Acute Liver Failure



  • A set of criteria has been proposed to diagnose pediatric acute liver failure (ALF).
    • Biochemical evidence of liver injury due to rapid loss of hepatocyte function
    • No previous history of chronic liver disease
    • Coagulopathy not responsive to vitamin K administration
    • International normalized ratio (INR) >1.5 in presence of encephalopathy or INR >2 without encephalopathy
  • In older children, in whom hepatic encephalopathy can be more easily assessed, ALF may more simply be defined as follows:
    • Onset of encephalopathy <8 weeks after the onset of symptoms referable to liver dysfunction in a patient without preexisting liver disease


  • Exact frequency of ALF in children is unknown but accounts for 10–15% of pediatric liver transplants in the United States annually.
  • In infants and children <3 years of age, indeterminate and metabolic etiologies predominate.
  • In older children, drug-induced toxicity (especially acetaminophen), autoimmune hepatitis become more common.
  • Infectious etiologies (e.g., viral hepatitis) vary in prevalence based on geographic region.


  • Hepatocellular necrosis leads to release of growth factors that promote hepatic regeneration.
  • Hepatic failure may become irreversible if:
    • The initial insult overcomes the liver’s regenerative capacity.
    • The offending agent or derangement is not eliminated or corrected.
    • Secondary complications, such as shock or disseminated intravascular coagulation, lead to further injury.


The major causes of ALF can be grouped into the following broad categories:

  • Indeterminate
  • Drug-induced/toxin
  • Metabolic/genetic
  • Infectious
  • Vascular/ischemic
  • Malignancy
  • Immune dysregulation

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