Since late 2021, clusters of acute severe hepatitis of unknown etiology in previously healthy children, including some requiring liver transplantation, have been reported worldwide. Co-infection with adeno-associated virus type 2 (AAV2) and human adenovirus species F type 41 (HAdV-F41) has been identified in most cases.
Global incidence peaked in 2022, and pediatric liver failure involving co-infection with AAV2 and HAdV-F41 has remained rare in recent years. We report 2 cases of pediatric liver failure associated with AAV2 and HAdV-F41 in California, USA, in March 2024 and January 2025.
The patients had high adenovirus loads (393,000 and 480,000 copies/mL), extended adenovirus viremia (2 and 3.5 months), and high AAV2 viral loads (1.3 and 1.0 × 106 copies/mL). One patient required liver transplantation; both patients recovered.
Our findings underscore the need for heightened physician awareness and expanded surveillance to identify and characterize new cases, improve understanding of underlying pathophysiology, clarify risk factors, and inform therapeutic strategies.