Emergency clinicians have another novel illness to be concerned about. Investigators are uncovering a small, but growing number of unusual cases of hepatitis in young children that is putting many of these patients at risk for bad outcomes.
While clinicians in Alabama identified the first nine cases, as of late May the CDC reported 180 pediatric cases, most of them in children younger than age 6 years, were under investigation for the illness in 36 states and territories. However, the agency also noted most of these were identified retrospectively, with cases possibly emerging as early as October 2021.1
As authorities scramble to pinpoint the causative factors, clinicians are urged to keep an eye out for any unusual cases of hepatitis. Act swiftly if a case is severe or there are signs of liver failure.
Early cases presented through the ED at Children’s of Alabama, according to Helena Gutierrez, MD, a specialist in the division of pediatric gastroenterology, hepatology, and nutrition at the University of Alabama at Birmingham (UAB). “The majority of these cases presented with initial symptoms of vomiting and diarrhea. Subsequently, some of them improved, and some of them stayed the same. The main concerning symptom was jaundice ... and that prompted the parents to seek medical attention,” she explains.
Gutierrez says staff screened patients for various viruses, with tests returning positive for adenovirus 41 for all. “We wondered if maybe there was an outbreak, or if all these kids were coming from the same town,” she says. “But as they started to present, we mapped [the cases] out, and they came from different regions in Alabama.”
None of the children seen with the illness at UAB were positive for any of the typical viruses associated with hepatitis (e.g., hepatitis A, B, C, or E). Also, none of the children tested positive for COVID-19. However, in two children, their illness progressed to liver failure, and they had to be transported to hospitals out of state to receive transplants.
A recent CDC report shed more light on the laboratory findings associated with these cases.2 For instance, many of the patients recorded high liver enzyme readings. Also, all but one recorded elevated levels of bilirubin, and six tested positive for Epstein-Barr virus.
The report authors noted autoimmune hepatitis, urinary tract infection, and Wilson’s disease were ruled out in all the Alabama cases. Further, while no patient had a previously known case of COVID-19, the Alabama team plans to conduct further testing for antibodies to see if there is a possibility for any potential link to SARS-CoV-2.
Kathryn Smith, MD, a pediatric hepatologist at Johns Hopkins Children’s Center in Baltimore, says while she has seen some recent cases of hepatitis, none of the patients have tested positive for adenovirus. However, she urges frontline providers to conduct appropriate screening in a child who presents with jaundice and any kind of infectious findings, such as cough, cold, diarrhea, vomiting, or fever.
If the child tests positive for hepatitis, the treatment will depend on the underlying etiology. “Hepatitis is just a blanket term for inflammation of the liver,” Smith notes. “Generally, if you have a child who comes in with an infection presentation, then the treatment would depend on what it was.”
Smith adds any virus can cause elevated liver enzymes, but hepatitis A is something to think about in that case. This illness, as well as most viral causes of hepatitis, usually resolves on its own. Alternatively, if the hepatitis is caused by an autoimmune process, then steroids might be appropriate. “It really depends on what kind of information you obtain from the evaluation,” Smith says.
However, in these more unusual adenovirus cases, there is heightened concern because this etiology is leading to liver failure for some. If patients are in liver failure, Smith suggests ordering a complete metabolic panel, a complete blood count, and a prothrombin time test/international normalized ratio (PT/INR) to check for coagulation factors. “Determine if the child is actually in liver failure, or [he or she] has severe hepatitis,” she adds.
In the ED at Johns Hopkins, Smith notes there a is process in place so children with either severe hepatitis or liver failure can go directly to Smith or her specialist colleagues. Smith urges other hospitals and EDs to implement similar mechanisms to expedite care in these cases, if they are not in place already.
“When you start to get to liver failure, essentially you have unchecked inflammation to the point where the liver is not able to complete its functions,” explains Smith, who uses the term “synthetic function” to describe whether the liver can produce clotting factors, sugar, and detoxify by removing ammonia from the blood.
When synthetic function is deteriorating, inflammation can overwhelm the liver. “In cases where you have a child who presents with very elevated liver enzymes and elevated PT/INR — and maybe elevated ammonia ... then you have to be very cautious in monitoring and watching [the case]. The patient can progress to liver failure very quickly,” Smith stresses.
Further, she notes clinicians should not be encouraged by normal liver enzyme levels if the other important lab readings, such as assessments of coagulation factors and sugar levels, are abnormal. “That’s when you can get in trouble,” Smith warns.
Although adenovirus 41 remains high on the list of potential causes of the unusual hepatitis cases, investigators are not finding adenovirus in liver tissue samples taken from these patients. In many cases, adenovirus is not turning up in plasma either, but is detected in whole blood — a more sensitive test. The search for a root cause continues well beyond the adenovirus.
“We don’t know why [this is primarily occurring] in young children,” Gutierrez says. “The majority of cases are in children under the age of 10. Out of those, the vast majority are actually even younger than 5.”
One hypothesis is that with all the COVID-19 pandemic-related lockdowns, children have not been exposed to the number of pathogens they normally would. Now, they are responding differently to something new. Investigators also have not ruled out COVID-19 as at least one factor in the unusual outbreak, perhaps from past illnesses that were not diagnosed as SARS-CoV-2 at the time.
REFERENCES
- Centers for Disease Control and Prevention. Update on children with acute hepatitis of unknown cause. May 18, 2022.
- 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.
Emergency clinicians have another novel illness to be concerned about. Investigators are uncovering a small, but growing number of unusual cases of hepatitis in young children that is putting many of these patients at risk for bad outcomes.
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