Acute hepatitis of unknown aetiology in children: a clinical update on the recent outbreak with mechanistic insights

Since April 2022, over 1000 children across 35 countries have developed episodes of acute hepatitis of unknown origin. At King's College Hospital, a total of 65 children were referred with acute hepatitis of unknown etiology, with 10 of these children presenting with acute liver dysfunction leading to acute liver failure. Multiple hypotheses have been proposed and continue to be investigated worldwide. In this review, we explore the current understanding of potential aetiologies for this outbreak. We further characterize the proposed immunological mechanisms of liver injury in these cases. Health alerts have been triggered across multiple countries with regards to reports of severe adenovirus-associated acute hepatitis in previously well children. Multiple hypotheses have been proposed and continue to be investigated worldwide. In this review, we discuss the potential aetiologies and underlying mechanisms of liver injury of this outbreak.