Temozolomide-induced biliary ductopenia: a case report

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.