Definition and classification of acute-on-chronic liver diseases

Table 1 Evolution of the definition of acute-on-chronic liver diseases

Ref.	Definition of AoCLD	Chronic liver disease status	Clinical features
Kohn et al[7], 1993	A type of disease that may develop into hepatic encephalopathy	Liver cirrhosis	Hepatic encephalopathy
Clemmesen et al[8,9], 1999	A class of diseases of hepatic encephalopathy based on CLD	Liver cirrhosis or non-cirrhosis	Hepatic encephalopathy
Agarwal et al[10], 2009	Acute decompensation occurs on CLD	Liver cirrhosis	Acute decompensation events
Jagadisan et al[11], 2012	Acute liver injury superimposed on the basis of CLD including ACLF and non-ACLF	Liver cirrhosis or non-cirrhosis	Acute liver injury and/or acute decompensation events
Tasneem and Luck[12], 2017	Acute liver injury on the basis of CLD that does not meet the criteria of ACLF	Liver cirrhosis or non-cirrhosis	Acute liver injury
Caracuel et al[13], 2019	A clinical syndrome characterized by decompensated cirrhosis, portal hypertension, and visceral hyperdynamic circulation	Liver cirrhosis	Acute decompensation events
Qiao et al[6], 2021	Acute exacerbations of various CLD (including cirrhosis and non-cirrhosis), including ACLF and non-ACLF	Liver cirrhosis or non-cirrhosis	Acute liver injury and/or acute decompensation events

CLD: Chronic liver disease; AoCLD: Acute-on-chronic-liver disease; ACLF: Acute-on-chronic liver failure.

Table 2 Brief definition and diagnostic criteria for each clinical type related to acute-on-chronic liver diseases

Clinical classification	Brief definition	Diagnostic criteria
CLD	It refers to a cluster of diseases with varying degrees of intrahepatic inflammatory necrosis and/or fibrosis caused by different aetiologies with a history of liver dysfunction for over 6 mo[16]	No
Liver cirrhosis	Liver cirrhosis is a consequence of chronic liver inflammation that is followed by diffuse hepatic fibrosis, where in the normal hepatic architecture is replaced by regenerative hepatic nodules[57]. (1) C-LC, patients with cirrhosis without any cirrhosis-related symptoms or complication; and (2) D-LC, patients with cirrhosis with cirrhosis-related complications such as ascites, variceal bleeding, hepatic encephalopathy, or non-obstructive jaundice	Diagnosis of cirrhosis is based on one of the following criteria[56]: (1) Histologically cirrhosis; (2) gastroesophageal varices or digestive tract ectopic varices on the basis of excluding non-cirrhotic portal hypertension; (3) imaging reveals cirrhosis or portal hypertension; and (4) meeting two or more of the four criteria: PLT < 100 × 109/L without any other reasons; ALB < 35g/L, excluding malnutrition or kidney diseases; INR > 1.3 or PT prolonged; APRI > 2
AoCLD	Acute liver injury, acute decompensation or acute liver failure occurs on the basis of CLD in a short period[16]	(1) Increased ALT/AST and TBil levels on the basis of CLD within 1 wk[16]; and (2) acute decompensation of liver cirrhosis, or liver failure on the basis of CLD within 1 mo[16]
ACLF	Acute liver failure or decompensation occurs on the basis of CLD in a short period: (1) Type-A, ACLF occurs on the basis of chronic hepatitis; (2) Type-B, ACLF occurs on the basis of compensated cirrhosis; and (3) Type-C, ACLF occurs on the basis of decompensated cirrhosis	(1) Acute or subacute deterioration of pre-existing chronic liver disease[34]; (2) extreme fatigue with severe digestive symptoms; and (3) TBil ≥ 10 mg/dL or daily rise ≥ 1 mg/dL, and INR ≥ 1.5 (or) PTA ≤ 40%[34]
Non-ACLF
CHAE	Chronic hepatitis acute aggravation in a short period	Intermittent transaminase elevation that exceeds 5 times the ULN or 2 times the baseline level in a short period (usually 1 wk)[44]
LC-A	Cirrhosis changes from the quiescent to the active stage without acute decompensation	(1) Liver fibrosis and liver inflammation simultaneously coexist; (2) a rapid increase in the liver stiffness value and serum liver fibrosis markers in a short period (usually 1 wk)[52,53]; and (3) increase in ALT and TBil and decrease in the albumin level to varying degrees[54]
LC-AD	Occurrence of acute decompensation in cirrhotic patients with/without previous decompensation in a short period (within 1 mo) under the action of acute incentives	Acute decompensated events, including ascites, hepatic encephalopathy, jaundice and gastrointestinal bleeding that occur in cirrhotic patients within 1 mo[14,58,60]

CLD: Chronic liver disease; C-LC: Compensated liver cirrhosis; D-LC: Decompensated liver cirrhosis; PLT: Platelet; ALB: Albumin; INR: International normalized ratio; APRI: Aspartate aminotransferase-to-platelet ratio; AoCLD: Acute-on-chronic-liver disease; ACLF: Acute-on-chronic liver failure; CHAE: Chronic hepatitis with acute exacerbation; LC-A: Liver cirrhosis active phase; LC-AD: Liver cirrhosis acute decompensation; ALT: Alanine Aminotransferase; AST: Aspartate aminotransferase; TBil: Total Bilirubin.