Large cohort data link elevated LPS levels in the portal system with increased TLR4 activation, initiating a proinflammatory cascade via the NF-κB pathway, a mechanism that is commonly observed in patients with NAFLD (Smith et al., 2020; Lu et al., 2024; Wu et al., 2024) (Figure 3). Here, NFKB1 is linked to metabolic dysfunction-associated steatotic liver disease.