The inflammatory mediator TNF-α is considered a central mediator in the pathogenesis of both ALD and NAFLD.39 Despite the fact that Kupffer cells are the main targets of LPS in the liver, it is the HSCs to promote TLR4-dependent fibrosis.40 LPS can activate HSCs in vitro and in vivo, and Kupffer cells strongly enhance this process by producing transforming growth factor beta (TGF-β) and increasing the sensitivity of HSCs to TGF-β. The gene discussed is TLR4; the disease is metabolic dysfunction-associated steatotic liver disease.