The 2022 Childhood Hepatitis Outbreak: What We Know Now

In 2022, a mysterious and unexplained outbreak of acute severe hepatitis began striking previously healthy children. As cases began to escalate between April and July of that year, more than 1,000 children globally (and at least 350 children in the United States) were diagnosed with hepatitis. The hallmark of the disease is liver inflammation. According to the World Health Organization, nearly 50 children who were infected ended up needing liver transplants; 22 of the infected children died from the disease.¹

The mystery behind this sudden outbreak left families devastated and the medical community puzzled, sparking a number of research studies aimed at uncovering the root cause. Finally, nearly a year later in January 2023, it was learned that three independent studies published in the multidisciplinary science journal Nature all came to a similar conclusion: The presence of the adeno-associated virus 2 (AAV2) in the blood and livers of infected children might be the clue researchers were looking for.²

AAV2 is a common childhood virus that the study authors found was present among nearly all of the children with unexplained acute hepatitis; many were also infected with multiple “helper” viruses. And, although the researchers can’t say for sure, the timing of the outbreak may have been associated with the global loosening of COVID-19 pandemic restrictions after periods of relative isolation.

“Children were suddenly exposed to a barrage of viruses after lockdowns, or had poorly trained immune systems that led to an increased susceptibility to otherwise harmless viruses,” said Frank Tacke, MD, PhD, associate professor for hepato-gastroenterology and executive senior physician at the Department of Medicine III of the University Hospital Aachen, Germany, in an editorial published alongside the new studies. “The fact that three independent groups found this from different areas of the world actually makes it really convincing.”³

One of the studies conducted at the University of California, San Francisco (UCSF) analyzed tissue samples from children in the United States and detected AAV2 in 93 percent of 14 cases. The researchers also found that all children infected with AAV2 had co-infection with a “helper” virus — either human herpes virus 6 or Epstein-Barr virus — that might promote AAV2 replication. The UCSF study concluded that for a small subset of these children, getting more than one infection at the same time may have made them more vulnerable to severe hepatitis.

“We were surprised by the fact that the infections we detected in these children were caused not by an unusual, emerging virus, but by common childhood viral pathogens,” said Charles Chiu, MD, PhD, professor of laboratory medicine in the Division of Infectious Diseases, director of the UCSF Clinical Microbiology Laboratory and senior author of the paper. “That’s what led us to speculate that the timing of the outbreak was probably related to the really unusual situations we were going through with COVID-19-related school and daycare closures and social restrictions. It may have been an unintended consequence of what we have experienced during the last two to three years of the pandemic.”⁴

The findings from the UCSF study mirrored the results of two concurrent studies conducted in the United Kingdom, Dr. Chiu said. These identified the same AAV2 strain. All three studies also identified co-infections from multiple viruses and about 75 percent of the children in the U.S. study had at least three or four viral infections.

Other key takeaways included:

• Children may be especially vulnerable to more severe hepatitis triggered by co-infections.
• While infections from adeno-associated viruses can occur at any age, the peak is typically between ages 1 and 5 years.
• The median age of the affected children in the study was 3 years old.
• The findings from all of these studies were published in March 2023.