LAUSR

NAFLD is projected to become the leading cause of 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 NAFLD patients with pre-cirrhotic liver disease who have a high enough HCC risk to justify HCC screening represents one of the greatest clinical challenges in NAFLD. Validated strategies to estimate HCC risk in NAFLD patients by combining multiple risk factors and fibrosis stage into "HCC Risk Calculators" are not yet available. Development of such tools would enable risk stratification, identification or high-risk patients even in the absence of cirrhosis, and individualized, risk-based surveillance strategies.