WHAT IS CAUSING THE LATEST HEPATITIS OUTBREAK IN CHILDREN?

Hepatitis is a major global health problem. Recent outbreaks of hepatitis particularly in children all over the world are worrying to health professionals. But what is hepatitis? Is it life-threatening? Read on to learn more.

What is hepatitis?

Hepatitis is a medical term used to denote liver inflammation. Any liver disease that causes inflammation to the liver can therefore cause hepatitis. Most of the time hepatitis is a result of viral infection.

Whenever the liver is inflamed there is overall stress on the whole body. This is because the liver has the responsibility of carrying out various functions within the body.

As various factors can cause hepatitis, the outcome can be mild to life-threatening. (1)

What are the causes of hepatitis?

Hepatitis can happen due to many causes. The most common cause of hepatitis is a cluster of viruses known as hepatitis viruses. The specific type of virus can vary from region to region. The causes of hepatitis are (2, 3):

• Alcohol-induced hepatitis
• Autoimmune hepatitis
• Drug-related hepatitis
• Hepatitis viruses type A, B, C, D, E
• The recent global outbreak has been hypothesized to be caused by adenovirus.

Adenoviruses are a large group of viruses that can infect a wide range of animals as well as humans. Adenoviruses cause mild illness in humans, most of the time. They are known to cause respiratory illness, red-eye or conjunctivitis and diarrhea and vomiting.

The subtype associated with the current acute hepatitis outbreak in children is called adenovirus subtype 41. Adenovirus 41 subtype causes mild to moderate episodes of diarrhea, vomiting and stomach pain. (2, 3)

How common is hepatitis?

Hepatitis is found commonly all over the world. However, different regions in the world have different types of hepatitis with different causes. For example, developing nations in Africa and Asia frequently have Hepatitis A and Hepatitis E outbreaks. This is because these types are transmitted fecal-orally, largely owing to the contaminated drinking water with feces. (4)

Similarly, in areas of the world where drug abuse is high, cases of hepatitis B and C are usually high. Some countries have increased cases of hepatitis due to the drinking culture which results in alcohol-related liver damage. (4)   

Recent Adenovirus Hepatitis Outbreak

The recent outbreak of hepatitis in children however has been assumed to be associated with a different group of viruses other than the hepatitis virus, known as adenovirus. Previous research showed adenovirus to cause hepatitis in people with weak immunity. (5)

Adenoviruses are a large group of viruses that can infect a wide range of animals as well as humans. Adenoviruses cause mild illness in humans, most of the time. They are known to cause respiratory illness, red-eye or conjunctivitis and diarrhea and vomiting.

The subtype associated with the current acute hepatitis outbreak in children is called adenovirus subtype 41. Adenovirus 41 subtype causes mild to moderate episodes of diarrhea, vomiting and stomach pain. (2, 3) 

How the adenovirus hepatitis outbreak is affecting children globally?

Where was the outbreak first reported?

WHO was notified regarding a severe form of hepatitis on 5^th April 2022 from central Scotland and the United Kingdom. Within 3 days the number had increased from 10 cases to 74 cases. All of these cases were reported after negative results for other known forms of hepatitis. (3, 6)

As of now, daily cases are rising all over Europe and even the United States of America.

Why did this outbreak occur in children?

Research is still being done as to why this outbreak affected children mostly.

From what is known, adenovirus transmission is believed to happen fecal-orally. Various agencies are trying to understand the actual reason.

As of now, people are encouraged to go to the nearest hospital and report if they find symptoms similar to hepatitis.

What is Adenovirus?

Adenovirus hepatitis has a similar presentation to the other forms of hepatitis.

The common signs and symptoms usually seen with adenovirus hepatitis are (6, 7, 8, 9)

• fatigue
• flu-like symptoms
• dark coloured urine
• pale-coloured stool
• abdominal pain
• loss of appetite
• unexplained weight loss
• yellowing of skin and eyes which is known as jaundice
• vomiting
• co-existing respiratory illness

How is Adenovirus hepatitis diagnosed?

Your doctor will diagnose hepatitis based on medical history, physical examinations and lab tests. (6, 7, 8, 9)

Usually, you will be asked to provide a detailed account of the symptoms. Your doctor will then conduct a clinical examination.

This includes looking for signs of jaundice or liver injury. The doctor can feel the abdomen and press in certain areas to look for tenderness and identify whether the liver is swollen or not.

WHO, the United Kingdom Health Security Agency (UKHSA) and the CDC have also provided a guideline to conduct specific tests and identify the case. This includes a number of specific tests and ruling out the usual causes of hepatitis. (5, 6, 9, 10)

How is Adenovirus hepatitis testing done?

As per the vigorous testing guidelines provided by various agencies globally, testing is being done and a “leave no stone unturned” approach is being followed. The tests include:

Liver function tests

There are certain enzymes which are specific to the functioning of the liver. When the liver is damaged or inflamed, the level of these enzymes can be raised. One such enzyme used for the diagnosis is Aspartate Transaminase (AST). AST levels greater than 500 International Units per litre are being taken as a cutoff for diagnosis. However, other causes need to be ruled out first. (5, 8, 10)

Blood tests

• Blood tests being done include basic blood-work panels, toxicological sampling and other specifically targeted tests.
• Specific blood tests are able to detect the presence or absence of viruses or their markers in the body. This is known as a serology test. This test helps to identify specific viruses.
• Polymerase Chain Reaction(PCR) testing against various viruses including adenovirus is also being done.

Stool Test

The stool is also being tested to find out the presence or absence of various viruses.

