Table 1.

Causes of pediatric acute liver failure—age based with diagnostic evaluation

Age	Most common causes	Diagnostic evaluation
All patients	Idiopathic or indeterminate (incomplete evaluation) Drug toxicity or ingestions Infectious causes Autoimmune hepatitis Metabolic causes Other causes	Liver function tests: AST, ALT, GGT, alkaline phosphatase, fractionated bilirubin, albumin, total protein) Coagulation factors and profile: PT-INR, aPTT, fibrinogen, factors V, VII, VIII Serum ammonia level and blood gas Complete blood count with platelets and differential Complete metabolic panel including electrolytes, BUN, creatinine, blood glucose, calcium, magnesium and phosphorus Imaging studies: ultrasound liver with Doppler study Tissue diagnosis: liver biopsy; muscle biopsy as indicated
Infants ≤ 1 year	Idiopathic or indeterminate Infectious (HSV 1 and 2—most common, enterovirus, adenovirus, hepatitis B, hepatitis C, EBV, CMV, HHV 6, parvovirus, etc.) Metabolic (fatty acid defects, mitochondrial defects, galactosemia, tyrosinemia, neonatal hemochromatosis, etc.) Other diseases—congenital heart defects, accidental drug overdose or ingestion	Viral PCR for EBV, CMV, enterovirus, adenovirus, HHV-6, HSV 1 and 2, parvovirus. Viral hepatitis serology including anti-HAV IgM, HBsAg, anti-HBe IgM and IgG, anti-HCV, and anti-HEV Serum lactate, pyruvate, amino acid profile, carnitine profile, acyl-carnitine profile, ferritin, iron, TIBC; urine amino acid/organic acid profile, urine succinylacetone Serum acetaminophen level, urine toxicology screen
Pre-adolescent	Idiopathic or indeterminate
	Drug toxicity or accidental ingestion (acetaminophen, acetylsalicylic acid, valproic acid, etc.)	Serum acetaminophen level, urine toxicology screen
	Metabolic diseases (Wilson’s disease, fatty acid oxidation defects, mitochondrial defects, etc.)	As above, plus serum Ceruloplasmin and 24-hr urine copper.
	Infectious causes (hepatitis A, B, C, D, E, non-A, non-B viral hepatitis, EBV, CMV, enterovirus, adenovirus, HHV-6, parvovirus, etc.)	As above
	Autoimmune hepatitis	Antinuclear antibody, anti-smooth muscle antibody, anti-liver-kidney microsome antibody
Adolescent	Drug toxicity, toxin ingestion, accidental or intentional drug overdose (acetaminophen, tetracycline, ecstasy, toxic mushroom Amanita phalloides poisoning, etc.) Autoimmune hepatitis Wilson’s disease and other metabolic diseases Infectious diseases (hepatitis A, B, C, D, E, non-A, non-B viral hepatitis, EBV, CMV, etc.)	As above

HSV, herpes simplex virus; EBV, Epstein-Barr virus; CMV, cytomegalovirus; HHV-6, human herpesvirus 6; AST, aspartate aminotransferase; ALT, alanine aminotransferase; GGT, gamma glutamyl transferase; PT-INR, prothrombin time and international normalized ratio; aPTT, activated partial thromboplastin time; PCR, polymerase chain reaction; HAV, hepatitis A virus; HBsAg, hepatitis B surface antigen; HCV, hepatitis C virus; HEV, hepatitis E virus; TIBC, total iron binding capacity