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Although cirrhosis is a key risk factor for the development of hepatocellularcarcinoma (HCC), mounting evidence indicates that in a subset of patientspresenting with non-alcoholic steatohepatitis (NASH), HCC manifests in theabsence of cirrhosis. Given the sheer size of the non-alcoholic fatty liverdisease (NAFLD) epidemic, and the dismal prognosis associated with late-stageprimary liver cancer, there is an urgent need for HCC surveillance in the NASHpatient. In the present study, adult male mice randomized to control diet or afast food diet (FFD) were followed for up to 14 mo and serum level of a panelof HCC-relevant biomarkers was compared with liver biopsies at 3 and 14 mo.Both NAFLD Activity Score (NAS) and hepatic hydroxyproline content wereelevated at 3 and 14 mo on FFD. Picrosirius red staining of liver sectionsrevealed a filigree pattern of fibrillar collagen deposition with no cirrhosisat 14 mo on FFD. Nevertheless, 46% of animals bore one or more tumors on theirlivers confirmed as HCC in hematoxylin-eosin-stained liver sections. Receiveroperating characteristic (ROC) curves analysis for serum levels of the HCCbiomarkers osteopontin (OPN), alpha-fetoprotein (AFP) and Dickkopf-1 (DKK1)returned concordance-statistic/area under ROC curve of > 0.89. These datasuggest that serum levels of OPN (threshold, 218 ng/mL; sensitivity, 82%;specificity, 86%), AFP (136 ng/mL; 91%; 97%) and DKK1 (2.4 ng/mL; 82%; 81%) arediagnostic for HCC in a clinically relevant model of NASH

A Circulating Biomarker-based Framework for Diagnosis of Hepatocellular  Carcinoma in a Clinically Relevant Model of Non-alcoholic Steatohepatitis; An  OAD to NASH