Acute liver failure is rare in the neonatal and infant population; however, when encountered, it requires timely diagnosis, management, and identification of the underlying etiology to provide the best clinical outcomes. Here, we present a case of new-onset liver failure in a 4-month-old infant. She had previously been diagnosed with neonatal mucocutaneous herpes simplex virus disease, but had been healthy in the interval, and was referred to our hospital for evaluation of possible need for liver transplantation because of a rapidly progressing pace of disease. In this diagnostic dilemma article, we review the case history and presentation and consider the differential diagnosis from the points of view of the primary and consultative teams. We then follow the clinical evolution of disease, identify a final diagnosis, and explore the short- and long-term management and health implications of the diagnosis. This case should be of interest to primary care providers, intensivists who care for neonates or infants, and specialists who encounter liver failure in their clinical practice.
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