Intriguingly, NASH-HCC showed a unique tumor signature characterized by bile and fatty acid signaling, oxidative stress, inflammation, and mitochondrial dysfunction and in patients who carried the PNPLA3 I148M variant it was enriched in defective pathways of DNA repair and reduced TP53 signaling, thus reinforcing the role of this polymorphism in HCC development. The gene discussed is PNPLA3; the disease is metabolic dysfunction-associated steatohepatitis.