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
metalloproteinase-1(TIMP-1), Rac1 and p22phox which represent oxidant stress were also
measured by real-time RT-PCR before and after 6 months of therapy.