Reviews | How to Think About Unexplained Cases of Severe Hepatitis in Children

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As if parents didn’t have enough to worry about – a global pandemic, a shortage of baby formula – there’s a mysterious new disease afflicting young children in the form of severe hepatitis.

Here’s the bottom line: it’s no reason to panic, but it’s worth watching out for. Parents should also be wary of speculation about the disease. There are still a lot of things we don’t know.

The Centers for Disease Control and Prevention is investigating at least 109 cases of the disease in the United States. Similar illnesses have been reported in at least two dozen countries, from Argentina to Denmark to Indonesia. Worldwide there are around 450 reports, with the highest numbers in Britain and the United States.

Many cases are serious. Among the American children affected, more than 90% required hospitalization. Fifteen required liver transplants. Five died.

The disease appears to be concentrated in young children. According to the CDC, most of those affected are under the age of 5, with the median age being just 2. Many are previously healthy children who have no known underlying medical conditions. Cases have been detected in 25 states and there is no clear geographical distribution.

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So far, the cause is unknown. “Hepatitis” is a general term for inflammation of the liver for which there are many causes. Hepatitis A, B, and C viruses (and, less commonly, hepatitis D and E viruses) are known to induce liver inflammation. In adults, alcohol is another major cause of hepatitis. Certain medications and toxins can also damage the liver and lead to severe inflammation. But none of the affected children tested positive for hepatitis viruses or were exposed to alcohol, drugs or toxins.

The one thing many have in common is testing positive for adenovirus, which is a common virus that causes colds, gastrointestinal upset, and other mild flu-like illnesses. The CDC said more than half of US cases tested positive for adenovirus, and the UK Health Security Agency reported that more than 70% of their cases tested positive as well. There is also a specific type of adenovirus, adenovirus 41, which has been detected in many children in the United States, Great Britain and Europe.

The actual percentage of positive adenovirus cases could be even higher, as cases could have been missed given the way samples are collected. The CDC has issued an alert to clinicians asking health care providers to be on the lookout and use specialized methods for adenovirus testing.

Although adenovirus is a main hypothesis, it could turn out to be purely association, not causation. After all, adenoviruses don’t usually cause liver inflammation in healthy people. They have also been around for years without being linked to acute hepatitis.

Yet there is precedent for an existing virus to induce a new syndrome. In 2012, a polio-like disease called acute flaccid myelitis suddenly appeared, causing weakness in the arms or legs of healthy children that often persisted for months or years. The terrifying but extremely rare disease was ultimately found to be linked to another common virus, a type of enterovirus. It remains unclear why most children who encounter enteroviruses have runny noses and upset stomachs while a very small minority have suffered serious consequences.

Adenovirus could act similarly to an enterovirus, although given the timing of the coronavirus pandemic, active research is underway to determine if there is an association with covid-19. Some scientists have speculated that a previous infection with a coronavirus could “prime” an autoimmune reaction that could be made worse by subsequent exposure to an adenovirus. But coronavirus has only been identified in 18% of reported cases in Britain. A CDC report of nine children hospitalized in Alabama found that none of them had an acute covid-19 infection or a documented history of past infection.

Still others wondered if two years of masking and social distancing might have made children’s immune systems less able to fight off existing viruses. We do not know. What we do know is that there is no association with the coronavirus vaccine, as most children with this hepatitis are not old enough to be eligible for vaccination.

It will take time for researchers to identify a cause. We may never find one. What is disconcerting for parents is that there is not much that can be done to prevent this rare and alarming disease. If major theories are correct, adenoviruses are exceptionally common, and the CDC estimates that 75% of children have already contracted the coronavirus.

Parents can, however, seek immediate medical attention in case of jaundice and insist on good hand washing to reduce the transmission of many diseases. And health care providers should be on high alert to perform the necessary tests and notify state health authorities accordingly.

As the coronavirus pandemic has taught us, emerging diseases require surveillance, research and vigilance. Hepatitis is no different.

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