|APASL definition45||EASL-CLIF definition9||NACSELD definition7||WGO proposal8|
|Category of study that led to the definition||Report of a consensus involving international experts from the APASL||Prospective, observational study in 1343 patients with cirrhosis admitted to 29 Liver Units in 12 European countries (CANONIC study), in the context of the EASL-CLIF Consortium||Prospective, observational study in 507 patients with cirrhosis hospitalised in 18 Liver Units across the USA and Canada, in the context of the NACSELD Consortium||Report of a consensus involving international experts from the WGO|
|Population considered in the definition||
||Patients with chronic liver disease with or without previously diagnosed cirrhosis|
|Population excluded of the definition||
|A priori criteria of severity||Experts consider the failing liver as the driver of severity||
||Prespecified criteria for organ failures (see table 2)||Not developed but stated CLIF-SOFA ‘is an important step in this direction’|
|Basis of the definition||Liver failure is defined as jaundice (a serum bilirubin level of ≥5 mg/dL) and coagulopathy (an INR of ≥1.5 or prothrombin activity of <40%). Liver failure is complicated within 4 weeks by clinical ascites and/or encephalopathy in patients with previously diagnosed or undiagnosed chronic liver disease (including cirrhosis)||
||ACLF is a syndrome characterised by acute hepatic decompensation resulting in liver failure (jaundice and prolongation of the INR) and one or more extrahepatic organ failures that is associated with increased mortality within a period of 28 days and up to 3 months from onset|
|Comments||The APASL definition has been used to enrol patients in randomised clinical trials evaluating different interventions11||
||The probability of survival at 30 days was:
||WGO divides ACLF into three categories:
*Acute decompensation was defined by the recent development of ascites, encephalopathy, GI haemorrhage, bacterial infection or any combination of these.
†In the NACSELD study, definitions of infections were as follows: (1) spontaneous bacteraemia: positive blood cultures without a source of infection; (2) spontaneous bacterial peritonitis: ascitic fluid polymorphonuclear cells >250/µL; (3) lower respiratory tract infections: new pulmonary infiltrate in the presence of: (i) at least one respiratory symptom (cough, sputum production, dyspnoea, pleuritic pain) with (ii) at least one finding on auscultation (rales or crepitation) or one sign of infection (core body temperature >38 C or <36 C, shivering or leucocyte count >10 000/mm3 or <4000/mm3) in the absence of antibiotics; (4) Clostridium difficile infection: diarrhoea with a positive C. difficile assay; (5) bacterial enterocolitis: diarrhoea or dysentery with a positive stool culture for Salmonella, Shigella, Yersinia, Campylobacter or pathogenic Escherichia coli; (6) soft-tissue/skin infection: fever with cellulitis; (7) urinary tract infection: urine white blood cell >15/high-power field with either positive urine Gram stain or culture; (8) intra-abdominal infections: diverticulitis, appendicitis, cholangitis, etc; (9) other infections not covered above and (10) fungal infections as a separate category. Definition of each organ failure used in the NACSELD study is given in table 2.
APASL, Asian Pacific Association for the Study of the Liver; CANONIC, EASL-CLIF Acute-on-Chronic Liver Failure in Cirrhosis; EASL-CLIF, European Association for the Study of Liver-Chronic Liver failure; INR, international normalised ratio; NACSELD, North American Consortium for Study of End-stage Liver Disease; SOFA, Sequential Organ Failure Assessment; WGO, World Gastroenterology Organisation.