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

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:
  1. 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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