Development and validation of a prognostic score to predict mortality in patients with acute on chronic liver failure.

Background & Aims. Acute-on Chronic Liver Failure (ACLF) is a frequent syndrome (30% prevalence) characterized by acute decompensation of cirrhosis, organ failure(s) and high short-term mortality. This study develops and validates a specific prognostic score for ACLF patients. Methods. Data from 1,349 patients included in the CANONIC study were used. First, a simplified organ function scoring system (CLIF-Consortium Organ Failure score, CLIF-C OFs) to diagnose ACLF was developed using data from all patients. Subsequently, in 275 patients with ACLF, CLIF-C OFs and two other independent predictors of mortality (age and white-cell count) were combined to develop a specific prognostic score for ACLF (CLIF CONSORTIUM score for ACLF, CLIF-C ACLFs). Concordance index (C-index) was used to compare the discrimination abilities of CLIF-C ACLFs, MELD (MELDs), MELD-Sodium (MELD-Nas) and Child-Pugh (CPs) scores. CLIF-C ACLFs was validated in an external cohort and assessed for sequential use. Results. CLIF-C ACLFs showed a significantly higher predictive accuracy than MELDs, MELD-Nas and CPs, reducing (19-28%) the corresponding prediction error rates at all the main time-points after ACLF diagnosis (28, 90, 180 and 365 days) in both the CANONIC and the external validation cohort. CLIF-C ACLFs computed at 48 hours, 3-7 days and 8-15 days after ACLF diagnosis predicted 28-day mortality significantly better than at diagnosis. Conclusions. CLIF-C ACLFs at ACLF diagnosis is superior to MELDs and MELD-Nas in predicting mortality. CLIF-C ACLFs is a clinically relevant, validated scoring system that can be used sequentially to stratify the risk of mortality in ACLF patients.