Epidemiology and risk-stratification of NAFLD-associated HCC

Non-alcoholic fatty liver disease (NAFLD) is projected to become the leading cause of hepatocellular carcinoma (HCC) in many countries. Many risk factors for NAFLD are also independently associated with HCC, including obesity, diabetes, Hispanic ethnicity and genetic polymorphisms in PNPLA3, TM6SF2, GCKR, MBOAT7 and HSD17B13. Steatosis-related lipotoxicity and oxidative DNA damage can induce hepatocarcinogenesis. These factors may explain the association between NAFLD and HCC, especially in the absence of cirrhosis. In fact, NAFLD/NASH is a leading cause of HCC in the absence of cirrhosis. Identifying patients with pre-cirrhotic NAFLD who have a high enough HCC risk to justify HCC screening represents one of the greatest clinical challenges in NAFLD. Validated models that combine multiple risk factors and fibrosis stage into "HCC risk calculators" are not yet available for patients with NAFLD. Development of such tools would enable risk stratification, identification of high-risk patients even in the absence of cirrhosis, and individualised (risk-based) surveillance strategies.