Investigators may have uncovered the factors contributing to the global hepatitis outbreak among pediatric patients that took place in 2022, according to a recent systematic review and meta-analysis published by Phan et al in Journal of Infection. Early in 2022, over 1,000 pediatric patients in 35 countries across the world experienced severe acute hepatitis of unknown etiology. Consequently, these patients had severe adverse outcomes—including neurologic symptoms, long-term sequelae, acute liver failure and subsequent transplantation, and mortality. In the recent analysis, the investigators used the MEDLINE and Embase databases to identify 33 studies involving 3,636 pediatric patients with a median age of 3.5 years who had severe acute hepatitis of unknown etiology from 2019 to 2022. They then reviewed the patients’ demographics, clinical presentation, outcomes, and diagnostic testing for coinfections. Among the patients, 5.9% (n = 214) of them received liver transplants and 1.8% (n = 66) died. The investigators reported that the most common coinfections involved adenovirus and adeno-associated virus 2, but patients also presented with pathogens for enterovirus, rhinovirus, and herpesvirus. They proposed that infections with these viruses as well as altered responses to the pathogens because of limited exposure during the COVID-19 pandemic may have contributed to the increased risk and prevalence of severe acute hepatitis in this patient population.