Sirolimus-associated hepatotoxicity: case report and review of the literature

Abstract

Brock Macdonald1, Evi Vakiani2, Rhonda K Yantiss3, Jun Lee4, Robert S Brown Jr5, Samuel H Sigal61Division of Gastroenterology, Department of Medicine, University of California-San Francisco, San Francisco, CA, 2Department of Pathology, Memorial Sloan–Kettering Cancer Center, New York, NY, 3Department of Pathology and Laboratory Medicine, New York Weill Cornell Medical College, New York, NY, 4Division of Nephrology, Department of Medicine, Weill Cornell Medical College, New York, NY, 5Division of Gastroenterology, Department of Medicine, Columbia University College of Physicians and Surgeons, New York, NY, 6Division of Gastroenterology and Hepatology, Department of Medicine, New York University, New York, NY, USAAbstract: The use of sirolimus as an alternative to calcineurin inhibitors for posttransplant immunosuppression is associated with a variety of inflammatory conditions. In this report, we describe the case of a 34-year-old man who developed abnormal liver tests 6 years after live-donor kidney transplantation and 5 years after initiation of sirolimus-based immunosuppression. Elevated aminotransferase levels persisted after withdrawal of potentially hepatotoxic medications, and serologic evaluation for viral hepatitis, autoimmune disease, and genetic disorders was unrevealing. Liver biopsy revealed prominent hepatocellular injury associated with a mixed inflammatory infiltrate and liver tests normalized within 2 weeks of discontinuation of sirolimus. In this report, we review previous reports of sirolimus hepatotoxicity and propose a unifying hypothesis for the various inflammatory conditions that have been attributed to sirolimus.Keywords: sirolimus, immunosuppression, transplant, inflammatory conditions, hepatotoxicity