Pediatric (neonatal and infantile) jaundice resulting from underlying cholestasis (caused by conjugated hyperbilirubinemia) is always pathological and requires prompt evaluation. Pediatric cholestasis can be caused by medical or surgical factors and, if left untreated, can lead to irreversible liver damage. Timely recognition of pediatric cholestasis and identification of the underlying etiology are paramount to improve outcomes. The broad spectrum of causes potentially underlying pediatric cholestasis requires a multidisciplinary diagnostic approach, and each aspect must be interpreted in the concomitant clinical picture. A liver biopsy is one component of a complex diagnostic puzzle. However, interpreting a liver biopsy performed on a newborn/infant with conjugated/direct hyperbilirubinemia can be a challenging task, as these biopsies are rarely encountered in general hospitals. The aim of this review is to provide a practical and simplified approach to pediatric cholestasis with examples of real clinical cases we have encountered and discuss key features, both histological and clinical, that can help narrow the differential diagnosis and identify treatable causes.
Arienzo et al. (2026) studied this question.