Document Detail

A rodent model of NASH with cirrhosis, oval cell proliferation and hepatocellular carcinoma.
MedLine Citation:
PMID:  18929425     Owner:  NLM     Status:  MEDLINE    
BACKGROUND/AIMS: Hepatocellular carcinoma (HCC) is a well recognized complication of advanced NASH (non-alcoholic steatohepatitis). We sought to produce a rat model of NASH, cirrhosis and HCC. METHODS: Adult Sprague-Dawley rats, weighing 250-300g, were fed a choline-deficient, high trans-fat diet and exposed to DEN in drinking water. After 16 weeks, the animals underwent liver ultrasound (US), sacrifice and assessment by microscopy, immunohistochemistry and transmission electron microscopy (TEM). RESULTS: US revealed steatosis and focal lesions in 6 of 7. All had steatohepatitis defined as inflammation, advanced fibrosis and ballooning with Mallory-Denk bodies (MDB) with frank cirrhosis in 6. Areas of more severe injury were associated with anti-CK19 positive ductular reaction. HCC, present in all, were macro-trabecullar or solid with polyhedral cells with foci of steatosis and ballooned cells. CK19 was positive in single or solid nests of oval cells and in neoplastic hepatocytes. TEM showed ballooning with small droplet fat, dilated endoplasmic reticulum and MDB in non-neoplastic hepatocytes and small droplet steatosis in some cancer cells. CONCLUSIONS: This model replicated many features of NASH including steatohepatitis with ballooning, fibrosis, cirrhosis and hepatocellular carcinoma. Oval cell proliferation was evident and the presence anti-CK 19 positivity in the cancer suggests oval cell origin of the malignancy.
Vicência M R de Lima; Claudia P M S Oliveira; Venancio A F Alves; Maria Cristina Chammas; Ellen Pierre Oliveira; José Tadeu Stefano; Evandro Sobroza de Mello; Giovanni Guido Cerri; Flair José Carrilho; Stephen H Caldwell
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-09-24
Journal Detail:
Title:  Journal of hepatology     Volume:  49     ISSN:  0168-8278     ISO Abbreviation:  J. Hepatol.     Publication Date:  2008 Dec 
Date Detail:
Created Date:  2008-11-17     Completed Date:  2009-01-23     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8503886     Medline TA:  J Hepatol     Country:  England    
Other Details:
Languages:  eng     Pagination:  1055-61     Citation Subset:  IM    
Department of Gastroenterology, University of São Paulo School of Medicine, Av. Dr. Enéas de Carvalho Aguiar No. 255, Instituto Central, # 9159, São Paulo 05403-000, Brazil.
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MeSH Terms
Carcinoma, Hepatocellular / complications,  pathology*,  ultrasonography
Cell Division
Choline Deficiency / pathology
Dietary Fats / pharmacology
Disease Models, Animal*
Fatty Liver / etiology,  pathology*,  ultrasonography
Hepatocytes / pathology,  ultrastructure
Liver Cirrhosis / etiology,  pathology,  ultrasonography
Liver Neoplasms / complications,  pathology*,  ultrasonography
Microscopy, Electron, Transmission
Rats, Sprague-Dawley*
Reg. No./Substance:
0/Dietary Fats

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