Study Design and Participants

This was a retrospective cohort study performed at a single center in southern China. Consecutive HBV-ACLF patients treated at the Third Affiliated Hospital of Sun Yat-sen University from January 2010 to June 2016 were included for model development (derivation cohort; n = 1,353). An second, independent cohort of HBV-ACLF patients with the same inclusion and exclusion criteria treated at the same institution from July 2016 to March 2018 were included to validate the model (validation cohort; n = 669).

Inclusion criteria for the study were based on the consensus recommendations of the Asian Pacific Association for the Study of the Liver (APASL) 2014 (10), and Diagnostic and Treatment Guidelines for Liver Failure in China (15). The study inclusion criteria were: (1) ACLF, characterized by acute hepatic deterioration manifesting as jaundice (TBil ≥ 10× the upper limit of normal, in micromoles per liter) and coagulopathy (INR ≥ 1.5, or prothrombin activity < 40%), complicated within 4 weeks by ascites and/or encephalopathy in patients with previously diagnosed or undiagnosed chronic liver disease; (2) Positive serum HBV surface antigen (HBsAg) for more than 6 months; (3) Age > 18 years. Exclusion criteria were: (1) Systemic or local malignancy; (2) HIV infection or other immunodeficiency disease; (3) hepatitis C virus (HCV) infection; (4) Marked organ dysfunction (e.g., renal dysfunction) not related to liver disease (detailed definitions are presented in the Supplementary Material); (5) Pregnancy or lactation; (6) Incomplete data or lost to follow-up; (7) Hospital stay < 1 day.

All patients received comprehensive medical treatment as required, including nutritional supplementation, administration of human serum albumin (ALB), and appropriate treatment for complications such as infections (e.g., respiratory tract, urinary tract, biliary tract, digestive tract, and spontaneous peritonitis), HE, gastrointestinal bleeding (GB), and hepatorenal syndrome (HRS).

This study conformed strictly to the Ethical Guidelines of the 1975 Declaration of Helsinki. The study protocol was approved by the Ethics Committee on Clinical Trials of the Third Affiliated Hospital of Sun Yat-sen University. Due to the retrospective nature of the study, informed consent was waived. This study is registered at ClinicalTrials.gov ({"type":"clinical-trial","attrs":{"text":"NCT03992898","term_id":"NCT03992898"}}NCT03992898).