title: Acute-on-chronic liver failure is a distinct syndrome that develops in patients with acute decompensation of cirrhosis.
abstract: OBJECTIVE
  Patients with cirrhosis hospitalized for an acute decompensation (AD) and organ failure are at risk for imminent death and considered to have acute-on-chronic liver failure (ACLF). However, there are no established diagnostic criteria for ACLF, so little is known about its development and progression. We aimed to identify diagnostic criteria of ACLF and describe the development of this syndrome in European patients with AD.
  
  
  METHODS
  We collected data from 1343 hospitalized patients with cirrhosis and AD from February to September 2011 at 29 liver units in 8 European countries. We used the organ failure and mortality data to define ACLF grades, assess mortality, and identify differences between ACLF and AD. We established diagnostic criteria for ACLF based on analyses of patients with organ failure (defined by the chronic liver failure-sequential organ failure assessment [CLIF-SOFA] score) and high 28-day mortality rate (>15%).
  
  
  RESULTS
  Of the patients assessed, 303 had ACLF when the study began, 112 developed ACLF, and 928 did not have ACLF. The 28-day mortality rate among patients who had ACLF when the study began was 33.9%, among those who developed ACLF was 29.7%, and among those who did not have ACLF was 1.9%. Patients with ACLF were younger and more frequently alcoholic, had more associated bacterial infections, and had higher numbers of leukocytes and higher plasma levels of C-reactive protein than patients without ACLF (P < .001). Higher CLIF-SOFA scores and leukocyte counts were independent predictors of mortality in patients with ACLF. In patients without a prior history of AD, ACLF was unexpectedly characterized by higher numbers of organ failures, leukocyte count, and mortality compared with ACLF in patients with a prior history of AD.
  
  
  CONCLUSIONS
  We analyzed data from patients with cirrhosis and AD to establish diagnostic criteria for ACLF and showed that it is distinct from AD, based not only on the presence of organ failure(s) and high mortality rate but also on age, precipitating events, and systemic inflammation. ACLF mortality is associated with loss of organ function and high leukocyte counts. ACLF is especially severe in patients with no prior history of AD.
authors.affiliation: Service d'Hépatologie, Hôpital Beaujon, Assistance Publique-Hôpitaux de Paris, Clichy, France.
authors.forename: Richard
authors.initials: R
authors.lastname: Moreau
authors.forename: Rajiv
authors.initials: R
authors.lastname: Jalan
authors.forename: Pere
authors.initials: P
authors.lastname: Gines
authors.forename: Marco
authors.initials: M
authors.lastname: Pavesi
authors.forename: Paolo
authors.initials: P
authors.lastname: Angeli
authors.forename: Juan
authors.initials: J
authors.lastname: Cordoba
authors.forename: Francois
authors.initials: F
authors.lastname: Durand
authors.forename: Thierry
authors.initials: T
authors.lastname: Gustot
authors.forename: Faouzi
authors.initials: F
authors.lastname: Saliba
authors.forename: Marco
authors.initials: M
authors.lastname: Domenicali
authors.forename: Alexander
authors.initials: A
authors.lastname: Gerbes
authors.forename: Julia
authors.initials: J
authors.lastname: Wendon
authors.forename: Carlo
authors.initials: C
authors.lastname: Alessandria
authors.forename: Wim
authors.initials: W
authors.lastname: Laleman
authors.forename: Stefan
authors.initials: S
authors.lastname: Zeuzem
authors.forename: Jonel
authors.initials: J
authors.lastname: Trebicka
authors.forename: Mauro
authors.initials: M
authors.lastname: Bernardi
authors.forename: Vicente
authors.initials: V
authors.lastname: Arroyo
mesh_terms: D000328:Adult; D000368:Aged; D015331:Cohort Studies; D018450:Disease Progression; D058625:End Stage Liver Disease / Q000150:complications / Q000175:diagnosis* / Q000401:mortality; D005260:Female; D006801:Humans; D008103:Liver Cirrhosis / Q000150:complications* / Q000401:mortality; D017114:Liver Failure, Acute / Q000150:complications / Q000175:diagnosis* / Q000401:mortality; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D011446:Prospective Studies; D012720:Severity of Illness Index; D013577:Syndrome