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Nat Rev Dis Primers. 2016 Jun 9;2:16041. doi: 10.1038/nrdp.2016.41.

Acute-on-chronic liver failure in cirrhosis.

Arroyo V1,2,3, Moreau R1,3,4,5,6,7, Kamath PS8, Jalan R1,3,9,10, Ginès P1,3,11, Nevens F1,3,12, Fernández J1,3,11, To U13,14, García-Tsao G13,14, Schnabl B15,16.

Author information

European Foundation for the Study of Chronic Liver Failure (EF-CLIF), Travessera de Gracia 11, 08021 Barcelona, Spain.
Grifols Chair for the Study of Cirrhosis, Barcelona, Spain.
European Association for the Study of the Liver-Chronic Liver Failure (EASL-CLIF) Consortium, Barcelona, Spain.
Inserm, U 1149, Centre de Recherche sur l'Inflammation (CRI), Paris, France.
Université Paris Diderot, Faculté de Médecine, Paris, France.
Département Hospitalo-Universitaire (DHU) UNITY, Service d'Hépatologie, Hôpital Beaujon, AP-HP, Clichy, France.
Laboratoire d'Excellence (Labex) Inflamex, ComUE Sorbonne Paris Cité, Paris, France.
Division of Gastroenterology, Hepatology and Internal Medicine, Mayo Clinic College of Medicine, Rochester, Minnesota, USA.
Institute of Hepatology, UCL Medical School, London, UK.
Royal Free Hospital, UCL Medical School, London, UK.
Liver Unit, Hospital Clinic, University of Barcelona, Barcelona, Spain.
Department of Hepatology, University Hospitals KU Leuven, Leuven, Belgium.
Yale Digestive Diseases, Temple Medical Center, New Haven, Connecticut, USA.
Veterans Administration, Yale-New Haven Hospital, New Haven, Connecticut, USA.
Department of Medicine, University of California San Diego, La Jolla, San Diego, California, USA.
Department of Medicine, VA San Diego Health Care System, San Diego, California, USA.


The definition of acute-on-chronic liver failure (ACLF) remains contested. In Europe and North America, the term is generally applied according to the European Association for the Study of the Liver-Chronic Liver Failure (EASL-CLIF) Consortium guidelines, which defines this condition as a syndrome that develops in patients with cirrhosis and is characterized by acute decompensation, organ failure and high short-term mortality. One-third of patients who are hospitalized for acute decompensation present with ACLF at admission or develop the syndrome during hospitalization. ACLF frequently occurs in a closed temporal relationship to a precipitating event, such as bacterial infection or acute alcoholic, drug-induced or viral hepatitis. However, no precipitating event can be identified in approximately 40% of patients. The mechanisms of ACLF involve systemic inflammation due to infections, acute liver damage and, in cases without precipitating events, probably intestinal translocation of bacteria or bacterial products. ACLF is graded into three stages (ACLF grades 1-3) on the basis of the number of organ failures, with higher grades associated with increased mortality. Liver and renal failures are the most common organ failures, followed by coagulation, brain, circulatory and respiratory failure. The 28-day mortality rate associated with ACLF is 30%. Depending on the grade, ACLF can be reversed using standard therapy in only 16-51% of patients, leaving a considerable proportion of patients with ACLF that remains steady or progresses. Liver transplantation in selected patients with ACLF grade 2 and ACLF grade 3 increases the 6-month survival from 10% to 80%.

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