Inhibitory effect of angiotensin II receptor antagonist on hepatic stellate cell activation in non-alcoholic steatohepatitis.
OBJECTIVE
To investigate the efficacy of angiotensin II receptor antagonist on hepatic stellate cells (HSCs) activation in the patients with non-alcoholic steatohepatitis (NASH).


METHODS
Seven patients with NASH were prescribed losartan, a selective angiotensin II type 1 receptor antagonist (50 mg/d) for 48 wk. Liver biopsies were performed both at the entry and end of the study in all patients. Quiescent and activated HSCs were identified by double immunostaining using anti-p75 and -smooth muscle actin antibodies, and the number of each phenotype was counted. Similarly, the liver specimens obtained from the eight patients with non-alcoholic fatty liver (NAFL) were also examined as controls.


RESULTS
In NASH hepatic tissues, activated HSCs were dominantly distributed as compared with those in NAFL. The 48-wk losartan treatment induced a remarkable decrease in activated HSCs and a mild increase in quiescent phenotypes.


CONCLUSIONS
Our data suggest the crucial involvement of HSCs in anti-fibrotic effect of angiotensin II receptor antagonist on patients with NASH.
Second Department of Medicine, Asahikawa Medical College, Midorigaoka higashi 2-1-1-1, Asahikawa 078-8510, Japan. yokohama@reha.or.jp
Shiro
S
Yokohama
Yoshihiko
Y
Tokusashi
Kimihide
K
Nakamura
Yosui
Y
Tamaki
Satoshi
S
Okamoto
Mituyoshi
M
Okada
Kazunobu
K
Aso
Takenao
T
Hasegawa
Masaru
M
Aoshima
Naoyuki
N
Miyokawa
Masakazu
M
Haneda
Masashi
M
Yoneda
D000328:Adult; D000368:Aged; D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D005234:Fatty Liver / Q000188:drug therapy* / Q000473:pathology; D005260:Female; D006801:Humans; D008099:Liver / Q000166:cytology / Q000187:drug effects*; D008103:Liver Cirrhosis / Q000517:prevention & control*; D019808:Losartan / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D016212:Transforming Growth Factor beta / Q000097:blood; D053773:Transforming Growth Factor beta1
D047228:Angiotensin II Type 1 Receptor Blockers; C508960:TGFB1 protein, human; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D019808:Losartan