Tacrolimus as a liver flush solution to ameliorate the effects of ischemia/reperfusion injury following liver transplantation

Abstract

The goal of this report is to evaluate in a prospective randomized fashion the effect of flushing hepatic allografts with tacrolimus before transplantation. A prospective, double-blinded, randomized trial was performed. Twenty patients receiving orthotopic liver transplants from October 2000 to October 2001 were randomized into two groups. Group 1 (active) was administered tacrolimus, 20 ng/mL, plus Plasma-lyte A (Baxter Healthcare Corp, Deerfield, IL) liver flush solution; and group 2 (placebo) was administered only Plasma-lyte A. Ischemia/ reperfusion injury was assessed in both groups after transplantation by means of serum laboratory values to assess hepatocellular damage, synthetic function, and ion transport capacity. Peak values were recorded for each parameter, and their distributions were compared. There were no statistically significant differences between groups for age, sex, total ischemia time, or cause of liver disease. Global multivariate comparison of peak changes in all measures of liver function indicated liver injury was significantly lower with tacrolimus treatment than placebo (P ‫؍‬ .01). The sample median for group 1 was less than for group 2 in all parameters measured. Individual statistical comparison showed that peak changes from baseline aspartate aminotransferase and activated partial thromboplastin time values were significantly improved (P < .05) with tacrolimus treatment than placebo treatment. In this prospective, double-blinded, randomized trial, we show that flushing the liver before transplantation with Plasmalyte A containing tacrolimus results in superior early graft function and decreased hepatocellular injury after reperfusion compared with flushing with Plasma-lyte A alone. (Liver Transpl 2003;9:144-149.)

rPSGL-Ig for Improvement of Early Liver Allograft Function: A Double-Blind, Placebo-Controlled, Single-Center Phase II Study†

“…Other clinical strategies reported to ameliorate IRI in liver transplantation include donor treatment with steroids (30), caspase inhibition (31), ATG induction therapy (32), donor organ flush with calcineurin inhibitor (33) and nitric oxide (NO) inhalation (34). All these studies report somewhat improved posttransplant liver function resulting from experimental treatments, with ATG allowing for more compromised liver grafts to be transplanted with less clinical evidence of IRI and improved function.…”

Molecular Mediators of Liver Ischemia and Reperfusion Injury: A Brief Review

“…Tacrolimus administered to livers in a flush-solution before transplantation resulted in improved early organ function and decreased hepatocellular damage (110). Various molecular pathways may have contributed to the beneficial effects, including anti-inflammation and preservation of mitochondrial function (110).…”

Experimental Studies on Protective Effects of FK506 Against Hepatic Ischemia-Reperfusion Injury

“…In a previous trial, Peter et al demonstrated a significant reduction of aminotransferase levels following the transplantation of normal livers rinsed with 20 ng/ml FK506 (tacrolimus) (35). Although the results of this trial were promising, the clinical impact was limited by the small number of patients included (n=20).…”