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The UK Health Security Agency (UKHSA) has detected higher than usual rates of liver inflammation (hepatitis) in children.
Prof Graham Cooke, NIHR Research Professor of Infectious Diseases, Imperial College London, said:
“Hepatitis is a broad term to describe inflammation of the liver from a range of causes which may be infectious or a consequence of exposure to a toxic substance, including alcohol and some medications. Globally, the most important causes are viruses that have adapted to infect the liver (viral hepatitis A-E, and particularly hepatitis B and C). Early tests appear to have excluded these as a cause in the hepatitis currently under investigation.
“Mild hepatitis is very common in children following a range of viral infections, but what is being seen at the moment is quite different. Children are experiencing more severe inflammation, in a few cases leading the liver to fail and require transplantation.
“From the information in the public domain, it’s hard to know the most likely cause. Evidence of SARS-CoV-2 and another, unrelated, virus (adenovirus) has been found in some children, but both are common in the community at the moment, and so their presence might be co-incidental. UKHSA will be carrying out careful studies to identify risk factors shared by those with severe hepatitis to give more clues as to the cause. If the hepatitis was a result of COVID it would be surprising not to see it more widely distributed across the country given the high prevalence of SARSCoV2 at the moment.
“More detailed investigation of new cases is a key part of what’s now needed and UKHSA has issued guidance for testing affected children. Clinicians need to be on the look-out for unusual hepatitis and discuss cases to their local public health team.”
Prof Simon Taylor-Robinson, Hepatologist, Imperial College London, said:
“‘Hepar’ is Greek for liver, and ‘itis’ means inflammation – so hepatitis means inflammation of the liver. Hepatitis can be caused by a variety of things, e.g. being overweight, drugs, medicines, alcohol, certain inflammatory or genetic conditions, and in later life also immune conditions. Most of these aren’t a problem in children, but one of the likeliest causes is viral.
“When there is a cluster of cases like this I think it is likely there is a viral cause.
“A whole host of viruses can cause hepatitis – hepatitis A to E are well-known, and Epstein Barr virus (that causes glandular fever) can be another cause. I would expect the authorities to have tested these children for Epstein Barr, but not necessarily as it is a more unusual cause. Adenoviruses are viruses that normally cause the common cold, but some can be more severe and can rarely cause liver inflammation. It is not uncommon to have adenoviruses in spring time. And there are other viruses around too – COVID-19 has been associated with inflammation of many other body organs. At the moment we don’t know what the cause is or if any of these viruses are implicated. It is also difficult to work out cause and effect because viruses can be common anyway so might be present but not necessarily the cause.
“To get clinical hepatitis (including yellowing, or “jaundice”) is quite rare. It is not uncommon to feel unwell, nauseated and even vomit, while showing some abnormalities in blood tests that show liver inflammation – that is called biochemical hepatitis. I don’t know whether some or all of these children had hepatitis with jaundice or just biochemical hepatitis.
“With jaundice, yellowing is usually first noticed in the whites of the eyes; if it becomes more severe you can develop tenderness over the liver area, along with tiredness or in children, sleepiness.
“Treatment is usually supportive – with hydration and management of temperature – because the problem normally resolves. The liver has an amazing ability to regenerate itself after an insult – generally within a few days or weeks things settle back down with this supportive treatment. If blood tests are significantly abnormal treatment would be in hospital as in rare cases, the liver injury can require more specialised medical intervention.
“At the moment it doesn’t seem a cause for widespread alarm because numbers are small. If parents are worried about symptoms in their children they should contact their GP.
“The medical and public health authorities are working hard to work out whether there are common links with these cases, but if adenoviruses are suspected, it means the same sorts of precautions as for other viruses with attention to hand washing and alcohol sanitisers, for example, to prevent viral spreading. This is something with which the public is familiar these days due to COVID.”
Prof Alastair Sutcliffe, Professor of General Paediatrics, UCL, said:
“‘Itis’ means inflammation, and thus appendicitis, meaning inflammation of the appendix, dermatitis of the dermis or skin, you get the idea.
