Is COVID-19 Related to Pediatric Cases of Hepatitis?

In April 2022, cases of hepatitis of unknown cause in children were first identified in the United Kingdom and Northern Ireland. About a week later, the World Health Organization (WHO) revealed that at least 169 pediatric cases of acute hepatitis of unknown origin had been reported from more than 12 countries.

The unexpected and significant increase in cases of hepatitis in previously healthy children prompted health authorities worldwide to investigate the cases and try to determine the cause.

In the United States, the Centers for Disease Control and Prevention (CDC) stated that it was investigating about 180 reports of pediatric patients with hepatitis of unknown cause as of May 18. The CDC is working with health departments across the country to look for possible causes and identify more hepatitis cases.

While there is no definitive evidence of a link, one possibility being explored is whether the hepatitis cases in kids could be related to COVID-19.

What Do We Know So Far?

Between October 2021 and February 2022, the CDC identified nine children who had been hospitalized with acute hepatitis in the U.S.

The patients’ test results ruled out many possible causes of pediatric hepatitis, including:

• Hepatitis viruses A, B, and C
• Autoimmune hepatitis
• Wilson’s disease
• Bacteremia
• Urinary tract infections
• SARS-CoV-2 (the virus that causes COVID-19)

Could Adenovirus and COVID-19 Be to Blame?

Early investigations didn't link the hepatitis cases to COVID-19 at all. But a newer, small study suggests the link is possible.

All nine kids with hepatitis identified by the CDC had adenovirus in their blood samples—but not COVID. The family of viruses is common and causes things like colds and pink eye.

While adenovirus has been a strong lead for researchers to explore, the cause of the hepatitis cases is still currently unknown.

“The WHO and the CDC are working with public health officials to monitor and understand an increase in hepatitis of unknown cause recently reported in children,” Michael Wilsey, MD, a pediatric gastroenterologist and vice-chair of the Division of Gastroenterology at Johns Hopkins All Children’s Hospital, told Verywell.

In early June, a study published in the Journal of Pediatric Gastroenterology and Nutrition reported five cases of pediatric patients who recovered from COVID-19 but later developed liver injury—either acute liver failure or hepatitis with cholestasis.

In this group of patients, adenovirus was not found in the children’s livers—which suggests the virus was not the cause of the illness. The researchers thought that the liver problems could have been a post-infectious immune reaction similar to MIS-C or immune dysregulation from prior infection with SARS-CoV-2.

However, Wilsey said that “it may be too soon to tell whether a previous infection with the COVID-19 virus is related to the recent rise in hepatitis cases in children with unknown etiology.”

Can COVID Cause Hepatitis?

Although the five pediatric cases present a new hypothesis for the unexplained cases of hepatitis, it does not establish a causal connection. Wilsey said that while viral infections can prime the immune system to have an inflammatory response, an association does not necessarily mean causation.

Alexander Weymann, MD, a pediatric gastroenterologist, hepatologist, and the director of the Liver Center at Nationwide Children’s Hospital, told Verywell that it’s hypothetically possible for COVID to cause hepatitis.

According to Weymann, liver inflammation can be caused not only by viruses that directly infect and damage liver cells (such as hepatitis B or C) but also by infections that aren’t known to attack liver tissues directly.

“In the case of SARS-CoV-2, we do know that various forms of liver disease occur in COVID-19, but the mechanisms are poorly understood,” said Weymann. “SARS-CoV-2 has been detected in liver cells, but that does not necessarily mean that their infection by the virus directly causes inflammation and damage.”

More research is needed on pediatric cases of hepatitis of unknown cause, including whether they could be related to COVID infection or even long COVID.

Can You Prevent Hepatitis? 

Viruses, medications, and health conditions can all cause hepatitis. You can’t always avoid these factors, which means you may not be able to prevent hepatitis.

According to Weymann, the following strategies can help prevent some types of hepatitis:

• Get vaccinated against hepatitis A and hepatitis B
• Avoid exposure to blood, saliva, or body fluids from persons with hepatitis or mononucleosis caused by the Epstein-Barr virus (EBV)
• Do not eat potentially infected food such as raw or undercooked shellfish
• Do not drink non-bottled, non-boiled water in areas where hepatitis E is common
• Practice proper, frequent handwashing
• Stay away from people who have symptoms of a cold or stomach bug

Know the Signs of Hepatitis

Caregivers of young children should know the signs and symptoms of hepatitis. Weymann said that the most important sign a person could have hepatitis (or liver disease in general) is yellowing of the skin and the white part of the eyes (jaundice).

Other symptoms of hepatitis include:

• Pain or discomfort in the abdomen
• Abdominal tenderness or distension
• Swelling of legs or feet
• Joint pain
• Easy bruising or prolonged bleeding
• Fever with no obvious explanation
• Change in mental status

However, hepatitis symptoms can be vague. Weymann said that while fatigue, loss of appetite, nausea, and vomiting can be symptoms of hepatitis, they can also be symptoms of other more common illnesses.

What Caregivers Can Do

“If parents detect or suspect symptoms of hepatitis in their child, they should contact their pediatrician or primary care provider immediately,” said Weymann. “Hepatitis, while often mild and self-limited, can be or become a serious and even life-threatening illness.”

As for COVID? Even if the virus is not causing hepatitis in kids, it can still lead to severe illness and even death. Right now, the best way to protect children against the risks of COVID is vaccination.

“It is too soon to tell if there is a definitive link between past COVID-19 infection and liver disease in children,” said Wilsey. “Current CDC guidelines and routine supportive care should be followed for children with diagnosed or suspected SARS-CoV-2 viral infection.”