The World Health Organization (WHO) reports, as of May 10, 2022, reports at least 348 cases of acute hepatitis of unknown origin in children one month to 16 years of age; 70 cases in 13 countries are pending investigation. Only 6 countries have reported > 5 cases to WHO. Of cases reported globally, 163 (46%) are reported from the United Kingdom. As of May 6, 2022, the US CDC reported 109 cases of acute hepatitis among children in 24 states; 5 deaths were reported. Adenovirus infection remains the leading suspect as the cause of these clusters of cases. In the United Kingdom, 91 (72%) of 126 ill children tested were positive for adenovirus. Of 18 children with adenovirus tested, all 18 had adenovirus F type 41. The F type 41 type is a cause of gastrointestinal distress, which aligns with patient reports of symptoms.  

What are the data for adenovirus as a cause of acute hepatitis before these recent cases?

Adenovirus hepatitis is relatively uncommon and is detected most frequently in immunosuppressed persons. Among those patients with adenovirus, rates of hepatitis range from < 5% among persons with various causes of immunosuppression to 18% among adults receiving bone marrow transplants. The mortality rates of these immunosuppressed patients with adenovirus hepatitis are approximately 50%.  Adenovirus hepatitis is rare among patients with no immune suppression.

Searching for answers

As the investigation continues, we will learn more. Perhaps a large increase in the number of children exposed to adenovirus, is revealing a previously under recognized outcome. Improved viral surveillance from the response to the COVID-19 pandemic might be improving detection of other viral infections. 

Data are needed regarding co-morbidities or other exposures which increase the virulence of  adenovirus infection or increase host susceptibility. Of interest, SARS-CoV-2 was identified in 24 of 132 cases tested in the United Kingdom. Other co-factors including toxins and other infectious agents remain possibilities.

Some have postulated the social distancing measures taken during the pandemic response might have increased children’s susceptibility to adenovirus infection. 

Perhaps there are substantive genetic changes increasing adenovirus virulence. The structure of adenovirus F 41 was recently mapped. Also, other causes of acute hepatitis remain possibilities. The differential diagnosis of acute liver disease in children includes a range of infectious, metabolic, and other conditions. Indeed, many cases do not have specific diagnoses, yet liver failure and transplantation were rare before this outbreak.

Reports of additional cases will assist investigations. The US CDC requests reports of acute hepatitis, ALT> 500 U/L, of an unknown cause among children less than ten years of age. WHO advises Member States to investigate and report cases of persons 16 years or younger presenting with acute hepatitis (non-hep A-E), AST or ALT >500 IU/L, of unknown origin, and persons of any age with hepatitis who were in close contact with these pediatric cases. The European CDC has established a surveillance system for acute hepatitis of unknown origin among children and adolescents. 

Share your perspectives

What is the most likely cause of acute hepatitis in these children? Are all the cases epidemiologically related? Are cases occurring in your area? Email the Coalition at globalhep [at] taskforce.org.