Adenovirus infection associated with hepatitis of unknown cause in children

1. Adenovirus was found to be associated with the emerging hepatitis of unknown cause in children in the United Kingdom (UK).

2. Despite a small number of fulminant liver failure requiring transplant, there were no deaths in the study, and patients were discharged home following treatment.

Evidence Rating Level: 2 (Good)

Study Rundown: Acute hepatitis if an unknown cause has been emerging in hundreds of children worldwide, with the highest numbers in the UK and other parts of Europe. These children presented with acute hepatitis and negative tests for infective, toxic, congenital, or other identifiable causes. A small number of cases progressed to liver failure necessitating transplantation. Molecular testing has revealed a correlation between this hepatitis and human adenovirus, although their specific relationship is still under investigation. The current observational cohort study examined these hepatitis cases at a pediatric liver-transplantation center in the UK. Children presented with jaundice, vomiting, and diarrhea. Human adenovirus was identified in the majority of the patients who underwent testing. Six children developed liver failure requiring transplantation. There were no deaths and all patients were subsequently discharged home. As new cases continue to emerge, this study served as a starting point to identify acute hepatitis of unknown cause in children and provides early evidence of its association with adenovirus.

Click here to read the study in NEJM

In-Depth [retrospective cohort]: This retrospective cohort study involved children referred to one pediatric liver-transplantation center in the UK due to acute hepatitis of unknown cause, between January 1 and April 11, 2022. Patients were screened if they were 16 years of age or younger and had a presentation consistent with the definition of acute hepatitis not due to hepatitis A-E, metabolic, inherited or genetic, congenital or mechanical causes, with serum aminotransferase level >500 IU/L. All children included in this study were 10 years of age or younger. Clinical outcomes were categorized into improvement, liver transplantation, and death. Overall, 44 children were included in this study, all but three were previously healthy. The median age was 4 (range, 1 to 7). The most common presentations prompting medical attention were jaundice (93%), vomiting (54%), diarrhea (32%), abdominal pain (27%), and lethargy (23%). None of the children had been vaccinated against SARS-CoV-2. 11 of the 39 children (28%) who underwent PCR testing tested positive for SARS-CoV-2, while 5 of the 13 children (38%) who underwent SARS-CoV-2 antibody testing tested positive. Most notably, 30 children underwent adenovirus testing, 27 (90%) of whom tested positive. The median adenovirus viral load was also significantly higher in children who needed liver transplantation compared to those who did not. A total of 38 children spontaneously improved while six developed acute liver failure and underwent transplantation. All children were subsequently discharged home. Despite the small cohort size precluding statistical analyses, the study provided early evidence of the association between adenovirus and acute hepatitis of unknown cause in children.

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