Associating Appendicitis with Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD): A Novel Insight into an Unexpected Connection

Background: The gut microbiome modulates the liver immune microenvironment and is deeply integrated into the pathophysiology of metabolic dysfunction-associated steatotic liver disease (MASLD). Appendectomies, which are performed in almost all patients diagnosed with appendicitis, cause long-term alterations to the gut microbiome, providing a potential link with the development of MASLD. We therefore investigated a potential link between appendicitis and the presence of MASLD in a large cohort of outpatients in Germany. Methods: The present study included 26,717 individuals with and 26,717 without appendicitis. Univariable Cox-regression analyses were conducted to assess the association between appendicitis and MASLD. Results: During the long-term follow-up, 4.8% of patients with appendicitis and 3.4% of those in the non-appendicitis group were diagnosed with MASLD (p < 0.001), corresponding to an incidence of 5.4 (appendicitis cohort) versus 3.5 (non-appendicitis cohort) cases per 1000 patient years. These findings were confirmed in regression analysis, revealing a strong and statistically significant association between appendicitis and the development of MASLD (HR: 1.57; 95% CI: 1.39-1.78). This link was observed for all age groups and was independent of patients' sex. Conclusion: We provide evidence from a large cohort of outpatients in Germany suggesting a link between appendicitis and MASLD. This might help to better stratify patients according to their individual risk for the development of chronic liver diseases.