Background and aimsAcute variceal bleeding (AVB) is a life-threatening complication of cirrhosis. Acute-on-chronic liver failure (ACLF) is a syndrome characterized by acute decompensation of cirrhosis, multiple organ failures and high short-term mortality. This study aimed to evaluate the role of ACLF in the risk stratification of cirrhotic patients with AVB.MethodsProspective data of 335 cirrhotic patients hospitalized for AVB were retrospectively extracted from Medical Information Mart for Intensive Care (MIMIC)-IV database. ACLF was defined by European Association for the Study of Liver-Chronic Liver Failure Consortium and diagnosed/graded with chronic liver failure-organ failure (CLIF-OF) score. Cox-proportional hazards regression analysis was performed to identify the risk factors for 6-week morality in AVB patients. Discrimination and calibration of prognostic scores were evaluated by plotting the receiver operating characteristics (ROC) curve and calibration curve, respectively. Overall performance was assessed by calculating the Brier score and R2value.ResultsA total of 181 (54.0%) patients were diagnosed with ACLF (grade 1: 18.2%, grade 2: 33.7%, grade 3: 48.1%) at admission. The 6-week mortality in patients with ACLF was significantly higher than that in patients without ACLF (43.6%vs.8.4%,P< 0.001) and increased in line with the severity of ACLF (22.5%, 34.2% and 63.8% for ACLF grade 1, 2 and 3,P< 0.001). In multivariate analysis, presence of ACLF remained as an independent risk factor for 6-week mortality after adjusting for confounding factors (HR = 2.12,P= 0.03). The discrimination, calibration and overall performance of CLIF-C ACLF and CLIF-C AD were superior to the traditional prognostic scores (CTP, MELD and MELD-Na) in the prediction of 6-week mortality of patients with and without ACLF, respectively.ConclusionThe prognosis of cirrhotic patients with AVB is poor when accompanied by ACLF. ACLF at admission is an independent predictor for the 6-week mortality in cirrhotic patients with AVB. CLIF-C ACLF and CLIF-C AD are the best prognostic scores in AVB patients with and without ACLF, respectively, and can be used for the risk stratification of these two distinct entities.