Table 1

Characteristics of the available definitions for acute-on-chronic liver failure (ACLF)

APASL definition45EASL-CLIF definition9NACSELD definition7WGO proposal8
Category of study that led to the definitionReport of a consensus involving international experts from the APASLProspective, 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 ConsortiumProspective, observational study in 507 patients with cirrhosis hospitalised in 18 Liver Units across the USA and Canada, in the context of the NACSELD ConsortiumReport of a consensus involving international experts from the WGO
Population considered in the definition
  • Acute liver deterioration (see below) in patients with previously diagnosed or undiagnosed chronic liver disease (including cirrhosis)

  • Both compensated cirrhosis and non-cirrhotic chronic liver disease (non-alcoholic fatty liver disease, related chronic hepatic injury or chronic hepatitis with fibrosis, or fibrosis due to other reasons) qualify as chronic liver disease

  • Patients with an acute decompensation of cirrhosis*

  • Patients with prior decompensation of cirrhosis are included

  • Patients with infection at admission or during hospital stay†

  • Patients with prior decompensation of cirrhosis are included

Patients with chronic liver disease with or without previously diagnosed cirrhosis
Population excluded of the definition
  • Patients with bacterial infections

  • Patients with cirrhosis and known prior decompensation (jaundice, encephalopathy or ascites) who develop acute deterioration of their clinical status that is either related or unrelated to precipitating events are considered to have acute decompensation but not ACLF

  • Admission for scheduled procedure or treatment

  • Hepatocellular carcinoma outside Milan criteria

  • Severe chronic extrahepatic diseases

  • HIV infection; ongoing immunosuppressive treatments

  • Outpatients with infection

  • HIV infection

  • Prior organ transplant

  • Disseminated malignancies

Not stated
A priori criteria of severityExperts consider the failing liver as the driver of severity
  • Pre-specified criteria for organ failure(s) (according to the CLIF-SOFA scale; see table 2)

  • Association of organ failures at enrolment and a 28-day transplant-free mortality of 15% or more

Prespecified criteria for organ failures (see table 2)Not developed but stated CLIF-SOFA ‘is an important step in this direction’
Basis of the definitionLiver 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)
  • Absence of ACLF because 28-day mortality is <5% in patients with:

    • No organ failure

    • Single organ failure in patients with a serum creatinine level of <1.5 mg/dL and no hepatic encephalopathy

    • Cerebral failure in patients with a serum creatinine level of <1.5 mg/dL

  • ACLF grade 1 because 28-day mortality is 22% in patients with:

    • Single kidney failure

    • Single liver, coagulation, circulatory or lung failure that is associated with a serum creatinine level of 1.5–1.9 mg/dL and/or hepatic encephalopathy grade 1 or grade 2

    • Single brain failure with a serum creatinine level of 1.5–1.9 mg/dL

  • ACLF grade 2 because 28-day mortality is 32% in patients with:

    • Two organs failures

  • ACLF grade 3 because 28-day mortality is 77% in patients with:

    • Three organ failures or more

  • Absence of ACLF:

  • No organ failure

  • Presence of any single organ failure

  • Presence of ACLF (called here infection-related ACLF)

  • Two organ failures or more

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
CommentsThe APASL definition has been used to enrol patients in randomised clinical trials evaluating different interventions11
  • The CLIF-SOFA score has been subsequently simplified10

  • A score predicting mortality of patients with ACLF, taking into account the new score, age and white cell count has been established10

The probability of survival at 30 days was:
  • 96% in the absence of organ failure

  • Not significantly decreased in patients with single kidney failure

  • Significantly decreased in patients with any other single ‘non-kidney’ organ failure

  • Significantly decreased with two organ failures or more

WGO divides ACLF into three categories:
  • Type A: chronic liver disease

  • Type B: compensated cirrhosis

  • Type C: decompensated cirrhosis

  • *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.