What do we know about the mysterious new hepatitis cases in children?

On 15 April 2022, the World Health Organization (WHO) published news of an outbreak of acute hepatitis of unknown origin in 74 children across the United Kingdom.

An update published just over a week later, on 23 April, revealed that similar hepatitis cases had been reported across several other European countries, as well as Israel and the United States. Since then, likely cases have been reported by media in Canada, Japan and Indonesia, and the current number of reported cases sits at nearly 200. Sadly, four children are reported to have died so far.

As we have learned from the COVID-19 pandemic, misinformation thrives in the context of limited data and understandable fear and concern.

So, what do we know about these mystery hepatitis cases, and what should we be aware of as the situation evolves?

What is hepatitis?

Hepatitis is inflammation of the liver. This organ is key to processes including detoxification and the regulation of our metabolism. Therefore, liver damage can be very serious and even life-threatening.

Hepatitis can be caused by a viral infection (referred to as viral hepatitis), immune system issues, or exposure to alcohol, drugs or other toxins. It can be either acute (short-term) or chronic (long-term). The current outbreak is characterised by cases of acute hepatitis in children who have an elevated level of liver enzymes in their blood.

There are five main viruses known to cause viral hepatitis in humans – hepatitis virus A, B, C, D and E. According to the WHO, hepatitis B and C collectively form the most common cause of death from liver cirrhosis, liver cancer and viral hepatitis. It is estimated that 345 million people are infected with hepatitis B or C. Effective vaccines can protect against hepatitis B, D and E.

What do we know so far about the new hepatitis of unknown origin?

While the condition is still rare, clinicians and public health experts are concerned because the recent outbreak of hepatitis in children does not appear to be caused by any of the five known human hepatitis viruses. According to the WHO’s report on 23 April, these viruses had not been detected in any of the reported cases.

However, a different type of virus – adenovirus – was detected in at least 74 cases of the unusual childhood hepatitis.

“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,” explains Vinod Balasubramaniam, a virologist at Monash University Malaysia. However, adenoviruses have been known to cause rare cases of hepatitis in immunocompromised patients.

“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,” says Balasubramaniam.

In particular, scientists’ eyes are trained on a strain of adenovirus called F41, which has been confirmed as present in several of the recent hepatitis cases. F41 typically causes gastroenteritis, but it can infect other body sites as well.

“They are very clever DNA viruses and capable of infecting different organs,” says Peter White, a professor in microbiology and molecular biology at the University of New South Wales (UNSW). For instance, some people will experience both respiratory and gastrointestinal symptoms when infected with adenovirus.

“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,” White says. “I’d be looking at sequencing the whole virus to get the full genome … to look for recombination or mutation that enables this change to allow it to affect the liver cells.”

At least 20 patients in the hepatitis outbreak were also infected with SARS-CoV-2 (the virus that causes COVID-19), and 19 of these were infected with both SARS-CoV-2 and adenovirus – raising the possibility that co-infection by the two viruses may be involved in the disease.

“Might this be a manifestation of co-infection with both adenovirus and COVID-19 in young children with an underlying rare genetic problem?” asks Robert Booy, an expert on infectious diseases and vaccines, and honorary professor at the University of Sydney. Booy also acts as a consultant to vaccine manufacturers.

The WHO notes that adenovirus infections had recently been increasing in the UK and the Netherlands, which have both reported cases of the unusual hepatitis. In addition, young children may be more susceptible to adenovirus infections since their immune systems have had limited exposure to viruses during COVID-19 lockdowns and restrictions.

However, we don’t have enough evidence yet to confidently point the finger at adenoviruses, COVID-19, or any other particular cause.

“All of the known causes of hepatitis, ranging from viruses to drugs and toxins, are being considered,” says Andrew Lloyd, an infectious diseases physician and hepatitis researcher at the Kirby Institute at UNSW.

Ian Gust AO, a professor emeritus and medical virologist who has worked on hepatitis A vaccines, says that any new disease agent – such as a novel virus – is likely to be identified quickly given the tools we already have at our disposal for tracking COVID-19.

“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,” he says.

Are the new hepatitis cases caused by COVID-19 vaccines?

This is extremely unlikely.

First Draft, a non-profit organisation tracking online misinformation and disinformation, has reported that unconfirmed rumours of cases of the hepatitis of unknown origin in Shanghai and Beijing have been circulating on social media.

Chinese-language Tweets posted on 26 April shared unverified WeChat screenshots and linked the rumoured cases to misleading claims about lockdowns (Beijing is not currently in lockdown). The following day, comments on the Hong Kong forum LIHKG repeated the unverified claims about a case in Shanghai and speculated that the hepatitis could be a “bioweapon” or “vaccine-induced”.

However, the hepatitis is extremely unlikely to be induced by COVID-19 vaccines, as very few of the children who have had the condition have been vaccinated against COVID-19. Many were under the age of five and were not eligible for vaccination.

Similarly, there is no evidence to support the idea that the hepatitis cases are caused by an engineered virus or bioweapon. Viruses do naturally mutate and change slightly over time, as the emergence of successive SARS-CoV-2 variants has shown.

As the situation develops further and more information emerges, experts suggest typical hygiene measures that reduce the spread of infections can be followed in the interim: for example, washing hands, disinfecting surfaces, and covering coughs.

Additional research by Esther Chan, bureau editor for First Draft APAC. First Draft is a non-profit global organisation that researches online misinformation and disinformation.

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