Risks of Acute Cholecystitis, Acute Pancreatitis, and Acute Appendicitis in Patients with Dengue Fever: A Population-Based Cohort Study in Taiwan

Abstract

Introduction: Although cases of acute cholecystitis, acute pancreatitis, and acute appendicitis following dengue virus infections have been documented, very few large-scale studies have investigated the postdengue risk of these acute abdominal conditions. Methods: This retrospective population-based cohort study included all patients with laboratory-confirmed dengue from 2002 to 2015 in Taiwan and 1:4 nondengue individuals matched by age, sex, area of residence, and symptom onset time. Multivariate Cox proportional hazards regression models were used to investigate the short-term (≤ 30 days), medium-term (31–365 days), and long-term (> 1 year) risks of acute cholecystitis, pancreatitis, and appendicitis after dengue infection, adjusted for age, sex, area of residence, urbanization level, monthly income level, and comorbidities. Bonferroni correction was used for multiple testing; E-values were used to assess the robustness of the results to unmeasured confounding. Results: This study included 65,694 individuals with dengue and 262,776 individuals without dengue. Patients with dengue had a significantly increased risk of acute cholecystitis (adjusted hazard ratio (aHR) 60.21; 95% CI 29.11–124.54; P < 0.0001, E-value = 119.92) and acute pancreatitis (aHR 17.13; 95% CI 7.66–38.29; P < 0.0001, E-value = 33.75) within the first 30 days postinfection compared to those without dengue, but this increased risk was not present after that. The incidence rates of acute cholecystitis and pancreatitis in the first 30 days were 18.79 and 5.27 per 10,000, respectively. No increased risk of acute appendicitis was observed among patients with acute dengue infection. Conclusion: This study was the first large epidemiological study to show a significantly increased risk of acute cholecystitis and pancreatitis among patients with dengue during the acute phase of dengue infection, while no such association was observed for acute appendicitis. Early identification of acute cholecystitis and pancreatitis in patients with dengue is crucial for preventing fatal complications.