What is the definition of acute liver failure in pediatrics?

Definition of Pediatric Acute Liver Failure

Pediatric acute liver failure (PALF) is defined by three essential criteria: (1) absence of known chronic liver disease, (2) liver-based coagulopathy not responsive to parenteral vitamin K, and (3) INR between 1.5-1.9 with clinical encephalopathy OR INR ≥2.0 regardless of encephalopathy presence. 1

Core Diagnostic Criteria

The definition established by the Pediatric Acute Liver Failure Study Group serves as the standard entry criteria for identifying children requiring focused diagnostic and management strategies 1:

• No pre-existing chronic liver disease - This distinguishes PALF from acute-on-chronic liver failure 1
• Biochemical evidence of acute hepatocellular injury - Elevated transaminases indicating liver cell damage 2, 3
• Liver-based coagulopathy unresponsive to vitamin K - Must document lack of correction after parenteral vitamin K administration 1
• INR thresholds with or without encephalopathy:
  • INR 1.5-1.9 with clinical evidence of encephalopathy, OR
  • INR ≥2.0 regardless of encephalopathy presence 1

Key Distinction from Adult Definition

Unlike adult acute liver failure, the presence of hepatic encephalopathy is NOT required to establish the diagnosis of PALF. 2, 3 This is a critical difference because:

• Encephalopathy may be subclinical or difficult to assess in neonates and young infants 4, 3
• The INR threshold alone (≥2.0) is sufficient for diagnosis when other criteria are met 1
• Children can deteriorate rapidly before encephalopathy becomes clinically apparent 1

Clinical Context and Timeframe

The condition represents a rapidly evolving syndrome characterized by abrupt onset of hepatocellular dysfunction 1, 2, 5:

• Illness duration should be less than 26 weeks from onset of symptoms 1
• Certain conditions may be included despite possible underlying cirrhosis if disease recognized for ≤26 weeks: Wilson's disease, vertically-acquired hepatitis B, or autoimmune hepatitis 1
• Clinical deterioration can occur rapidly and unexpectedly, with changes in consciousness evolving hour-by-hour 1

Age-Specific Considerations

The diagnostic approach and etiology differ significantly between age groups 1, 2:

• Neonates and infants: Metabolic disorders and infections predominate 2, 4
• Children and adolescents: Viral hepatitis, drug-induced injury, and autoimmune conditions more common 2, 4
• Encephalopathy assessment is particularly challenging in neonates, where it may be subclinical 4, 3

Common Diagnostic Pitfalls

Avoid these critical errors when evaluating suspected PALF 1, 2:

• Do not wait for encephalopathy to develop before making the diagnosis if INR ≥2.0 1
• Do not assume chronic liver disease is absent without careful history and examination for stigmata of cirrhosis 1
• Do not delay vitamin K administration - coagulopathy must be documented as unresponsive to parenteral vitamin K 1
• Do not overlook treatable causes - herpes simplex, gestational alloimmune liver disease, autoimmune hepatitis, and Wilson's disease require specific urgent therapies 1

Immediate Clinical Implications

Once PALF is diagnosed, immediate actions are mandatory 1:

• Early contact with or referral to a pediatric liver transplant center for multidisciplinary care (Grade 1-B recommendation) 1
• Transfer to intensive care unit given risk of rapid deterioration 1
• Urgent diagnostic workup to establish etiology and identify treatable conditions 1
• Assessment for liver transplantation candidacy, as children may experience rapid death 1