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. Here, NFE2L2 is linked to metabolic dysfunction-associated steatohepatitis.