title: Development and validation of a prognostic score to predict mortality in patients with acute-on-chronic liver failure.
abstract: OBJECTIVE
  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.
authors.affiliation: Liver Failure Group, UCL Institute for Liver and Digestive Health, UCL Medical School, Royal Free Hospital, London, United Kingdom.
authors.forename: Rajiv
authors.initials: R
authors.lastname: Jalan
authors.affiliation: Hôpital Paul Brousse, Villejuif, France; Unité INSERM U785, Paris, France.
authors.forename: Faouzi
authors.initials: F
authors.lastname: Saliba
authors.affiliation: Data Management Centre of the EASL CLIF Consortium, Barcelona, Spain.
authors.forename: Marco
authors.initials: M
authors.lastname: Pavesi
authors.affiliation: Data Management Centre of the EASL CLIF Consortium, Barcelona, Spain.
authors.forename: Alex
authors.initials: A
authors.lastname: Amoros
authors.affiliation: INSERM U773 and Service d'Hépatologie, Hôpital Beaujon, Clichy, France.
authors.forename: Richard
authors.initials: R
authors.lastname: Moreau
authors.affiliation: Hospital Clinic, Barcelona, Spain. Electronic address: PGINES@clinic.ub.es.
authors.forename: Pere
authors.initials: P
authors.lastname: Ginès
authors.affiliation: Hôpital Paul Brousse, Villejuif, France; Unité INSERM U785, Paris, France.
authors.forename: Eric
authors.initials: E
authors.lastname: Levesque
authors.affiliation: INSERM U773 and Service d'Hépatologie, Hôpital Beaujon, Clichy, France.
authors.forename: Francois
authors.initials: F
authors.lastname: Durand
authors.affiliation: University of Padova, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Angeli
authors.affiliation: Policlinico St Orsola Malpighi, Bologna, Italy.
authors.forename: Paolo
authors.initials: P
authors.lastname: Caraceni
authors.affiliation: Ludwig Maximilian University Munich, Klinikum der Universität München, Germany.
authors.forename: Corinna
authors.initials: C
authors.lastname: Hopf
authors.affiliation: University of Turin, Italy.
authors.forename: Carlo
authors.initials: C
authors.lastname: Alessandria
authors.affiliation: Hospital Clinic, Barcelona, Spain.
authors.forename: Ezequiel
authors.initials: E
authors.lastname: Rodriguez
authors.affiliation: King's College Hospital, London, UK.
authors.forename: Pablo
authors.initials: P
authors.lastname: Solis-Muñoz
authors.affiliation: University Hospital Gasthuisberg, Leuven, Belgium.
authors.forename: Wim
authors.initials: W
authors.lastname: Laleman
authors.affiliation: University Hospital Bonn, Germany.
authors.forename: Jonel
authors.initials: J
authors.lastname: Trebicka
authors.affiliation: J.W. Goethe University Hospital, Frankfurt, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Zeuzem
authors.affiliation: Erasme Hospital Brussels, Belgium.
authors.forename: Thierry
authors.initials: T
authors.lastname: Gustot
authors.affiliation: Liver Failure Group, UCL Institute for Liver and Digestive Health, UCL Medical School, Royal Free Hospital, London, United Kingdom.
authors.forename: Rajeshwar
authors.initials: R
authors.lastname: Mookerjee
authors.affiliation: INSERM U773 and Service d'Hépatologie, Hôpital Beaujon, Clichy, France.
authors.forename: Laure
authors.initials: L
authors.lastname: Elkrief
authors.affiliation: Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
authors.forename: German
authors.initials: G
authors.lastname: Soriano
authors.affiliation: Hospital Vall d'Hebron, Barcelona, Spain.
authors.forename: Joan
authors.initials: J
authors.lastname: Cordoba
authors.affiliation: Policlinico St Orsola Malpighi, Bologna, Italy.
authors.forename: Filippo
authors.initials: F
authors.lastname: Morando
authors.affiliation: Ludwig Maximilian University Munich, Klinikum der Universität München, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Gerbes
authors.affiliation: Liver Failure Group, UCL Institute for Liver and Digestive Health, UCL Medical School, Royal Free Hospital, London, United Kingdom.
authors.forename: Banwari
authors.initials: B
authors.lastname: Agarwal
authors.affiliation: Hôpital Paul Brousse, Villejuif, France; Unité INSERM U785, Paris, France.
authors.forename: Didier
authors.initials: D
authors.lastname: Samuel
authors.affiliation: Policlinico St Orsola Malpighi, Bologna, Italy; EASL-CLIF Consortium.
authors.forename: Mauro
authors.initials: M
authors.lastname: Bernardi
authors.affiliation: EASL-CLIF Consortium.
authors.forename: Vicente
authors.initials: V
authors.lastname: Arroyo
mesh_terms: D065290:Acute-On-Chronic Liver Failure / Q000175:diagnosis / Q000401:mortality*; D000328:Adult; D000368:Aged; D015331:Cohort Studies; D016208:Databases, Factual; D005060:Europe / Q000453:epidemiology; D005260:Female; D006801:Humans; D008103:Liver Cirrhosis / Q000401:mortality; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012720:Severity of Illness Index; D013997:Time Factors
keywords: Acute-on-chronic liver failure; Cirrhosis; Multi-organ failure; Prognosis; Sepsis