Severe acute hepatitis of unknown cause in children


July 1, 2022

Severe acute hepatitis of unknown cause in children[1] is the name given to an epidemic outbreak in several countries of liver disease of unknown origin,[4] reported for the first time by the United Kingdom to the World Health Organization ( WHO) on April 5, 2022 due to an increase in the number of cases of severe acute hepatitis in previously healthy children under ten years of age without infection by hepatitis A to E viruses.[5] Subsequently, the United States notified the detection that had been made in October 2021 of a group of cases of the same pathology, also of idiopathic origin, in a pediatric hospital in Alabama.[2] The disease does not have a confirmed case definition, only probable cases, defined by the WHO and the European Center for Disease Prevention and Control (ECDC) as any person under 16 years of age who has acute hepatitis not caused by the hepatitis A to E —or other known causes, such as metabolic, autoimmune, drug or infection disorders— with elevation of serum transaminases above 500 IU/L.[6] One of the main hypotheses of its etiology is a adenovirus infection, detected in the majority of British cases, specifically the F41 subtype. On June 24, the WHO reported 920 probable cases in 33 countries and eighteen deaths, in addition to establishing the global risk of the outbreak as "moderate".[3]


In a Eurosurveillance article on the first cases reported in Scotland, it was reported that the epidemiological and clinical information showed that, within the clinical manifestations, there were vomiting in the previous weeks, jaundice and considerably elevated levels of alanine aminotransferase (ALT), in some cases higher than 2000 IU/L. In addition, the patients had tested negative for hepatitis A, B, C, and E viruses (with one case pending reporting at the time and one with an insufficient sample for hepatitis B testing). The provisional case definitions used on that occasion were:[7] Shortly after, when the number of Scottish cases was already ten, most presented with jaundice, diarrhea, vomiting and abdominal pain.[8] For its part, in the report of the cases of Alabama (United States), the Centers for Disease Control and Prevention (CDC) stated: “Before hospitalization, among the nine patients, seven had vomiting, six had diarrhea, and three had upper respiratory symptoms. At the time of hospital admission, eight patients had [visible jaundice in the sclera], seven had hepatomegaly, six had jaundice, and one had encephalopathy.” Likewise, all cases presented elevated transaminases, with ALT between 603 and 4696 IU/L, AST between 447 and 4000 IU/L, while total bilirubin varied between normal and high ranges (0.23 to 13.5 mg/dL). ).[2] The ages of the patients vary from one month to sixteen years; When reporting the situation, the World Health Organization (WHO) and the European Center for Disease Prevention and Control (ECDC) provided a provisional definition of "probable case" and specified that there was no definition for a "confirmed case" :[9]​ Also, the ECDC added that: "Cases of hepatitis with known etiology, such as those caused by specific infectious diseases, drug toxicity, and inherited or autoimmune metabolic disorders, should not be reported under this protocol."[6] The clinic described by the WHO describes the disease as "acute hepatitis with marked elevation of liver enzymes":[5]



In its first report on the cases registered in the United Kingdom, the WHO stated that the patients had tested negative for the virus of the virus.