SAT-267 Adult Vanishing Bile Duct Syndrome with Hyperlipidemia, Secondary to Pembrolizumab

Abstract Disclosure: J. Martone: None. S. Douglas: None. M. Kristan: None. Introduction: Vanishing bile duct syndrome (VBDS) is a rare progressive condition defined by loss of intrahepatic bile ducts with complications of cholestasis and liver dysfunction. VBDS can be idiopathic, autoimmune, viral, due to malignancy, or secondary as a drug-induced side effect. Hyperlipidemia, though rare, is a severe side effect of VBDS in adults and is thought to be due to disrupted bile acid metabolism and lipid homeostasis. Management of drug-induced VBDS with hyperlipidemia has been underreported in the literature with one previous report. Ursodiol was initiated with subsequent improvement in the patient’s condition. Further documentation of ursodiol’s effect on drug-induced VBDS with hyperlipidemia is critical to patient outcomes. Case Report: A 61-year-old female with a history of metastatic sarcomatoid carcinoma of the breast presented with immune-mediated liver injury thought to be secondary to pembrolizumab, an immune checkpoint inhibitor. The patient had been on a stable dose of pembrolizumab for four months when routine labs revealed alarming liver function tests (LFTs), including elevated aspartate aminotransferase (AST), Alanine aminotransferase (ALT), alkaline phosphatase (ALP) and total bilirubin. A diagnosis of immunotherapy-induced autoimmune hepatitis was reached, prompting the discontinuation of pembrolizumab and initiation of prednisone (80 mg), CellCept (2000 mg), and adriamycin cytoxan. Three months later, LFTs showed a continued elevation in total bilirubin, leading to a diagnosis of choledocholithiasis. Cholecystectomy and liver biopsy resulted in immune-mediated cholangiopathy with VBDS, likely due to pembrolizumab. The case was further complicated by hospital admission for sepsis days before the cholecystectomy, and steroid-induced hyperglycemia, hyponatremia, and Cushing syndrome. Prednisone was tapered to 40 mg daily. Additionally, repeat labs resulted in high total cholesterol (1168 mg/dL) and triglycerides (593 mg/dL). Ursodiol (500 mg BID) was initiated for VBDS with hyperlipidemia. One month post ursodiol, AST has declined from 350 to 127, ALT declined from 350 to 149, ALP declined from 1020 to 502, while total bilirubin has decreased from 10.1 to 7.5. Discussion: This case highlights VBDS with hyperlipidemia as a significant complication of pembrolizumab therapy. Physicians should consider VBDS secondary to pembrolizumab in the setting of prolonged elevated LFTs beginning 1-6 months after drug initiation. VBDS with hyperlipidemia is poorly researched in adults, with only one other case that resulted in LFT and lipid abnormalities being improved by ursodiol treatment. Further research regarding ursodiol treatment in VBDS is critical for adult VBDS cases complicated by hyperlipidemia. Presentation: Saturday, July 12, 2025