Elshaer, Amani

Eosinophilic esophagitis (EoE) and inflammatory bowel disease (IBD) are immune-mediated disorders of the gastrointestinal (GI) tract that, despite involving different tissues, are increasingly recognized to coexist. Epidemiologic studies demonstrate a bidirectional association, with patients affected by one condition showing a higher-than-expected prevalence of the other, suggesting shared susceptibility rather than incidental overlap. Genetic and epigenetic data support partial convergence in immune regulatory pathways, while epithelial barrier dysfunction and antigen-driven immune activation emerge as common upstream features. Overlapping cytokine networks, including IL-4, IL-13, and IL-23 signaling, contribute to chronic inflammation in both diseases, although differences in tissue environment and immune dominance give rise to distinct inflammatory phenotypes and clinical behavior. Clinical outcomes in patients with dual diagnoses appear heterogeneous, with available data suggesting neither uniformly worsened nor clearly protective disease courses, underscoring the complexity of shared immune mechanisms operating within different anatomic contexts. Beyond inflammatory activity, coexistence of EoE and IBD poses important nutritional and quality-of-life challenges, as overlapping dietary restrictions and chronic symptoms increase the risk of malnutrition, micronutrient deficiencies, and psychosocial burden. Current therapies remain disease-specific, with strong evidence supporting proton pump inhibitors, swallowed topical steroids, dietary therapy, and dupilumab in EoE, and biologics and small molecules targeting TNF-α, IL-12/23, IL-23, integrins, and JAK–STAT signaling in IBD, while evidence guiding treatment in patients with dual diagnosis remains limited. Together, current evidence supports a framework of shared immune machinery with tissue-specific expression that explains coexistence while preserving the distinct identities of EoE and IBD. By integrating emerging genetic, immunologic, and clinical evidence, this review aims to provide a framework for understanding and managing patients with coexisting EoE and IBD.

Background: Given aspirin’s biologic plausibility for antifibrotic and antineoplastic effects, we conducted a systematic review and meta-analysis to examine the association between aspirin use and major liver-related outcomes in metabolic dysfunction-associated steatotic liver disease (MASLD). To our knowledge, this is the first systematic review and meta-analysis restricted exclusively to patients with biopsy- or registry-confirmed MASLD. Methods: A comprehensive search of Ovid MEDLINE, Ovid EMBASE, Scopus, and Web of Science was performed in October 2025. Studies enrolling adults with a confirmed MASLD diagnosis were included; those with viral hepatitis or alcohol-related liver disease were excluded. Outcomes assessed included hepatocellular carcinoma (HCC), fibrosis progression, cirrhosis, all-cause and liver-related mortality, gastrointestinal (GI) bleeding, hemorrhagic stroke, and liver disease progression. Hazard ratios (HRs) with 95% CIs were pooled using random-effects models. Heterogeneity was assessed using I2 statistics. Results: Seven studies met the eligibility criteria, with approximately 720,000 individuals included. Pooled analysis showed that aspirin use was associated with a significantly lower HCC risk (HR 0.59; 95% CI 0.43–0.81; I2 = 83%). No statistically significant association was found between aspirin use and cirrhosis incidence (HR 0.55; 95% CI 0.13–2.37; I2 = 83.4%) or GI bleeding (HR 1.11; 95% CI 0.74–1.66; I2 = 98.9%). Among the two studies that explored all-cause mortality, aspirin was associated with a modest but statistically significant reduction in all-cause mortality (HR 0.86; 95% CI 0.78–0.95; I2 = 0%). Conclusions: Aspirin use is associated with a reduced risk of HCC and all-cause mortality in MASLD without significantly increasing GI bleeding or hemorrhagic strokes. These associations may reflect aspirin’s anti-inflammatory properties in liver disease. Further RCTs are needed to verify the causal role of aspirin in MASLD management.