SINGAPORE - The number of cases linked to the worldwide acute hepatitis outbreak has risen to 348 probable cases in 20 countries, the World Health Organisation (WHO) reported on Tuesday (May 10).

An additional 70 cases from 13 other countries are currently pending classification as tests are being completed.

In a disease outbreak news update on WHO's website on April 23, when there were at least 169 reported cases, the children with acute hepatitis were found to be aged between one month and 16 years old.

Some of them required a liver transplant.

Last month, Singapore's Ministry of Health (MOH) announced that a 10-month-old boy here was diagnosed with acute hepatitis.

Investigations are ongoing to determine if his case is similar to that of the global outbreak.

WHO said the current leading hypotheses for the outbreak remain an adenovirus.

An adenovirus is a common virus that can cause a wide range of illnesses from respiratory to acute gastroenteritis.

The Straits Times speaks to experts about the likelihood of an adenovirus infection, and the symptoms parents should look out for if they suspect their child has acute hepatitis.

Q: What is acute hepatitis and what are some symptoms?

A: Acute hepatitis refers to liver inflammation.

Early symptoms include tummy pain or discomfort, loss of appetite, nausea, vomiting and diarrhoea, said Dr Chan Si Min, head and senior consultant of the division of paediatric infectious diseases at Khoo Teck Puat - National University Children's Medical Institute in National University Hospital.

Some children may have a fever during or just before hepatitis, or become lethargic with body aches.

Hepatitis can also lead to jaundice, which is the yellowing of the eyes or skin, and can lead to itchy skin, pale stools and dark urine.

Q: What are the causes of and treatments for hepatitis?

A: Dr Chan said the possible causes of hepatitis include viral infections, bacterial infections, drugs or medications, and other long-term medical conditions such as metabolic and cardiac conditions which affect the liver.

Many different viral infections such as hepatitis A, B or C, influenza, adenovirus and dengue can cause hepatitis.

Some vaccines taken during childhood such as the hepatitis B, pneumococcal and influenza vaccines can prevent some of these infections.

Dr Chan said there is no specific treatment for acute hepatitis other than medications to support the liver function and complications of liver failure.

"Parents should be aware of the warning symptoms of hepatitis, and seek medical review if they occur, but not be unduly worried.

"A blood test may be done to look for liver inflammation, and samples such as nasal, blood or stool samples can be sent to detect the presence of adenovirus and other infections," she added.

Dr Chiou Fang Kuan, head and senior consultant of gastroenterology, hepatology and nutrition service at KK Women's and Children's Hospital (KKH), said: "At KKH, while we do see a few cases of severe acute hepatitis in children each year, it is not a common condition."

Some possible known causes aside from viral infections include autoimmune disease, metabolic disorder and drug- or toxin-induced liver injury.

However, in up to 40 per cent of cases of severe hepatitis, no cause is found despite extensive investigations, he added.

MOH had previously said that laboratory tests on the 10-month-old boy has turned out negative for hepatitis type A, B, C and E viruses.

Q: What is an adenovirus infection and can it cause acute hepatitis?

A: Dr Chan said the adenovirus was found in many of the reported hepatitis cases affecting children worldwide.

The virus is one with many genetic variants, said Dr Chan, adding that infection can occur at any age, although mainly in young children, and at any time of the year.

The virus usually causes fever, respiratory illness (cough, cold, sore throat), gastroenteritis (stomach inflammation) and conjunctivitis (red eyes).

More serious infections may cause pneumonia, hepatitis or meningoencephalitis, which affects the brain.

The virus is usually spread by respiratory droplets or secretions, or via direct contact with an infected person, stools or a contaminated surface.

Associate Professor Thoon Koh Cheng, head and senior consultant of the infectious disease service at KKH, said the hospital did manage cases of adenovirus-related hepatitis in the past but these were rare.

The patients showed severe or widespread adenovirus infection, he added.

Dr Chiou said adenovirus infections do not "typically" cause hepatitis alone, but it is like any viral infection that can be associated with the development of hepatitis along with other respiratory or gastrointestinal symptoms.

He added that it is not common for adenovirus to be the primary cause of acute hepatitis in healthy individuals.

The possibility of a new virus causing hepatitis cases worldwide is still being investigated, said Dr Chiou.

Q: Could there be a link between Covid-19 and hepatitis?

A: Many of the children diagnosed with acute hepatitis worldwide were extensively tested for Covid-19 and the majority were found to be negative for the virus, said Associate Professor Hsu Li Yang.

Prof Hsu, vice-dean (Global Health) at National University of Singapore's Saw Swee Hock School of Public Health, added that many of those who were affected were unvaccinated against Covid-19.

This means the acute hepatitis they contracted was not a rare side effect of Covid-19 vaccines.

MOH had noted that while the 10-month-old boy in Singapore was infected with Covid-19 in December 2021, there is currently no evidence to show the acute hepatitis he was diagnosed with is related to Covid-19.

Q: What is adenovirus type 41 and could it be the culprit for acute hepatitis among children?

A: Ms Philippa Easterbrook, from WHO's global hepatitis programme, told a press conference on Tuesday that around 70 per cent of the acute hepatitis cases tested positive for the adenovirus type 41.

The adenovirus type 41 is an enteric adenovirus, which means it relates to the intestines.

It has been known to cause clusters of illness, but not severe hepatitis in otherwise healthy children, said Assistant Research Professor Kristen Coleman from the University of Maryland's School of Public Health.

It is instead typically associated with mild to moderate gastroenteritis, which includes symptoms of diarrhoea, vomiting and abdominal pain.

Prof Hsu said it is unclear if the acute hepatitis reported in children is solely an adenovirus infection.

"Although a significant proportion of the affected children tested positive for adenovirus 41, this is not a virus that is known to cause severe hepatitis, whether in sick or healthy children," he added.

"The children are otherwise also not epidemiologically linked - one would expect to find more cases of hepatitis among infected children in households, for instance."

Prof Hsu said that in tests done in the United States where the children's livers were biopsied or sampled, no evidence of viral infection - or much less an adenovirus - was found despite clear evidence of liver inflammation.

"Either the adenovirus is a red herring, or the infection combined with a second unknown but rare trigger leads to the development of hepatitis," he said.