Cause of acute hepatitis in children is one step closer

After it was announced in April that there was a sharp increase in severe hepatitis of unknown cause in children, progress has been made in identifying the cause and the number of cases appears to be decreasing.

Ruben de Kleine, pediatric liver transplant surgeon at UMC Groningen: ‘From a recent overview in the trade magazine of the European Center of Disease Control, the number of cases of severe hepatitis among young children appears to be decreasing. But what this means for the coming autumn is unclear: is there a new wave on the way or not?’ The article describes 427 children (<16 years of age) with acute hepatitis of unknown cause who were treated by countries in the United States from October 1, 2021 to June 16, 2022 via the European Surveillance System (TESSy). WHO-regio Europe (53 countries) have been reported. About 77 percent of the reported children were under the age of 5. From the beginning of May (week 18) there has been a decrease in the number of reports. The researchers note that this may still be a distorted picture because it sometimes takes several weeks after the first symptoms for hepatitis to develop. Another finding is that it seems that the United Kingdom (UK) has relatively more cases and with a different disease course than other countries, but this may also be due to variation in, among other things, the surveillance data and admission criteria. The WHO reported in July that more than a thousand children worldwide have been reported with this possible condition.

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Possible cause

Two research groups from the UK to report on July 25 that they have a hypothesis about the cause of the hepatitis. The idea is that at least two viral infections are needed to trigger the disease: an adenovirus or herpes virus, in combination with adeno-associated virus-2 (AAV2). The study has not yet undergone peer review. Blood tests and – if a liver transplant had taken place – liver tests in a total of 35 children showed that a large proportion tested positive for AAV2, a parvovirus that cannot replicate without the presence of another ‘helper’ virus. Ruben de Kleine is also doing this together with fellow researchers in Groningen and the LUMC research in the Dutch children with hepatitis of unknown cause and also indicates that this new player, AAV2, may be of interest: ‘We always thought that AAV2 was a ‘innocent bystander‘, but it may play more of a role than we thought. At the same time, certain predisposing factors are probably also involved, such as those related to the immune system. We are now conducting further research into five of the most seriously ill children, four of whom received a liver transplant.’

The last word on the cause has not yet been said. ‘It is now especially important that we secure material and data for all children and future new cases with this hepatitis’, says de Kleine.



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