Performance of the China-CLIF framework in acute-on-chronic liver failure: a multicohort study across all aetiologies

Background Acute-on-chronic liver failure (ACLF) of various aetiologies is a complex syndrome with high short-term mortality and significant global burden. Objective To explore easily applicable diagnostic criteria and an accurate prognostic score for ACLF. Design Clinical data from 5288 patients (after exclusions from 7388 screened) with acute deterioration of chronic liver disease across various aetiologies were used to evaluate the performance of European Chronic Liver Failure (CLIF) and Chinese Group on the Study of Severe Hepatitis B (COSSH) criteria. Three non-Asian cohorts were performed to validate the results. Results CLIF criteria categorised 844 patients as ACLF (28-day/90-day liver transplantation (LT)-free mortality: 40.7%/57.0%; 321 with non-hepatitis B virus (HBV) aetiology, 523 with HBV aetiology), while COSSH criteria categorised 2038 patients as ACLF (mortality: 27.3%/41.0%; 602 with non-HBV aetiology, 1436 with HBV aetiology). COSSH criteria identified 22.6% (1194/5288) more patients (mortality: 19.1%/31.4%) compared with CLIF criteria, including 14.2% non-HBV patients (mortality: 15.9%/33.3%). COSSH criteria produced a more reasonable epidemiological pyramid-like distribution across severity grades (grades 1–3: 63.4%/27.5%/9.1% vs CLIF’s grades 1–3: 25.8%/56.3%/17.9%). COSSH-ACLF II score showed the highest predictive values for 28-day/90-day LT-free mortality in both cirrhotic and all ACLF patients with various aetiologies, outperforming the CLIF-C ACLF and other scores. The comparable performance of China-CLIFs (renamed from COSSH-ACLFs) was validated in three non-Asian cohorts. Conclusions This study evaluated the broader applicability of the China-CLIF framework across diverse aetiologies and varying severity levels of ACLF. These findings may provide a valuable foundation for harmonising ACLF diagnostic and prognostic system.