Description

• 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

Epidemiology

• 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.

Pathophysiology

• 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.

Etiology

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