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 nonalcoholic steatohepatitis (NASH) represent an increasingly important underlying aetiology of hepatocellular carcinoma (HCC). HCCs arising from lipotoxicity-mediated chronic inflammation are characterised by several unique features: in contrast to virally 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 are more frequently diagnosed at an advanced stage. While locoregional treatments are probably equally effective regardless of HCC aetiology, the picture is less clear for systemic therapy. Tyrosine kinase inhibitors are probably equally effective, while there have been initial signals that immune checkpoint inhibitors may be less effective in NAFLD-HCC than in viral HCC. Current international clinical practice guidelines for HCC do not consider aetiology, as there are insufficient data to draw specific conclusions or to recommend aetiology-specific modifications to the current management of patients with HCC. However, in light of the growing relevance of NAFLD-HCC, future clinical trials should assess whether HCC aetiology - and NAFLD/NASH in particular - influence the safety and efficacy of a given treatment. (c) 2021 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

Automated summary

Given the global increase in obesity and type 2 diabetes, non-alcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) are becoming important causes of hepatocellular carcinoma (HCC). HCCs caused by chronic inflammation mediated by lipotoxicity have unique characteristics, such as occurring in up to 50% of NAFLD-HCC patients without cirrhosis and having a lower annual incidence, leading to challenges in surveillance strategies. Locoregional treatments may be equally effective regardless of HCC etiology, but the effectiveness of systemic therapy is less clear. Tyrosine kinase inhibitors are likely equally effective, while there are initial signals that immune checkpoint inhibitors may be less effective in NAFLD-HCC compared to viral HCC.