKGROUND
  The renin-angiotensin system plays an important role in hepatic fibrosis and portal hypertension. We evaluated the long-term effects of olmesartan, an angiotensin type 1 (AT1) receptor blocker, on hemodynamics and liver fibrosis.
  
  
  METHODS
  Forty-eight selected patients with cirrhosis were randomly divided into two groups of 24 patients each, those who received and those who did not receive olmesartan treatment for 1 year. Hepatic hemodynamic studies, and measurements of transforming growth factor-beta1 (TGF-beta1) and blood markers of hepatic fibrosis, including serum hyaluronic acid (HA), type IV collagen, and procollagen III N-terminal propeptide levels, were also performed at the beginning and end of the study.
  
  
  RESULTS
  The median dose of the final drug administration was 20 mg (range 10-40 mg). Olmesartan reduced the hepatic venous pressure gradient (HVPG) by -12.9 ± 9.1% (p = 0.035) after 1 year. No significant changes were seen in controls. Six of the 24 patients (25%) in the olmesartan group showed a >20% reduction of HVPG from baseline values. TGF-beta1 was significantly decreased in patients who received olmesartan (7.0 ± 8.2 vs. 3.1 ± 1.6 ng/mL, p = 0.046) but there was no decrease in the controls. A significant trend was shown by correlating HA and TGF-beta1 variations in cirrhosis patients (p = 0.018, r = 0.377). Fibrosis markers were unchanged at the end of the study in both groups.
  
  
  CONCLUSIONS
  Olmesartan induced a mild reduction of portal pressure and TGF-beta1 for 1 year, but did not suppress hepatic fibrosis markers.
authors.affiliation: Department of Gastroenterology, Kitasato University East Hospital, 2-1-1 Asamizodai, Minami-ku, Sagamihara, Kanagawa 252-0380, Japan. hisashi7@kitasato-u.ac.jp
authors.forename: Hisashi
authors.initials: H
authors.lastname: Hidaka
authors.forename: Takahide
authors.initials: T
authors.lastname: Nakazawa
authors.forename: Akitaka
authors.initials: A
authors.lastname: Shibuya
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Minamino
authors.forename: Juichi
authors.initials: J
authors.lastname: Takada
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Yusuke
authors.initials: Y
authors.lastname: Okuwaki
authors.forename: Masaaki
authors.initials: M
authors.lastname: Watanabe
authors.forename: Wasaburo
authors.initials: W
authors.lastname: Koizumi
mesh_terms: D000368:Aged; D047228:Angiotensin II Type 1 Receptor Blockers / Q000008:administration & dosage*; D015415:Biomarkers; D024141:Collagen Type IV / Q000097:blood / Q000187:drug effects; D004932:Esophageal and Gastric Varices / Q000473:pathology; D005260:Female; D006801:Humans; D006820:Hyaluronic Acid / Q000097:blood; D007093:Imidazoles / Q000008:administration & dosage*; D008103:Liver Cirrhosis / Q000188:drug therapy* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010446:Peptide Fragments / Q000097:blood / Q000187:drug effects; D017082:Portal Pressure / Q000187:drug effects*; D011347:Procollagen / Q000097:blood / Q000187:drug effects; D011446:Prospective Studies; D013777:Tetrazoles / Q000008:administration & dosage*; D053773:Transforming Growth Factor beta1 / Q000378:metabolism*
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D015415:Biomarkers; D024141:Collagen Type IV; D007093:Imidazoles; D010446:Peptide Fragments; D011347:Procollagen; D013777:Tetrazoles; D053773:Transforming Growth Factor beta1; C041876:procollagen Type III-N-terminal peptide; C437965:olmesartan; D006820:Hyaluronic Acid