title: Clinical Course of acute-on-chronic liver failure syndrome and effects on prognosis.
abstract: Acute-on-chronic liver failure (ACLF) is characterized by acute decompensation (AD) of cirrhosis, organ failure(s), and high 28-day mortality. We investigated whether assessments of patients at specific time points predicted their need for liver transplantation (LT) or the potential futility of their care. We assessed clinical courses of 388 patients who had ACLF at enrollment, from February through September 2011, or during early (28-day) follow-up of the prospective multicenter European Chronic Liver Failure (CLIF) ACLF in Cirrhosis study. We assessed ACLF grades at different time points to define disease resolution, improvement, worsening, or steady or fluctuating course. ACLF resolved or improved in 49.2%, had a steady or fluctuating course in 30.4%, and worsened in 20.4%. The 28-day transplant-free mortality was low-to-moderate (6%-18%) in patients with nonsevere early course (final no ACLF or ACLF-1) and high-to-very high (42%-92%) in those with severe early course (final ACLF-2 or -3) independently of initial grades. Independent predictors of course severity were CLIF Consortium ACLF score (CLIF-C ACLFs) and presence of liver failure (total bilirubin ≥12 mg/dL) at ACLF diagnosis. Eighty-one percent had their final ACLF grade at 1 week, resulting in accurate prediction of short- (28-day) and mid-term (90-day) mortality by ACLF grade at 3-7 days. Among patients that underwent early LT, 75% survived for at least 1 year. Among patients with ≥4 organ failures, or CLIF-C ACLFs >64 at days 3-7 days, and did not undergo LT, mortality was 100% by 28 days.
  
  
  CONCLUSIONS
  Assessment of ACLF patients at 3-7 days of the syndrome provides a tool to define the emergency of LT and a rational basis for intensive care discontinuation owing to futility.
authors: Erasme Hospital, Université Libre de Bruxelles, Brussels, Belgium.
authors: Thierry
authors: T
authors: Gustot
authors: Hospital Clínic, Barcelona, Spain.
authors: Javier
authors: J
authors: Fernandez
authors: Data Management Center of the EASL-CLIF Consortium, CIBEReHD, Barcelona, Spain.
authors: Elisabet
authors: E
authors: Garcia
authors: University of Padova, Padova, Italy.
authors: Filippo
authors: F
authors: Morando
authors: Policlinico St Orsola Malpighi, Bologna, Italy.
authors: Paolo
authors: P
authors: Caraceni
authors: University of Turin, Turin, Italy.
authors: Carlo
authors: C
authors: Alessandria
authors: University Hospital Gasthuisberg, Leuven, Belgium.
authors: Wim
authors: W
authors: Laleman
authors: University Hospital Bonn, Bonn, Germany.
authors: Jonel
authors: J
authors: Trebicka
authors: Hôpital Beaujon, Clichy, France.
authors: Laure
authors: L
authors: Elkrief
authors: University of Munich, Klinikum der LMU, Munich, Germany.
authors: Corinna
authors: C
authors: Hopf
authors: Kinǵs College Hospital, London, London, UK.
authors: Pablo
authors: P
authors: Solís-Munoz
authors: Hopital Paul Brousse, Villejuif, France.
authors: Faouzi
authors: F
authors: Saliba
authors: J.W. Goethe University Hospital, Frankfurt, Germany.
authors: Stefan
authors: S
authors: Zeuzem
authors: Hospital Ramón y Cajal, Madrid, Spain.
authors: Augustin
authors: A
authors: Albillos
authors: University Hospital Hambourg-Eppendorf, Germany.
authors: Daniel
authors: D
authors: Benten
authors: Reina Sofía University Hospital, Córdoba, Spain.
authors: José Luis
authors: JL
authors: Montero-Alvarez
authors: Hospital Gregorio Marañón, Madrid, Spain.
authors: Maria Teresa
authors: MT
authors: Chivas
authors: Hospital de la Santa Creu i Sant Pau, Barcelona, Spain.
authors: Mar
authors: M
authors: Concepción
authors: Hospital Vall d'Hebron, Barcelona, Spain.
authors: Juan
authors: J
authors: Córdoba
authors: St Vincent's University Hospital, Dublin, Ireland.
authors: Aiden
authors: A
authors: McCormick
authors: Medical University of Graz, Graz, Austria.
authors: Rudolf
authors: R
authors: Stauber
authors: Medical University of Innsbruck, Innsbruck, Austria.
authors: Wolfgang
authors: W
authors: Vogel
authors: University of Berne, Berne, Switzerland.
authors: Andrea
authors: http://orcid.org/0000-0002-4401-2340
authors: A
authors: de Gottardi
authors: J.W. Goethe University Hospital, Frankfurt, Germany.
authors: Tania M
authors: TM
authors: Welzel
authors: Policlinico St Orsola Malpighi, Bologna, Italy.
authors: Marco
authors: M
authors: Domenicali
authors: University of Turin, Turin, Italy.
authors: Alessandro
authors: A
authors: Risso
authors: Kinǵs College Hospital, London, London, UK.
authors: Julia
authors: J
authors: Wendon
authors: Data Management Center of the EASL-CLIF Consortium, CIBEReHD, Barcelona, Spain.
authors: Carme
authors: C
authors: Deulofeu
authors: University of Padova, Padova, Italy.
authors: Paolo
authors: P
authors: Angeli
authors: Hôpital Beaujon, Clichy, France.
authors: François
authors: F
authors: Durand
authors: Data Management Center of the EASL-CLIF Consortium, CIBEReHD, Barcelona, Spain.
authors: Marco
authors: M
authors: Pavesi
authors: University of Munich, Klinikum der LMU, Munich, Germany.
authors: Alexander
authors: A
authors: Gerbes
authors: Royal Free Hospital, London, UK.
authors: Rajiv
authors: R
authors: Jalan
authors: Hôpital Beaujon, Clichy, France.
authors: Richard
authors: R
authors: Moreau
authors: Hospital Clínic, Barcelona, Spain.
authors: Pere
authors: P
authors: Ginés
authors: EASL-CLIF Consortium, Barcelona, Spain.
authors: Mauro
authors: M
authors: Bernardi
authors: EASL-CLIF Consortium, Barcelona, Spain.
authors: Vicente
authors: V
authors: Arroyo
mesh_terms: D065290:Acute-On-Chronic Liver Failure / Q000175:diagnosis / Q000401:mortality* / Q000628:therapy; D000328:Adult; D000368:Aged; D005060:Europe / Q000453:epidemiology; D006801:Humans; D016031:Liver Transplantation; D008875:Middle Aged; D011379:Prognosis