Reduced expression or loss of NRF2 and/or PPARγ may increase oxidative stress that acts as “second hit” in NASH; in fact, on the basis of experimental evidence, we may hypothesize that NRF2, together with PPARγ, preserves from the progression of NASH throughout protective effects on oxidative stress, inflammation, and lipid metabolism. This evidence concerns the gene PPARG and metabolic dysfunction-associated steatohepatitis.