The World Health Organization (WHO) reports, that since the WHO Disease Outbreak News on Acute hepatitis of unknown aetiology – the United Kingdom of Great Britain and Northern Ireland was published on 15 April 2022, there have been continuing further reports of cases of acute hepatitis of unknown origin among young children. It is not yet clear if there has been an increase in hepatitis cases, or an increase in awareness of hepatitis cases that occur at the expected rate but go undetected. While adenovirus is a possible hypothesis, investigations are ongoing for the causative agent.
As of 21 April 2022, at least 169 cases of acute hepatitis of unknown origin have been reported from 11 countries in the WHO European Region and one country in the WHO Region of the Americas (Figure 1). Cases have been reported in the United Kingdom of Great Britain and Northern Ireland (the United Kingdom) (114), Spain (13), Israel (12), the United States of America (9), Denmark (6), Ireland (<5), The Netherlands (4), Italy (4), Norway (2), France (2), Romania (1), and Belgium (1). Cases are aged 1 month to 16 years old. Seventeen children (approximately 10%) have required liver transplantation; at least one death has been reported.
The clinical syndrome among identified cases is acute hepatitis (liver inflammation) with markedly elevated liver enzymes. Many cases reported gastrointestinal symptoms including abdominal pain, diarrhoea and vomiting preceding presentation with severe acute hepatitis, and increased levels of liver enzymes (aspartate transaminase (AST) or alanine aminotransaminase (ALT) greater the 500 IU/L) and jaundice. Most cases did not have a fever. The common viruses that cause acute viral hepatitis (hepatitis viruses A, B, C, D and E) have not been detected in any of these cases. International travel or links to other countries based on the currently available information have not been identified as factors.
Adenovirus has been detected in at least 74 cases, and of the number of cases with information on molecular testing, 18 have been identified as F type 41. SARS-CoV-2 was identified in 20 cases of those that were tested. Furthermore, 19 were detected with a SARS-CoV-2 and adenovirus co-infection.
The United Kingdom, where the majority of cases have been reported to date, has recently observed a significant increase in adenovirus infections in the community (particularly detected in faecal samples in children) following low levels of circulation earlier in the COVID-19 pandemic. The Netherlands also reported concurrent increasing community adenovirus circulation.
Nevertheless, due to enhanced laboratory testing for adenovirus, this could represent the identification of an existing rare outcome occurring at levels not previously detected that is now being recognized due to increased testing.