Explainer: What is the 'mysterious' acute hepatitis among children, should Singapore be worried?

SINGAPORE — Three children in Singapore are among the 650 children worldwide believed to have contracted acute hepatitis — or liver inflammation — from an undetermined cause. 

Little is known about the disease, which is the reason for it being dubbed the “mysterious liver disease”, aside from it affecting children aged 16 or younger.

And of the 650 cases reported to the World Health Organization (WHO) as of May 27, at least 38 children required a liver transplant, and there have been nine deaths.

WHO added that the actual number of cases might be underestimated due to limited surveillance capacities, and the disease is still under investigation. It has assessed the risk of the disease at the global level as "moderate".

The first in Singapore found to have contracted acute hepatitis is a 10-month-old, the Ministry of Health (MOH) said on April 30. 

The ministry would later announce on May 31 that a three-year-old and an eight-year-old were found to have developed the disease in October and November 2021 respectively after MOH conducted a retrospective investigation.

But what is this mysterious acute hepatitis and should Singapore be concerned about it? TODAY asked experts to shed some light.

WHAT IS ACUTE HEPATITIS AND WHEN WAS IT FIRST DETECTED?

Since Oct 1, 2021, children 16 years old and under have been found with cases of hepatitis that are not hepatitis A, B, C, D or E. These cases have been classified by WHO as acute hepatitis.

In a report by the organisation on April 23, it noted that many victims reported gastrointestinal symptoms such as abdominal pain, diarrhea and vomiting. Children were also found that have increased levels of liver enzymes and jaundice.

Children were not found to have any viruses that may cause common types of hepatitis A, B, C, D or E.

The disease was first detected in October 2021 at a hospital in Alabama after five children were admitted with liver damage from an unknown cause.

While WHO has reported 650 probable cases of the disease from 33 countries, there are 99 additional cases pending classification. 

Three-quarters (75.4 per cent) of the probable cases are children under five years old, said WHO.

The United Kingdom currently has the most number of cases, with 222 children believed to have contracted acute hepatitis, of which 11 required a liver transplant. The United States, which has the second-most cases, reported 15 of its 216 cases required a liver transplant.

Closer to home, Indonesia reported on May 13 that seven children have died of the disease last month.

WHAT CAUSES IT?

While there is no exact cause for the virus just yet as researchers are still looking into the disease, a popular hypothesis is adenoviruses.

This is because WHO reported that of 181 cases tested for adenovirus of "any specimen type", 110, or 60.8 per cent, tested positive.

According to Professor Dale Fisher, a senior consultant at the National University Hospital's Division of Infectious Diseases, adenoviruses are a common family of DNA viruses that spread between humans by "droplets or fecal routes", and can survive in the environment.

"They are common causes of respiratory and gastrointestinal disease and can also cause conjunctivitis and bladder infection," said Prof Fisher.

Dr Paul Tambyah, President of the Asia Pacific Society of Clinical Microbiology and Infection, added that Singapore has had a bad adenovirus outbreak, known as adenovirus type seven, from November 2012 to July 2013 which caused respiratory symptoms among children and military personnel. 

"Hepatitis was not a prominent feature of that outbreak caused by adenovirus type seven," he said.

Dr Tambyah also added that adenovirus is not commonly associated with hepatitis, although there have been cases among immunocompromised children and adults.

IS IT ASSOCIATED WITH COVID-19?

The cause is still unknown but linking it to Covid-19 is "naturally tempting", Prof Fisher said. 

WHO reported that of 188 cases tested for Covid-19, only 23, or 12.2 per cent, tested positive. A smaller study of serology results revealed that of the 26 cases whose information was available, 19 had previous infections.

The organisation also noted that the hypothesis that acute hepatitis is a side effect of Covid-19 vaccines is not supported as most of the affected children did not receive such vaccinations.

"The majority were under five years old, and so were unvaccinated, making it hard to link the hepatitis to vaccination," said Prof Fisher.

But there is one way the pandemic could have contributed to the disease. Over the past two years, there had been a decline in other infectious illnesses and therefore one’s immunity to these, Prof Fisher pointed out. 

"The easing of restrictions may have left these children more vulnerable to another infection," he said. 

CAN SINGAPORE PREVENT AN OUTBREAK OF ACUTE HEPATITIS?

Singapore "certainly" has the means to prevent an outbreak once the health authorities know the source and the mode of transmission, said Prof Fisher. 

"But currently we don’t know the role of the implicated adenovirus or its relationship with other viruses or with past Covid infections," he said. 

"Is there a novel virus still undetected and adenovirus is only being found because we are looking so hard for it? We can’t know how to prevent before we know the cause."

However, Dr Tambyah is hopeful more information regarding the acute hepatitis can be found in a couple of months as pathologists and researchers can study the tissue from the highly damaged livers of children who required liver transplants.

"Many of these (transplant) cases have occurred in Europe and North America where there are a number of liver experts who are adept at finding viruses in liver tissues," he said.

He is also optimistic that children with the disease can be quickly detected and treated before major complications set in as medical staff are keeping a lookout for acute hepatitis, and he expects to see more cases in the coming days.

Similar to Prof Fisher, Dr Tambyah said that it is too early to tell if a spread can be prevented, how the disease is spread or what causes it. Regardless, early treatment is key, he said.

He noted that Singapore has dealt with disease outbreaks that spread among children before, such as polio outbreaks in the 1950s and hand, foot and mouth disease outbreaks in the early 2000s.

"Most of these viruses actually spread rapidly through the population until enough people have been infected so there are no longer enough susceptible ones to be infected," he said.

"The key is to identify those at risk of complications or those who are not well and ensure that they are treated appropriately."

Prof Fisher believes that there could underreporting of acute hepatitis cases globally, especially of milder cases. 

"Furthermore the investigations required to understand the causes are incomplete in most cases," he said. "This makes understanding the cause harder and therefore a longer process."