From Liver Fat to Cancer: Perils of the Western Diet

Simple Summary Non-alcoholic steatohepatitis (NASH) is a common liver disease, characterized by fatty liver, chronic tissue damage, inflammation and fibrosis. NASH greatly increases the risk of the most common liver cancer, hepatocellular carcinoma (HCC), a leading cause of cancer related deaths worldwide. Here, we discuss how the Western Diet contributes to NASH and HCC development with a special emphasis on the roles of cholesterol and different metabolic regulators. Hepatocellular carcinoma (HCC), the most common type of primary liver cancer provides the prototypical example of an obesity-related cancer. The obesity epidemic gave rise to an enormous increase in the incidence of non-alcoholic fatty liver disease (NAFLD), a condition that affects one third of American adults. In about 20% of these individuals, simple liver steatosis (hepatosteatosis) progresses to non-alcoholic steatohepatitis (NASH) characterized by chronic liver injury, inflammation, and fibrosis. In addition to liver failure, NASH greatly increases the risk of HCC. Here we discuss the metabolic processes that control the progression from NAFLD to NASH and from NASH to HCC, with a special emphasis on the role of free-non-esterified cholesterol in the process.