Multivariate metabotyping of plasma predicts survival in patients with decompensated cirrhosis
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 1349 patients included in the CANONIC study were used. First, a simplified organ function scoring system (CLIF Consortium Organ Failure score, CLIF-C OFs) was developed to diagnose ACLF using data from all patients. Subsequently, in 275 patients with ACLF, CLIF-C OFs and two other independent predictors of mortality (age and white blood cell count) were combined to develop a specific prognostic score for ACLF (CLIF Consortium ACLF score [CLIF-C ACLFs]). A concordance index (C-index) was used to compare the discrimination abilities of CLIF-C ACLF, MELD, MELD-sodium (MELD-Na), and Child-Pugh (CPs) scores. The CLIF-C ACLFs was validated in an external cohort and assessed for sequential use. RESULTS The 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 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 h, 3-7 days, and 8-15 days after ACLF diagnosis predicted the 28-day mortality significantly better than at diagnosis. CONCLUSIONS The CLIF-C ACLFs at ACLF diagnosis is superior to the MELDs and MELD-Nas in predicting mortality. The CLIF-C ACLFs is a clinically relevant, validated scoring system that can be used sequentially to stratify the risk of mortality in ACLF patients.