Balakrishnan Asha, Ledford Robert, Jaglal Michael
Department of Internal Medicine, University of South Florida, Tampa, FL, USA.
Department of Malignant Hematology, H. Lee Moffitt Cancer and Research Institute, 12902 Magnolia Drive, Tampa, FL, 33612, USA.
J Med Case Rep. 2016 Feb 5;10:33. doi: 10.1186/s13256-016-0804-z.
Temozolomide is an alkylating agent used along with concurrent radiation therapy in the treatment of glioblastoma. The primary adverse effect of temozolomide is bone marrow suppression with resulting cytopenias. There have been reported cases of temozolomide-induced hepatotoxicity, including fatal liver failure, associated with reactivation of the hepatitis virus or with concurrent use of other hepatotoxic drugs. In this report, we describe a unique mechanism of temozolomide-induced liver injury with supporting histopathology.
Our patient, a 58-year-old African american woman with glioblastoma, was treated with concurrent radiation and temozolomide therapy. After 6 weeks of treatment, she developed worsening transaminitis and bilirubinemia with liver biopsy results consistent with drug-induced cholestasis and ductopenia. After cessation of drug treatment, her hyperbilirubinemia progressed with a peak bilirubin of 36.8 mg/dl. A repeat liver biopsy revealed severe biliary ductopenia consistent with vanishing bile duct syndrome.
We present a rare case of a patient with biliary ductopenia as an adverse effect of temozolomide. During radiation and temozolomide therapy, blood counts and liver enzymes should be carefully monitored for the development of cholestatic liver injury. We recommend monitoring with weekly liver function tests and minimizing drugs that are metabolized by the liver during chemoradiation for glioblastoma.
替莫唑胺是一种烷化剂，与同步放疗联合用于治疗胶质母细胞瘤。替莫唑胺的主要不良反应是骨髓抑制导致血细胞减少。已有替莫唑胺诱发肝毒性的病例报道，包括致命性肝衰竭，与肝炎病毒再激活或同时使用其他肝毒性药物有关。在本报告中，我们描述了一种独特的替莫唑胺诱发肝损伤机制，并提供了支持性的组织病理学证据。
我们的患者是一名58岁患有胶质母细胞瘤的非裔美国女性，接受同步放疗和替莫唑胺治疗。治疗6周后，她出现转氨酶升高和胆红素血症加重，肝活检结果符合药物性胆汁淤积和胆管减少症。停药后，她的高胆红素血症仍继续进展，胆红素峰值达到36.8mg/dl。再次肝活检显示严重的胆管减少，符合胆管消失综合征。
我们报告了一例罕见的替莫唑胺不良反应导致胆管减少症的病例。在放疗和替莫唑胺治疗期间，应密切监测血细胞计数和肝酶，以发现胆汁淤积性肝损伤。我们建议每周进行肝功能检查，并在胶质母细胞瘤放化疗期间尽量减少经肝脏代谢的药物使用。
