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Copyright ©2006 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Jan 14, 2006; 12(2): 322-326
Published online Jan 14, 2006. 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, Yoshihiko Tokusashi, Kimihide Nakamura, Yosui Tamaki, Satoshi Okamoto, Mituyoshi Okada, Kazunobu Aso, Takenao Hasegawa, Masaru Aoshima, Naoyuki Miyokawa, Masakazu Haneda, Masashi Yoneda
Shiro Yokohama, Yosui Tamaki, Satoshi Okamoto, Mituyoshi Okada, Kazunobu Aso, Takenao Hasegawa, Masaru Aoshima, Masakazu Haneda, Second Department of Medicine, Asahikawa Medical College, Asahikawa, Japan
Yoshihiko Tokusashi, Naoyuki Miyokawa, Department of Surgical Pathology, Asahikawa Medical College, Asahikawa, Japan
Masashi Yoneda, Department of Gastroenterology, Dokkyo University School of Medicine, Mibu, Japan
Kimihide Nakamura, Health Care Administration Center, Obihiro University of Agriculture and Veterinary Medicine, Obihiro, Japan
Supported by a Grant-in-Aid for Scientific Research (C) from the Japan Society for the Promotion of Science, No. 15590613, and a grant for Research on Intractable Disease from the Japanese Ministry of Public Welfare
Correspondence to: Dr. Shiro Yokohama, Second Department of Medicine, Asahikawa Medical College, Midorigaoka higashi 2-1-1-1, Asahikawa 078-8510, Japan. yokohama@reha.or.jp
Telephone: +81-166-682454 Fax: +81-166-682459
Received: May 31, 2005
Revised: June 8, 2005
Accepted: June 24, 2005
Published online: January 14, 2006
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 α-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.

Keywords: NASH, NAFLD, Hepatic fibrosis, HSC, Losartan