What is the difference between acute liver failure and acute liver injury in a patient with suspected liver dysfunction?

Acute Liver Failure vs Acute Liver Injury: Key Distinctions

Acute liver failure (ALF) is a distinct clinical syndrome requiring coagulopathy (INR ≥1.5) plus hepatic encephalopathy in patients without preexisting liver disease, whereas acute liver injury refers to hepatocellular damage with elevated aminotransferases but without the mandatory presence of both coagulopathy and encephalopathy. 1, 2

Defining Acute Liver Failure

ALF requires all three essential components to be present simultaneously: 1, 2

• Absence of preexisting chronic liver disease (this distinguishes ALF from acute-on-chronic liver failure)
• Coagulopathy with INR ≥1.5 (or prothrombin time ratio <50%)
• Hepatic encephalopathy (altered mentation ranging from subtle cognitive changes to coma)
• Rapid progression with symptom onset in less than 26 weeks 1, 3

The pediatric definition is slightly more nuanced, requiring liver-based coagulopathy unresponsive to parenteral vitamin K with either INR 1.5-1.9 plus clinical encephalopathy OR INR ≥2.0 regardless of encephalopathy presence. 4

Defining Acute Liver Injury

Acute liver injury represents a broader, less severe category characterized by: 5, 6

• Elevated aminotransferases (ALT/AST) indicating hepatocellular damage
• May or may not have coagulopathy
• May or may not have encephalopathy
• Preserved synthetic liver function in many cases
• Can resolve without progression to failure 5

Critical distinction: A patient can have marked aminotransferase elevations (even >1000 IU/L) but if they lack both coagulopathy AND encephalopathy, they have acute liver injury, not acute liver failure. 6, 7

Clinical Severity Stratification

When coagulopathy exists without encephalopathy, some authorities use intermediate terminology: 1

• Severe acute liver injury: Prothrombin time ratio <50% without encephalopathy
• Fulminant hepatitis/Serious ALF: Prothrombin time ratio <50% with encephalopathy 1

Common Pitfalls to Avoid

Do not diagnose ALF in patients with known cirrhosis or chronic liver disease, even if previously compensated—these patients have acute-on-chronic liver failure (ACLF) by definition, which has fundamentally different management and prognosis. 1, 8

Do not use aminotransferase levels alone to distinguish injury from failure. The magnitude of ALT/AST elevation does not reliably predict clinical outcome or define ALF. For example, ischemic "shock liver" can produce ALT >10,000 IU/L but may resolve rapidly with cardiovascular stabilization without meeting ALF criteria. 5

Recognize that certain presentations can be deceptive: Wilson disease presenting as ALF typically shows relatively modest aminotransferase elevations (often <2000 IU/L) despite severe liver failure, combined with Coombs-negative hemolysis and disproportionately low alkaline phosphatase. 5

Management Implications

The distinction carries immediate prognostic and therapeutic consequences: 1, 2

• ALF patients require: Immediate ICU-level care, early contact with liver transplant center (Grade 1-B recommendation), monitoring for multi-organ failure, and transplant evaluation 4, 1
• Acute liver injury patients: Can often be managed with outpatient monitoring, removal of offending agent, and serial laboratory assessment until resolution 5

For acute liver injury without failure criteria, follow-up should continue until complete resolution of abnormal liver parameters, typically monitoring every 1-2 weeks initially. If abnormalities persist beyond 12 months, consider progression to chronic liver disease. 5

Timeframe Considerations

Both conditions involve symptom onset less than 26 weeks, distinguishing them from chronic liver disease. However, certain conditions may be included in ALF definitions despite possible underlying cirrhosis if disease recognized for ≤26 weeks: Wilson disease, vertically-acquired hepatitis B, or autoimmune hepatitis. 4, 1

Diagnostic Workup Differences

For suspected ALF, urgent comprehensive evaluation is mandatory including: 5, 1

• Viral serologies (HAV, HBV, HCV, HDV, HEV)
• Acetaminophen level
• Autoimmune markers (ANA, ASMA, immunoglobulins)
• Ceruloplasmin and serum copper (Wilson disease)
• Pregnancy test in women of childbearing age
• Imaging to exclude vascular causes (Budd-Chiari, ischemia)

For acute liver injury, the workup can be more measured and staged based on severity and clinical context, though similar etiologic evaluation is appropriate. 5