A ‘two hit' mechanism has been proposed to drive NASH pathogenesis.27 The first hit is associated with steatosis and sensitizes the liver to additional proinflammatory insults (second hit), such as LPS, which aggravate liver injury and contribute to the development of NASH.28, 29 We hypothesized that, as a consequence of increased plasma LPS, ER stress could be induced and lead to NLRP3 inflammasome activation and hepatocyte death associated with NASH. This evidence concerns the gene NLRP3 and steatosis.