267 Unmasking PFIC3: A Diagnostic Challenge in Pediatric Liver Disease

Introduction/Objective Progressive familial intrahepatic cholestasis type 3 (PFIC-3) is a rare autosomal recessive disorder caused by mutations in the ABCB4 gene, which encodes the multidrug resistance protein-3 (MDR3). The clinical and histological overlap of PFIC-3 with autoimmune hepatitis (AIH) and Wilson’s disease is under-recognized. Methods/Case Report This is an IRB-approved, retrospective, clinicopathologic review of five patients with PFIC3 from 2014 to 2024. Results Median age at presentation was 11 years (range: 6- 16 years), with 75% males. Liver panel showed elevated AST, ALT, ALP, GGT, and bile acids. One patient (25%) was ANA and anti-SM positive, with histology mimicking AIH-PSC overlap, yet failed to respond to steroids. Elevated tissue and 24-hour urine copper was noted in 50%, leading to suspicion of Wilson’s disease. Gallstones were observed in 60%, mild intrahepatic biliary duct dilatation in 40%, and biliary strictures in 20%. MDR3 IHC demonstrated patchy to diffuse loss in 60%. Three patients have undergone liver transplantation to date at a mean age of 8.2 years (range 8 to 11). Conclusion PFIC-3 can mimic AIH/PSC and Wilson’s disease, leading to diagnostic challenges. Multidisciplinary management, including increased awareness of PFIC3 and genetic testing, can aid in timely diagnosis and prevent unnecessary interventions.