DISCUSSION
The nationwide cohort study indicated that the appendectomy cohort exhibited a higher incidence rate of IBDs than did the comparison cohort regardless of age, sex, and comorbidity. The appendectomy cohort had a 2.78-fold higher adjusted HR of IBDs (2.23-fold higher adjusted HR of UC and 3.48-fold higher adjusted HR of CD) than did the comparison cohort. Our results were comparable with a large case–control study, which showed a 1.6 and 2.5 times higher risk of UC and CD after appendectomy based on inpatient records from Veterans Affairs hospitals in the United States [15].
Andersson et al. [14,16] reported that appendectomy is associated with an increased CD risk but a decreased risk of subsequent UC through an observational study of the Swedish Inpatient Registry. However, a retrospective case–control study from 2 Chinese hospitals did not show a significant negative association between appendectomy and UC occurrence [17].
Although IBD prevalence is higher in Western countries than in Taiwan, the incidence and prevalence of IBD have been rapidly increasing in Taiwan [10,18,19]. The exact IBD pathogenesis remains to be elucidated, although IBD is generally considered to be related to genetic susceptibility and environmental factors [20,21]. Epigenetic modifications influenced by gut microbiota and diet may pay a role in IBD development [22,23]. Western-style diet may predispose people to IBD [24]. Many people in Taiwan have shifted to a Western-style diet, which may be associated with an increased IBD incidence in Taiwan [25].
The vermiform appendix contains substantial lymphoid tissue and may act as a microbial reservoir for beneficial microbes to reinoculate the gut if required [6]. The appendix provides a complex microbial environment for the homeostasis of immunologically and metabolically active organs [26,27]. Therefore, the appendix may serve as an organ to induce and maintain the mucosal immune system. An animal study indicated that appendectomy impairs intestinal immunity, which may be related to IBD development [28]. Gut microbiota alteration in IBD may activate immune responses, interfere in homeostasis, cause tissue injury, decrease the mucus layer, and enhance microbial penetration and bacterial persistence in the gut tissue [29].
Anderson et al. conducted a cohort study by recruiting patients who underwent appendectomy from the inpatient registry database of the Swedish National Board of Health and Welfare and indicated that appendectomy due to appendicitis is associated with a decreased risk of subsequent UC [16]. In contrast, no significant risk difference of UC was noted between appendectomy patients without inflammatory appendix and non-appendecomy controls [16]. However, our study showed that the appendectomy cohort had increased UC risk regardless of whether the patient had appendicitis. Moreover, the UC risk was significantly higher in the appendectomy cohort than the nonappendectomy cohort irrespective of the age at appendectomy. The difference between Western studies and our study may be due to racial variances and dysregulated gut microbiota due to environmental insults [30].
The appendectomy cohort, irrespective of appendicitis, exhibited a considerably increased CD risk compared with the nonappendectomy cohort. The findings were consistent with those of previous studies [14]. In addition, CD risk was significantly higher in the appendectomy cohort than in the nonappendectomy cohort irrespective of the age at appendectomy. The incidence rate of CD after appendectomy was the highest in the first 3 years. The risk of subsequent CD in the appendectomy cohort remained considerably higher than in the nonappendectomy cohort after 6 years following appendectomy.
This longitudinal cohort study estimated the incidence and risk of IBD in a large Asian population that underwent appendectomy. The study cohort could be followed throughout the follow-up period through NHIRD records because the NHI is mandatory and universal in Taiwan. However, several limitations should be noted when interpreting the results. First, coexistence of IBD and appendicitis was noted at appendectomy, which would be diagnosed by the pathologist. Second, the Western dietary habit of the study participants was not investigated in the current study. However, we controlled for the comorbidities of hyperlipidemia, diabetes, and hypertension to mediate the effect of a Western-style diet [31,32]. Third, familial history of IBD in the study participants was not available in the NHIRD, which may have influenced the study results.
In summary, a nationwide cohort study indicated that the incidence and risk of CD and UC are higher in the appendectomy cohort than in the nonappendectomy cohort. The results highlight that clinicians must be aware that Asian patients undergoing appendectomy may develop CD or UC.