Acute Hepatitis Cases in Children Show Declining Trend; Adenovirus, COVID-19 Remain Key Leads

Becky McCall

June 24, 2022

LONDON ― Case numbers of acute hepatitis in children show "a declining trajectory," and COVID-19 and adenovirus remain the most likely, but as yet unproven, causative agents, said experts in an update at the International Liver Congress (ILC) 2022.

Philippa Easterbrook, MD, medical expert at the World Health Organization (WHO) Global HIV, Hepatitis, and STI Programme, shared the latest case numbers and working hypotheses of possible causative agents in the outbreak of acute hepatitis among children in Europe and beyond.

Global data across the five WHO regions show there were 244 cases in the past month, bringing the total to 894 probable cases reported since October 2021 from 33 countries.

"It's important to remember that this includes new cases, as well as retrospectively identified cases," Easterbrook said. "Over half (52%) are from the European region, while 262 cases (30% of the global total) are from the United Kingdom."

Data from Europe and the United States show a declining trajectory of reports of new cases. "This is a positive development," she said.

The second highest reporting region is the Americas, she said, with 368 cases total, 290 cases of which come from the United States, accounting for 35% of the global total.

"Together the United Kingdom and the United States make up 65% of the global total," she said.

Easterbrook added that 17 of the 33 reporting countries had more than five cases. Most cases (75%) are in young children under 5 years of age.

Serious cases are relatively few, but 44 (5%) children have required liver transplantation. Data from the European region show that 30% have required intensive care at some point during their hospitalization. There have been 18 (2%) reported deaths.

Possible Post-COVID Phenomenon, Adenovirus Most Commonly Reported

Easterbrook acknowledged the emerging hypothesis of a post-COVID phenomenon.

"Is this a variant of the rare but recognized multisystem inflammatory syndrome condition in children that's been reported, often 1 to 2 months after COVID, causing widespread organ damage?" But she pointed out that the reported COVID cases with hepatitis "don't seem to fit these features."

Adenovirus remains the most commonly detected virus in acute hepatitis in children, found in 53% of cases overall, she said. The adenovirus detection rate is higher in the United Kingdom, at 68%.

"There are quite high rates of detection, but they're not in all cases. There does seem to be a high rate of detection in the younger age groups and in the those who are developing severe disease, so perhaps there is some link to severity," Easterbrook said.

The working hypotheses continue to favor adenovirus together with past or current SARS-CoV-2 infection, as proposed early in the outbreak, she said. "These either work independently or work together as cofactors in some way to result in hepatitis. And there has been some clear progress on this. WHO is bringing together the data from different countries on some of these working hypotheses."

Looking ahead, Easterbrook highlighted the importance of global data, especially given that two countries are reporting the majority of cases and in high numbers. "It's a mixed picture with different rates of adenovirus detection and of COVID," she said. "We need good-quality data collected in a standardized way." WHO is requesting that countries provide these data.

She also highlighted the need for good in-depth studies, citing the UK Health Security Agency (UKHSA) as an example of this. "There's only a few countries that have the capacity or the patient numbers to look at this in detail, for example, the UK and the UKHSA."

She noted that the UKHSA had laid out a comprehensive, systematic set of further investigations. For example, a case control study is trying to establish whether there is a difference in the rate of adenovirus detection in children with hepatitis compared to other hospitalized children at the same time. "This aims to really tease out whether adenovirus is a cause or just a bystander," she said.

She added that there were also genetic studies investigating whether genes were predisposing some children to develop a more severe form of disease. Other studies are evaluating the immune response of the patients.

Easterbrook added that the WHO will soon launch a global survey asking whether the reports of acute hepatitis are greater than the expected background rate for cases of hepatitis of unknown etiology.

Acute Hepatitis Is Not New, but High Caseload Is

Also speaking at the ILC special briefing was Maria Buti, MD, PhD, policy and public health chair for the European Association for the Study of the Liver, and chief of the internal medicine and hepatology department at Hospital General Universitari Valle Hebron in Barcelona, Spain.

Buti drew attention to the fact that severe acute hepatitis of unknown etiology in children is not new.

"We have cases of acute hepatitis that even needed liver transplantation some years ago, and every year in our clinics we see these type of patients," Buti remarked. What is really new, she added, is the amount of cases, particularly in the United Kingdom.

Easterbrook and Buti have disclosed no relevant financial relationships.

International Liver Congress (ILC) 2022: Press briefing. Presented June 23, 2022.

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