Acute hepatitis of unknown cause in children – we know this

As previously reported in Läkartidningen, the EU’s infection control authority ECDC warned in early April 2022 of an increase in unclear hepatitis in children [1].

Since the end of March 2022, more than 300 cases of acute fulminant hepatitis with transaminases> 8.5 μkat / l have been reported in more than 15 countries [2]. At the time of writing, the Swedish Public Health Agency has received reports of nine cases [3]. Analyzes from reported cases have given negative results for hepatitis A to E virus, leading to the term “acute non-A-E hepatitis”.

The development is now closely monitored by the World Health Organization (WHO) and by the Swedish Public Health Agency.

To date, acute non-A – E hepatitis has mainly affected previously healthy children under 16 (the majority under 10). A total of 18 children have undergone liver transplantation, and at least one child has died. The predominant symptoms include jaundice, vomiting, abdominal pain, putty-colored faeces, fatigue, diarrhea and nausea. Fever has only been reported in one third of children.

The etiology of acute non-A-E hepatitis in children is still unclear. An adenovirus infection is currently the most likely hypothesis [4], when adenovirus DNA was detected in 3/4 of the children. However, this hypothesis requires careful evaluation, as adenovirus 41F (the most common variant in ongoing outbreaks) does not lead to acute fulminant hepatitis in immunocompetent children. In addition, electron microscopy and immunohistochemical staining of liver biopsies from 6 children with acute non-A – E hepatitis have shown a total absence of adenovirus.

In this context, the presence of a cofactor that can lead to a more serious benign adenovirus infection in young children cannot be ruled out. Possible cofactors may be increased susceptibility to adenovirus as a result of lower exposure to the virus during the covid-19 pandemic, previous / concomitant infection with other viruses (including sars-cov-2) or exposure to toxins / environmental substances. An additional factor that may suggest an adenovirus as genesis is the presence of a new variant with increased hepatotropism and virulence.

The association between sars-cov-2 infection and non-A – E hepatitis is weak. Acute fulminant hepatitis has not been a common finding in covid-19 in children. A potential association between acute cases of non-A-E hepatitis and adverse reactions following covid-19 vaccination has previously been considered. However, current reports strongly emphasize the dominance of children who are not eligible for covid-19 vaccination.

An entirely new potential infectious agent should also be considered, with RNA viruses emerging as a primary candidate due to their ability for relatively rapid development, successful transmission between species and rapid change in virulence.

Studies of a possible link between cases of acute non-A – E hepatitis in the UK and toxic substances (for example in children’s clothing or food) have so far not shown significant findings. However, the toxicological investigations are still ongoing, and it remains to be seen whether any causal links can be established.

The Public Health Agency classifies a person who is 16 years or younger and who has fallen ill from 1 October 2021 with acute hepatitis (non-A – E) with AST and / or ALT above 8.5 μkat / l as a suspected case [5]. A person who has had contact with a suspected case and who has contracted acute hepatitis (non-A – E) is also defined (regardless of age) as a suspected case (epidemiologically linked case).

Investigation of suspected cases should be carried out in consultation with a pediatric hepatologist and clinical microbiologist. The Swedish Public Health Agency recommends sampling for adenovirus DNA from faeces, airways, whole blood and urine. If adenovirus is found, the sample is sent to the national reference laboratory for typing. All samples are saved in the biobank for possible future analyzes. If a liver biopsy is performed, the biopsy should be saved without formalin.

Finally, we would like to remind you that the easiest and cheapest way to prevent hepatitis is still good hand hygiene.

Read more:

Nine children in Sweden are suspected of having suffered from mysterious hepatitis 2022-05-12