S3455 PSC-PBC Overlap in the Setting of Inflammatory Bowel Disease: A Diagnostic Rarity

Introduction: Primary sclerosing cholangitis (PSC) and primary biliary cholangitis (PBC) are chronic autoimmune liver diseases with distinct clinical, serologic, and imaging profiles. Although both conditions can present with cholestatic liver enzyme abnormalities, their simultaneous occurrence is extremely uncommon and no formal diagnostic criteria exist for the overlap. We report a case of PSC–PBC overlap in a patient with ulcerative colitis, highlighting key diagnostic considerations in this unusual presentation. Case Description/Methods: A 57-year-old woman with long-standing ulcerative colitis on sulfasalazine had persistently elevated liver enzymes in cholestatic pattern since 2019. Initial labs showed ALP 403 U/L, ALT 103 U/L, AST 93 U/L, and a markedly elevated antimitochondrial antibody (AMA) titer of 125 (ULN 20). Antinuclear antibody (ANA) and anti-smooth muscle antibody (ASMA) were negative. An magnetic resonance imaging performed in late 2022 revealed segmental irregularity and dilation of intrahepatic bile ducts, most prominently in segment 4, raising concern for PSC. A liver biopsy showed prominent ductular proliferation with periductal neutrophils, occasional intraductal lymphocytes, and focal duct damage. Several ducts showed concentric periductal fibrosis. No florid duct lesions or granulomas were present. Given this serologic and histologic profile, ursodeoxycholic acid was initiated in 2023. A follow-up magnetic resonance cholangiopancreatography (MRCP) in May 2024 demonstrated cirrhotic changes, patchy hepatic steatosis, and classic beading of the intrahepatic bile ducts, along with confluent fibrosis in the left hepatic lobe—findings more consistent with PSC. Taken together, these features supported a diagnosis of PSC–PBC overlap. Discussion: While PSC is commonly associated with inflammatory bowel disease and PBC typically affects middle-aged women, the coexistence of both conditions in the same patient is rare. This case highlights the value of integrating serologic markers, liver histology, and imaging findings to identify overlap syndromes that fall outside standard diagnostic frameworks. Recognition of this entity is important, as management strategies and disease course may differ from either condition alone.