Clinical Guidance for Adenovirus Testing and Typing of Patients Under Investigation

Children with Acute Hepatitis of Unknown Etiology

CDC Health Alert Network:

On Thursday, April 21, 2022, CDC issued the Health Alert Network (HAN) Health Advisory to notify clinicians and public health authorities of children identified with hepatitis (CDC Hepatitis) and adenovirus infection (CDC Adenovirus). A cluster of pediatric cases of significant liver injury with positive adenovirus infection have been identified and reported to CDC since November 2021. A possible association between pediatric hepatitis and adenovirus infection is currently under investigation after subsequent laboratory testing identified adenovirus type 41 infection in several cases. Clinicians are recommended to consider adenovirus testing and to report such cases to their state or jurisdictional public health authorities and to CDC.

Patient Under Investigation: Children <10 years of age with elevated aspartate aminotransferase (AST) or alanine aminotransferase (ALT) (>500 U/L) who have an unknown etiology for their hepatitis (with or without any adenovirus testing results, independent of the results) since October 1, 2021.

A standard diagnostic workup for children with acute hepatitis should be done locally per treating clinicians.

Consider testing for adenovirus in the evaluation of children with acute hepatitis of unknown cause.

As listed below, please consider collection and submission of the following specimen types (if available) for adenovirus detection.

Because the potential relationship between adenovirus and acute hepatitis is still under a national epidemiologic investigation, please consider collection and submission of the following specimen types (if available) for adenovirus detection.

  • Blood specimen collected in purple top EDTA tube (whole blood, plasma) or serum; whole blood is preferred to plasma
  • Respiratory specimen (nasopharyngeal swab in VTM/UTM, sputum, or bronchioalveolar lavage [BAL])
  • Stool specimen (or rectal swab in VTM/UTM); whenever possible, a stool specimen is preferred to a rectal swab
  • If a liver biopsy has already been performed as clinically indicated, or from native liver explant or autopsy:
    • Formalin-fixed, paraffin embedded (FFPE) liver tissue
    • Fresh liver tissue, frozen on dry ice or liquid nitrogen immediately or as soon as possible, and stored at ≤ -70°C

Nucleic acid amplification testing (NAAT, e.g., PCR) is preferred for adenovirus detection (currently not available for FFPE liver biopsy or native liver explant). Testing whole blood by PCR may be more sensitive than testing plasma by PCR and is preferred.

Additional guidance from AAP: Red Book Online Outbreaks: Hepatitis Cases Possibly Associated with Adenoviral Infectionexternal icon

Additional guidance from North American Society For Pediatric Gastroenterology, Hepatology & Nutrition: iconexternal icon

Page last reviewed: May 6, 2022