“Hepatitis means inflammation of the liver, which is a key organ. If it is inflamed then this can be broken down into causes. 1. Chemical irritation from e.g. drugs and poisons, noting that the only difference between a poison and a drug is the dose, other chemicals such as so called homeopathic medications, etc. 2. The inflammation can be caused by infections such as viral hepatitis of which there are many viral causes. 3. It can be due to the liver getting blocked, the liver must continuously excrete bile, if the bile ducts (tubes) in the liver get obstructed or even blocked the liver becomes inflamed. 4. There are so called auto immune or ‘friendly fire’ types of hepatitis where the liver gets attacked by one’s own immune system such as in SLE (Systemic Lupus Eryethematosis).
“The core investigation to establish if a person has hepatitis is measure of liver enzymes which are via a blood test. Impaired liver function can show also as jaundice (a yellow discolouration of the skin and sclera).
“In an average week human beings are able to competently fend off exposure to many viruses, in the region of hundreds. Many circulate, noting that two mathematicians calculated that total volume of all the SARS CoV II virus in the entire planet is less than a coke can in volume!
“Our immune system can come under challenge when to these nefarious things are ‘first exposed.’ Many can result in low grade clinically undetectable asymptomatic liver infections. The big players are well known such as Hepatitis A (spread by infected food) or B (sex and needles), however it is known for example that adenoviruses infect the liver too. It’s possible that less exposure to infections over the last two years followed by increasing mixing now might mean some children are encountering infections for the first time in a while.
“What should one do as a parent, if a child gets hepatitis? Fortunately the vast majority of children will fully recover, the liver has huge regenerative capacity and is a rich source of stem cells.”
Prof Will Irving, Professor of Virology, University of Nottingham, said:
“Hepatitis means inflammation of the liver. There are many possible causes – in the UK, the commonest cause is probably toxin-mediated where the toxin is alcohol. The liver may also become inflamed in fatty liver disease associated with obesity. There are also a number of infections, mostly caused by viruses, which can cause inflammation of the liver.
“Hepatitis is unusual in children. In relation to viral hepatitis, infection in childhood very rarely causes clinical disease (this is true of most virus infections – the disease is often much worse if caught as an adult).
“The current crop of cases of hepatitis in children under the age of 10 years is therefore very unusual. At present, a specific cause has not been identified, but investigations are ongoing to try and find the cause. These include looking for toxins in samples from the patients (toxicology) and also trying to identify any virus which might be responsible.”
Prof Sheila Bird, Formerly Programme Leader, MRC Biostatistics Unit, University of Cambridge, said:
“UKHSA say: “While adenoviruses don’t typically cause hepatitis, it is a known rare complication of the virus”. Immediate questions are: how rare is this complication of adenovirus in children; is there a socio-demographic or geographical aspect to the confirmed cases thus far? I note that, only 49 (66%) out of UK’s 74 confirmed cases have occurred in England versus 25 elsewhere in the UK (including 13 in Scotland). However, according to mid-year 2020 population figures for UK1, England accounted for 85.3% of the UK’s children aged under 15 years, Scotland for 7.2%. Hence, the current shortfall in confirmed cases in England versus elsewhere in the UK is very highly statistically significant. Of course, reporting delays can result a strong statistical signal, and may account for the current geographical distribution.
“If reporting delay is not the explanation, then other and potentially important factors may underlie the relative undercount in England.
“Historically, transfusion has been implicated in the transmission of novel hepatitis viruses and would almost surely have been mentioned, had there been an excess of transfusion recipients among the 74 confirmed cases. Hence, attention being directed elsewhere.”
Declared interests
Prof Will Irving: “I currently chair the National Strategy Group for Viral Hepatitis (a multi-agency group with a number of remits including overseeing plans to eliminate hepatitis B and C virus infections as a public health concern). I have received research funding and consultancy fees from a number of pharmaceutical and diagnostic companies (I can supply details if required).”
Prof Sheila Bird: “SMB serves on the statistical expert group for the Infected Blood Inquiry.”
No others received.