ALT exceeds 2000 IU/L, a large number of acute severe hepatitis cases in children have emerged, and the reason is unknown!

The following article comes from Mays Medicine, author 457

On April 5, 2022, the UK health department notified WHO of 10 cases of acute severe hepatitis of unknown cause in children in Scotland. As of April 8, a total of 74 cases have been detected in the UK. Subsequently, Spain also reported three cases of severe hepatitis in children of unknown etiology on April 13. Similar cases have also been reported in Denmark and the Netherlands. On April 14, the U.S. Centers for Disease Control and Prevention said they were assisting in the investigation of nine children aged 1-6 in Alabama with acute severe hepatitis.

As these cases become public, more and more health departments begin extensive case-finding campaigns, with more numbers likely to be reported in the future.

In the UK, which currently has the largest number of cases, the children are concentrated in the age group of 2-5 years, and the main symptoms are vomiting, skin jaundice and yellowing of the whites of the eyes. The first batch of clinical data published by local researchers in "Eurosurveillance" on April 14 showed that the blood alanine aminotransferase (ALT) level of most children exceeded 2000IU/L, and the normal value should be in the 10-40IU/L.

Note: The admission time of 13 children with unexplained severe hepatitis in Scotland, UK, suddenly increased in March.

Note: Age distribution of 13 children diagnosed with severe hepatitis of unknown cause in Scotland, UK

As of April 12, there have been no deaths in any country, but some children are very ill, including 6 British children (6/74), 1 Spanish child (1/3), and 2 American children (2/9). ) requires liver transplantation.

Will Irving, professor of virology at the University of Nottingham, said the situation was unusual. Hepatitis cases in children under the age of 10 are very rare. In general, adults are more likely to develop severe liver disease, while children are usually not affected.

Just one week before the onset of illness, the children were healthy, and clinical records indicated that these children did not have any significant prior medical history, such as underlying immunodeficiency or treatment with immunosuppressants.

At present, we do not know the cause of severe hepatitis in children. The earliest guess is that it comes from toxic substances in food, drinking water or toys, but after inquiring and investigating the guardians, these possibilities are initially ruled out.

Hepatitis A, B, C, and E infection were also ruled out after several typical hepatitis virus tests were performed on children in the UK and Spain. Because the majority of children did not develop fever, or abnormal blood inflammatory markers, C-reactive protein, and white blood cell counts, bacteriological examinations were performed in a small number of patients, and no abnormalities were reported.

After that, the scientists further expanded the detection of viruses to those viruses that are not routinely tested for hepatitis, such as enteroviruses, paraenteroviruses, human herpesviruses 6 and 7, varicella zoster virus, and adenovirus.

In the end, they got some clues on the adenovirus - five of the 13 Scottish children announced in "European Surveillance" tested positive for adenovirus, and officials from the Alabama Department of Public Health also confirmed the local Five of the nine sick children were positive for adenovirus-41,

Adenovirus is mainly transmitted by respiratory tract or contact through respiratory droplets. After infection, it can cause cold symptoms, conjunctivitis, vomiting and diarrhea, but rarely hepatitis. Adenovirus-41, which was seen in the Alabama case, was also primarily responsible for childhood gastroenteritis.

As a seasonally transmitted virus, February-April is the peak period of adenovirus epidemics.

The Scottish researchers believe that if these severe hepatitis are really caused by adenovirus infection, it is either a completely new variant with unique clinical symptoms, or a conventionally circulating adenovirus variant, which is only caused by infection in children. more serious impact.

"During the Covid-19 epidemic, children who were isolated at home had less exposure to pathogens from the outside world, which may lead to their immune function not being exercised. When the UK began to lift Covid-19 restrictions, there was a marked increase in childhood viral infections, including adenovirus. infection”, virologist Professor Will Irving offered his view, but not absolute.

Note: The age distribution of adenovirus-positive cases detected by laboratories in the UK over the years shows that children aged 1-4 are the hardest hit areas for adenovirus infection

In addition to adenovirus infection, scientists also noticed that some children have recently tested positive for the new coronavirus, and the variant strain prevalent during this period was mainly Omicron BA.2. Modelling by the UK Office for National Statistics estimates that the proportion of the country's population with children aged 2-4 testing positive for SARS-CoV-2 was around 7% in early February, reached around 13% in mid-March, and dropped to 7% in early April.

Does previous coronavirus infection make children more susceptible to adenovirus infection? Will severe hepatitis be a long-term sequelae of children infected with the new coronavirus? In all kinds of weak evidence, we have to think more, and even the emergence of a new toxin is possible.

UK authorities are currently conducting further investigations, including more detailed exposure history, toxicology testing, more comprehensive virology/microbiology testing, and organizing experts to conduct a thorough investigation of suspected cases.

The WHO stated that the immediate priority is to identify the etiology to guide further clinical and public health actions. Any epidemiological link between cases may provide an indication for tracing the source of the disease, and the spatiotemporal links between cases should be carefully investigated, as well as possible risk factors among their contacts.

WHO will closely monitor emerging severe hepatitis in children and strongly recommends that countries identify, investigate and report potential cases that meet the case definition.

A confirmed case is defined as: since January 1, 2022, children 10 years and younger with acute hepatitis (not caused by hepatitis A, B, C, D, E) and aspartate aminotransferase (AST) or alanine Acid transaminase (ALT) exceeds 500U/L.

Probable cases were defined as: as of January 1, 2022, aged 11-16 years, with acute hepatitis (not caused by hepatitis A, B, C, D, E) and aspartate aminotransferase (AST) or Alanine aminotransferase (ALT) exceeds 500U/L.

Epidemiologically related cases: Suffering from acute hepatitis (not caused by hepatitis A, B, C, D, E) and close contact with a confirmed case since January 1, 2022.

Reference:

[1]https://www.science.org/content/article/mysterious-hepatitis-outbreak-sickens-young-children-europe-cdc-probes-cases-alabama

[2]https://www.eurosurveillance.org/content/10.2807/1560-7917.ES.2022.27.15.2200318#metrics_content

[3]https://www.who.int/emergencies/disease-outbreak-news/item/acute-hepatitis-of-unknown-aetiology---the-united-kingdom-of-great-britain-and-northern-ireland

Human adenoviruses (EAds) are classified into 47 serotypes and six subgenera (A-F) with different tropisms. In recent years adenovirus type 40 (Ad40) and 41 (Ad41) of subgenus F have been shown to be causative agents in enteric infections, which is second in importance only to rotaviruses as a cause of infantile gastroenteritis. Infection with EAds occurs worldwide and has been associated with 4-17% of cases of diarrhoea in children. Ad40 and Ad41 primarily affect young children less than 2 years of age and occur throughout the year. The clinical characteristics include watery diarrhoea accompanied by vomiting, low grade fever and mild dehydration. A distinct feature of EAds infection is the protracted diarrhoea (mean 8.6 and 12.2 days for Ad40 and Ad41, respectively)

The Bioperfectus Enteric Adenovirus Real Time PCR Kit is an in vitro diagnostic test, based on real-time PCR technology, for the detection of DNA from the Enteric Adenovirus. Specimens can be obtained from human stool.