Recently, a sudden rise in acute severe hepatitis with unknown cause in children is being reported from multiple countries around the world, attracting the attention of clinicians, scientists and policymakers.

According to the World Health Organisation (WHO), approximately 10 per cent of these affected children required liver transplantation, which is, indeed, a matter of grave concern.

Since the beginning of 2022, cases have been identified across the United Kingdom, especially among children younger than 5 years old. However, the children's age ranges from 1 month to16 years old. According to the UK Health Security Agency (UKHSA), jaundice (yellow discoloration of the skin, the whites of the eyes, mucous membrane) and vomiting are the most common symptoms found among the children affected. Besides, abdominal pain, nausea and diarrhoea were also evident among them.

These signs and symptoms are similar to those of viral hepatitis.

The most frequent causes of viral hepatitis, such as A, B, C, D and E, however, have not been detected in the affected children. Hepatitis viruses A and E are primarily transmitted through ingestion of contaminated food and water, while B and C are commonly transmitted through sexual contact, exposure to infective blood, and sharing of needles. Fever, loss of appetite, nausea, vomiting, dark urine, clay-coloured stool, joint pain and jaundice are the main signs and symptoms of hepatitis.

In general, hepatitis A and E does not need special treatment. A safe and effective vaccine against hepatitis B is available, while new "direct acting" antiviral medicines for hepatitis Care now available worldwide, including in Nepal.

Surprisingly, adenovirus, commonly known as the respiratory virus, was detected in the affected children.

It spreads mainly by close contact, respiratory droplets and fomites. More than 50 types of adenovirus can cause infections in humans.

Adenovirus "type 41" was identified in the affected children. It can cause diarrhoea, vomiting, fever and may even cause hepatitis, but in immunocompromised children.

It is learnt that all children presented with acute severe hepatitis were previously healthy. It is, thus, very unusual to detect "type 41"adenovirus, causing acute severe hepatitis or even liver failure in previously healthy children. In the United States, all five children with acute hepatitis that were sequenced had adenovirus "type 41".

Based on these evidences, adenovirus is considered as one hypothesis for the underlying cause, although other possible explanations (other infectious or non-infectious and or environmental causes) are currently under intense investigation.

Post-acute COVID-19 syndrome, commonly known as long COVID or post-COVID syndrome, is a consequence following the acute phase of SARS-CoV-2 infection. Post-COVID syndrome has been widely observed during the first and second wave of COVID-19 in Nepal, especially in young adults. Extreme fatigue, mild fever, cough, shortness of breath, chest pain, fast and irregular heartbeat, sleeping difficulty, depression, brain fog and hair fall are the most commonly reported problems of post-COVID syndrome. However, data on it in children is scarce.

A recent study done by German scientists found that the incident rate of long-term health problems following COVID-19 in adults was significantly higher than in children/adolescents.

The Omicron variant/wave is found to be more infectious/fast spreading but less severe when compared to previous variants/waves for many reasons.

A recent study published by Centers for Disease Control and Prevention (CDC), USA, found that the Omicron variant led to higher COVID-19 hospitalisation among children (ages 4 or younger) than during the peak of the Delta variant wave. Acute severe hepatitis in children has emerged following the surge of the Omicron wave worldwide.

Coronavirus (SARS-CoV-2) may not be detected several days after the infection/ or onset of symptoms and antibodies after several weeks/months, meaning acute severe hepatitis, as a "Post-Omicron COVID-19 Syndrome" cannot simply be ruled out based on coronavirus negative test results.

On April23, the WHO released a statement regarding acute severe hepatitis of unknown origin in children and developed its working case definition. It also urged its member states to identify, investigate and report potential cases, if it is within the case definition.

A patient presenting with an acute hepatitis (non-hepatitis A to E) with serum transaminase > 500 IU/L (ALT or AST), who is 16 years old or younger, since October 1, 2021, is considered as a probable case.

Likewise, a patient presenting with an acute hepatitis (non -hepatitis A to E) of any age, who is a close contact of a probable case since October 1, 2021, is also considered as a potential case. At present, the WHO advises regular hand washing and respiratory hygiene as preventive measures for adenovirus and other common infections.

However, without identifying the causative agent of acute severe hepatitis, it's difficult to avoid spreading this mysterious liver disease in the coming days.

To sum up, acute severe hepatitis in children is being identified from different parts of the world. Nevertheless, its cause, so far, has remained a mystery for clinicians, scientists and policymakers, which is, indeed, a matter of grave concern. Severe hepatitis cases in children are on the rise amid the circulation of the Omicron wave (mutated and recombinant versions), with majority of the children under 5 years old (unvaccinated).The cases are being reported simultaneously from several countries, pinpointing the likely consequences of the "Post Omicron COVID-19 Syndrome", although more research needs to be done to corroborate this hypothesis/theory.

Dr Pun is Chief, Clinical Research Unit, Sukraraj Tropical & Infectious Disease Hospital

A version of this article appears in the print on May 13, 2022, of The Himalayan Times.