title: Hepatotoxicity caused by both tacrolimus and cyclosporine after living donor liver transplantation.
abstract: We present a case report of a posttransplant patient who had hepatotoxicity due to both tacrolimus and cyclosporine and cholestatic jaundice due to tacrolimus. The patient did not show sustained improvement in enzyme and bilirubin abnormalities after an initial change from tacrolimus to cyclosporine or with a change back to tacrolimus, but he ultimately showed improvement when the blood concentration of tacrolimus was lowered. A 56-year-old man with subacute fulminant hepatitis induced by acarbose was admitted to our hospital for living donor liver transplantation. The liver graft consisted of the left lobe from his ABO-identical son. The early posttransplant course was uneventful. The serum levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and total bilirubin improved initially, but the ALT and AST levels later increased. A liver biopsy suggested a presumptive diagnosis of drug reaction. All drugs were discontinued, the immunosuppressive agent was changed from tacrolimus to cyclosporine. After initial improvement, the ALT and AST levels increased again. Assuming a reaction to cyclosporine, we decreased the concentration of cyclosporine in the blood. The enzyme levels improved temporarily but again began to rise. We changed the immunosuppressive agent to tacrolimus, which resulted in improvements in the ALT and AST levels; however, the total bilirubin level increased. We interpreted this increase as tacrolimus-induced cholestasis; in response, we decreased the blood concentration of tacrolimus to between 3 and 5 ng/dL and added 1,000 mg of mycophenolate mofetil to the drug regimen. The patient recovered without further complications. Repeated liver biopsies throughout the hospital course suggested that the mild mononuclear cell infiltration observed in a few triads had not been caused by acute rejection but had possibly been drug-induced.
authors.affiliation: Surgery for Organ Function and Biological Regulation, Graduate School of Medicine, Nippon Medical School, Sendagi, Bunkyou-ku, Tokyo, Japan. Taniain@nms.ac.jp
authors.forename: Nobuhiko
authors.initials: N
authors.lastname: Taniai
authors.forename: Koho
authors.initials: K
authors.lastname: Akimaru
authors.forename: Yosinori
authors.initials: Y
authors.lastname: Ishikawa
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Kanada
authors.forename: Daisuke
authors.initials: D
authors.lastname: Kakinuma
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Mizuguchi
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Mamada
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yoshida
authors.forename: Takashi
authors.initials: T
authors.lastname: Tajiri
mesh_terms: D056486:Chemical and Drug Induced Liver Injury / Q000209:etiology*; D016572:Cyclosporine / Q000008:administration & dosage / Q000009:adverse effects*; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects*; D041781:Jaundice, Obstructive / Q000139:chemically induced; D016031:Liver Transplantation; D019520:Living Donors; D008297:Male; D008875:Middle Aged; D016559:Tacrolimus / Q000008:administration & dosage / Q000009:adverse effects*
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine; D016559:Tacrolimus