Consistent with the view that oxidative stress is pivotal in development of NASH, knockout of Nrf2 in mice profoundly predisposes to NASH stimulated by either a methionine- and choline-deficient (MCD) diet20, 21 or a HF diet.22, 23, 24 Although loss of Nrf2 increases sensitivity to NASH, it is less certain whether upregulation of Nrf2 by genetic or pharmacologic approaches decreases sensitivity to the disease. Here, NFE2L2 is linked to metabolic dysfunction-associated steatohepatitis.