Acute Hepatitis of Unknown Origin in Children: Early Observations from the 2022 Outbreak

Abstract

Recent reports of acute hepatitis of unknown origin in previously healthy children have been increasing worldwide. The main characteristics of the affected children were jaundice and gastrointestinal symptoms. Their serum aminotransaminase levels were above 500 IU/L, with negative tests for hepatitis viruses A-E. By 31 May 2022, the outbreak had affected over 800 children under the age of 16 years in more than 40 countries, resulting in acute liver failure in approximately 10%, including at least 21 deaths and 38 patients requiring liver transplantation. There was still no confirmed cause or causes, although there were several different working hypotheses, such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), adenovirus serotype 41, or SARS-CoV-2 superantigen-mediated immune cell activation. Here, we review early observations of the 2022 outbreak which may inform diagnosis, treatment, and prevention in the context of an overlapping COVID-19 pandemic.

Acute severe hepatitis outbreak in children: A perfect storm. What do we know, and what questions remain?

“…Following initial reports from the United Kingdom, nine children meeting the case definition were retrospectively identified from the United States (Gutierrez , and Japan's health ministry reported a case from Asia. By the end of April 2022, further cases had been reported from Europe, (Zhang et al, 2022). WHO data between 5 April and 8 July 2022 include data for 1010 probable cases from 35 countries representing five WHO regions, predominantly affecting Europe (Figure 2A).…”

Hepatitis of Unknown Origin in Children

“…On March 31, 2022, the first case of severe acute hepatitis of unknown origin in previously healthy children was reported in Scotland [1]. Since then, the significant increase in the incidence of the pathology has been clearly evidenced, reaching approximately 813 cases confirmed by the WHO in more than 40 countries belonging to regions of Europe, America and Asia by May 2022, of which the 38% required liver transplantation with 21 reported deaths [2][3][4]. According to current statistics, the main affected have been children between the ages of the first month of life and 16 Open Acc J Bio Sci.…”

The acute hepatitis outbreak in children in 2022: The story so far

“…In the first quarter of 2022, Public Health Scotland was alerted to an uptick in cases of severe acute hepatitis among children ages 3-5 years old (1). These children were previously healthy but presented with nausea, vomiting, and accelerated jaundice and marked transaminitis (2,3).…”

“…One third of children required intensive care admission, and about 10% required urgent liver transplantation for fulminant hepatic failure (4). Sadly, 2.2% of children with this mysterious illness have died to date, with most deaths in Asia (1,4).…”

“…While severe acute idiopathic hepatitis is not a new occurrence in children, the current incidence in the United Kingdom, for example, is 5-to 10-fold what it was in the pre-SARS-CoV-2 era (3). Epidemiologists have found that subjects neither had a travel history to a potentially endemic locale, nor a strong history of infectious contacts (1). No tested subjects were found positive for hepatitis A through E or SARS-CoV-2 (4).…”