Children in the US and Europe are suffering from hepatitis of unknown origin: WHO is alarmed

On April 15, 2022, the World Health Organization (WHO) reported an outbreak of acute hepatitis of unknown origin in children. New cases of acute hepatitis of unknown etiology continue to be reported in young children. WHO talked about the symptoms and possible pathogens of the disease.

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Basic data

As of 21 April 2022, there were at least 11 cases of acute hepatitis of unknown origin in 169 countries in the WHO European Region and one country in the WHO Region of the Americas. Cases found in UK (114), Spain (13), Israel (12), USA (9), Denmark (6), Ireland (5), Netherlands (4), Italy (4), Norway (2), France ( 2), Romania (1) and Belgium (1).

Diseases are mainly amenable to children and adolescents aged from 1 month to 16 years. 17 children (approximately 10%) required a liver transplant; At least one death has been reported.

Symptoms include acute hepatitis (inflammation of the liver) with marked elevation of liver enzymes. Gastrointestinal symptoms, including abdominal pain, diarrhea and vomiting, preceding severe acute hepatitis, as well as elevations of liver enzymes (aspartate aminotransaminase (AST) or alanine aminotransaminase (ALT) above 500 IU/L, and jaundice have been reported in many cases.

In most cases there was no fever. The common viruses that cause acute viral hepatitis (hepatitis A, B, C, D, and E) were not detected in any of these cases.

At the same time, it was not possible to connect the disease with travel to other countries.

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Adenovirus was detected in at least 74 cases, and of those with molecular testing information, 18 were identified as F type 41. SARS-CoV-2 was identified in 20 of those tested. In addition, 19 people were found to be co-infected with SARS-CoV-2 and adenovirus.

Britain, where the majority of cases have been reported to date, has recently seen a significant increase in the number of adenovirus infections in the population. The Netherlands has also reported an increase in adenovirus circulation.

Public health response

In countries where cases have been identified, further investigations are ongoing, including more detailed clinical and infection histories, and toxicology studies. Affected countries have also initiated increased surveillance efforts.

WHO and the European Center for Disease Prevention and Control (ECDC) are supporting countries in investigating and collecting information from countries reporting cases.

Risk assessment

Britain has reported for the first time an unexpected significant increase in cases of severe acute hepatitis of unknown origin in generally previously healthy children. Several other countries, notably Ireland and the Netherlands, also reported unexpected increases in such cases.

Although adenovirus is still only a hypothetical pathogen, it does not fully explain the severity of the clinical picture. Adenovirus type 4 infection has not previously been associated with such symptoms.

Adenoviruses are common pathogens that usually cause self-limited infections. They are spread from person to person and most commonly cause respiratory problems, but depending on the type, they can also cause other diseases such as gastroenteritis (inflammation of the stomach or intestines), conjunctivitis, and cystitis (bladder infection).

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There are over 50 types of immunologically distinct adenoviruses that can cause infections in humans. Adenovirus type 41 usually presents with diarrhea, vomiting, and fever, often accompanied by respiratory symptoms. Although cases of hepatitis have been reported in immunocompromised children with adenovirus infection, adenovirus type 41 is not known to cause hepatitis in otherwise healthy children.

Factors such as the increased susceptibility of young children due to lower levels of adenovirus circulation during the COVID-19 pandemic, the potential emergence of a new adenovirus, and SARS-CoV-2 co-infection need to be further explored.

Hypotheses related to the side effects of COVID-19 vaccines are currently unsupported as the vast majority of affected children have not been vaccinated against COVID-19.

With new case notifications constantly coming in, it is highly likely that more cases will be identified before the cause is found and more specific control and prevention measures can be implemented.

WHO recommendations

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 in order to further refine control and preventive measures. General measures to prevent adenovirus and other common infections include regular handwashing and respiratory hygiene.

WHO does not recommend any restrictions on travel or trade with countries where cases have been identified, based on currently available information.

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