Defining acute-on-chronic liver failure: East, West or Middle ground?

Table 1 Diagnostic criteria of acute-on-chronic liver failure as per the chronic liver failure acute-on-chronic liver failure in cirrhosis study

No ACLF - This group consists of 3 subgroups

Patients with no organ failure

Patients with a single "non-kidney" organ failure (i.e., single failure of the liver, coagulation, circulation, or respiration) who had a serum creatinine level < 1.5 mg/dL and no hepatic encephalopathy

Patients with single cerebral failure who had a serum creatinine level < 1.5 mg/dL

ACLF grade 1 - This group consists of 3 subgroups

Patients with single kidney failure

Patients with single failure of the liver, coagulation, circulation, or respiration who had a serum creatinine level ranging from 1.5 to 1.9 mg/dL and/or mild to moderate hepatic encephalopathy

Patients with single cerebral failure who had a serum creatinine level ranging from 1.5 and 1.9 mg/dL

ACLF grade 2 - This group consists of patients with 2 organ failures

ACLF grade 3 - This group consists of patients with 3 organ failures or more

Definitions of organ failures - CANONIC study

Liver failure - serum bilirubin level of 12.0 mg/dL or more

Kidney failure - serum creatinine level of 2.0 mg/dL or more, or the use of renal replacement therapy

Cerebral failure - grade III or IV hepatic encephalopathy

Coagulation failure - an international normalized ratio of more than 2.5 and/or a platelet count of 20 × 109/L or less

Circulatory failure - use of dopamine, dobutamine, or terlipressin

Respiratory failure - ratio of partial pressure of arterial oxygen to the fraction of inspired oxygen (FiO2) of 200 or less or a pulse oximetric saturation to FiO2 ratio of 200 or less

Adapted from Moreau et al[3]. ACLF: Acute-on-chronic liver failure; CANONIC: Chronic liver failure acute-on-chronic liver failure in cirrhosis.

Table 2 Principle differences in the definition and diagnostic criteria of acute-on-chronic liver failure between Asia-Pacific and West

	APASL definition	EASL-CLIF definition
Total bilirubin	5 mg/dL or more	12 mg/dL or more
INR	1.5 or more	2.5 or more
Hepatic encephalopathy	Any grade	Only grade III and IV
Ascites	May be present	Not included
Duration between insult and ACLF	4 wk	Not defined
Acute event - sepsis	No	Yes
Acute event - variceal bleeding	No unless producing jaundice and coagulopathy defining ACLF	Yes
Extra-hepatic organ involvement	No	Yes
What is chronic disease	Chronic liver disease with/without only compensated cirrhosis	Only cirrhosis, including those with prior decompensation

APASL: Asia-Pacific Association for the Study of Liver; EASL-CLIF: European Association for the Study of Liver-chronic Liver Failure; INR: International normalized ratio; ACLF: Acute-on-chronic liver failure.

Table 3 Acute insult/precipitating event in patients with acute-on-chronic liver failure

As per APASL criteria	As per EASL-CLIF criteria
Hepatotropic viral infections	Bacterial infection
Reactivation of HBV	Gastrointestinal hemorrhage
HEV super-infection	Active alcoholism within the past 3 mo
Active alcohol consumption (within last 28 d)	Other precipitating events
Drug induced liver injury	Transjugular intrahepatic portosystemic shunting
Complimentary and alternative medicines	Major surgery
Severe autoimmune hepatitis	Therapeutic paracentesis without use of intravenous albumin
Flare of Wilson's disease	Hepatitis
Non-hepatotropic insults (if producing direct hepatic insult)	Alcoholic hepatitis (liver biopsy required for diagnosis)
Surgery	No precipitating event identified
Trauma
Viral infections
No acute insult identifiable

Adapted from Sarin et al[8] and Moreau et al[3]. ACLF: Acute-on-chronic liver failure; APASL: Asia-Pacific Association for the Study of Liver; EASL-CLIF: European Association for the Study of Liver-chronic Liver Failure; HEV: Hepatitis E virus; HBV: Hepatitis B virus.

Table 4 Subtypes of acute-on-chronic liver failure as per World Gastroenterology Organization working party

Type A ACLF - non-cirrhotic chronic liver disease with an acute flare; often indistinguishable from acute or sub-acute liver failure

Reactivation of hepatitis B

Hepatitis A or E superimposed on chronic hepatitis B

Autoimmune hepatitis

Hepatitis E infection in patients at risk for NASH

Type B ACLF - well compensated cirrhosis with an acute insult

Type C ACLF - cirrhosis with previous hepatic decompensation

Adapted from Jalan et al[10]. ACLF: Acute-on-chronic liver failure; NASH: Non-alcoholic steatohepatitis.