Liver biopsy

Depending on the situation, your doctor may ask for a liver biopsy. Here, a small section of the liver is removed and analysed.

Ultrasound

Abdominal ultrasound has become a routine procedure in healthcare. This will help to view the underlying organs without the need of damaging them.

Sometimes, the doctor can order a CT scan or even an MRI, depending on the specific condition.

How is adenovirus hepatitis being treated?

Every case being treated cannot be exactly the same. Most of the cases are being treated like any other hepatitis case would be treated.

The treatment of adenovirus hepatitis is supportive and catered for the specific need of the individual patient.

 Most of the time, the treatment is carried out in hospitals to avoid rapid deterioration of the patient.

Having said that, with the recent outbreaks happening globally, more and more patients are requiring liver transplants, in preliminary reports. (5, 6, 9, 10)

Regardless of specific differences, in almost all adenovirus hepatitis, the patient will be advised to get adequate rest, drink plenty of fluids, get enough nutrients, and avoid alcohol. You will also be advised to avoid certain medications which cause toxicity to the liver.

How long can adenovirus symptoms last?

Usually, when inflammation of the liver lasts less than six months it is called acute hepatitis. However, there are some forms which can last for greater than six months. These are termed chronic hepatitis. (1, 4, 7, 8)

Can adenovirus hepatitis be fatal in children?

As of now, most of the cases have not been fatal. But with time the number of deaths has been increasing. Unofficial estimates from various news agencies around the world point this number to around 6 global deaths. The news of the latest deaths is coming from Indonesia. The children had symptoms of hepatitis and tested negative for hepatitis viruses A, B, C, D and E. However, it is unclear whether the children suffered from any autoimmune conditions.

The WHO, on the other hand, is yet to publish the official number of deaths.

Some patients who were admitted with acute hepatitis have recovered without any adverse events. However, some patients have required the need of liver transplantation.

Whether this particular outbreak will cause any chronic problems or hepatitis can not be predicted currently.

How this outbreak will pan out over the course of time is still under investigation. (5, 6, 9, 10)

How can adenovirus hepatitis transmission be prevented in children?

More and more reporting is suggesting that the adenovirus hypothesis might be true. However, it is still too early to come to a conclusion. (5)

Multiple reports have suggested that the symptoms might be a result of fecal-oral transmission. (5, 8, 10)

Based on the current reports, more emphasis is to be given to hand washing and hygiene to prevent transmission, while more concrete evidence comes to light. (5)

Takeaway

The recent global outbreak of hepatitis is a matter of global concern. This is because the usual causes of hepatitis do not seem to be associated with it. Adenovirus hepatitis, which is usually seen in immunocompromised patients, has been hypothesized to be the culprit.

The rising need for liver transplants in these patients is also worrying. It is still too early to pinpoint exactly why the outbreak of hepatitis is being seen or what the course of the disease will be.

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References:

• 1.Mehta, Parth. and Anil Kumar Reddy Reddivari. “Hepatitis.” StatPearls, StatPearls Publishing, 31 December 2021.
• 2.Schaberg, Kurt B et al. “Adenovirus Hepatitis: Clinicopathologic Analysis of 12 Consecutive Cases From a Single Institution.” The American journal of surgical pathology vol. 41,6 (2017): 810-819. doi:10.1097/PAS.0000000000000834
• 3.“Multi-Country – Acute, Severe Hepatitis of Unknown Origin in Children.” World Health Organization, World Health Organization, https://www.who.int/emergencies/disease-outbreak-news/item/2022-DON376.
• 4.Lanini, Simone et al. “Viral Hepatitis: Etiology, Epidemiology, Transmission, Diagnostics, Treatment, and Prevention.” Infectious disease clinics of North America vol. 33,4 (2019): 1045-1062. doi:10.1016/j.idc.2019.08.004
• 5. Marsh, Kimberly et al. “Investigation into cases of hepatitis of unknown aetiology among young children, Scotland, 1 January 2022 to 12 April 2022.” Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin vol. 27,15 (2022): 2200318. doi:10.2807/1560-7917.ES.2022.27.15.2200318
• 6. Acute Hepatitis of Unknown Aetiology – the United Kingdom of Great Britain and Northern Ireland, World Health Organization, https://www.who.int/emergencies/disease-outbreak-news/item/acute-hepatitis-of-unknown-aetiology---the-united-kingdom-of-great-britain-and-northern-ireland
• 7.Zarrin, Arash. and Hossein Akhondi. “Viral Hepatitis.” StatPearls, StatPearls Publishing, 19 January 2022.
• 8.“Viral Hepatitis.” Centers for Disease Control and Prevention, Centers for Disease Control and Prevention, 28 July 2020, https://www.cdc.gov/hepatitis/abc/index.htm#:~:text=Symptoms%20of%20hepatitis%20can%20include,%2C%20joint%20pain%2C%20and%20jaundice.
• 9. Baker JM, Buchfellner M, Britt W, et al. Acute Hepatitis and Adenovirus Infection Among Children — Alabama, October 2021–February 2022. MMWR Morb Mortal Wkly Rep 2022;71:638–640. DOI: http://dx.doi.org/10.15585/mmwr.mm7118e1external icon.
• 10. UK Health Security Agency. Increase in acute hepatitis cases of unknown aetiology in children. London, United Kingdom: Department of Health and Social Care, UK Health Security Agency; 2022. https://www.gov.uk/government/publications/hepatitis-increase-in-acute-cases-of-unknown-aetiology-in-children/increase-in-acute-hepatitis-cases-of-unknown-aetiology-in-children

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