Abstract Background and Aim Acute‐on‐chronic liver failure (ACLF) leads to multi‐organ failure related to high mortality rates. This study aimed to gather epidemiological data and validate a scoring system to predict mortality in ACLF. Methods This retrospective cohort study collected data from multicenter tertiary care hospitals in Thailand. A total of 638 hospitalized patients (acute decompensated liver disease [ADLD], 292 patients; ACLF, 346 patients) from January 2019 to June 2020 were enrolled in this study. We compared the mortality rate at days 30 and 90 between patients with ADLD and ACLF. Areas under the receiver operating characteristic (AUROC) curves of chronic liver failure–sequential organ failure assessment (CLIF‐SOFA) and other existing scoring systems were compared among patients with ACLF. Results The incidence of patients with ACLF was 54%. The main cause of chronic liver disease was alcohol (38%), with sepsis (50%) as the most common precipitating factor. ACLF with coagulopathy (AUROC 0.58, 95% confidence interval [CI]: 0.52–0.64), metabolic acidosis (AUROC 0.58, 95% CI: 0.52–0.64), and high aspartate aminotransferase (AST) (AUROC 0.59, 95% CI: 0.53–0.66) were associated with high 30‐day mortality. The 30‐day mortality rate of patients with acute decompensation and patients with ACLF was 46 and 58%, respectively. Respiratory system (P = 0.001) failure was the major end result in ACLF and constituted a significant factor to predict mortality. The AUROC of CLIF‐SOFA score was superior to that of the other predicted score (AUROC 0.64, 95% CI: 0.585–0.704). Conclusion Patients with ACLF with more organ failure and high CLIF‐SOFA score were associated with high short‐term mortality. Future studies should include an ACLF prospective registry to confirm these finding.
