NUK - logo
E-viri
Celotno besedilo
Recenzirano
  • A rodent model of NASH with...
    de Lima, Vicência M.R; Oliveira, Claudia P.M.S; Alves, Venancio A.F; Chammas, Maria Cristina; Oliveira, Ellen Pierre; Stefano, José Tadeu; de Mello, Evandro Sobroza; Cerri, Giovanni Guido; Carrilho, Flair José; Caldwell, Stephen H

    Journal of hepatology, 12/2008, Letnik: 49, Številka: 6
    Journal Article

    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 250–300 g, 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.