Patients With MASLD Had More Than 2 Times Higher Odds of Eosinophilic Esophagitis Across Age Groups

Adults with metabolic dysfunction–associated steatotic liver disease (MASLD) had significantly higher odds of developing eosinophilic esophagitis (EoE) and reflux-related esophageal conditions, according to a recent analysis of US electronic health records published in the Journal of Gastroenterology and Hepatology.¹

MASLD, EoE Show a Potential Connection Beyond Shared Risk Factors

MASLD now affects nearly 30% of adults worldwide, with its prevalence more than doubling over time, underscoring its growing public health burden.² Rather than being limited to the liver, it is increasingly recognized as a systemic condition tied to cardiovascular disease, diabetes, and cancer.¹ Obesity and visceral adiposity are established drivers of both MASLD and reflux-related esophageal conditions such as gastroesophageal reflux disease (GERD) and Barrett esophagus, but data linking MASLD specifically to EoE have been limited and inconsistent.

Given that obesity has been proposed as a nonallergic risk factor that can amplify the T helper 2 (Th2) inflammatory response underlying EoE, the researchers investigated whether MASLD independently increases the risk of EoE beyond shared metabolic and demographic factors.

MASLD May Independently Increase Risk of EoE Beyond Shared Comorbidities

Using the TriNetX US Collaborative Network, they identified more than 400,000 patients with MASLD and matched them 1:1 with controls without MASLD across 3 age strata, adjusting for demographics, metabolic and cardiovascular comorbidities, and gastrointestinal and atopic conditions with known or plausible links to EoE.

After matching, MASLD was associated with nearly 3 times higher odds of incident EoE in adults aged 18 to 44 years (OR, 2.905; 95% CI, 2.458-3.434) and more than double the odds in both individuals aged 45 to 64 years (OR, 2.423; 95% CI, 2.057-2.854) and those aged 65 and older (OR, 2.327; 95% CI, 1.606-3.371).

To test whether the association simply reflected greater diagnostic scrutiny of patients with MASLD, the researchers conducted 2 prespecified sensitivity analyses, 1 restricting both cohorts to patients who underwent upper endoscopy after cohort entry and another excluding anyone with a documented reflux diagnosis. The elevated odds of EoE persisted in both, particularly among younger and middle-aged adults. By contrast, the association in patients aged 65 and older did not reach statistical significance in the reflux-restricted analysis; the researchers said this likely reflects a small number of events after restriction.

MASLD was also tied to substantially higher odds of GERD and each of its phenotypes. Odds of GERD were highest in the youngest cohort (OR, 2.681; 95% CI, 2.623-2.739), followed by middle-aged adults (OR, 1.908; 95% CI, 1.877-1.939) and those aged 65 and older (OR, 1.696; 95% CI, 1.653-1.739). A similar age gradient emerged for nonerosive reflux disease, erosive esophagitis, and Barrett esophagus.

Patients with MASLD also reported significantly more heartburn and dysphagia across all age groups. The dysphagia association, however, narrowed considerably with age, from nearly 2-fold higher odds in younger adults (OR, 1.929; 95% CI, 1.850-2.012) to an 11% increase in the oldest group (OR, 1.113; 95% CI, 1.072-1.154).

The authors pointed to several biologically plausible mechanisms linking MASLD to esophageal disease. Visceral adiposity can raise intra-abdominal pressure and disrupt the esophagogastric junction, promoting reflux, while adipose-derived inflammatory mediators and elevated leptin levels, both common in MASLD, may impair esophageal mucosal defense and motility. For EoE specifically, obesity has been shown in preclinical models to amplify the Th2 immune response underlying eosinophilic inflammation, and shared cytokine pathways involving IL-4 and IL-13 offer a potential mechanistic bridge between the 2 conditions.

Findings Highlight Need for Further Research into MASLD, Esophageal Disease

As MASLD prevalence continues to rise, the study’s findings may have important implications for care management. EoE alone is associated with annual US health care costs exceeding $1.3 billion, driven largely by repeat endoscopies, elimination diets, and long-term maintenance therapy after diagnosis³; these costs could increase further when patients also require ongoing monitoring and treatment for MASLD.

Additionally, if MASLD independently increases the risk of EoE and GERD, rather than simply reflecting shared obesity or metabolic risk, health systems already caring for patients with MASLD through hepatology or endocrinology clinics may need to incorporate esophageal symptom screening into routine care instead of waiting for a gastroenterology referral.

For payers, given the elevated risk of both erosive esophageal disease and EoE, the findings also raise the question of whether patients with MASLD who report heartburn or dysphagia may warrant earlier consideration for upper endoscopy.¹ Current guidance from the American Society for Gastrointestinal Endoscopy already recommends endoscopy for GERD evaluation in patients who exhibit alarm symptoms or multiple risk factors for Barrett esophagus, suggesting MASLD could become an additional consideration in risk assessment.⁴

At the same time, the authors acknowledged several limitations, including the study’s reliance on electronic health record data, which may introduce bias because of coding inaccuracies and incomplete documentation.¹ In addition, although they identified an association, the researchers emphasized that the study cannot establish causation or determine the direction of the relationship between MASLD and EoE from this study alone. Consequently, they highlighted that further investigation is needed to build upon their findings.

“As MASLD prevalence continues to rise globally, clinicians should maintain increased vigilance for esophageal complications in this population,” they concluded. “Future prospective studies are needed to clarify causal mechanisms and determine whether targeted metabolic interventions can mitigate esophageal disease risk.”

References

1. Chowdhary R, Prasad S, Koo TH, et al. Burden of eosinophilic esophagitis and gastroesophageal reflux disease in metabolic dysfunction–associated steatotic liver disease: a comprehensive US healthcare analysis. J Gastroenterol Hepatol. Published online July 22, 2026. doi:10.1111/jgh.70609
2. Roderburg C, Loosen S, Kostev K, Demir M, Joerdens MS, Luedde T. Nonalcoholic fatty liver disease is associated with a higher incidence of coeliac disease. Eur J Gastroenterol Hepatol. 2022;34(3):328-331. doi:10.1097/MEG.0000000000002234
3. Jensen ET, Kappelman MD, Martin CF, Dellon ES. Health-care utilization, costs, and the burden of disease related to eosinophilic esophagitis in the United States. Am J Gastroenterol. 2015;110(5):626-632. doi:10.1038/ajg.2014.316
4. ASGE Standards of Practice Committee, Desai M, Ruan W, et al. American Society for Gastrointestinal Endoscopy guideline on the diagnosis and management of GERD: summary and recommendations. Gastrointest Endosc. 2025;101(2):267-284. doi:10.1016/j.gie.2024.10.008