<b><i>Background:</i></b> Acute cholangitis (AC) is a common emergency with a significant mortality risk. The Tokyo Guidelines (TG) provide recommendations for diagnosis, severity stratification, and management of AC. However, validation of the TG remains poor. This study aims to validate TG07, TG13, and TG18 criteria and identify predictors of in-hospital mortality in patients with AC. <b><i>Methods:</i></b> This is a retrospective audit of patients with a discharge diagnosis of AC in the year 2016. Demographic, clinical, investigation, management and mortality data were documented. We performed a multinomial logistic regression analysis with stepwise variable selection to identify severity predictors for in-hospital mortality. <b><i>Results:</i></b> Two hundred sixty-two patients with a median age of 75.9 years (IQR 64.8–82.8) years were included for analysis. TG13/TG18 diagnostic criteria were more sensitive than TG07 diagnostic criteria (85.1 vs. 75.2%; <i>p</i> < 0.006). The majority of the patients (<i>n</i> = 178; 67.9%) presented with abdominal pain, pyrexia (<i>n</i> = 156; 59.5%), and vomiting (<i>n</i> = 123; 46.9%). Blood cultures were positive in 95 (36.3%) patients, and 79 (83.2%) patients had monomicrobial growth. The 30-day, 90-day, and in-hospital mortality numbers were 3 (1.1%), 11 (4.2%), and 15 (5.7%), respectively. In multivariate analysis, type 2 diabetes mellitus (OR = 12.531; 95% CI 0.354–116.015; <i>p</i> = 0.026), systolic blood pressure <100 mm Hg (OR = 10.108; 95% CI 1.094–93.395; <i>p</i> = 0.041), Glasgow coma score <15 (OR = 38.16; 95% CI 1.804–807.191; <i>p</i> = 0.019), and malignancy (OR = 14.135; 95% CI 1.017–196.394; <i>p</i> = 0.049) predicted in-hospital mortality. <b><i>Conclusion:</i></b> TG13/18 diagnostic criteria are more sensitive than TG07 diagnostic criteria. Type 2 diabetes mellitus, systolic blood pressure <100 mm Hg, Glasgow coma score <15, and malignant etiology predict in-hospital mortality in patients with AC. These predictors could be considered in acute stratification and treatment of patients with AC.
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