Recommendations for minimum diagnostic evaluation by age in pediatric acute liver failure

Recommended tests	Indication	<3 months	3 months to 18 years
Blood and urine tests
Herpes blood PCR	Systemic herpes infection	X	X
Serum amino acid profile	Urea cycle, other metabolic defects	X	X
Ferritin	GALD screen	X
Lactate, pyruvate	Mitochondrial screen	X	X
Plasma acylcarnitine profile	FAO defects	X	X
Urine succinylacetone	Tyrosinemia	X
Enterovirus blood PCR	Systemic enterovirus infection	X	X (3 months to 3 years)
APAP level	APAP exposure		X
Hepatitis A virus IgM	Hepatitis A		X
Hepatitis B surface antigen	Hepatitis B		X
EBV VCA IgM or PCR	EBV infection		X
Antinuclear antibody	Autoimmune disease screen		X
Anti-smooth muscle antibody	Autoimmune disease screen		X
Liver kidney microsomal antibody	Autoimmune disease screen		X
IgG	Autoimmune disease screen		X
Ceruloplasmin	Wilson disease screen		X (4 to 18 years)
24-hour urine copper	Wilson disease screen		X (4 to 18 years)
Historical information
Drug history	Exposure to APAP, other drug, or herbal dietary supplement	X	X
Confirm newborn screen results	Galactosemia and tyrosinemia	X
Confirm maternal hepatitis B serology	Hepatitis B in newborn	X
Procedures
Abdominal ultrasound with Doppler	Vascular anomalies	X	X
Echocardiogram	Cardiac dysfunction	X	X
Conditional diagnostic screening
Blood culture	Sepsis
Viral testing for adenovirus*, enterovirus, HHV-6, parvovirus, influenza	Viral infection
Hepatitis E IgM	Hepatitis E
Soluble IL2R, ferritin, triglyceride level	HLH
Liver copper, Wilson gene mutation analysis	Wilson disease
MRI for extrahepatic iron deposition	GALD
Urine orotic acid	Urea cycle defects

PCR: polymerase chain reaction; GALD: gestational alloimmune liver disease; FAO: fatty acid oxidation; APAP: acetaminophen; IgM: immunoglobulin M; EBV: Epstein-Barr virus; VCA: viral capsid antigen; IgG: immunoglobulin G; HHV-6: human herpesvirus 6; IL2R: interleukin-2 receptor; HLH: hemophagocytic lymphohistiocytosis; MRI: magnetic resonance imaging.

* As of early 2022, adenovirus is under investigation as a possible cause of several clusters of acute hepatitis in young children. In such children, testing for adenovirus was suggested by the Centers for Disease Control and Prevention^[1].

Original table modified for this publication. From: Narkewicz MR, Horslen S, Hardison RM, et al. A Learning Collaborative Approach Increases Specificity of Diagnosis of Acute Liver Failure in Pediatric Patients. Clin Gastroenterol Hepatol 2018; 16:1801. Table used with the permission of Elsevier Inc. All rights reserved.

Reference:

Centers for Disease Control and Prevention. Recommendations for Adenovirus Testing and Reporting of Children with Acute Hepatitis of Unknown Etiology. 2022. Available at: https://emergency.cdc.gov/han/2022/han00462.asp (Accessed on April 21, 2022).

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Recommendations for minimum diagnostic evaluation by age in pediatric acute liver failure