Beneficial effects of candesartan, an angiotensin-blocking agent, on compensated alcoholic liver fibrosis - a randomized open-label controlled study.

Abstract

BACKGROUND:

Recent studies have shown that the renin-angiotensin system is implicated in hepatic fibrogenesis in vitro and in vivo. However, no study was done in humans with alcoholic liver disease.

AIM:

To investigate the antifibrotic effect of angiotensin II type 1 receptor (AT1-R) blocking agents (ARB) in patients with alcoholic liver disease.

METHODS:

The primary outcome was improvement in patients' histological features. Eighty-five patients with compensated alcoholic liver fibrosis (≥ F2) which was confirmed by baseline liver biopsy were randomized (intention-to-treat (ITT)) to receive either ARB, candesartan (8 mg/day) with ursodeoxycholic acid (UDCA) (600 mg/day) (n = 42) or UDCA alone (n = 43) as control for 6 months and follow-up liver biopsies were conducted.

RESULTS:

According to the Laennec fibrosis system, candesartan showed significantly higher rates of histological improvements (ITT, 33.3% vs. 11.6%, P = 0.020). In addition, the fibrosis score was significantly reduced from 3.4 ± 1.4 to 3.1 ± 1.5 (P = 0.005) in the candesartan group. Candesartan also reduced the area of fibrosis and α-smooth muscle actin positive from 11.3 ± 6.0 to 8.3 ± 4.7 and 28.7 ± 10.5 to 23.9 ± 10.3 (%), and the hydroxyproline levels (μg/g liver tissue) from 7.8 ± 2.4 to 6.3 ± 1.7 respectively (P < 0.05). In addition, the relative expression of transforming growth factor-β1(TGF-β1), collagen-1, AT1-R, tissue inhibitor of metalloproteinase 1 (TIMP-1), metalloproteinases2 (MMP2), Rac1 and p22phox by real-time RT-PCR decreased in the candesartan group (P < 0.05). Mean arterial blood pressure in the candesartan group decreased mildly but significantly (P < 0.001). No significant complications and side effects were observed during the present study.

CONCLUSIONS:

Administration of ARB in compensated alcoholic liver disease induces improvement of fibrosis in histological and quantitative measurements.

• Authors: Moon Young Kim, Mee Yon Cho, Soon Koo Baik, Phil Ho Jeong, Ki Tae Suk, Yoon Ok Jang, Chang Jin Yea, Jae Woo Kim, Hyun Soo Kim, Sang Ok Kwon, Byung Su Yoo, Jang Young Kim, Min Seob Eom, Seung Hwan Cha, Sei Jin Chang
• Journal: Liver international : official journal of the International Association for the Study of the Liver (Liver Int) Vol. 32 Issue 6 Pg. 977-87 (Jul 2012) ISSN: 1478-3231 [Electronic] United States
• PMID: 22364262 (Publication Type: Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
• Copyright: © 2012 John Wiley & Sons A/S.

Chemical References

• Angiotensin II Type 1 Receptor Blockers
• Benzimidazoles
• Biomarkers
• Biphenyl Compounds
• Tetrazoles
• Ursodeoxycholic Acid
• candesartan

Topics

• Adult
• Aged
• Angiotensin II Type 1 Receptor Blockers (adverse effects, therapeutic use)
• Benzimidazoles (adverse effects, therapeutic use)
• Biomarkers (metabolism)
• Biopsy
• Biphenyl Compounds
• Drug Therapy, Combination
• Female
• Gene Expression Regulation (drug effects)
• Humans
• Immunohistochemistry
• Liver (drug effects, metabolism, pathology)
• Liver Cirrhosis, Alcoholic (drug therapy, genetics, metabolism, pathology)
• Male
• Middle Aged
• Prospective Studies
• Republic of Korea
• Severity of Illness Index
• Tetrazoles (adverse effects, therapeutic use)
• Time Factors
• Treatment Outcome
• Ursodeoxycholic Acid (therapeutic use)