S3306 Vanishing Bile Duct Syndrome: A Case Report

Introduction: Vanishing bile duct syndrome (VBDS) is a rare, acquired form of cholestatic liver disease associated with hepatic ductopenia. Causes of VBDS include infections, autoimmune disease malignancy, idiopathic causes and drugs. Identifying the cause is essential for treatment. We present a case of suspected drug induced VBDS to increase awareness and discuss differential causes. Case Description/Methods: A 52-year-old woman with a history of hypertension (HTN), type I diabetes complicated by End Stage Renal Disease status post pancreatic (2007) and kidney transplant (2005) on azathioprine, presented with worsening fatigue and jaundice for 6-12 months. She endorsed weight loss, dyspnea and lower extremity (LE) edema. She denied abdominal pain or nausea/vomiting. She had rising leukocytosis over the past year with no clear source. Exam was significant for jaundice, scleral icterus, bilateral LE edema and rales. Labs showed significant leukocytosis, significantly elevated bilirubin (direct predominant) and alkaline phosphatase (ALP) with mild transaminemia. Infectious and autoimmune work up of her cholestatic liver injury was negative. Imaging showed lithiasis with no ductal dilation or inflammation. She continued to deteriorate, developing worsening cholestasis and undifferentiated shock. Liver and bone marrow biopsies revealed 35-50% ductal loss consistent with VBDS and myelodysplastic syndrome (MDS). She started minoxidil for HTN in March 2024, with her ALP rising by May. VBDS was suspected to be drug induced from minoxidil or azathioprine. Both were discontinued and ursodiol was initiated with mild improvement in ALP but worsening bilirubin. After a complex course, she passed away from cardiac arrest before recovery from VBDS could be appreciated. Discussion: With a negative infectious and autoimmune workup, and no known association between MDS and VBDS, medication was the most likely cause. Minoxidil was considered due to its temporal association with rising ALP. Azathioprine is also associated with both acute cholestatic injury and chronic hepatotoxicity. Both drugs have rarely been linked to VBDS. ALP improvement following cessation of both medications and initiation of ursodiol supports our conclusion. Identifying the offending agent is difficult with multiple potential causes. Drug induced VBDS follows a variable clinical course. The only treatment is cessation of the offending agent and ursodiol. Our case highlights the diagnostic uncertainty of VBDS.