Eosinophilic Esophagitis and Risk of Non-Alcoholic Fatty Liver Disease and Cirrhosis: A Multi-Center Retrospective Study

Background and Aim: Eosinophilic esophagitis (EoE) is a chronic Th2-mediated inflammatory disease. Given its systemic immune activation and eosinophil-rich pathology, this study aimed to evaluate the longitudinal risk of non-alcoholic fatty liver disease (NAFLD) and cirrhosis among patients with EoE. Methods: A retrospective cohort study was conducted using the TriNetX US Collaborative Network. Adults (≥18 years) with an EoE diagnosis were matched 1:1 with EoE-free controls based on demographics, comorbidities, and healthcare utilization. Patients with prior liver disease or malignancy were excluded. Incident NAFLD and cirrhosis were evaluated excluding diagnoses within 3 months of the index date. Sensitivity analyses explored alternative EoE definitions (proton pump inhibitor use, topical corticosteroids, endoscopy records) and longer wash-out periods. Results: Compared with matched controls, EoE patients had a significantly elevated risk of NAFLD (HR = 1.409, 95% CI: 1.277-1.555) and cirrhosis (HR = 1.529, 95% CI: 1.176-1.988). Elevated risks persisted using PPI-based (NAFLD: HR = 1.705, 95% CI: 1.535-1.894; cirrhosis: HR = 1.962, 95% CI: 1.478-2.605), steroid-based (NAFLD: HR = 1.746, 95% CI: 1.561-1.953; cirrhosis: HR = 2.101, 95% CI: 1.557-2.837), and endoscopy-based definitions (NAFLD: HR = 1.951, 95% CI: 1.506-2.528). Conclusions: EoE is associated with higher long-term risks of NAFLD and cirrhosis. These findings underscore the importance of hepatic surveillance and immune-metabolic research in EoE patients. However, potential residual confounder caused by comedications should be cautiously interpreted.