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Abstract
Abstract Background The appendix is implicated in inflammatory bowel disease (IBD) risk. However, the relationship of appendectomy for appendicitis versus other indications, when the appendix is not inflamed, with IBD onset is ambiguous. We conducted a population-based cohort study to explore the risk of ulcerative colitis (UC) and Crohn’s disease (CD) following appendectomy of the inflamed appendix and removal of the uninflamed appendix for other indications. Methods We conducted a matched cohort study where all individuals with appendectomy in the Danish National Patient Register between January 1997 and August 2022 were matched 1:10 by sex, year of birth and municipality of residence at the time of appendectomy to individuals without appendectomy. Study participants were excluded if they were not residents of Denmark for at least two years prior to the index date. Based on cross-linked data from the Danish Pathology Register, we categorized appendectomy cases into those with and without appendiceal inflammation. Follow up started 180 days after appendectomy until IBD diagnosis, based on primary and secondary diagnoses codes in the National Patient Register, emigration, death or end of the study period, whichever came first. We used Cox proportional hazards regression to calculate the hazard ratios and 95% confidence interval for outcomes UC and CD, in appendectomy cases with and without appendiceal inflammation, compared to individuals without appendectomy after adjusting for age at appendectomy (index date), sex, calendar year, urbanization, and municipal-level socioeconomic index. Results A total of 145,147 individuals who underwent appendectomy and 1,451,470 individuals without appendectomy were followed for a median of 12 (IQR 6,19) years. Of all individuals with appendiceal inflammation, no appendiceal inflammation, and individuals without appendectomy, 308, 149 and 6,052 were diagnosed with UC, and 336, 191 and 3,166 with CD, respectively, during follow up. Kaplan Meier curves are demonstrated in the Figure. The adjusted hazard ratio (95% CI) for UC among those with and without appendiceal inflammation, compared to individuals without appendectomy, was 0.65 (0.58 - 0.73) and 1.26 (1.06 - 1.50), respectively. Corresponding estimates for CD were 1.33 (1.19 - 1.50) and 3.13 (2.65 - 3.69), respectively. Conclusion In a nationwide cohort with long-term follow up data, appendectomy following appendiceal inflammation was protective against UC while appendectomy following no inflammation was associated with increase in UC risk. Appendectomy, irrespective of appendiceal inflammation, was associated with CD risk.
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