Objective:To evaluate the prognostic efficacy of the Chinese Group on the Study of Severe Hepatitis B (COSSH) acute-on-chronic liver failure (ACLF) II score (COSSH ACLF IIs) and associated risk stratification in predicting short-term prognosis of patients with hepatitis B virus-related ACLF (HBV-ACLF).Methods:Clinical data of 224 patients with HBV-ACLF admitted to the First Affiliated Hospital of Wannan Medical College and the First Hospital of Quanzhou, Fujian Medical University from January 2018 to December 2021 were retrospectively analyzed. The patients were divided into survival group ( n=171) and fatal group ( n=53) according to 28-day survival status. The values of the COSSH ACLF IIs, the Chronic Liver Failure-Consortium (CLIF-C) ACLF score (CLIF-C ACLFs), the CLIF-C organ failure score (CLIF-C OFs), the Model of End-stage Liver Disease (MELD) score (MELDs), the MELD-sodium score (MELD-Nas), and the Child-Turcotte-Pugh score (CTPs) for 28-day mortality prediction were compared using the area under the receiver operating characteristic curve (AUC). The patients were divided into groups according to COSSH ACLF classification and COSSH ACLF IIs risk stratification, respectively. The differences in 28-day mortality between groups were compared by Kaplan-Meir method, and the consistency of the two ACLF classification systems was compared by Kappa consistency test. Results:The AUC, sensitivity, and specificity of the COSSH ACLF IIs in 28-day mortality prediction were 0.885, 0.981 and 0.731, respectively. For predicting 28-day mortality, the COSSH ACLF IIs achieved a higher AUC than the CLIF-C OFs, the MELDs, the MELD-Nas, and the CTPs ( P<0.01), while there was no significant difference in AUC between the COSSH ACLF IIs and the CLIF-C ACLFs ( Z=1.696, P=0.090). The cumulative 28-day mortality rates significantly increased with the ascending of COSSH ACLF grade and risk strata of the COSSH ACLF IIs (11.7%, 43.5% and 93.3%, P<0.001; 14.2%, 41.0% and 81.3%, P<0.001). The two ACLF grading systems showed a consistency in severity stratification of HBV-ACLF patients (Kappa=0.478, P<0.001). Conclusion:The COSSH ACLF IIs shows an excellent prognostic performance in predicting short-term mortality of HBV-ACLF patients. Using the new risk stratification scale can simplify the severity stratification of HBV-ACLF patients.