title: Early cellular rejection after orthotopic liver transplantation correlates with low concentrations of FK506 in hepatic tissue.
abstract: We have previously reported that low hepatic tissue cyclosporine levels correlate with early cellular rejection after liver transplantation. The aim of this study is to determine whether there is a similar relationship in patients treated with FK506. Twenty-five liver biopsies were performed in 10 patients immunosuppressed with FK506 without cellular rejection: day 7 = 10; day 14 = 3; day 21 = 9; day 28 = 1; day 35 = 1; and day 42 = 1. These 10 patients without cellular rejection were compared with 7 patients immunosuppressed with FK506 with cellular rejection who underwent a total of 23 liver biopsies, including 9 biopsies that showed rejection: day 7 = 4; day 14 = 2; day 21 = 1; day 28 = 1; and day 49 = 1. There was no significant difference between the nonrejection and current rejection groups in the median plasma concentration of FK506, 0.9 ng/mL versus 0.9 ng/mL (P = .50). In contrast, the median hepatic tissue concentration of FK506 was significantly higher in the nonrejection group than it was in the current rejection group, 144 ng/g versus 48 ng/g (P = .02). In the current rejection group, 7 of 9 hepatic tissue concentrations of FK506 were < 100 ng/g, and in the nonrejection group, 18 of 25 hepatic tissue concentrations were > 100 ng/g. Low hepatic tissue concentrations of FK506 correlate with the occurrence of early cellular rejection after liver transplantation, in contrast to plasma concentrations of FK506. A hepatic tissue concentration of FK506 < 100 ng/g is 78% sensitive and 72% specific for cellular rejection.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Division of Gastroenterology and Internal Medicine, Mayo Clinic, Rochester, MN 55905.
authors.forename: W J
authors.initials: WJ
authors.lastname: Sandborn
authors.forename: G M
authors.initials: GM
authors.lastname: Lawson
authors.forename: T J
authors.initials: TJ
authors.lastname: Cody
authors.forename: M K
authors.initials: MK
authors.lastname: Porayko
authors.forename: J E
authors.initials: JE
authors.lastname: Hay
authors.forename: G J
authors.initials: GJ
authors.lastname: Gores
authors.forename: J L
authors.initials: JL
authors.lastname: Steers
authors.forename: R A
authors.initials: RA
authors.lastname: Krom
authors.forename: R H
authors.initials: RH
authors.lastname: Wiesner
mesh_terms: D000328:Adult; D001706:Biopsy; D005260:Female; D006084:Graft Rejection / Q000517:prevention & control; D006801:Humans; D008099:Liver / Q000378:metabolism* / Q000473:pathology; D016031:Liver Transplantation; D008297:Male; D008875:Middle Aged; D009994:Osmolar Concentration; D013256:Steroids / Q000627:therapeutic use; D016559:Tacrolimus / Q000097:blood / Q000493:pharmacokinetics* / Q000627:therapeutic use
chemical_list: D013256:Steroids; D016559:Tacrolimus