Indeed, both in rodents and in patients with NAFLD-HCC, the activation of HDAC8/EZH2 complex inhibits p53/p21-mediated apoptosis, cell-cycle arrest, and stimulates β-catenin-dependent cell proliferation, whereby controlling histone H4 deacetylation and H3 lysine 27 trimethylation. Here, CDKN1A is linked to metabolic dysfunction-associated steatotic liver disease.