Global outbreak of acute hepatitis in children: latest news - InSight+

Global outbreak of acute hepatitis in children: latest news – InSight+

NEW preprint research suggests that ongoing outbreaks of acute hepatitis in children may have a more complex cause than previously thought.

According to the World Health Organization, as of July 8, 2022, 35 countries have reported 1,010 probable cases of severe acute hepatitis of unknown cause in children, including 22 deaths and 46 liver transplants. Almost half of the cases occurred in the European region, followed by the Americas, the Western Pacific, Southeast Asia and the Eastern Mediterranean.

Until recently, these cases were thought to be related to prior adenovirus infection in the affected children. Two recent case series published by the company New England Journal of Medicine (here and here) concluded that human adenovirus viremia was present in the majority of children with acute hepatitis of unknown cause, but whether this association was causal was “unclear”.

But now two preprint studies published by MedRxiv – here led by Professor Emma Thompson of the Glasgow Center for Viral Research and the London School of Hygiene and Tropical Medicine, and here led by Professor Judith Breuer of University College London and Great Ormond Street Hospital – suggest an alternative explanation.

“These studies suggest that although adenovirus may play a role, the common feature is infection with a dependent, defective virus called adeno-associated virus,” said Associate Professor Simone Strasser, a hepatologist at the Australian National Liver Transplant Unit at the Royal Prince Alfred Hospital. and Immediate Past President of the Gastroenterological Society of Australia.

“It is dependent in the sense that it cannot replicate on its own and needs another virus, and in particular the outer envelope of another virus, in order to replicate.”

Thomson and colleagues reported that adeno-associated virus 2 (AAV2) was “detected in plasma of 9/9 and liver of 4/4 patients, but in 0/13 serum/plasma of age-matched healthy controls, 0/12 children with adenovirus (HAdV ) infection and normal liver function and 0/33 children admitted to hospital with hepatitis of other etiology’.

“AAV2 usually requires a co-infecting ‘helper’ virus to replicate [human adenovirus (HAdV)] or herpes virus. HAdV (species C and F) and human herpesvirus 6B (HHV6B) were detected in 6/9 and 3/9 affected cases, respectively, including 3/4 and 2/4 liver biopsies.

Similarly, Breuer and colleagues found that in the five liver transplant recipients in their study, high levels of AAV2 were detected in the explanted livers.

“AAV2 was also detected at high levels in blood in 10/11 non-transplanted cases,” they said. “Low levels [HAdV] and [HHV-6B]both of which allow lytic replication of AAV2, were also found in five explanted livers and blood from 15/17 and 6/9 of 23 non-transplant cases tested.

The figure also adds the findings of a Scottish study (Thomson et al) about a possible genetic predisposition.

“The HLA-DRB1*04:01 class II allele was identified in 8/9 cases (89%) compared to a 15.6% baseline frequency in Scottish blood donors, suggesting increased susceptibility in affected cases,” they said.

“AAV has not been found to cause human disease, but it is one of the viral vectors used for gene therapy because it can be engineered to deliver DNA to target cells,” said A/Professor Strasser. “It has been found to induce an immune response and abnormal liver enzymes in gene therapy studies.”

No association was found between SARS-CoV-2 infection and cases of acute hepatitis, nor was any association found with vaccination against COVID-19. Viral hepatitis A, B, C, D, and E were ruled out as causes in all reported cases.

A/Professor Strasser said InSight+ that to her knowledge no cases have yet been reported in Australia.

“There’s no particular reason why it hasn’t come up here yet,” she said. “Of course, everyone is looking for it. We often see acute liver failure and severe hepatitis in both children and adults.

“But there hasn’t been any unusual cluster of cases in Australia yet, or certainly no reports of this happening.”

According to HealthDirect, symptoms can include abdominal pain, diarrhea, vomiting, loss of appetite and jaundice, while most children do not have a fever.

A/Professor Strasser said InSight+ that general practitioners suspecting severe acute hepatitis should immediately refer the child to the nearest children’s hospital.

“This is not community management,” she said. “These children should be under the care of a hepatologist and liver failure unit.”

Even if an epidemic did occur in Australia, A/Professor Strasser was confident that transplant programs would not be further strained.

“Liver failure doesn’t happen very often in children,” she said. “In global reports, transplantation was required in about 5% of cases.

“In Australia, if a child needs a liver transplant, they get a liver transplant.”

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