Primary liver cancer, of which hepatocellular carcinoma (HCC) represents the vast majority of cases, is the second highest cause of cancer-related death world-wide (1). HCC typically occurs in the context of chronic liver injury due to chronic diseases, including: viral hepatitis; alcoholic liver disease and; obesity-related non-alcoholic fatty liver disease (NAFLD) and its progressive, inflammatory form;non-alcoholic steatohepatitis (NASH). Due to the liver’s unique regenerative ability, chronic injury is coupled with chronic repair, which, over time, leads to the accumulation of repair-related deposition of extracellular matrix (ECM) proteins, resulting in liver fibrosis. Fibrosis is mediated primarily by the proliferation of the normally quiescent hepatic stellate cells (HSCs) and their secretion of ECM proteins. Because HCC occurrence generally coincides with fibrosis and cirrhosis, it has commonly been accepted that these phenomena play a role in HCC progression. However, while viral hepatitis was classically the major cause of HCC, and can occur almost exclusively in parallel with fibrosis, NAFLD is emerging as a major determinant of HCC due to rising global obesity, and can occur in the absence of fibrosis and cirrhosis (2).