Childhood hepatitis: symptoms, cases in France, causes

SUMMARY :

Severe childhood hepatitis: what symptoms?
Unknown childhood hepatitis: how many cases in France?
Severe hepatitis: what are the possible causes?
Unknown childhood hepatitis: what do we know about the link with Covid-19?

Hepatitis of unknown origin in children : what to remember, the latest information as of July 27, 2022:

Two new studies published this Monday, July 25 have advanced new avenues to explain the causes of this infantile hepatitis. They first concluded that a Covid-19 infection was not a probable cause : no trace of coronavirus was found in the liver of the children studied and the proportion of antibodies against Covid-19 in the affected children was the same as in the non-sick children. This is another virus that has been singled out by scientists: the AAV2 virus (adeno-associated virus 2), detected in strong presence in sick children. To replicate, it needs another virus, an adenovirus, or more rarely the HHV6 virus, responsible for herpes. A co-infection with these two viruses would therefore be an explanation for these hepatitis of unknown origin.
Next to 1,010 children are now affected by acute hepatitis of unknown origin, according to the WHO. The vast majority of affected children are under the age of six, and around 5% of them have required a liver transplant.
22 children died of this hepatitis, again according to the WHO.
In China, the General Administration of Customs has announced that it is strengthening its medical checks at borders to prevent the introduction of acute hepatitis among children. “Passengers, especially children, with symptoms such as abdominal pain, diarrhea, vomiting and jaundice, who voluntarily report or are found at the scene, should undergo medical inspection in accordance with prescribed procedures“, relates the GlobalTimesmedia affiliated with the Chinese authorities.
On April 28, 2022, the European Diseases Agency (ECDC) classified as “public health event of concern“these unexplained cases of hepatitis.”The disease is quite rare and evidence of human-to-human transmission remains unclear. Cases in the European Union are sporadic with an unclear trend“, clarified the ECDC. The risk for children in Europe “cannot be accurately estimated“, according to the agency.”Nevertheless, considering the reported cases of acute liver failure, with cases requiring transplantation, the potential impact for the pediatric population is considered high..”

Severe childhood hepatitis: what symptoms?

These severe hepatitis mainly concern children under 10 years old. Symptoms of these severe liver inflammations include, according to a statement from the UK Health Safety Agency (UKHSA):

“dark urine
pale, gray stools
itchy skin,
yellowing of the eyes and skin,
nausea,
muscle and joint pain,
a high temperature,
abnormal tiredness,
loss of appetite
and stomach aches“.

Unknown childhood hepatitis: how many cases in France?

In France as of July 26, 2022, “nine possible cases have been reported and one is being investigated by medical teamsIare in charge of patients“, indicates Public Health France in its epidemiological point.

Health authorities nevertheless want to be reassuring : “The occurrence of these two cases is not unexpected and does not, at this stage, indicate an excess of cases in France.“.

Severe hepatitis: what are the possible causes?

According to the European Center for Disease Prevention and Control, “an infectious cause is most likely due to the clinical and epidemiological characteristics of case“. If it is not hepatitis A, B or C (since the HAV, HBV and HCV viruses have not been identified in any sick child), it could be a question of an infection by an adenovirus, according to the latest assumptions. Remember that there are about fifty adenoviruses, immunologically distinct, and generally responsible for colds or more severe respiratory infections.

A hypothesis confirmed by new work carried out in England and Scotland. Although they have not yet been validated by the scientific community, these studies confirm that hepatitis in young children could be caused by a co-infection with two viruses: AAV2 (adeno-associated virus 2) and an adenovirus or more rarely the HHV6 virus, responsible for herpes. “I think this is a plausible explanation for these cases“, confirmed Deirdre Kelly, professor of hepatology at the University of Birmingham. “It seems that co-infection plays a key role.”

Adenovirus has been detected in more than 70% of cases in the UK and mainly in the bloodsaid theUK Health Safety Agency (UKHSA). If the main hypothesis concerned adenovirus 41, responsible for liver damage and resulting in vomiting and diarrhea, it now seems not to be the only exclusive cause of the cases. “This suggests that adenovirus 41 is necessary but not sufficient,” Dr. Angela Rasmussen told Stat News.

Nevertheless, some questions persist. Scientists do not understand why some children have a severe form, in particular requiring a transplant. “Could one possibility be co-infection with more than a virus?“, wonders Dr. Kelly. The temporality of the arrival of cases also raises questions. “Why now ?” And “why in the context of some countries, and not others?, pointed out Dr. Zain Chagla, Canadian infectious disease specialist To here.radio-canada. According to one hypothesis, the confinements linked to the coronavirus could have had their impact, in particular by modifying the circulation of other already existing viruses and preventing children from developing certain immune defences.

In an interview given in June to Parisianthe infectiologist Bruno Lina had alerted: “We may never find the cause.”

Unknown childhood hepatitis: what do we know about the link with Covid-19?

While several studies claimed to have discovered a link between childhood hepatitis and a prior infection with Covid-19, these new studies suggest that hepatitis would have no link (or very little) with Covid-19. Indeed, the Covid-19 virus would not have been detected in the times of the sick children in the analysis sample.

SARS-CoV2 would nevertheless have the ability to increase the level of liver enzymes in the blood. According to the results of a study published in March 2021 – which compared 245,000 with Covid and 550,000 with other respiratory infections – THE hepatic risk was higher in the Covid cohort, in particular because of the excess of ALT and AST enzymes and biliurine, the pigment responsible for jaundice in hepatitis. The risk remained increased up to six months after infection, which “suggests acute and long-term hepatic sequelae in pediatric Covid-19 patients.” Normally without consequences, these liver damage can be serious, even in children without liver disease. A other study published in May 2022 in the Journal of Pediatric Gastroenterology and Nutrition had highlighted the case of a 3-year-old girl who, after having had a mild form of Covid-19, developed hepatitis of autoimmune origin.

On their side, in a joint bulletin published on May 13, the WHO and the European Center for Disease Prevention and Control (ECDC) had revealed that of 173 cases tested by PCR for Covid-19, 20 were found to be positive, or 11.6%. Serology results were only available for 19 cases, of which 14 (73.7%) were found to be positive. Finally, of the 56 cases with data on vaccination, 47 were not vaccinated, i.e. more than 80%.

Sources:

CDC Is Investigating 109 Cases of Hepatitis in Children, Including 5 Deaths, New York TimesMay 6, 2022
Hepatitis of unknown origin in childrenECDC, 19 April 2022
Multi-Country – Acute, severe hepatitis of unknown origin in children, WHO, 23 April 2022
Joint ECDC-WHO regional office for Europe hepatitis of unknown origin in children surveillance bulletin, 13 May 2022

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