title: Effect of intraportal infusion of tacrolimus on ischaemic reperfusion injury in orthotopic liver transplantation: a randomized controlled trial.
abstract: The increased use of older and/or marginal donor organs in liver transplantation over the last decade calls for strategies to minimize ischaemic reperfusion (I/R) injury to prevent early graft failure. Tacrolimus, a very potent and effective calcineurin inhibitor, was selected because of its ability to ameliorate I/R injury. A randomized, blinded, controlled single-centre trial of 26 liver transplant recipients was performed between February 2008 and December 2009. Donor organs were randomized to be perfused intraportally during liver transplantation with 1.5 l 5% albumin infusion containing either 20 ng/ml tacrolimus or placebo. The primary end point was liver function as assessed by aspartate transaminase (AST) or alanine transaminase (ALT) levels 6 days after transplantation. Treatment effectiveness was tested by transcriptome-wide analysis of biopsies. There was no difference in the primary end point, i.e. AST (IU/l) and ALT (IU/l) at day 6 after transplantation between groups. Furthermore, choleastatic parameters as well as parameters of liver synthesis were not different between groups. However, tacrolimus treatment suppressed inflammation and immune response in the transplanted liver on a genome-wide basis. Intrahepatic administration of tacrolimus did not result in a reduction of AST and ALT within the first week after transplantation.
authors.affiliation: Department of Transplantation, Medical University of Vienna, Währinger Gürtel 18-20, Vienna, Austria.
authors.forename: Ivan
authors.initials: I
authors.lastname: Kristo
authors.forename: Julia
authors.initials: J
authors.lastname: Wilflingseder
authors.forename: Alexander
authors.initials: A
authors.lastname: Kainz
authors.forename: Julian
authors.initials: J
authors.lastname: Marschalek
authors.forename: Thomas
authors.initials: T
authors.lastname: Wekerle
authors.forename: Ferdinand
authors.initials: F
authors.lastname: Mühlbacher
authors.forename: Rainer
authors.initials: R
authors.lastname: Oberbauer
authors.forename: Martin
authors.initials: M
authors.lastname: Bodingbauer
mesh_terms: D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D001219:Aspartate Aminotransferases / Q000097:blood; D005260:Female; D020869:Gene Expression Profiling; D006084:Graft Rejection / Q000517:prevention & control; D006505:Hepatitis / Q000188:drug therapy; D006801:Humans; D007262:Infusions, Intravenous; D008099:Liver / Q000201:enzymology; D016031:Liver Transplantation / Q000009:adverse effects* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D011169:Portal Vein; D015427:Reperfusion Injury / Q000517:prevention & control*; D016559:Tacrolimus / Q000008:administration & dosage*
chemical_list: D001219:Aspartate Aminotransferases; D000410:Alanine Transaminase; D016559:Tacrolimus