The effect of steroid pretreatment of deceased organ donors on liver allograft function: A blinded randomized placebo-controlled trial

Abstract

Background & AimsBrain death-associated inflammatory response contributes to increased risk of impaired early liver allograft function, which might be counterbalanced by steroid pretreatment of the organ donor. The aim of this randomized controlled trial was to elucidate whether steroid pretreatment of liver donors improves early liver allograft function, prevents rejection and prolongs survival.MethodsA placebo-controlled blinded randomized clinical trial was performed in three different centers in Austria and Hungary between 2006 and 2008. Ninety deceased organ donors received either 1000 mg of methylprednisolone or placebo 6 h before recovery of organs. The primary end point was the concentration slope of transaminases within the first week. The secondary end point included survival and biopsy-confirmed acute rejection (BCAR) within 3 years after transplantation.ResultsOf the 90 randomized donors, 83 recipients were eligible for study. The trajectories of ALT and AST were not different between treatments (p = 0.40 and p = 0.13, respectively). Eight subjects died in the steroid and 13 in the placebo group within 3 years after engraftment (RR = 0.63 95% CI [0.29, 1.36], p = 0.31). Eleven recipients experienced biopsy-confirmed rejection (BCAR) in the steroid and 11 in the placebo group (RR = 1.02 95% CI [0.50, 2.10], p = 1.00). No effect modification could be identified in the predefined strata of donor age, sex, cold ischemic time, and cause of donor death.ConclusionsSteroid pretreatment of organ donors did not improve outcomes after liver transplantation.

Steroid Anti-Inflammatory Effects Did Not Improve Organ Quality in Brain-Dead Rats

“…These results are in line with a randomized clinical trial by Kotsch et al [ 6 ] demonstrating a significant downregulation of proinflammatory cytokines which was associated with a reduced incidence of acute rejection in the liver transplantation setting. In contrast, Amarschek et al [ 44 ] conclude that steroid donor treatment did not improve outcomes after liver transplantation, but no inflammatory markers were measured in this study. Others in the realms of kidney transplantation have failed to detect a significant improvement in the incidence or duration of posttransplantation acute renal failure in allograft recipients when 1 g of methylprednisolone is administered to donors 3 hours prior to explantation, despite the suppression of inflammatory response in transplanted kidneys [ 45 ].…”

Control of Ischemia-Reperfusion Injury in Liver Transplantation: Potentials for Increasing the Donor Pool

“…Methylprednisolone treatment in liver donors (two studies, 183 participants [43,44]) showed no effect on acute rejection rates within the first 6 months after LT. Antidiuretic hormone treatment in kidney donors (two studies, 222 participants [45,46]) showed no benefit in the prevention of delayed graft function. The effect of ischemic preconditioning for 10 min on outcomes after LT was analyzed in 7 studies with a total of 334 participants [47,48,49,50,51,52,53], and showed improved short-term liver function by enhancement of AST and INR levels within the first days post-transplantation but had no effect on long-term transplant outcomes.…”

Corticosteroids in the management of brain-dead potential organ donors: a systematic review

“…30 Both RCTs evaluating liver recipients used two different immunosuppressive regimens: the first one combined a calcineurin inhibitor to mycophenolate mofetil and steroids without using induction therapy, 30 whereas the second one used antithymocyte globulin and high-dose dexamethasone as induction therapy followed by maintenance treatment with a calcineurin inhibitor. 34 In one recent study evaluating kidney recipients' outcome, the immunosuppressive regimen consisted of a calcineurin inhibitor-based maintenance therapy with or without induction therapy depending on different risk factors. Anti-CD25s were the preferred induction agents.…”

“…30 34 The first found a decreased rate of ischaemia -reperfusion injury defined as an increase in liver enzyme values (AST/ALT), 30 whereas the second showed that liver enzymes had a similar trajectory posttransplantation. 34 Again, Kotsch and colleagues found a decrease in the rate of grade one to three biopsyproven acute rejections within the first 6 months posttransplantation, 30 whereas Amatschek and colleagues found no difference in mortality, biopsy-proven acute rejections, or graft loss within 3 yr posttransplant. 34 The six other trials evaluating graft outcomes only included pretreated kidney donors.…”

“…34 Again, Kotsch and colleagues found a decrease in the rate of grade one to three biopsyproven acute rejections within the first 6 months posttransplantation, 30 whereas Amatschek and colleagues found no difference in mortality, biopsy-proven acute rejections, or graft loss within 3 yr posttransplant. 34 The six other trials evaluating graft outcomes only included pretreated kidney donors. 24 -28 33 They all found no difference in kidney graft function or survival either at 1-week posttransplantation 33 or up to 12 months posttransplantation.…”