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Effects of 1-year administration of olmesartan on portal pressure and TGF-beta1 in selected patients with cirrhosis: a randomized controlled trial

  • Original Article—Liver, Pancreas, and Biliary Tract
  • Published:
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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.

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Abbreviations

TGF-beta1:

Transforming growth factor-beta1

AT1:

Angiotensin type 1

HA:

Hyaluronic acid

HVPG:

Hepatic venous pressure gradient

Ang II:

Angiotensin II

RAS:

Renin–angiotensin system

HSC:

Hepatic stellate cell

NASH:

Nonalcoholic steatohepatitis

ARB:

Angiotensin receptor blocker

PIIINP:

Procollagen III N-terminal propeptide

MAP:

Mean arterial pressure

ELISA:

Enzyme-linked immunosorbent assay

HABP:

Hyaluronic acid binding protein

RIA:

Radioimmunoassay

EIA:

Enzyme immunoassay

WHVP:

Wedged hepatic venous pressure

FHVP:

Free hepatic vein pressure

NSBB:

Nonselective beta-blocker

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Acknowledgments

The authors thank the radiologists of Kitasato University East Hospital for their technical assistance. We also thank Robert E. Brandt (Founder and CEO, MedEd Japan) for editing the manuscript.

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Gastroenterology, Kitasato University East Hospital, 2-1-1 Asamizodai, Minami-ku, Sagamihara, Kanagawa, 252-0380, Japan

    Hisashi Hidaka, Takahide Nakazawa, Akitaka Shibuya, Tsutomu Minamino, Juichi Takada, Yoshiaki Tanaka, Yusuke Okuwaki, Masaaki Watanabe & Wasaburo Koizumi

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  1. Hisashi Hidaka
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  2. Takahide Nakazawa
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  3. Akitaka Shibuya
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  4. Tsutomu Minamino
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  5. Juichi Takada
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  6. Yoshiaki Tanaka
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  7. Yusuke Okuwaki
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  8. Masaaki Watanabe
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  9. Wasaburo Koizumi
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Corresponding author

Correspondence to Hisashi Hidaka.

Additional information

The trial described in this work has been registered under the following trial number UMIN000003975.

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Hidaka, H., Nakazawa, T., Shibuya, A. et al. Effects of 1-year administration of olmesartan on portal pressure and TGF-beta1 in selected patients with cirrhosis: a randomized controlled trial. J Gastroenterol 46, 1316–1323 (2011). https://doi.org/10.1007/s00535-011-0449-z

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  • DOI: https://doi.org/10.1007/s00535-011-0449-z

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