A week ago, on April 15, local time, WHO issued an announcement that the United Kingdom recently reported cases of hepatitis of unknown etiology found in children.
As of 8 April, the number of such cases reported across the UK has risen to 74, with the main cases being children under 10 years of age, with the main symptoms including jaundice, diarrhoea, vomiting and abdominal pain, some of whom are in severe condition, the report said.
A week later, on April 21, local time, the latest report from the UK Health Security Agency (UKHSA) showed that according to the investigation, 34 cases of unexplained young children's hepatitis were found in the UK last week, and the total number of cases has reached 108. In these cases, eight children underwent liver transplants due to their severe condition.
(Source: UKHSA)
According to the health reminder released by the US Centers for Disease Control and Prevention (CDC) on the 21st, the first case of unexplained hepatitis in children in the United States has appeared in October 2021 in a children's hospital in Alabama, which has treated 5 children with unexplained severe liver injury (including some acute liver failure).
To date, cases of unexplained hepatitis in children have been reported in the United Kingdom, the United States, France, Spain, the Netherlands, Israel, Belgium, Romania, Norway, Denmark, Portugal and other countries.
What is unexplained hepatitis?
According to the etiology, hepatitis can be generally divided into: viral hepatitis, autoimmune liver disease, drug and toxic hepatitis, alcoholic liver disease, non-alcoholic fatty liver disease, metabolic disorder liver disease and so on.
In addition, there are some hepatitis that cannot be clearly caused by laboratory tests, histological examinations and other diagnostic methods at this stage, which is clinically called "unexplained hepatitis". It has been reported in the literature that the incidence of unexplained hepatitis is about 5% to 30%.
As with other hepatitis, the symptoms of unexplained hepatitis may be optional, the severity of the disease is also different, and some can even cause liver failure, progression to cirrhosis, hepatocellular liver cancer; the course of the disease can be fulminant, acute and chronic; the age of onset and susceptible people are not limited.
For the unexplained hepatitis in children in Europe and the United States, the US Centers for Disease Control and Prevention pointed out that the symptoms of these hepatitis cases include fever, fatigue, loss of appetite, nausea, vomiting, abdominal pain, dark urine, light stool color, joint pain and jaundice. Some children are even in serious condition and need a liver transplant.
(Source: CDC)
According to the Infectious Disease Threat Report released by the European Centre for Disease Control and Prevention, 17-23 April 2022, 8 children in the UK have received liver transplants, 4 children in other EU countries need liver transplants, and 2 children in Israel have received liver transplants. In the United States, there are also 2 children who are seriously ill and need a liver transplant.
The new coronavirus and adenovirus are the most suspected
Among the possible causes of unexplained hepatitis, viral infection is an important part of it.
The Report of the British Health Safety Agency (UKHSA) on the 21st pointed out that 77% of the cases tested positive for adenovirus, suggesting that the unexplained hepatitis in children may be related to adenovirus infection, and relevant personnel are studying whether the genome of adenovirus has changed.
This is also confirmed by the case report published by the Scottish Department of Public Health (PHS) in Eurosurveillance (Eurovision Surveillance), which tested positive for adenovirus and 5 positive for COVID-19 out of 13 reported in Scotland (2 of whom were 3 months before admission, 2 within 11 days of admission, and 1 of whom were positive at admission).
(Source: Eurosurveillance)
In this regard, the Scottish Department of Public Health tends to believe that adenovirus infection is the most likely to cause hepatitis, but it does not rule out the possibility of new coronavirus or new virus.
Adenovirus was first isolated from human adenoid tissue in 1953, hence the name adenovirus. It has an affinity for the lymph glands and can lurk in the lymph glands for a long time. They can cause a variety of diseases, including upper respiratory tract infections, conjunctivitis (eye infections), bladder infections, pneumonia, encephalitis and gastroenteritis.
However, for people with normal immunity, adenovirus is less pathogenic, and only mild self-limiting symptoms occur after human infection with wild-type adenovirus, and adenovirus infection can only lead to serious consequences in immunocompromised people (organ transplants, AIDS patients, etc.).
