Unusual Hepatitis in Children Results in Two Deaths

Source: Freepik

Mysterious hepatitis cases have now spread across the world, including Japan and China, and have caused two deaths in children.

The Wisconsin Department of Health Services (DHS) is currently investigating four cases of unexplained liver damage in children. According to the health alert, one of the cases required a liver transplant while another resulted in a fatality. This brings the global tally of deaths from unusual hepatitis in children to two.

The  Wisconsin Department of Health Services (DHS) is issuing this Health Alert Network (HAN) Health Advisory to notify clinicians and public health authorities of a recent increase in cases of acute hepatitis and adenovirus infection in children.


Wisconsin is not the only US state to have reported cases of the mysterious disease. Earlier this month, Alabama identified nine cases, Illinois three, and North Carolina reported two cases of unusual hepatitis. As a result, the US Centers for Disease Control and Prevention (CDC) issued a health advisory alerting public health officials of the outbreak. And further recommends testing for adenovirus in children with acute liver inflammation.

The mystery disease outbreak first began in the UK when doctors began reporting several hospitalizations among children from acute hepatitis. Health officials across England, Scotland, Wales and Northern Ireland reported cases of unusual hepatitis. At the time, the health officials investigated a wide range of potential causes, including COVID vaccines and environmental factors. However, since a majority of the cases tested positive for SARS-CoV-2 and adenovirus, researchers focused their attention on viral causes. Moreover, health officials issued warnings to parents to stay vigilant for signs and symptoms of hepatitis.

Hepatitis generally presents with fever, yellow discolouration of the skin and sclera, nausea, vomiting, and diarrhoea. In severe cases, children can also develop liver failure; thus, resulting in a liver transplant. So far, approximately 10% (17) of the affected children have undergone a liver transplant.

Link to Adenovirus Not Proven

What makes the hepatitis cases unusual is the failure to detect the usual culprits, Hepatitis A to E virus. Instead, a majority of the cases have tested positive for adenoviruses. As per the World Health Organization (WHO), researchers have detected adenovirus in 74 cases. 18 of these had the strain F type 41 of the virus. Moreover, 20 of the cases tested positive for SARS-CoV-2 while 19 had a coronavirus and adenovirus co-infection. Therefore, researchers are suspecting adenovirus infection as a possible contributing factor in the outbreak. However, the link is yet to be proven.

There are very few case reports in the global literature of adenovirus infection being associated with hepatitis in immunocompetent children (or adults) – so if it transpires that adenoviral infection is involved in causing this disease outbreak, there will be a need to explain why the natural history of adenovirus infection has changed so dramatically in 2022.

Professor Will Irving, University of Nottingham

There are more than 50 types of adenoviruses that cause infections in humans. They mostly cause respiratory infections, gastroenteritis, conjunctivitis, cystitis, and neurological symptoms. The implicated adenovirus strain, type 41, generally presents as acute gastroenteritis in children. Symptoms include fever, abdominal pain, diarrhoea, and vomiting, but can often be accompanied by respiratory symptoms. While the disease is mostly self-limiting in immunocompetent individuals, in immunocompromised children it can cause hepatitis. However, it does not cause hepatitis in otherwise healthy children.

Since the pandemic likely reduced the children’s exposure to common viruses, health experts hypothesize that it made them more vulnerable to hepatitis. Moreover, a change in the genome of adenovirus could also be a factor in the outbreak.

Hepatitis Cases Spread Worldwide

According to WHO’s recent update, as of 21st April, a total of 169 hepatitis cases have come forward. These cases occurred in the UK, Spain, Israel, Denmark, Ireland, the Netherlands, Italy, Norway, France, Romania, and Belgium. The children ranged from 1 month to 16 years of age. Earlier this week, Japan, Canada, and China also reported cases of the mystery liver disease.

According to Japan’s Ministry of Health, Labour and Welfare a child younger than 16 years of age underwent hospitalization from hepatitis. This is Japan’s first probable case of unusual hepatitis. The World Health Organization (WHO) describes a probable case as a person presenting with an acute hepatitis (non hepA-E) with serum transaminase >500 IU/L (AST or ALT), who is 16 years and younger, since 1 October 2021.

The number of cases currently remains low. However, the UK Health Security Agency (UKHSA) has asked parents and guardians to stay aware of the symptoms of the disease. So far, two deaths have occurred among children. However, it is unclear what caused the two death or where they occurred.

The likelihood of your child developing hepatitis is extremely low. However, we continue to remind parents to be alert to the signs of hepatitis – particularly jaundice, which is easiest to spot as a yellow tinge in the whites of the eyes – and contact your doctor if you are concerned.

Dr. Meera Chand, Director of Clinical and Emerging Infections at UKHSA

WHO has not called for any travel and/or trade restrictions with countries reporting cases.


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