Standardised data is needed to decode mystery hepatitis in children

There is a declining trajectory seen in Europe and the US among the cases of hepatitis of unknown origin. [SHUTTERSTOCK/Amani A]

While the rate of diagnoses of hepatitis cases of unknown origin among children has started to decrease, scientists’ understanding of the infections remains “mixed” – in part, due to a lack of standardisation of data collection across the globe.

While cases of acute hepatitis of unknown origin are nothing new among children, the recent rise in diagnoses – with apparently no discernable cause – has mystified scientists.

Speaking on Thursday (23 June) at a press briefing at the International Liver Congress in London, Phillippa Easterbrook, technical lead of the World Health Organisation’s (WHO) headquarters, said cases “have always been identified at a low level”.

The severity seen in recent weeks is not unique either, Maria Buti, Policy and Public Health Chair at the European Association for the Study of the Liver (EASL) added. “We had cases of acute hepatitis that even needed liver transplantation some years ago and every year in our clinic we see this type of patient,” she said.

However, what remains unique is the volume of cases seen, particularly in the United Kingdom, which accounts for approximately 260 out of the nearly 900 worldwide.

Also unique is how little is known about how the infections occurred. While the declining trajectory seen in Europe and the US among the cases of hepatitis of unknown origin is a “positive development,” the reasons for both the surge and the recent decline are still unknown, Easterbrook said.

The main suspects so far are adenovirus and COVID-19 – either independently or working as cofactors to result in hepatitis. 

Adenovirus was found in half of the samples in Europe, while active infection with COVID-19 was detected in 10% of the cases in Europe and the US. Easterbrook highlighted that information on previous infections is important, but it is difficult to gather information on antibody positivity. 

There are over 30 countries that reported acute hepatitis cases of unknown origin and around half of the countries have up to five cases.

Overall, half of the cases worldwide are coming from the WHO’s Europe region. The majority of cases – 75% – are seen in young children less than five years of age. Of the cases in Europe that have follow-up information, around 30% required admission to intensive care and nearly 20% needed a liver transplant. 

The severity of mysterious hepatitis among children "very unusual"

Cases of hepatitis of unknown origin among children have now been recorded in 20 countries in Europe. While hepatitis of unknown origin is reported every year, the severity of cases this time is “very unusual”, medical experts say. 

The search for comparable data

Whether this is genuinely a new phenomenon is a question that researchers are trying to answer, Easterbrook said. “My sense is that we do have a bit of a mixed picture,” she continued.

While some investigators in Europe and the US have concluded that this is likely to be a new phenomenon, and they have “good data on this”, other countries have reported the opposite.

The lack of standardisation in surveillance globally is to blame for this mixed picture. Countries vary in how they report data, for example regarding age distribution, as well as whether they test for adenovirus.

“Everyone investigates in different ways,” Easterbrook said, adding that “we really need to have good quality data collected in a standardised way”. 

Further complications

Part of the conundrum, Easterbrook said, is that complex expensive genetic tests are harder to access in low and middle-income countries, so several variables are inconsistently factored in.

Andreas Hoefer, microbiology and molecular surveillance expert at European Centre for Disease Prevention and Control (ECDC) said in a WHO webinar on Wednesday that within Europe there are also issues with a lack of samples in laboratories.

This is not because of “not wanting to share” but rather because “the ethical considerations required for taking extra sample volumes from children is very complicated, and an ethical committee approval is needed to do this.”

“It is very urgent that we find a way to collect, share and store sufficient sample investigations,” Hoefer said. 

Adenovirus, COVID-19 examined as possible cause for mysterious hepatitis

As acute hepatitis cases of unknown origin continue to grow across the globe, the investigation into its origin is ongoing. While the leading hypothesis is adenovirus, the link to COVID-19 is also being looked at. 

Lessons for the future

The EASL’s Buti highlighted that ongoing investigations might pave the way for a better understanding of acute hepatitis in children. “This will help in the future diagnostics in children because this makes an intensive data study,” she said.

According to Easterbrook, this is “an opportunity to really try nail down a bit more understanding about this”.

“Pediatric haematologists are delighted because they’ve been waiting for this moment to draw attention to something that’s rare and unusual,” she said.

[Edited by Nathalie Weatherald]

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