Cases of Hepatitis of Unknown Origin in Children Raise Alarm

This article was originally published in French on Medscape.

Europe — After several cases of acute hepatitis of unknown origin in children in the United Kingdom were reported, further cases have now been reported in France (two cases), Denmark, Ireland, the Netherlands, and Spain. More than 80 cases have been reported overall, raising fears of an epidemic, according to the European Centre for Disease Prevention and Control (ECDC) in a press release. [Editor's note: The ECDC released new data that the case count has climbed to about 190, as of April 29, 2022.]

Furthermore, nine cases have allegedly been reported since last autumn in Alabama in the United States. These cases have mainly been in children aged 1-6 years.

Investigations are ongoing in all these countries, particularly as the "exact causes of these cases of acute hepatitis remain unknown." Nevertheless, the team working on these cases in the United Kingdom believes that, based on clinical and epidemiologic data, the cause is probably infectious in origin.

Coordinated by the ECDC, European medical societies such as the European Association for the Study of the Liver and the European Society of Clinical Microbiology and Infectious Diseases (ESCMID) are working together to promote information sharing, according to the European agency.

Potential Infectious Agent

For context, on April 5, the United Kingdom reported about 10 cases of acute hepatitis of unknown origin in children younger than 10 in Scotland with no underlying conditions. Seven days later, the UK reported that 61 additional cases were under investigation in England, Wales, and Northern Ireland, the majority of which were in children aged 2-5 years.

The cases in the United Kingdom presented with severe acute hepatitis, with increased liver enzyme levels (aspartate aminotransferase [AST] and alanine aminotransferase [ALT] levels above 500 IU/L), and most presented with jaundice. Some reported gastrointestinal symptoms such as abdominal pain, diarrhea, and vomiting in the previous weeks.

The majority had no fever.

Although no deaths had been reported as of April 15, some cases needed to be seen by a liver specialist in the hospital, and others had to undergo transplantation (six transplants in Europe and two in the United States).

Initial hypotheses have focused on a potential infectious agent or exposure to a toxin. No link to COVID-19 vaccination has been established.

Which Type of Hepatitis?

The ECDC reports that laboratory tests have ruled out the possibility of attributing the cases to type A, B, C, D, and E viral hepatitis. Of the 13 cases in Scotland, three tested positive for SARS-CoV-2, five were negative, and two had contracted COVID over the course of the last 3 months.

One positive test for adenovirus was found in five of the 13 Scottish cases, out of the 11 that were tested. All the cases reported in the United States tested positive for an adenovirus, five of which were for adenovirus type 41, which is responsible for inflammation of the bowel. Investigations are ongoing to assess any possible involvement of this virus in other cases. It should be noted that adenoviruses can cause hepatitis in children, but generally only in those who are immunosuppressed.

The pandemic could be another possible explanation, Nancy Reau, MD, head of the hepatology department at Rush University, Chicago, told Medscape Medical News. "The possibility that these cases are linked to COVID still exists," she said. Some cases in the United Kingdom tested positive for COVID-19; none of these children had received the COVID-19 vaccine.

"COVID has been regularly seen to raise liver markers. It has also been shown to affect organs other than the lungs," she stated. "It could be the case that, as it evolves, this virus has the potential to cause hepatitis in children."

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