What’s behind mysterious rise in liver disease among children?

Health experts around the world are investigating a rise in the number of cases of hepatitis, or liver inflammation, in children. The illness was first reported in a small number of children in the United Kingdom between January and April this year, but since then there have been reports of cases across Europe, parts of the United States, and one case in Asia.

According to the World Health Organization (WHO), as of April 21, 2022, at least 169 cases of acute hepatitis of unknown origin have been reported. Countries reporting cases include the UK, US, Spain, Israel, Denmark, Ireland, the Netherlands, Italy, Norway, France, Romania and Belgium. On Monday Japan announced its first case, and Canada said it was also investigating reports of similar cases. Globally, the confirmed cases are in patients aged one month to 16 years old. Seventeen children – approximately 10 percent – have required a liver transplant. At least one death has been reported.

While hepatitis in children is not unheard of, the severity of these infections makes them unusual. The fact that these infections are occurring in previously healthy children is also a cause for concern. That some of these children needed a liver transplant makes the case for understanding the cause behind this mystery illness even more urgent.

More unusual still, these cases are not linked to any of the five typical strains of hepatitis – A, B, C, D and E. The children involved have tested negative for these specific viruses.

What is hepatitis?

Hepatitis is a broad term that refers to inflammation of the liver.

The liver is a vital organ located on the top right side of the abdomen. It has over 500 known functions including filtering blood, aiding in digestion, helping in the management of blood glucose levels, regulating and producing proteins, clearing the blood of drugs and other poisonous substances, managing blood iron levels, and resisting infections by making immune factors and removing bacteria from the bloodstream.

When the liver becomes inflamed – as is the case in hepatitis – these functions can become impaired.

Hepatitis is usually the result of a viral infection (hepatitis A, B, C, D, E) or liver damage caused by drinking alcohol, and in some cases it can happen as a result of the body’s own immune system attacking liver cells. Some types of hepatitis will pass without any serious problems, while others can be long-lasting (chronic) and cause scarring of the liver (cirrhosis), loss of liver function and, in some cases, liver cancer.

In the early or acute stages, children and adults who suffer from hepatitis may have no symptoms and may not realise they have it. But if symptoms do develop, they are often non-specific and can include:

• Muscle and joint pain
• A high temperature
• Feeling and being sick
• Lethargy
• Stomach pain
• Dark urine
• Pale, grey-coloured stools
• Yellowing of the eyes and skin (jaundice)

Children with these symptoms, particularly if they are not settling, should be taken to see the doctor. Most types of hepatitis can be treated or resolve on their own, but in some cases the disease can progress and cause liver failure, where the liver stops functioning altogether. If this happens, a liver transplant is needed.

What is causing this sudden rise in hepatitis in children?

The cases of hepatitis seen in children so far have not been caused by the usual hepatitis viruses. Experts believe the illness is being caused by a group of viruses known as adenoviruses – a common group of viruses known to cause a range of illnesses from tummy upsets to upper respiratory tract infections, predominantly in children.

There are 88 types of adenoviruses known to infect humans, and these are grouped into seven different species, A through G. They are spread through close personal contact, respiratory droplets, and contaminated surfaces.

Most adenovirus infections are self-limited in healthy children and adults and are treated with supportive measures such as fluids and rest. Fatal infections can occur in immunocompromised children and adults and less frequently in the healthy. They do not generally cause infections as serious as hepatitis in otherwise healthy children, though individual case reports of this happening in the past have been documented.

Although the numbers of children who have been identified as having hepatitis across the world remain relatively small, it is still more than what healthcare professionals are used to seeing and has prompted health organisations to put out alerts to say urgent investigations are under way.

The investigations will focus on whether a group of viruses that usually cause a mild infection in most people has changed, or if it is the response to the virus by the host that has altered.

Scientists and clinicians are now investigating whether there has been a change in the genetic make-up of the virus that might trigger liver inflammation more easily. The UK Health Security Agency (UKHSA) says a strain of adenovirus called F41 is looking like the most probable cause (PDF). This is not a new strain of adenovirus, and usually causes diarrhoea in children and is commonly spread through the faecal-oral route. It is presently unknown whether there is a new variant of the F41 adenovirus that makes it more dangerous to the liver in children or if certain children are responding to it in an unusual way.

One potential hypothesis scientists are looking into is that children were less exposed to these common viruses while COVID-19 restrictions were in place, preventing social mixing. Now, as things open up and children begin mixing again, they are suddenly being exposed to a number of viruses in quick succession and their immune systems are over-responding, which eventually leads to inflammation of the liver.

Though most of the children who have had the mystery hepatitis have been under age five, some have been older and this theory, though widely reported, does not carry substance for them as they are likely to have been exposed to adenoviruses when they were younger – before the pandemic began.

Another possible hypothesis is that a prior infection with the SARS-CoV-2 virus could be linked to the rise in cases of hepatitis in children. Some, though not all, of the children in the UK who were diagnosed with hepatitis tested positive for COVID; the theory being looked into asks whether a previous or current infection with COVID-19 could make children more susceptible to hepatitis when then infected with an adenovirus. While isolated cases of hepatitis have been reported in patients with severe COVID, this is rare.

Importantly, none of the children in the UK – which has seen the majority of cases of hepatitis in children – had received any of the COVID-19 vaccinations, making the link between the disease and these vaccines impossible.

What should parents do?

It is important to remember that although this is a worrying condition, it has so far only affected a small number of children globally. If a child has any of the symptoms above, particularly if they are persistent or unexplained, parents should seek medical advice.

Children should be encouraged to partake in simple hygiene activities, such as regularly washing their hands, especially after using the bathroom or before eating food. Children experiencing symptoms of a gastrointestinal infection, such as vomiting and diarrhoea, should stay at home and not return to school or nursery until 48 hours after the symptoms have stopped.

Simple respiratory hygiene during upper respiratory tract viral infections is also important; children should be shown how to blow or wipe their noses with a tissue, which should then be placed in a bin and the child should then wash their hands.