EXPERT REACTION: Mysterious hepatitis outbreak in kids

Hepatitis is inflammation of the liver and there are five known hepatitis viruses, A,B,C,D, and E, and we've known a lot about them since the 70s through to the discovery of hepatitis C in 1989. 

Other viruses which affect the whole body can also cause hepatitis, including some herpes virus infections and even measles, but the five main human hepatitis viruses  A,B,C,D, and E are well known, and well characterised. 

So if we get a hepatitis causing virus that is not one of those, then that's something new that we haven't seen for 30 years. 

The likely candidate is a type of adenovirus called F41, which is known for causing gastroenteritis in children. It also causes eye infections for type B viruses. It causes about 10-15% of global respiratory infections which we would call the “common cold”, mainly in kids, and about 5% of gastroenteritis cases in Sydney. 

It is a big DNA virus that is capable causing both gastrointestinal and respiratory illnesses. There are about 113 different types of adenovirus, but F41 and a few of the others are well known to cause gastro.  

Now, having said that, they are very clever DNA viruses and capable of infecting different organs. For example if you get cold-like symptoms from an adenovirus you may also get gastro a few days later, or if you get gastro from F41 adenovirus you will sometimes also get respiratory symptoms. Because it has the weaponry to infect more than one organ. 

The liver is really like the helper of the gastrointestinal system, so if the virus is now capable of infecting the liver, that would not be a surprise to me or any other virologist.

If this virus now infects liver cells, that would indicate a tropism change and I would say this suggests something must have changed with the virus. 

In Australia,  the F41 type causes around 70% of the adenovirus gastro that we see clinically, and it normally only results in a mild gastro in the kids

I'd be looking at sequencing the whole virus to get the full genome. That is probably what is rapidly taking place now, sequencing to look for recombination or mutation that enables this change to allow it to affect the liver cells.

• What do we know about this new condition?  

"Relatively little, except that it appears to be a new form of viral hepatitis (that is inflammation of the liver) affecting young children. The illness was first recognised in England, Europe and most recently in the USA, and is sometimes causing serious liver disease requiring hospitalisation and even liver transplantation."

• What might be causing it?

"All of the known causes of hepatitis, ranging from viruses to drugs and toxins, are being considered. The information to date suggests that a strain of adenovirus (type 41) is a possible cause. There are many different strains of adenoviruses which are a common cause of generally minor infections in children causing illnesses ranging from gastroenteritis to common colds and conjunctivitis with most adenovirus infections occurring in healthy children causing no symptoms at all. This particular strain is a well-recognised cause of diarrhoea in children."

• What is the likelihood of seeing cases in Australia?

"It is not yet possible to predict whether the illness will occur in Australia – until we can confirm the cause and the pattern of spread. The fact that it has occurred initially in England and then in Europe suggests that it can spread between countries."

• What can we do to help protect our kids?

"It is not yet possible to confidently advise on protective measures, but adenovirus 41 is spread by what is called faecal-oral transmission and is controlled by handwashing after going to the toilet and use of disinfectants to clean surfaces.

The recent series of unexplained cases of hepatitis in children around the world has caused quite a stir.

Reports from World Health Organization (WHO) have indicated that at least 169 cases were recorded of children being diagnosed with hepatitis, including in other parts of the world (US, UK, EU countries). Most of these cases were of acute hepatitis, which causes liver inflammation with reported symptoms like abdominal pain, diarrhoea and vomiting preceding presentation with severe acute hepatitis and increased levels of liver enzymes and jaundice.

Interestingly, Adenovirus, which is a family of viruses that usually cause colds among other symptoms, has been found in at least 74 cases worldwide and has been suggested as being a potential causative agent of this outbreak.

Adenovirus is a group of viruses that commonly cause cold or flu-like symptoms, fever, sore throat, acute bronchitis, pneumonia, conjunctivitis, acute inflammation of the stomach, diarrhoea, vomiting, nausea and stomach pain.

In terms of transmission, it is known to spread from one person to another through close contact, coughing, sneezing and even by touching an object containing adenovirus and then further touching the mouth, nose or eyes. However, usually the infection does not last long and is not severe in kids unless if they are immunocompromised.

In immunocompromised patients, Adenoviruses can on rare occasions cause hepatitis. In my opinion, the sudden surge of the infection in kids is very rare, especially in children who don’t appear to be immunocompromised.

If Adenovirus is the cause of these cases, there could be a possibility that a newer variant of adenovirus has emerged that more easily causes hepatitis.

Another angle of investigation worth looking at is whether co-infection with COVID-19 in these children with Adenovirus has any role in inducing this acute condition.

Further investigations are needed to confirm this and in the meantime parents and children should practice proper hygiene such as handwashing along with good respiratory hygiene/cough etiquette.

 

It's too early to make any definitive statements as there is insufficient clinical, laboratory and epidemiological data to determine whether the cases are caused by an infection, toxicity or something else. Given the powerful tools now available and recent experience with SARS, COVID etc, if a novel agent is involved it is reasonable to expect that it will be identified quickly.

If the answer is more complex, for example, an unexpected toxicity or an unusual interaction between two or more agents, then it is likely to take longer to unravel.