A Hematologic Masquerader: Progressive Familial Intrahepatic Cholestasis Type 3 Presenting as Anemia, Hepatosplenomegaly, and Recurrent Bleeding in a Child

ABSTRACT

Progressive familial intrahepatic cholestasis type 3 (PFIC‐3), caused by pathogenic variants in the ABCB4 gene, is a rare inherited cholestatic liver disorder that often presents later in childhood. In some patients, hematologic manifestations may dominate the clinical picture and delay recognition of the underlying liver disease. We report a 4‐year‐old girl referred for evaluation of anemia, hepatosplenomegaly, and recurrent bleeding. Initial investigation focused on primary hematologic causes. However, imaging revealed portal hypertension with esophageal varices, and genetic testing identified a homozygous pathogenic ABCB4 variant, confirming the diagnosis of PFIC‐3. This case highlights how chronic cholestatic liver disease may masquerade as a primary hematologic disorder and emphasizes the importance of considering systemic causes in children presenting with anemia, hepatosplenomegaly, and bleeding manifestations. Early recognition of underlying liver disease is essential to facilitate appropriate multidisciplinary management and prevent potentially life‐threatening complications.