More Unusual Child Hepatitis Cases In Malaysia Possible

Experts agree that severe acute hepatitis in children is uncommon, though they differ in their views on the link of the liver disease to Covid-19 and adenovirus.

KUALA LUMPUR, May 23 – The sharp rise in mysterious severe hepatitis among children in the United Kingdom and the United States suggests that more cases are possible in Malaysia that has confirmed one case so far.

Senior consultant paediatrician and researcher Dr Amar-Singh HSS told CodeBlue that while it is very difficult to speculate the potential spread of the serious liver disease, given its unclear cause, the significant increase in cases in the UK and the US that has reported more than 100 cases each does suggest that many “more cases are possible” in Malaysia.

To date, over 348 probable cases of acute hepatitis in children have been reported in 21 countries, according to the World Health Organization (WHO) in a technical note on May 10, with 26 children requiring liver transplantation. Fifteen countries have reported five or fewer cases. It’s unclear whether Malaysia is included in the WHO’s list of probable cases.

On May 6, the Ministry of Health (MOH) reported severe hepatitis in a boy aged four in Sabah who did not have any underlying disease except Covid-19 infection, with investigations ongoing to determine if this is a case of acute hepatitis of “unknown origin” reported internationally.

The four-year and 11-month-old Malaysian child with liver inflammation – who had symptoms of jaundice, fever, lack of appetite, nausea, and vomiting – sought treatment from a hospital in Sabah last March and successfully received a liver transplant on March 30 at a hospital in the Klang Valley after his condition deteriorated. He was discharged last April 21 in good health.

The liver transplant team at Universiti Malaya Medical Centre (UMMC), as well as Dr Alvin Khoh from Gleneagles Hospital in Kota Kinabalu, in a separate statement later attributed a potential link of the severe acute hepatitis in their patient to complications from Covid-19 infection.

Experts agree that severe acute hepatitis in children is uncommon, though they differ in their views on the disease’s link to Covid-19 and adenovirus, a common pathogen that usually causes respiratory illness, which has been identified in at least 74 cases as of April 21, 2022, according to the WHO.

Dr Amar said attributing adenovirus as a possible cause for acute hepatitis of unknown origin among young children does not appear to explain the severity of the clinical picture.

He noted that prior case reports of severe hepatitis due to adenovirus infection usually occur in immunocompromised children, not healthy children. “The majority of the children currently suspected to have this acute, severe hepatitis are previously healthy young children (75 per cent under five years of age),” Dr Amar said.

While Covid-19 vaccines can be definitively ruled out as a cause for these acute hepatitis paediatriac cases, Dr Amar said there is still a possibility that Covid-19 could play a role, though this has yet to be conclusively proven.

Dr Amar cited a recent study conducted by Japanese researchers that looked at the relationship between the cumulative number of Omicron cases in countries and the reported number of probable cases of severe child hepatitis.

“They suggest that we should consider the ‘possibility that infection with Omicron has some relation to the occurrence of severe hepatitis in children’. Hence, it is still too early to speculate as to the definitive cause, or even if multiple different causative agents are involved,” Dr Amar said.

Consultant physician, gastroenterologist and hepatologist at Pantai Hospital Ampang Dr Chieng Jin Yu seems to think otherwise. Dr Chieng told CodeBlue that severe hepatitis is not a common feature in children with Covid-19, making the hypothesis unlikely.

“Covid-19 infection is the ‘hot’ topic around the world nowadays. However, these hepatitis cases don’t seem to be related to Covid-19 infection. Only 16 per cent of the cases reported in the UK had an ongoing Covid-19 infection at the time of testing,” Dr Chieng said.

Dr Chieng also discounted any links between the child hepatitis disease with the Covid-19 vaccine, with current data suggesting that the relationship is unlikely.

“As we know, some Covid-19 vaccines, which are of adenoviral vaccine, use a modified version of adenovirus 26, or a modified version of the adenoviral vector ChAdOx1 that may cause the common cold. However, this strain of adenovirus is different from the one that was found from these young patients,” Dr Chieng said.

The AstraZeneca Covid-19 vaccine is a ChAdOx1-S recombinant vaccine developed by the University of Oxford and AstraZeneca. The Janssen Covid-19 Vaccine by Johnson & Johnson is an adenovirus serotype 26 (Ad26) vector-based vaccine.

CanSino Biologics’ Convidecia vaccine is a modified form of adenovirus type 5, or Ad5. Moscow’s Sputnik V vaccine by the Gamaleya Institute is based on Ad5 and a second less common adenovirus.

Dr Chieng said in England and Scotland, 75 per cent and 50 per cent of cases respectively tested positive for adenovirus, with adenovirus type 41 identified in a significant number of cases.

“Adenovirus is a common virus that can cause respiratory symptoms (cough, running nose, sore throat) or gastro-intestinal symptoms (vomiting and diarrhoea). In most cases, they’re of limited duration and seldom progress into serious conditions,” Dr Chieng said.

“Although the WHO had mentioned the possibility of adenovirus as an etiology – or origin – of this mysterious severe acute hepatitis, it hasn’t been confirmed as the cause for the disease,” Dr Chieng added.

Another hypothesis being investigated is whether lockdowns due to Covid-19 may have weakened children’s immunity due to lower exposure to pathogens, Dr Chieng said. However, more investigation and data are needed to establish the connection.

Dr Chieng expects the MOH to keep a close watch on the trend of the mysterious disease in the country, and work closely with WHO, amid limited global information of the disease.

He also advised the public to practise regular hand washing and respiratory hygiene as preventive measures against the adenovirus and other common infections.

Meanwhile, Dr Amar said there should be heightened vigilance by the MOH and the public as to the symptoms of hepatitis and for sick patients to seek early medical care.

“While we are still unaware of the cause, it would be prudent to continue to protect our children and limit their exposure risk to Covid-19 infection,” Dr Amar added.

The US Centers for Disease Control and Prevention (CDC) said in a statement that 180 paediatric cases of severe hepatitis of unknown cause have been reported in 36 states and territories as of May 18.

The CDC said adenovirus has been detected in nearly half of the children and “continues to be a strong lead”, adding that further lab tests are being conducted to examine the virus genome and other potential pathogens that may be the cause of the liver disease, like Covid-19.

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