In this regard, the explanation given by the Scottish Department of Public Health is that many young children may not have been exposed to many common viruses due to the long-term isolation during the epidemic, and when masks are removed and social isolation measures are lifted, they become more vulnerable to external infections.
(Source: Figureworm Creative)
In addition to adenovirus, the suspicion of the new crown virus is also very large.
The Schneider Children's Medical Center in Israel investigated 12 previously reported cases of unexplained hepatitis in children (these 12 cases are not recent, the time span is 14 months, the first case was detected in February 2021), found that 11 of them were infected with the new crown virus, and after excluding other possible causes, the Israeli Ministry of Health believes that 5 of the 12 children are sequelae of the new crown, from the new crown virus infection to the onset of hepatitis, the time interval is about 3.5 months.
However, it is clear that these children with unexplained hepatitis are not related to the COVID-19 vaccine, and the UK Health Safety Agency noted that none of these children with unexplained hepatitis have been vaccinated against COVID-19.
Hepatitis of unknown origin may be autoimmune hepatitis
In addition to viral infections, other Israeli hepatologists believe that this hepatitis is actually our familiar autoimmune hepatitis (AIH), but the serological test results are not typical.
(Israeli Professor Rifaat Safadi on autoimmune hepatitis original text/source: Haaretz)
Autoimmune hepatitis refers to liver inflammation caused by the attack of the autoimmune system on the liver, and clinical features include elevated serum aminotransferase levels, hyperimmunoglobulin G (IgG)emia, positive serum autoantibodies, and moderate to severe interfacial hepatitis in liver histology.
The etiology of autoimmune hepatitis is unknown, with genetic predisposition, most patients have insidious onset, no obvious symptoms or only non-specific symptoms such as fatigue, a small number of patients have acute onset, and even develop acute liver failure, about 1/3 of patients are initially diagnosed as cirrhosis.
According to autoantibodies, autoimmune hepatitis can be divided into type 1 AIH and type 2 AIH, of which type 1 occurs mainly in adults and type 2 is mainly in children.
In short, although the recent news about children's unexplained hepatitis has been frequently reported, cases in some of these countries are not recent, but found in the process of retrospective investigation after the WHO issued relevant announcements, and the relevant specific situation is still under further investigation, we do not have to panic too much, whether it is adenovirus or the new crown virus, pay attention to personal hygiene, wash hands frequently, wear masks, gather less and other conventional protective means can be effectively prevented.
Edit: Dr. Spring Rain
bibliography:
Peng Jing. Clinical and histological features of unexplained hepatitis[D].Third Military Medical University, 2014.
[2] CDC,CDC Alerts Providers to Hepatitis Cases of Unknown Origin,https://www.cdc.gov/media/releases/2022/s0421-hepatitis-alert.html
[3] European Centre for Disease Prevention and Control,Communicable disease threats report, 17-23 April 2022, week 16,https://www.ecdc.europa.eu/en/publications-data/communicable-disease-threats-report-17-23-april-2022-week-16
[4] UKHSA,Increase in hepatitis (liver inflammation) cases in children under investigation,https://www.gov.uk/government/news/increase-in-hepatitis-liver-inflammation-cases-in-children-under-investigation
[5] Marsh Kimberly, Tayler Rachel, Pollock Louisa, Roy Kirsty, Lakha Fatim, Ho Antonia, Henderson David, Divala Titus, Currie Sandra, Yirrell David, Lockhart Michael, Rossi Maria K., Phin Nick. Investigation into cases of hepatitis of unknown aetiology among young children, Scotland, 1 January 2022 to 12 April 2022. Euro Surveill. 2022;27(15):pii=2200318. https://doi.org/10.2807/1560-7917.ES.2022.27.15.2200318
[6] Haaretz,Explainer | Everything You Need to Know About the Hepatitis Outbreak Among Children,https://www.haaretz.com/israel-news/everything-you-need-to-know-about-the-hepatitis-outbreak-among-children-1.10754895
Hepatology Branch of Chinese Medical Association. Guidelines for the diagnosis and treatment of autoimmune hepatitis (2021)[J]. Journal of Clinical Hepatobiliary Diseases,2022,38(1):42-49. DOI:10.3969/j.issn.1001-5256.2022.01.008.