Acute hepatitis of unknown etiology in children: Comparison between the U.K., U.S., and Japan, and ingenious clinical practice attempts

Abstract

In 2022, cases of pediatric acute hepatitis of unknown origin increased in the United Kingdom. Initially, with the relaxation of Coronavirus disease 2019 measures, adenovirusʼs prevalence was noted. Moreover, metagenomic analysis suggested that adeno-associated virus type 2 (AAV2) was the causative agent; high lev-els of AAV2 were detected in many affected children. HLA-DRB1*04:01 was also detected, indicating a possible genetic predisposition. Acute liver failure sometimes occurs with gene therapy using intravenous infusion with AAV9 vectors, which might be a related condition. Some cases of hepatitis are also caused by sever acute respi-ratory syndrome coronavirus 2. In Japan, postpandemic pediatric hepatitis cases have not increased compared to prepandemic cases, and AAV2 has rarely been detected―differing from the reports and results from the United Kingdom and United States. Historically, approximately 40% of pediatric acute liver failure cases have an unknown origin, and AAV is presumed to be involved in some of these cases.