In fact, the World Health Organisation say there have been over 650 cases reported from 33 countries Worldwide between 5th April and the 26th May, but this is likely to be an underestimate due to many countries not looking for specific causes of hepatitis, but rather assuming it is due to Hepatitis Viruses A-E because the tests to confirm the cause are not always routinely available.
The other striking thing about these cases, above and beyond the unknown cause, is that the hepatitis appears to be more severe than hepatitis normally is in children.
The UK has been investigating this outbreak for most of the year and has pretty thorough data from 1st January to the 3rd of May. In this period there were 163 cases of which 11 required liver transplants. No patients have died so far in the UK, but in the USA 20 of 109 cases required liver transplants, and 3 died. Needless to say, this is worrying, as severe liver failure or death from acute hepatitis in children is usually very, very, rare.
What is hepatitis and how does it present?
Hepatitis is inflammation of the liver. It presents with:
- Jaundice – yellowing of the skin and eyes due to the build up of bilirubin in blood which has a yellow colour (think of The Simpson’s and you won’t be far wrong!)
- Dark urine – as bilirubin gets into urine it makes the urine dark
- Pale grey poo – bilirubin is normally excreted into the gut making poo brown (although there are other reasons as well, but let’s not go there!) but if bilirubin is not excreted by the liver into the gut the poo stays pale and grey
- Itchy skin – caused by the build-up of bilirubin and bile salts in skin
- Muscles and joint pains
- Nausea and vomiting
- Loss of appetite
- Abdominal pain – especially right upper quadrant pain over the liver
Normally the liver is very good at recovering and regrowing after damage has been caused. Even the ancient Greeks knew this. In the Greek legends Prometheus was punished by Zeus because he stole fire to give back to mankind. He was chained to a rock in the Caucasus Mountains, and every day an eagle came and ate part of his liver. Each night, his liver would regrow, which meant he had to endure his punishment for eternity. Okay, the liver takes a bit longer than a night to regrow but you get the (very graphic!) picture.
In the case of severe liver failure, the damage to the liver is too much for the liver to cope with and it dies completely. In this situation the patient either gets a liver transplant, or they die; we do not have a machine that effectively performs the function of the liver in the way we do with kidneys and dialysis.
The other thing that is a bit weird about the current outbreak is that all the cases are in children, with nearly 60% being 3-5 years old. Cases do not appear to be occurring in adults suggesting adults are not susceptible or are immune to whatever is causing the hepatitis.
What are the current hypotheses?
A lot of work has been done to try and identify the cause of the hepatitis outbreak. The most common and consistent finding so far is the presence of Adenovirus DNA in the blood of about 70% of the patients. At the moment this is the top of the possible causes although it is not confirmed and Adenovirus infections in children are very common so it is possible this could be coincidental. At the moment nothing will be ruled out until it has definitely been shown to not be the cause.
The current possible hypotheses are:
- An unusual Adenovirus infection due to:
- Abnormal patient response to the Adenovirus leading to hepatitis
- Very high rates of population Adenovirus infection meaning the outbreak of hepatitis looks bigger than normal (lots of cases means relatively more “rare” complications)
- Abnormal response to Adenovirus due to immune priming by SARS CoV2 which is also very common at the moment (SARS CoV2 is making patients respond to Adenoviruses in a weird way)
- Abnormal response to Adenovirus due to coinfection with another as yet unidentified virus
- Abnormal response to Adenovirus due to exposure to an unidentified toxin, drug or environmental chemical
- A new variant of Adenovirus
- A post-infection syndrome due to past SARS CoV2 infection
- A drug, toxin or environmental exposure (without blaming any viruses)
- A novel unknown pathogen yet to be discovered (oh goody, another new virus!!!)
- A new variant of SARS CoV2
Although the list of possible hypotheses is very long, the Adenovirus hypothesis is number 1.
Another bit of supporting evidence for the Adenovirus hypothesis is that in 27 of 35 children who had their Adenoviruses typed by molecular methods, the Adenovirus was shown to always be type 41F. Again, this doesn’t prove Adenovirus 41F is the cause, as it could just be the common Adenovirus circulating within the population at the moment, but it is suggestive that there might be something special about this particular virus.
So far, no toxin or drug has been found. Some background use of paracetamol (a hepatotoxic drug) has been found, but the levels in the patients is consistent with treatment doses not toxic doses.
The most important theory that has been excluded is that the cause might be the Covid vaccinations. IT IS NOT! These children (under 5 years old) are too young to have been vaccinated.
So, where are we now?
Well, the hunt for the cause continues. Paediatricians, Virologists and Microbiologists around the UK are on the look out for cases of unexplained hepatitis, especially in children. Any child with hepatitis (whatever the cause) should be notified to the Health Security Agency as soon as possible so they can continue to build up a picture of who is getting hepatitis and what they might have been exposed to. Children with hepatitis should have ALL these tests sent for possible causes:
- Serum for Hepatitis Viruses A-E
- Whole blood (EDTA, normally the purple tube) for Adenovirus PCR
- Throat swab for Adenovirus PCR
In the meantime, what can we do?
How to prevent infection
Even though we don’t know the cause of these cases of acute hepatitis in children we can have a pretty good guess at how to stop them.
Adenoviruses are spread by droplets, in the same way as SARS CoV2… so wash your hands regularly, don’t sneeze in people’s faces and cover your mouth when you cough! Oh, how quickly we forget…