Early cellular rejection after orthotopic liver transplantation correlates with low concentrations of FK506 in hepatic tissue

William J. Sandborn, George M. Lawson, Timothy J. Cody, Michael K. Porayko, J. Eileen Hay, Gregory J. Gores, Jeffery L. Steers, Ruud A.F. Krom, Russell H. Wiesner

Research output: Contribution to journalArticlepeer-review

32 Scopus citations

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. These findings support the hypothesis that low hepatic tissue concentrations of immunosuppressives may lead to cellular rejection after liver transplantation.

Original languageEnglish (US)
Pages (from-to)70-76
Number of pages7
JournalHepatology
Volume21
Issue number1
DOIs
StatePublished - Jan 1995

ASJC Scopus subject areas

  • Hepatology

Fingerprint

Dive into the research topics of 'Early cellular rejection after orthotopic liver transplantation correlates with low concentrations of FK506 in hepatic tissue'. Together they form a unique fingerprint.

Cite this