Recent Increase in Incidence of Severe Acute Hepatitis of Unknown Etiology in Children is Associated with Infection with Adenovirus and Other Nonhepatotropic Viruses

Abstract

Objective: To evaluate whether the nature and severity of non-A-E severe acute hepatitis in children noted by the World Health Organization from late 2021 through early 2022 was indeed increased in 2021-2022 compared with prior years.

Study design: We performed a single-center, retrospective study to track the etiology and outcomes of children with non-A-E severe acute hepatitis in 2021-2022 compared with the prior 3-year periods (2018-2019, 2019-2020, and 2020-2021). We queried electronic medical records of children ≤16 years of age with alanine or aspartate aminotransferase levels of >500 IU. Data were analyzed for the periods of October 1, 2021, to May 1, 2022, and compared with the same time periods in 2018-2021.

Results: Of 107 children meeting entry criteria, 82 cases occurred from October to May of 2018-2022. The average annual case number was 16.3 in 2018-2021 compared with a 2-fold increase (to 33) in 2021-2022 (P = .0054). Analyses of etiologies showed that this increase was associated with a higher number of children who tested positive for viruses (n = 16) when compared with the average of 3.7 for 2018-2021 (P = .018). Adenovirus (26.1%) and severe acute respiratory syndrome coronavirus-2 (10.3%) were the most frequently detected viruses in 2021-2022. Despite evidence of acute liver failure in 37.8% of children in the entire cohort and in 47% of those with viral infection, the overall survival rate was high at 91.4% and 88.9%, respectively.

Conclusions: The number of children with severe acute hepatitis in our center increased from 2021 to May 2022, with a greater frequency of cases associated with adenovirus, yet transplant-free survival remains high.

Keywords: acute liver failure; adenovirus; hepatitis; pediatrics.

Figure 1.

A. Flow diagram showing the enrollment of subjects and formation of the final cohort of children with severe acute hepatitis for the period of October 1-May 31 of 2018-2022. B. Bar graph showing the number of cases of severe acute hepatitis in children according to etiology during October 1-May 31 for 2018-2022. C. Dot plot depicting each child with severe acute hepatitis in each study period according to age in years. Bar graphs represent the total number in each period, with the red bar representing the focus period of October 1, 2021-May 31, 2022.

Figure 2.

A. Graph depicts the percentage of children with severe acute hepatitis tested positive in relation to the number of total tests for individual or group of viruses during October 1-May 31 for 2018-2022. B. Graph depicts the percentage of children with severe acute hepatitis tested for viruses during October 1-May 31 for 2018-2022. Red = positive, blue = negative, gray = not tested. Other = influenza, rhinovirus, respiratory syncytial virus (RSV), parainfluenza, BK virus, norovirus, rotavirus, sapovirus, astrovirus, or parechovirus.