NAFLD-driven HCC: Safety and efficacy of current and emerging treatment options.

In light of a global rise in obesity and type 2 diabetes, non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) represent an increasingly important underlying etiology of hepatocellular carcinoma (HCC). HCCs arising from lipotoxicity-mediated chronic inflammation due to excessive accumulation of neutral lipids in the liver are characterized by several unique features: In contrast to viral-driven HCC, up to 50% of NAFLD-HCC occurs in patients without cirrhosis, and annual HCC incidence is comparatively low, complicating current surveillance strategies. On average, patients are older and diagnosis occurs more frequently at an advanced stage. Locoregional treatments are probably equally effective regardless of HCC etiology. For systemic therapy the picture is less clear. Tyrosine kinase inhibitors are probably equally effective, while there have been first signals that immune checkpoint inhibitors may be less effective in NAFLD-HCC than in viral HCC. To date, treatment recommendations for HCC by international guidelines do not take the underlying etiology into consideration. This review article summarizes the currently available evidence for the efficacy and safety of the various treatment modalities for HCC. There are insufficient data to draw any conclusion and to modify the current management of HCC patients with regard to etiology. However, in light of the growing relevance of NAFLD-HCC, future clinical trials should assess whether HCC etiology - and NAFLD/NASH in particular - influence the safety and efficacy of a given treatment.