Clinical Trial: Effect of Candesartan in Alcoholic Liver Fibrosis

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Beneficial Effect of Angiotensin-blocking Agent Candesartan on Alcoholic Liver Fibrosis: A Randomized Controlled Trial

Brief Summary:

Background:

Alcohol is one of principal causes of hepatic fibrosis. Although the most effective treatment for alcoholic hepatic fibrosis is abstinence of alcohol consumption, additive treatment to reduce the accumulation of scar tissue can accelerate the improvement of hepatic fibrosis in alcoholic liver disease. The renin-angiotensin system can be an attractive antifibrotic target in liver. Several lines of evidence indicate that overproduction of angiotensin II(ANG II) in chronic liver injury stimulates the activation of hepatic stellate cells(HSCs) attributed to fibrogenesis. Additionally, the antifibrotic effect of ANG II blocking agent has been shown in various animal models and hepatitis C patients. Hence, drugs that inhibit the renin-angiotensin system have promise in ameliorating hepatic fibrosis in chronic liver injury. However, no study has been conducted in patients with alcoholic liver disease to evaluate the effect ANG II type I receptor blocking agent on hepatic fibrosis.

Aim:

This study aimed to investigate the safety and the efficacy of chronic administration of candesartan to hepatic fibrosis patients with alcoholic liver disease.

Methods

1) Patients with liver fibrosis(F2) were randomized to receive either the angiotensin receptor blocker(ARB), candesartan(8 mg/day) with ursodeoxycholic acid(UDCA)(600 mg/day)(n = 42), or UDCA alone(n = 43) as control for 6 months. 2)All enrolled patients underwent liver biopsies twice for measurement of fibrosis score, area of fibrosis and alpha-smooth muscle actin(SMA) positive and hydroxyproline. 3) Transforming growth factor-beta1(TGF-beta1), collagen-1, angiotensin II type I receptor(AT1-R), tissue inhibitor of metallopr

Detailed Summary:
Sponsor: Yonsei University

Current Primary Outcome: Improvement of histologic grade of hepatic fibrosis [ Time Frame: 6 month later ]

Original Primary Outcome: Same as current

Current Secondary Outcome: estimation of safety of candesartan in hepatic fibrosis [ Time Frame: 6 month later ]

Original Secondary Outcome: Same as current

Information By: Yonsei University

Dates:
Date Received: October 6, 2009
Date Started: September 2005
Date Completion:
Last Updated: October 6, 2009
Last Verified: October 2009