Moreover, in 1380 patients with NAFLD, among whom 121 had HCC, Longo et al. [82] evaluated the impact of the three variants, I148M PNPLA3, rs641738 MBOAT7, and E167K TM6SF2, showing that the co-presence of these three at-risk variants was related to enhanced levels of markers of liver damage, advanced steatosis, inflammation, ballooning, fibrosis, and approximately a two-fold higher risk of HCC [82]. This evidence concerns the gene PNPLA3 and metabolic dysfunction-associated steatotic liver disease.