ACLF Definition
ACLF (Acute-on-Chronic Liver Failure) is a severe syndrome occurring in patients with chronic liver disease or cirrhosis, characterized by acute deterioration with organ system failures and high short-term mortality (≥20% at 28 days). 1
Core Diagnostic Components
The most recent AASLD guidance (2024) establishes that all three of the following elements must be present for ACLF diagnosis: 1
- Acute onset with rapid clinical deterioration in patients with chronic liver disease (with or without cirrhosis)
- Liver failure defined by elevated bilirubin AND elevated INR 1
- At least one extrahepatic organ failure (neurologic, circulatory, respiratory, or renal) 1
Organ System Failures
ACLF is characterized by functional failure of one or more of six major organ systems: 1
- Liver
- Kidney
- Brain (cerebral)
- Coagulation
- Circulation
- Respiration
These failures are assessed using the CLIF-SOFA (Chronic Liver Failure-Sequential Organ Failure Assessment) score. 2, 3
Severity Grading
ACLF is graded based on the number of organ failures: 1, 2, 3
- ACLF Grade 1: Single organ failure (renal failure OR single non-renal organ failure with renal dysfunction and/or cerebral dysfunction)
- ACLF Grade 2: Two organ failures
- ACLF Grade 3: Three or more organ failures
The 28-day mortality increases dramatically with grade: 23% for ACLF-1 to 74% for ACLF-3. 3
Key Distinguishing Features from Simple Decompensation
ACLF differs fundamentally from acutely decompensated cirrhosis without ACLF in mortality risk: 1
- ACLF: ≥20% mortality at 28 days
- Acutely decompensated cirrhosis without ACLF: ≤5% mortality at 28 days
ACLF is associated with intense systemic inflammation driven by pathogen-associated and damage-associated molecular patterns, leading to organ failures through tissue hypoperfusion, immune-mediated damage, and mitochondrial dysfunction. 4
Important Definitional Controversies
Multiple competing definitions exist globally, creating clinical confusion: 1, 2
EASL-CLIF (European): Most widely accepted definition, includes patients with any prior decompensation, considers both intrahepatic and extrahepatic precipitants (infections, bleeding, surgery), evaluates all six organ systems 1
APASL (Asia-Pacific): Restricted to acute intrahepatic precipitants only, excludes bacterial infection/bleeding/surgery as triggers, applies to both cirrhosis and non-cirrhotic chronic liver disease 1
NACSELD (North American): Captures only the most severe patients requiring organ support, does not consider liver dysfunction severity or coagulopathy 1
These definitions likely characterize different stages of the same condition, with APASL identifying early disease, EASL-CLIF capturing intermediate stages, and NACSELD identifying late/preterminal stages. 1, 2
Clinical Context and Precipitants
ACLF may be induced by acute precipitants including: 1
- Intrahepatic insults (alcohol-associated hepatitis, viral hepatitis reactivation, drug-induced liver injury)
- Extrahepatic insults (bacterial infections, gastrointestinal bleeding, surgery)
- Frequently no precipitant is identified 5
The syndrome develops through a "Golden Window" period of approximately 7 days, after which most patients develop sepsis and extrahepatic organ failure. 6
Critical Clinical Pitfall
Do not confuse ACLF with "Acute Cardiac Life Support" - this is a fundamental misunderstanding. ACLF exclusively refers to Acute-on-Chronic Liver Failure in hepatology. 1