We know more about the mysterious epidemic of acute hepatitis that raged among young children last spring in Europe, particularly in France and the United Kingdom. Recent studies point to a co-infection with two common viruses in children. Which ?
We know a little more about the mysterious epidemic “strange and alarming” ofchildhood hepatitisof unknown cause which appeared in the spring of 2022 worldwide, including in France. Indeed, several hundred cases of acute hepatitis had been reported in healthy children. Among the warning symptoms that were mentioned were: jaundice, diarrhea, vomiting and abdominal pain… So what do we know about the origin of these hepatitis? The report of 3 studies (a Scottish, an English and an American) published on March 30, 2023 in the journal Natureprovide the beginning of an answer and point the finger at the adeno-associated virus type 2 (AAV2) which was found at high levels in 93% of affected children in the United States, 81% in Scotland and 96.4% in England. When it is alone, this virus does not cause illness because the child’s immune system defends itself. To replicate in liver cells, it needs another so-called “helper” virus. Here too, leads are being advanced. In 13 out of 14 American children, Epstein-Barr virus or human herpes virus (HHV-6B) have been detected. In British children, these same herpes viruses and adenoviruses have been identified at low levels. Also, in all the children studied, the Scottish researchers identified a gene involved in the identification of cells infected by the immune system, which would constitute a risk factor for the onset of acute hepatitis.
How many cases of childhood hepatitis in the world?
Hepatitis seems to affect children under 10 more. THE latest bulletin from Public Health France (October 1, 2022) states:
- As of September 29, 2022, 555 cases of acute hepatitis of unknown origin in children aged 16 or less have been reported by 20 countries in the European Union and European Economic Area (277 cases) and the United Kingdom (278 cases). 44 new cases have been reported compared to the balance sheet of August 25 with a significant and continuous decrease in the number of reported cases.
- As of July 8, 2022, a total of 1,010 probable cases have been reported by 35 countries in five WHO regions, it is not currently possible to know if they represent an excess of cases or if it is the usual number of cases in most countries.
How many cases of childhood hepatitis in France?
As of October 1, 2022, 10 possible cases were reported by medical teams, in connection with Public Health France, indicates the health authority in its press release. “Cases of acute hepatitis of undetermined etiology in children are not uncommon. The occurrence of these two cases is not unexpected and does not, at this stage, indicate an excess of cases in France.“, continues the health authority.
Definition of a possible case of acute hepatitis (updated May 23, 2022)► Child under the age of 18, presenting for acute hepatitis with cytolysis (AST and/or ALT) > 500 IU/L, since January 1, 2022, for whom is found:
OR
– Hepatotoxicity linked to a drug listed on the international website “LiverTox”: https://www.ncbi.nlm.nih.gov/books/NBK547852/; – Infection with a virus classically responsible for acute hepatitis: HAV, HBV, HCV, HDV, HEV, HSV; – Hepatopathy (a1AT deficiency, Wilson’s disease, autoimmune hepatitis, progressive familial intrahepatic cholestasis), metabolic disease, acute leukemia, liver shock, hypoxic hepatitis ( neonatal anoxo-ischemia in particular), from a traumatic cause |
|---|
Are these cases of hepatitis serious?
“This is’a serious phenomenon [qui touche] healthy children“, insisted Deirdre Kelly, pediatric hepatologist at Birmingham Children’s Hospital in the United Kingdom, quoted by the journal Science. Among all the cases identified, 17 children needed a liver transplant. At least a death has been declared.
“The adenovirus or the Covid virus are not viruses known to attack liver cells and cause real hepatitis”
What are the possible causes of these acute hepatitis in children?
The current main hypothesis is thata cofactor affecting young children with adenovirus infection, which would be mild under normal circumstances, but which may trigger a more serious or liver infection. In effect, three studies (one Scottish, one English and one American) published on March 30, 2023 in the journal Naturehighlighted the role of adeno-associated virus type 2 (AAV2), found at high levels in 93% of sick children in the United States, 81% in Scotland and 96.4% in England. Alone, this virus does not cause disease. It can replicate in liver cells but for that it needs another so-called “helper” virus which could be a Epstein-Barr viruses, human herpes viruses (HHV-6B) or an adenovirus. In addition, the Scottish researchers have identified a gene involved in the identification of infected cells by the immune system, which would constitute a risk factor for the onset of acute hepatitis. Other infectious or toxic agents (e.g. Covid) are still under investigation and have not been ruled out but are considered less plausible. “Hepatitis of undetermined origin still exists. Even if we carry out all the examinations and sweep all the known causes, there are always unexplained cases. But it is necessary to eliminate the most important causes, to find a treatment and to guarantee a good vital prognosis.“, confided to us Pr Patrick Marcellin, hepatologist, whom we had interviewed on April 22, 2022.
