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. 2006 Jan 14;12(2):322-6.
doi: 10.3748/wjg.v12.i2.322.

Inhibitory effect of angiotensin II receptor antagonist on hepatic stellate cell activation in non-alcoholic steatohepatitis

Shiro Yokohama  1 , Yoshihiko Tokusashi, Kimihide Nakamura, Yosui Tamaki, Satoshi Okamoto, Mituyoshi Okada, Kazunobu Aso, Takenao Hasegawa, Masaru Aoshima, Naoyuki Miyokawa, Masakazu Haneda, Masashi Yoneda
Affiliations

Inhibitory effect of angiotensin II receptor antagonist on hepatic stellate cell activation in non-alcoholic steatohepatitis

Shiro Yokohama et al. World J Gastroenterol. .

Abstract

Aim: 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.

Conclusion: Our data suggest the crucial involvement of HSCs in anti-fibrotic effect of angiotensin II receptor antagonist on patients with NASH.

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Figures

Figure 1
Figure 1
Expression of HSCs in patients with NASH and NAFL (× 400). Liver sections were immunostained with both monoclonal anti-p75 antibody and monoclonal anti-α-SMA antibodies. Although most perisinusoidal HSCs were quiescent form (arrow heads) in NAFL, a number of arrow head were detected in the patient with NASH (arrow heads).
Figure 2
Figure 2
Significant decrease of activated and quiescent HSCs by 48-wk losartan treatment in a patient with NASH (double immunostaining with anti-p75 and α-SMA antibodies, × 200).
Figure 3
Figure 3
Average numbers of HSCs in five fields per slide at x200 magnification. A: number of activated HSCs; B: averaged ratio of activated HSCs to quiescent HSCs (Act-/Qui- Ratio: a ratio of activated HSCs to quiescent HSCs); C: averaged number of quiescent HSCs.
See this image and copyright information in PMC

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