P1007 - Temozalmide-Induced Vanishing Bile Duct Syndrome

Tanya Ray, MD¹, Niala Moallem, MD², Aaron Silver, MD^3
1University of Connecticut, Hartford, CT; ²University of Connecticut, Farmington, CT; ³Hartford Hospital, Hartford, NJ

Introduction: Temozolomide is an oral alkylating agent used with radiotherapy as a first line treatment for glioblastoma. Commonly known side effects of temozolomide include nausea, fatigue, and bone marrow suppression. The narrow side effect profile of temozolomide makes it a preferred agent (3). We present a rare case of drug induced liver injury with temozolomide.

Case Description/Methods: A 71 year old male with glioblastoma undergoing treatment with TRIDENT clinical trial (tumor treating fields + radiation + temozolomide) presented with generalized weakness and skin discoloration. Physical exam was notable for severe jaundice and abdominal tenderness. Labs showed total bilirubin 6.6, AST 146, ALT 149, Alk P 481–R factor 0.8 was consistent with a cholestatic injury pattern.. Abdominal ultrasound revealed hepatomegaly. Abdominal MRI showed normal biliary system. Autoimmune serologies, acute hepatitis panel, and CMV were negative. While valproic acid hepatotoxicity typically presents with a hepatocellular or mixed injury pattern, there was sufficient concern for valproic acid hepatotoxicity that it was replaced with Vimpat. Levocarnitine and NAC were started. LFTs increased with peak values: T bili 14.2, AST 239, ALT 265, Alk phos 661. He underwent liver biopsy and while awaiting results, was initiated on ursodiol.

Discussion: Pathology report revealed portal based chronic inflammation associated with bile duct damage ranging from moderate to severe bile duct damage to ductopenia, moderate to severe hepatocellular cholestasis, and very early portal fibrosis. This is consistent with drug-induced ductopenia cholestasis, also known as vanishing bile duct syndrome, a rare, but serious form of cholestatic disease. There have been a few case reports published with temozolomide liver toxicity, however they have been associated with monotherapy and dosages of 150 mg or greater. However, our patient was taking temozolomide 60 mg daily. The mechanism of action of temozolomide induced hepatotoxicity is not well understood, as this drug does not require hepatic activation. Treatment of biliary ductopenia includes supportive care, removal of the offending agent, ursodeoxycholic acid, and immunosuppression (2). Given pathology consistent with temozolomide induced liver injury and improvement with ursodiol, we concluded temozolomide was the likely the culprit for liver injury, rather than valproic acid, which though a more common culprit for DILI than temozolomide, did not fit this patient’s clinical picture.


Disclosures:


Tanya Ray, MD¹, Niala Moallem, MD², Aaron Silver, MD³. P1007 - Temozalmide-Induced Vanishing Bile Duct Syndrome, ACG 2023 Annual Scientific Meeting Abstracts. Vancouver, BC, Canada: American College of Gastroenterology.