Unexplained acute hepatitis cases in children near 200 worldwide as authorities investigate cause
There are now almost 200 cases of unexplained severe hepatitis affecting children around the world, a European health official said on Tuesday, 24 April 2022. Britain is the country worst-affected, with 111 cases at the last count. A further 40 cases have been identified in the European Union and European Economic Area, European Centre for Disease Prevention and Control (ECDC) director Dr Andrea Ammon said. Cases have also been confirmed in the United States and Israel. "Investigations are ongoing in all the countries reporting cases but at present the exact cause of this hepatitis still remains unknown," Dr Ammon told a press conference in Stockholm. She added that there is currently no known link between the cases or any connection to travel. Severe hepatitis or liver inflammation, is rare in young children. The current outbreak has led to at least 17 liver transplants in patients aged under 16 and one death, according to the World Health Organiation (WHO). The ECDC declined to confirm in which country the death had occurred, saying that the information was "confidential". The UK Health Security Agency (UKHSA) has said that no hepatitis deaths among children have been recorded in Britain.
The World Health Organisation (WHO) reported: 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. 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 one month to 16 years old. Seventeen children (approximately 10 percent) 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 recognised due to increased testing.
Adenovirus to blame?
While the possible cause is not yet certain, Ammon named adenovirus, a common virus that typically causes flu-like or gastrointestinal symptoms, as a possible trigger for hepatitis in the affected children. "The investigations right now point towards a link to adenovirus infection," she said.
Hepatitis is usually the result of a different infection by the hepatitis A, B, C, D or E viruses but signs of these have not been present in the cases identified worldwide so far.
Asked whether the uptick in hepatitis cases among children was simply a result of increased monitoring, Dr Ammon said that it was unlikely such infections would have gone unnoticed in the past. "A baseline number [of cases] is difficult to do because the adenovirus is not under routine surveillance," she said.
'On the other hand, since it's such a severe and unusual feature, I would expect it would have been noticed previously," she added.
Dr Ammon refused to be drawn on whether a possible drop in immunity caused by two years of COVID-19 related lockdown and social distancing could be a factor in the cases, saying "it could be one factor but I can neither confirm nor deny that because it's still under investigation right now".
Hepatitis: What to look out for
Dr Ammon told reporters that the cases of hepatitis had displayed similar symptoms. "The most common clinical presentation was jaundice, getting yellow in the skin and the eyes, followed by vomiting or gastrointestinal symptoms," she said.
Ammon's advice echoed a Monday update from Dr Meera Chand, Director of Clinical and Emerging Infections at the UKHSA, who said parents and guardians should be alert to the symptoms of hepatitis, including jaundice. "Children experiencing symptoms of a gastrointestinal infection including vomiting and diarrhoea should stay at home and not return to school or nursery until 48 hours after the symptoms have stopped," Dr Chand said.
The typical patient with unexplained acute hepatitis was a child under five years old, the UKHSA said. Most patients initially suffered from nausea and diarrhoea and later developed jaundice, the agency added.
Further work is required to identify additional cases, both in currently affected countries and elsewhere. The priority is to determine the cause of these cases to further refine control and prevention actions. Common prevention measures for adenovirus and other common infections involve regular hand washing and respiratory hygiene.
Member States are strongly encouraged to identify, investigate and report potential cases fitting the case definition1. Epidemiological and risk factor information should be collected and submitted by Member States to WHO and partner agencies through agreed reporting mechanisms. Any epidemiological links between or among the cases might provide clues for tracking the source of illness. Temporal and geographical information about the cases, as well as their close contacts should be reviewed for potential risk factors.
WHO recommends that testing of blood (with initial anecdotal experience that whole blood is more sensitive than serum), serum, urine, stool, and respiratory samples, as well as liver biopsy samples (when available) should be undertaken, with further virus characterization including sequencing. Other infectious and non-infectious causes need to be thoroughly investigated.
WHO does not recommend any restriction on travel and/or trade with the United Kingdom, or any other country where cases are identified, based on the currently available information.
Source: Reuters, Euro News, The World Health Organisation (WHO)