THE hepatitis viruses (A, B, C, E and D) have been excluded after laboratory tests while further investigations are underway to understand the etiology of these cases, the WHO says. “The increase is unexpected and the usual causes have been ruled out“, indicated the Regional Office of the World Health Organization (WHO) for Europe in a press release dated April 15, 2022. “Early epidemiological investigations of cases in the UK based on trawl questionnaires failed to identify any notable common exposure (including food, drugs or toxins),” it said. European Center for Disease Control and Prevention (ECDC), April 28, 2022.
The Covid at the origin of these hepatitis?
THE Sars-CoV-2, virus responsible for Covid, was also detected in several children (at least in 20 cases among the children tested). However, this is only a guess:the evidence is too thin to solve the mystery“, say researchers and doctors. “The adenovirus or the Covid virus are viruses that can give a small elevation of transaminases, reflecting the impact of viral infection. On the other hand, these are not viruses known to attack liver cells and cause real hepatitis“details Pr Patrick Marcellin, hepatologist, interviewed by the Journal des Femmes Santé on April 22, 2022. Indeed, the clinical syndrome among the cases identified is acute hepatitis (inflammation of the liver) with markedly elevated liver enzymes (aspartate transaminase (AST) Or alanine aminotransaminase (ALT) greater than 500 IU/L). Many cases have reported gastrointestinal symptoms, including abdominal pain, diarrhea and vomiting preceding the presentation of severe acute hepatitis and jaundice. Most cases had no fever. Genetic characterization of viruses should be undertaken to determine any potential association between the cases. This hepatitis epidemic is still under active investigation.
What treatment for childhood hepatitis?
According the course of action developed by Public Health France (updated May 23, 2022), any acute hepatitis with AST and/or ALT > 500 IU/L in a child should lead to a complete first-line etiological assessment, looking for an etiology, in particular infectious, toxic, immuno-haematological, auto-immune, metabolic, vascular or chronic liver disease. No hypothesis should be dismissed out of hand. This etiological assessment must be based in particular on blood, respiratory, urine, stool and liver biopsy samples (ideally). All of these samples must be stored in optimal conditions for subsequent research, in particular metagenomics. At the end of the 1st etiological assessment:
- If the search for adenovirus and/or SARS-CoV-2 is POSITIVE (regardless of the sample) AND that NO other etiology is found, the case is considered possible and must give rise to a report to Public Health France. The samples must be sent for metagenomic analysis.
- If the search for adenovirus and/or SARS-CoV-2 on respiratory and/or stool samples is POSITIVE AND ONLY ONE other etiology is found (or strongly suspected), the case is considered possible and must give rise to a report to Public Health France. In this case, it is requested, as far as possible, to carry out an additional search for this or these viruses on whole blood (EDTA tube, on a previous sample if the case is declared retrospectively) if not carried out. Samples must also be kept until validation of the case by a multi-disciplinary group, for possible metagenomic analysis.
- If the search for adenovirus and SARS-CoV-2 is NEGATIVE (regardless of the sample) AND that NO other etiology is found, the case is considered possible and must give rise to a report to Public Health France. The samples must be sent for metagenomic analysis.
- If the search for adenovirus and SARS-CoV-2 on respiratory, stool and, if possible, blood samples is NEGATIVE AND ONE other etiology is found (or strongly suspected), the case is excluded and does not give rise to a report.
Can we travel despite these cases of hepatitis?
Yes. WHO does not recommend no restrictions on travel and/or trade, especially with the United Kingdom, or any other country where cases are identified, based on currently available information.
What prevention to avoid hepatitis?
Faecal-oral exposure to viruses such as adenoviruses is more likely in young children, says the European Center for Disease Control and Prevention (ECDC). “We therefore recommend reinforcing general good hygiene practices (including careful hand hygiene, surface cleaning and disinfection) in environments frequented by young children”
Sources: Acute hepatitis of unknown aetiology – the United Kingdom of Great Britain and Northern Ireland, WHO, April 15, 2022 / Mysterious hepatitis outbreak sickens young children in Europe as CDC probes cases in Alabama, Science, April 15, 2022