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Original ArticleFree Preview

Clinical Spectrum of Children with Acute Hepatitis of Unknown Cause

List of authors.
  • Chayarani Kelgeri, M.D.,
  • Michael Couper, M.B., Ch.B.,
  • Girish L. Gupte, M.D.,
  • Alexandra Brant, M.Sc.,
  • Mitul Patel, M.D.,
  • Lauren Johansen, M.B., B.S.,
  • Joseph Valamparampil, M.D.,
  • Evelyn Ong, F.R.C.S.,
  • Hermien Hartog, Ph.D.,
  • M.T.P.R. Perera, M.D.,
  • Darius Mirza, M.S., F.R.C.S.,
  • Indra van Mourik, M.D.,
  • Khalid Sharif, F.R.C.S., F.C.P.S.,
  • and Jane Hartley, M.Med.Sc., Ph.D.

Abstract

Background

Since January 2022, there has been an increase in reports of cases of acute hepatitis of unknown cause in children. Although cases have been reported across multiple continents, most have been reported in the United Kingdom. Investigations are ongoing to identify the causative agent or agents.

Methods

We conducted a retrospective study involving children referred to a single pediatric liver-transplantation center in the United Kingdom between January 1 and April 11, 2022. These children were 10 years of age or younger and had hepatitis that met the case definition of the U.K. Health Security Agency for confirmed acute hepatitis that was not hepatitis A through E and did not have a metabolic, inherited or genetic, congenital, or mechanical cause, in the context of a serum aminotransferase level greater than 500 IU per liter. We reviewed medical records and documented demographic characteristics, clinical features, and results of liver biochemical, serologic, and molecular tests for hepatotropic and other viruses, as well as radiologic and clinical outcomes. The outcomes were classified as an improving condition, liver transplantation, or death.

Results

A total of 44 children had hepatitis that met the confirmed case definition, and most were previously healthy. The median age was 4 years (range, 1 to 7). Common presenting features were jaundice (in 93% of the children), vomiting (in 54%), and diarrhea (in 32%). Among the 30 patients who underwent molecular testing for human adenovirus, 27 (90%) were positive. Fulminant liver failure developed in 6 patients (14%), all of whom received a liver transplant. None of the patients died. All the children, including the 6 who received liver transplants, were discharged home.

Conclusions

In this series involving 44 young children with acute hepatitis of uncertain cause, human adenovirus was isolated in most of the children, but its role in the pathogenesis of this illness has not been established.

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Funding and Disclosures

Disclosure forms provided by the authors are available with the full text of this article at NEJM.org.

This article was published on July 13, 2022, at NEJM.org.

Author Affiliations

From the Liver Unit, Birmingham Women’s and Children’s NHS Foundation Trust (C.K., M.C., G.L.G., A.B., L.J., J.V., E.O., H.H., M.T.P.R.P., D.M., I.V.M., K.S., J.H., M.P.), the Centre for Liver and Gastrointestinal Research, University of Birmingham (D.M.), and the Liver Unit, Queen Elizabeth Hospital (H.H., M.T.P.R.P., D.M.) — all in Birmingham, United Kingdom.

Dr. Kelgeri can be contacted at or at the Liver Unit, Birmingham Women’s and Children’s NHS Foundation Trust, Birmingham B4 6NH, United Kingdom.