Decline of Pediatric Acute Hepatitis of Unknown Etiology During the Coronavirus Disease 2019 Pandemic in Japan

Background Pediatric acute hepatitis of unknown etiology (AHUE) has been reported globally since April 2022. The purpose of the present study was to investigate the impact of coronavirus disease 2019 (COVID-19) pandemic on the incidence of AHUE in Japan. Methods A nationwide survey of AHUE was conducted in 2510 pediatric hospitals by the Japan Pediatric Society. We retrospectively reviewed AHUE cases, defined by the World Health Organization's working case definition, and compared the incidence, clinical characteristics, and causative pathogens before the COVID-19 pandemic period (pre-pandemic, January 2017 to December 2019) and during the pandemic period (pandemic, January 2020 to June 2022). Results In total, 707 cases (450 pre-pandemic, 257 pandemic) were reported. The median age was 3 years (interquartile range (IQR): 1-9 years), and 43.8% were female. The number of AHUE cases decreased significantly in the pandemic period (102.8 cases/year) compared with the pre-pandemic period (150.0 cases/year). Investigations of pathogens causing AHUE demonstrated that the most common cause was unknown, accounting for 64% and 75% of cases in the pre-pandemic and pandemic periods, respectively. Among those whose pathogens were identified, the most common pathogens were Epstein-Barr virus (9.6%), cytomegalovirus (6.2%), and influenza (4.0%) in the pre-pandemic, and 7.0%, 3.5%, and 0.4%, respectively, in the pandemic period. SARS-CoV-2 and adenovirus were only 2.7% and 1.9%, respectively, in the pandemic period. Conclusions The number of AHUE cases decreased during the COVID-19 pandemic compared with the pre-pandemic period, and no increase in adenovirus-associated disease or severe cases was observed in Japan.