title: Recurrence of hepatic artery thrombosis following acute tacrolimus overdose in pediatric liver transplant recipient.
abstract: Acute overdose of tacrolimus appears to cause no or minimal adverse clinical consequences. We encountered a pediatric case who underwent liver transplantation associated with hepatic artery thrombosis (HAT), which recurred following acute tacrolimus overdose. A 10-month-old girl underwent living-related liver transplantation because of biliary atresia. To reconstruct the hepatic artery, the right gastroepiploic artery of the donor was interposed between the right hepatic artery of the recipient (2.5 mm in diameter) and the left hepatic graft artery (1 mm in diameter) under microscopy. On postoperative day 4, Doppler ultrasonography showed a remarkable reduction in hepatic arterial flow, which was consistent with HAT. The patient underwent immediate hepatic arteriography and balloon angioplasty. The stenotic sites were dilated by the procedure. Tacrolimus was infused intravenously after transplantation and the infusion rate was adjusted to achieve a target concentration of 18-22 ng/mL, which remained stable until the morning of day 6. An unexpectedly high blood concentration of tacrolimus (57.4 ng/mL) was detected at 6:00 PM on day 6, and tacrolimus was discontinued at 9:00 PM; however, the tacrolimus level reached 119.5 ng/mL at 0:00 h on day 7. While the concentration decreased to 55.2 ng/mL on the morning of day 7, the hepatic arterial flow could not be observed by Doppler ultrasonography. Emergent hepatic arteriography showed stenosis of the artery at the proximal site of the anastomosis. Balloon angioplasty was again performed and the stenotic site was successfully dilated. High level of tacrolimus exposure to the hepatic artery with injured endothelium by preceding angioplasty may have been related to the recurrence of HAT in the present case.
authors.affiliation: Department of Transplantation Surgery, Jichi Medical School Hospital, Tochigi, Japan.
authors.forename: Soshi
authors.initials: S
authors.lastname: Takahashi
authors.forename: Koh-ichi
authors.initials: K
authors.lastname: Sugimoto
authors.forename: Shuji
authors.initials: S
authors.lastname: Hishikawa
authors.forename: Koichi
authors.initials: K
authors.lastname: Mizuta
authors.forename: Akio
authors.initials: A
authors.lastname: Fujimura
authors.forename: Hideo
authors.initials: H
authors.lastname: Kawarasaki
mesh_terms: D001806:Blood Urea Nitrogen; D002648:Child; D002761:Cholangitis / Q000175:diagnosis / Q000628:therapy; D003404:Creatinine / Q000097:blood; D004322:Drainage; D016903:Drug Monitoring / Q000379:methods; D062787:Drug Overdose; D005260:Female; D006499:Hepatic Artery / Q000000981:diagnostic imaging; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000009:adverse effects* / Q000097:blood; D007262:Infusions, Intravenous; D016031:Liver Transplantation / Q000009:adverse effects / Q000276:immunology*; D011183:Postoperative Complications / Q000175:diagnosis*; D012008:Recurrence; D016559:Tacrolimus / Q000008:administration & dosage / Q000009:adverse effects* / Q000097:blood; D013927:Thrombosis / Q000139:chemically induced* / Q000000981:diagnostic imaging; D016896:Treatment Outcome; D014463:Ultrasonography
chemical_list: D007166:Immunosuppressive Agents; D003404:Creatinine; D016559:Tacrolimus