Stimulation of the LPS-TLR4 signaling pathway eventually leads to the release of proinflammatory mediators like tumor necrosis factor-α (TNF-α) and interleukin 6 (IL-6).34 LPS also mediates signaling through MyD88-independent pathway, but the activation of MAPK and NF-kB occurs in a delayed manner.35 In both ALD and NAFLD progression, TLR4 signaling is considered a key pathway, and, very interestingly, it is reported that mice deficient in TLR4 are resistant to both alcohol-induced liver injury and NAFLD.36,37. This evidence concerns the gene TNF and metabolic dysfunction-associated steatotic liver disease.