Colorado reports 13 cases of rare but serious mystery hepatitis in children

Colorado has reported 13 cases of unexplained hepatitis in children since November, with about half appearing in the last two months.

Worldwide, about 450 children have been identified as having what the U.S. Centers for Disease Control and Prevention is calling acute hepatitis of unknown cause, and 11 have died. Five deaths and 180 possible cases in 36 states have been reported in the United States since October.

Hepatitis is an umbrella term referring to inflammation in the liver. The most common cause is an infection with one of five viruses, known as hepatitis A, B, C, D and E. Heavy alcohol use can also cause liver inflammation, as can certain chemicals and excessive use of common medications, like acetaminophen.

“It’s important to note that severe hepatitis in children remains rare,” CDC officials said in a statement this week. “However, we encourage parents and caregivers to be aware of the symptoms of hepatitis — particularly jaundice, which is a yellowing of the skin or eyes — and to contact their child’s health care provider with any concern.”

The Colorado Department of Public Health and Environment, like most state health departments, didn’t track hepatitis cases caused by something other than viruses until clusters of unexplained illnesses emerged last year in other states and countries. That makes it difficult to be sure if 13 cases is unusual.

The state is investigating six cases between November and March, four in April and three in May, all in children younger than 10.

Dr. Amy Feldman, director of the liver transplant program at Children’s Hospital Colorado, said when a child comes in with signs of hepatitis, they check for those risk factors — other than heavy drinking, which isn’t relevant for kids — as well as genetic conditions that can harm the liver.

“There are times when kids come in with liver inflammation and it’s not clear why, and most of the time they get better on their own,” she said.

The most distinctive sign of hepatitis is yellowing of the skin or eyes. Other possible symptoms are fever, fatigue, joint pain, loss of appetite, nausea, vomiting, abdominal pain, dark urine and unusually light-colored stools.

The condition can necessitate a liver transplant. The percentage of children who needed transplants among the possible cases in the United States has been dropping, but that could reflect a change in reporting, as hospitals and physicians start flagging children who aren’t as seriously ill.

The five hepatitis viruses have been ruled out as a cause in the cases under investigation. So has COVID-19 vaccination, since the vast majority of the affected children were too young to receive the shot. The Centers for Disease Control and Prevention has also said there’s no sign bacterial infections or genetic conditions known to cause liver failure are involved.

The leading hypothesis now is that adenovirus 41 might be responsible. Typically, that virus causes gastrointestinal symptoms, with the possibility of liver injury in children with compromised immune systems. About half of American children with unexplained hepatitis tested positive for adenovirus 41, though it hasn’t been found in the Colorado children, Feldman said.

It’s possible that the children who didn’t test positive had adenovirus 41 at some point, but it no longer showed up in their feces by the time they were sick enough to seek care. On the other hand, adenoviruses are common, so finding them in significant numbers of seriously ill children doesn’t prove they caused the illness.

Other theories include that adenovirus 41 may not itself be a problem, but is interacting with something else in the children’s environment. It’s also possible that some of the cases flagged for review wouldn’t have drawn attention in previous years, because they’re not above the “background” rate in their states.

If adenovirus 41 is the culprit, there are several possible explanations for why it could be causing severe illness in more children:

• Lower levels of immunity, since children were exposed to fewer viruses over the last two years due to the pandemic
• Co-infection with COVID-19
• A large number of children getting it at the same time when COVID-19 precautions were lifted, essentially pushing multiple years’ worth of complications into a smaller window
• New mutations that made the virus more dangerous

The current outbreak of unexplained illness shares some similarities with the emergence of acute flaccid myelitis about eight years ago. Some children developed muscle weakness or paralysis with no clear cause, with increased numbers every other year from 2014 to 2018. (The expected 2020 wave didn’t come, perhaps because of COVID-19 precautions.)

The top theory is that an enterovirus, which usually causes common colds, was involved, either by directly attacking the nervous system or through an immune overreaction.

Regardless of what’s causing the hepatitis cases, treatment depends on how well the child’s liver is functioning, Feldman said. Some children who come in with jaundice only need fluids, rest and monitoring to make sure their condition doesn’t deteriorate. Those whose livers aren’t working well may need supplemental glucose and products to help with blood clotting, with only the sickest needing a liver transplant, she said.

Parents should take their children to a doctor if they notice signs of hepatitis, but shouldn’t be excessively worried, Feldman said.

“While this is very serious… this is an extremely rare thing to happen in children,” said Feldman, who was aware of five of the Colorado cases — and said none of those required liver transplants. “Thankfully, all of these children got better.”