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Acute Hepatitis of Unknown Etiology Among Children

Information for healthcare providers about acute hepatitis of unknown etiology and adenovirus among children.

Last updated: May 6, 2022


Acute severe hepatitis among children that is likely associated with adenovirus was recently recognized globally. This information supports clinicians caring for pediatric patients presenting with hepatitis of unknown etiology by providing information on monitoring, testing and reporting.

  • PHO Advisory - Acute Hepatitis of unknown etiology and potential link to adenovirus infection among children (May 06, 2022)

Any cases that do not have a clear etiology of severe hepatitis in children 16 years of age or under are reportable to public health.

Please check back as information will be updated as it becomes available.

Overview

Acute severe hepatitis has been recognized globally, often associated with illness in children under the age of 10 of which a high proportion have been co-infected with SARS-CoV-2. As of April 25, 2022, at least 169 cases  have been reported in pediatric patients (1 month to 16 years old) from 12 countries.

Cause of illness

These cases tested negative for the usual viral causes of hepatitis A, B, C, D, and E, as well as other viruses that can occasionally cause hepatitis (e.g., Epstein Barr Virus and Cytomegalovirus).

A detailed report from the UK indicated that Adenovirus was detected in 74 of 85 cases tested; 18 were identified as type 41. SARS-CoV-2 was detected in less than 10% of cases tested so far.

Severity of disease

The severity of the disease in these young, otherwise healthy children is concerning. Seventeen children (approximately 10%) have required a liver transplant. To date one child has been reported to have died of liver failure..

Situation in Canada and B.C.

The Public Health Agency of Canada (PHAC) is currently investigating several cases of severe liver disease of unknown origin among children in Canada.

The BC Centre for Disease Control (BCCDC), BC Children’s Hospital and BC Women’s Hospital are aware and monitoring this emerging issue.

Investigations from global community

  • The European Centre for Disease Prevention and Control (ECDC) reports that UK laboratory investigations excluded viral hepatitis types A, B, C, D and E in all cases.
  • Detailed information collected about food, drink and personal habits has so far failed to identify any common exposure. No link to COVID-19 vaccines has been identified.
  • The UK Health Security Agency (UKHSA) has identified adenovirus as the most common pathogen in 40 of 53 (75%) confirmed cases of sudden onset of acute hepatitis (liver inflammation) in children under the age of 10 years.
  • While adenovirus is a possible hypothesis, investigations are ongoing to identify the causative agent.
Patient care

Given the complexity of diagnosis, when a case of hepatitis is suspected in children (age 16 years or under), it is important to seek advice from those with expertise in hepatology, infectious diseases, and microbiology to ensure that appropriate investigations are organized.  This includes testing stool, whole blood and respiratory samples for adenovirus and other agents.

Recommendations for Infection Prevention and Control

Recommendations for Patient Management

  • Severe acute hepatitis carries a high mortality in the pediatric population. Early consultation with pediatric hepatology, infectious diseases, and microbiology is strongly recommended to ensure timely care and investigations. Consultation is available through the BC Children's Hospital switchboard at 604-875-2345.

Symptoms

  • Hepatitis (A to E): Symptoms include fever, fatigue, loss of appetite, nausea, vomiting, abdominal pain, dark urine, light-colored stools, joint pain and/or jaundice. Cases of sudden onset hepatitis in the UK have predominately been in children under 5 years old with initial symptoms of gastroenteritis illness (diarrhea and nausea) followed by jaundice.  Treatment of hepatitis depends on underlying etiology.
  • Adenovirus:  Symptoms include common cold or flu-like symptoms, fever, sore throat, acute bronchitis, pneumonia, pink eye, and/or acute gastroenteritis (i.e., diarrhea, vomiting and stomach pain).  There is no specific treatment for adenovirus infections.

Testing

  • Testing for following pathogens/aetiologies is advised in consultation with pediatric infectious diseases and microbiology:  
    • Hepatitis A, B, C, and E; Hepatitis D should be considered for patients positive for Hep B
    • Cytomegalovirus and Epstein-Barr virus
    • SARS-CoV-2 (PCR and serology), influenza, RSV 
    • Adenovirus: A Nucleic Acid Amplification Test (NAAT) (e.g., PCR) is preferable and may be done on respiratory specimens, stool or rectal swabs, or blood:
      • Indicate “Undiagnosed Acute Hepatitis” under the “Reason for Test” section of the lab requisition.
      • Respiratory and stool samples can be sent to most local laboratories for adenovirus testing. 
      • Blood and other samples should be sent to the BC Children’s and Women’s Hospital Microbiology Laboratory.
      • Samples positive for adenovirus are forwarded to the BCCDC Public Health Laboratory for strain typing.
    • Wilson’s Disease: ceruloplasmin
    • Autoimmune: ANA, Ig 
    • INR (indicator of severity of liver dysfunction)
  • The differential for undifferentiated hepatitis is broad, and investigations should be guided by the clinical picture in consultation with pediatric sub-specialty services. Other causes of hepatitis, including non-infectious causes, should be considered:
    • Infectious: (Parvovirus B19, HSV, HHV-6, VZV, HIV, Enterovirus, Norovirus, Rotavirus, Leptospirosis, Tuberculosis, Lymphocytic choriomeningitis virus etc.)
    • Toxic: acetaminophen, prescription medications, mushroom poisoning etc.
    • Vascular: shock and portal hypertension
    • Inborne errors of metabolism
    • Heat stroke
    • Malignancy 
    • Muscle disorders (i.e. polymyositis)
Reporting

The Provincial Health Officer (PHO) has determined that severe hepatitis (AST/ALT >500IU/L) of unknown origin in children age 16 or less is a reportable illness and has reason to believe that the reportable illness or event may have a serious impact on public health. Pediatric hepatologists at BCCH can assist with determination of reportability. 

Clinicians must report to their regional public health office any child 16 years of age or younger with elevated AST and ALT (>500 U/L) who have unknown etiology for their hepatitis. 

To report
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SOURCE: Acute Hepatitis of Unknown Etiology Among Children ( )
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