In the present study, activation of IGF1 and TGF-β was associated with up-regulated Wnt/β-catenin signaling, NRIP1, Nrf2 signaling and decrease of CK8 and CK18 levels in human NASH HCCs, correlated with suppression of PPARs, HNF4A, CAR, PXR and, in contrast, overexpression of PHBs and activation of SREBP-1 and LXRα, leading to enhanced lipid biogenesis and cholesterol synthesis, development of oxidative stress and suppression of mitochondrial function. This evidence concerns the gene HNF4A and metabolic dysfunction-associated steatohepatitis.