Table 1.

Pathogenetic mechanisms of NAFLD in IBD patients. As discussed throughout the text, different IBD-specific risk factors act through multifaceted mechanisms in promoting NAFLD onset. Unfortunately, some specific molecular pathways still need to be clarified.

Risk Factors	Pathogenetic Mechanisms
Disease Activity	Increased intestinal permeability and translocation of inflammatory products Systemic inflammation with increased level of circulating proinflamatory cytokines (e.g., TNF-alpha, IL-6)
Surgical Resections	Resection of the ileum results in a reduction in circulating FGF19 levels, subsequently leading to alterations in bile acid metabolism, glucose metabolism, reduced fatty acid oxidation, and increased triglyceride synthesis Resection of the small intestine and ascending colon leads to reduced circulating levels of GLP-1 and GIP, resulting in accelerated gastric emptying, heightened insulin resistance, and increased appetite
Enteral and Parenteral Nutrition	PN can cause hepatic damage through direct mechanisms (e.g., lipid deposition due to PN lipid emulsions) and indirect mechanisms (e.g., gut mucosal atrophy) EN may mitigate the negative effects of PN on liver health by activating protective molecular pathways (e.g., FXR–FGF19 pathway, TGR5–GLP2 pathway)
Gut Microbiota	Dysbiotic unbalanced equilibrium between anti-inflammatory and pro-inflammatory bacterial metabolites lower the levels of protective short-chain fatty acids (SCFAs) and increase production of lipopolysaccharide (LPS) Increased intestinal permeability and translocation of inflammatory products
IBD Medications	Anti-TNF-alpha treatments may reduce systemic inflammation and intestinal disease activity but may also predispose to metabolic syndrome and insulin resistance, especially in CD patients Data on the association between specific medications (e.g., corticosteroids, biological agents) and NAFLD are conflicting and require further investigation