Thursday, July 7

Hepatitis of unknown origin in children: different hypotheses and no certainty

It all started on April 5, when the United Kingdom notified the World Health Organization (WHO) 10 cases of severe acute hepatitis of unknown etiology in previously healthy children under 10 years of age in Scotland. After starting a national investigationthree days later, 74 cases had been identified in this population.

Now, the total number of cases worldwide is 614, including 14 deaths reported in Ireland (1), Indonesia (6), Mexico (1), Palestine (1) and the United States (5), according to the last update Report on the Threats of Communicable Diseases of the European Center for Disease Control and Prevention (ECDC).

The origin of the disease remains a mystery. From the first moment, different hypotheses were handled, the last one is a relationship with SARS-Cov-2 infection

In the European Union, until May 19, 2022, there have been reports 125 cases of acute hepatitis in children aged 16 years and younger in 14 countries: Austria (2), Belgium (9), Cyprus (2), Denmark (6), France (2), Greece (3), Ireland (6), Italy (35) , the Netherlands (6), Norway (4), Poland (3), Portugal (12), Spain (26) and Sweden (9). Among all these, six required a liver transplant.

As he ECDC such as the US Centers for Disease Control and Prevention (CDC) have joined the WHO in proclaiming the international alert. Although every year there are episodes of hepatitis of unknown origin in children, countries such as the United Kingdom, Ireland and the Netherlands have reported them above expectations. It is not, at the moment, the case of Spain.

Uncertain origin of this hepatitis

That yes, the origin of the disease it remains a mystery. Laboratory tests excluded all hepatitis viruses (A, B, C, D, and E) in these children. From the first moment different hypotheses were handled. One of the possible causes under investigation is that they are related to an adenovirus infection (particularly type F41), after being detected in most of the cases analyzed.

These are common pathogens in humans that can cause diseases in the respiratory tract, eyes, intestine, liver, urinary tract and adenoids or vegetations. As SINC Francisco Rodríguez, responsible for laboratory diagnosis of viral hepatitis at the Vall d’Hebron Hospital, explains, “adenoviruses are ubiquitous and very common during this time, so it would not be uncommon for children to have them like any healthy person ”.

“However, this type of adenovirus is not related to severe hepatitis in immunocompetent children, as has been observed so far. This suggests that there may be other factors at play, ”says the specialist.

In fact, other theories such as companion animals have been considered. The UK Health Security Agency (UKHSA) has investigated this cause after detecting that 70% of affected minors (64 of 92 children) have a dog or have had recent contact with one. But the relationship has not been confirmed either.

The coronavirus, the latest hypothesis

Recently, a new item published in the magazine The Lancet Gastroenterology and Hepatology has put on the table another risky conjecture: infection by SARS-CoV-2. This comes after his relationship with the covid-19 vaccine.

However, for now the most likely cause remains adenovirus. Although the association is not yet confirmed

“Although this last theory is not yet accepted, this article does not describe something impossible”, points out to SINC Marina Berenguer, professor at the University of Valencia and researcher at the CIBEREHD.

“For example, in women a condition called autoimmune hepatitis is quite common. Suddenly, the immune system attacks the liver, and sometimes it manifests as fulminant hepatitis, like the cases that are being reported in 2022, ”he adds.

“The hypothesis put forward in this new article is that there may be a persistence of SARS-CoV-2 antigenic material in the intestine, but this has not been proven nor are there sufficiently conclusive studies. At the moment the most plausible assumption is still the adenovirus”, insists Berenguer.

back to adenovirus

From the UKHSA they maintain that their investigations still “continue to suggest that there is an association with adenovirus F41”. The second report from the British authority corroborated what was detected in the first report, discovering this adenovirus in 51 of the 62 cases. However, they say, it has not been tested on a set of blood and stool samples for most of them.

“The theory that is being debated the most is that it could be an aberrant immunological reaction to the adenovirus, in the context of a lack of antigenic stimuli for a couple of years due to the fact that we have been more ‘closed’”, continues Berenguer.

The theory that is being debated the most is that it could be an aberrant immunological reaction to the adenovirus, in the context of a lack of antigenic stimuli for a couple of years due to the fact that we have been more ‘locked up’

Marina Berenguer

For Will Irving, Professor of Virology at the University of Nottingham (United Kingdom), “the relationship with adenovirus infection remains tempting: a certain possibility, but not yet proven. There are very few case reports in the world literature of hepatitis-associated adenovirus infection in immunocompetent children or adults.

“If it turns out that adenovirus infection is involved in the cause of this disease outbreak, it will be necessary to explain why the natural history of the infection has changed so dramatically in 2022”, he states in statements to the Science Media Center From United Kingdom.

Health alert or expected situation

Each year there are episodes of unknown hepatitis (of unknown origin), so finding cases is not in itself an alarm signal. Therefore, the remarkable thing is not to find them, but to do it above what was expected, as several states have already done.

“In Spain we are not in a situation that is different from that expected in terms of the proportion of cases. But as is always done, any episode must be studied to see the possible cause and follow up. This situation cannot be underestimated,” Rodríguez stresses.

Much data is needed for the finding of a possible cause to be credible. And today in our country we do not have them. But in the UK I’m sure progress is being made faster

Francis Rodriguez
Vall d’Hebron Hospital

“The problem is that finding the person or persons responsible for these cases of hepatitis will not be easy, it can take several weeks,” says Berenguer, head of the Hepatology and Liver Transplantation group at the La Fe Health Research Institute.

“A lot of data is needed for the finding of a possible cause to be credible. And today in our country we do not have them. But in the United Kingdom I am sure that progress is being made more rapidly”, concludes Rodríguez.