Acute hepatitis of unknown origin in children: analysis of probable etiologies

Abstract

Background. An outbreak of hepatitis of unknown origin in children aged 1 month — 16 years was first reported by the WHO in April 2022. It was accompanied by a high frequency of acute liver failure, and up to 5 % of children required liver transplantation. The purpose of the review was to determine probable etiological factors and mechanisms of acute hepatitis of unknown origin based on a systematic analysis of literary sources. Materials and methods. We conducted a search for studies on cases or case series of acute hepatitis of unknown origin in the PubMed between January 2022 and February 2023. A combination of the following terms was used for the search: “unknown hepatitis”, “hepatitis of unknown origin”, “non-A-E hepatitis”, “hepatitis of unknown etiology” and “children”. Results. According to the search results, 312 publications were found. After the selection, 14 publications were included in the review. A systematic analysis of 1,188 cases of acute hepatitis of unknown origin, which corresponded to the identified case, showed a high variability of causative agents. However, most children were tested positive for adenovirus (almost 57 %), and 14 % of children had a positive PCR for SARS-CoV-2. Among other viruses detected in children, viruses of the herpes family should be noted, especially human herpesvirus 7 (34.2 %), human herpesvirus 6 (20 %), Epstein-Barr virus (18.2 %), cytomegalovirus (9.2 %). Rhinovirus (40.7 %), enterovirus/rhinovirus (28.7 %), parainfluenza virus (15.4 %), streptococcal infection, and other pathogens were also found. Conclusions. Viruses, genetic predisposition and other factors that change the body’s immune response play an important role in the development of an outbreak of severe hepatitis. Systematic analysis has shown that human adenovirus most often acts as a helper for adeno-associated virus 2, which plays a major role in initiating an immune response in genetically predisposed individuals, causing acute hepatitis and acute liver failure. SARS-CoV-2 infection probably also plays a certain role in immune activation and in the development of hyperinflammation, as do other viruses that act as helpers for adeno-associated virus 2. Continued collection of detailed clinical, microbiological, and epidemiological data on probable cases, as well as well-planned and coordinated follow-up studies are necessary to identify risk factors and other etiological factors associated with this disease.