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Nonalcoholic steatohepatitis and hepatocellular carcinoma in galectin‐3 knockout mice
Author(s) -
Nakanishi Yuko,
Tsuneyama Koichi,
Nomoto Kazuhiro,
Fujimoto Makoto,
Salunga Thucydides L.,
Nakajima Takahiko,
Miwa Shigeharu,
Murai Yoshihiro,
Hayashi Shinichi,
Kato Ichiro,
Hiraga Koichi,
Hsu Daniel K.,
Liu FuTong,
Takano Yasuo
Publication year - 2008
Publication title -
hepatology research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.123
H-Index - 75
eISSN - 1872-034X
pISSN - 1386-6346
DOI - 10.1111/j.1872-034x.2008.00395.x
Subject(s) - hepatocellular carcinoma , nonalcoholic fatty liver disease , nonalcoholic steatohepatitis , medicine , knockout mouse , pathology , steatohepatitis , fibrosis , nuclear atypia , steatosis , liver disease , liver cancer , carcinogenesis , chronic liver disease , gastroenterology , fatty liver , cancer , disease , immunohistochemistry , cirrhosis , receptor
Aim:  Nonalcoholic fatty liver disease (NAFLD) represents a growing health concern due to its rapidly increasing prevalence worldwide. Nonalcoholic steatohepatitis (NASH) is a progressing form of NAFLD, and recently many studies have reported that it could eventually develop into hepatocellular carcinoma (HCC). We previously reported that 6‐month‐old male galectin‐3 knockout (gal3 −/− ) mice developed clinicopathological features similar to those of NAFLD in humans. Our aim was to investigate the changes in liver histology in gal3 −/− mice by long‐term observation. Methods:  We initially investigated three 15‐month‐old gal3 −/− mice, of which two developed multiple liver nodules with dysplastic changes. Then, we histopathologically examined the liver specimens of the 15‐, 20‐ and 25‐month‐old gal3 −/− mice and attempted to evaluate the liver morphology by contrast enhanced computed tomography (CT) before sacrifice. Results:  At the age of 15 months or later, gal3 −/− mice developed liver nodules with varying degrees of architectural and nuclear atypia based on mild to moderate delicate zone 3 fibrosis. In addition, we successfully confirmed the presence of some of the liver nodules by CT. We report herein that gal3 −/− mice develop dysplastic liver nodules and HCC. Conclusions:  We believe that it would be interesting to use this murine model to investigate liver carcinogenesis based on a natural history of NAFLD. Furthermore, CT scanning might be a useful tool for longitudinal evaluation of morphological changes in vivo .

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