@article{3030795,
    title = "Key features of the environment promoting liver cancer in the absence of
cirrhosis",
    author = "Zaki, Marco Youssef William and Mahdi, Ahmed Khairallah and Patman, and Gillian Lucinda and Whitehead, Anna and Mauricio, Joao Pais and McCain, and Misti Vanette and Televantou, Despina and Abou-Beih, Sameh and and Ramon-Gil, Erik and Watson, Robyn and Cox, Charlotte and Leslie, Jack and and Wilson, Caroline and Govaere, Olivier and Lunec, John and Mann, and Derek Austin and Nakjang, Sirintra and Oakley, Fiona and Shukla, Ruchi and and Anstee, Quentin Mark and Tiniakos, Dina and Reeves, Helen Louise",
    journal = "Scientific Reports",
    year = "2021",
    volume = "11",
    number = "1",
    publisher = "NATURE PORTFOLIO",
    issn = "2045-2322",
    doi = "10.1038/s41598-021-96076-2",
    abstract = "The prevalence of obesity and non-alcoholic fatty liver disease (NAFLD)
associated hepatocellular carcinoma (HCC) is rising, even in the absence
of cirrhosis. We aimed to develop a murine model that would facilitate
further understanding of NAFLD-HCC pathogenesis. A total of 144 C3H/He
mice were fed either control or American lifestyle (ALIOS) diet, with or
without interventions, for up to 48 weeks of age. Gross, liver
histology, immunohistochemistry (IHC) and RNA-sequencing data were
interpreted alongside human datasets. The ALIOS diet promoted obesity,
elevated liver weight, impaired glucose tolerance, non-alcoholic fatty
liver disease (NAFLD) and spontaneous HCC. Liver weight, fasting blood
glucose, steatosis, lobular inflammation and lipogranulomas were
associated with development of HCC, as were markers of hepatocyte
proliferation and DNA damage. An antioxidant diminished cellular injury,
fibrosis and DNA damage, but not lobular inflammation, lipogranulomas,
proliferation and HCC development. An acquired CD44 phenotype in
macrophages was associated with type 2 diabetes and NAFLD-HCC. In this
diet induced NASH and HCC (DINAH) model, key features of obesity
associated NAFLD-HCC have been reproduced, highlighting roles for
hepatic steatosis and proliferation, with the acquisition of lobular
inflammation and CD44 positive macrophages in the development of
HCC-even in the absence of progressive injury and fibrosis."
}