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: Hisashi Hidaka, Takahide Nakazawa, Akitaka Shibuya, Tsutomu Minamino, Juichi Takada, Yoshiaki Tanaka, Yusuke Okuwaki, Masaaki Watanabe, Wasaburo Koizumi
• Journal: Journal of gastroenterology (J Gastroenterol) Vol. 46 Issue 11 Pg. 1316-23 (Nov 2011) ISSN: 1435-5922 [Electronic] Japan
• PMID: 21850387 (Publication Type: Journal Article, Randomized Controlled Trial)

Chemical References

• Angiotensin II Type 1 Receptor Blockers
• Biomarkers
• Collagen Type IV
• Imidazoles
• Peptide Fragments
• Procollagen
• Tetrazoles
• Transforming Growth Factor beta1
• procollagen Type III-N-terminal peptide
• olmesartan
• Hyaluronic Acid

Topics

• Aged
• Angiotensin II Type 1 Receptor Blockers (administration & dosage)
• Biomarkers
• Collagen Type IV (blood, drug effects)
• Esophageal and Gastric Varices (pathology)
• Female
• Humans
• Hyaluronic Acid (blood)
• Imidazoles (administration & dosage)
• Liver Cirrhosis (drug therapy, metabolism)
• Male
• Middle Aged
• Peptide Fragments (blood, drug effects)
• Portal Pressure (drug effects)
• Procollagen (blood, drug effects)
• Prospective Studies
• Tetrazoles (administration & dosage)
• Transforming Growth Factor beta1 (metabolism)