ABO-incompatible liver transplantation for critically ill adult patients

Abstract

Liver transplantation across the ABO barrier remains a controversial issue. Early results were poor, with 5-year graft survivals often as low as 20%. ABO-incompatible (ABO-In) transplants were associated with a high risk of antibody-mediated rejection, severe cell-mediated rejection, vascular thrombosis and ischaemic bile duct complications [1][2][3][4]. However, more recent experiences indicate improving results, with up to 60% 5-year graft survival reported [5][6][7]. Such progress presumably reflects peritransplant management and improving potency of immunosuppression. Protocols appear to have evolved from triple-[1,2] to quadruple-drug immunosuppression with frequent addition of plasmapheresis, splenectomy or intra-vascular infusion of methylprednisolone or prostaglandin E1 [6,8,9]. ABO-incompatible liver transplants have been most frequently utilized for two indications: emergency transplants for acute liver failure or in cases of living-related donor transplants, when no ABO-compatible (ABO-C) donor is available. The risk of rejection in a critically ill patient with acute liver failure, often with concomitant renal dysfunction, is probably lower than in a stable recipient undergoing elective ABO-In living donor transplant. One can thus ponder whether the trend towards more aggressive immunosuppression, especially when including splenectomy or intravascular infusion, should be similarly applied to both ABO-In transplant indications.This study specifically addressed the problem of emergency liver transplant in high status adult patients experi- Summary ABO incompatible (ABO-In) liver transplant remains a controversial solution to acute liver failure in adults. Adult liver recipients with acute liver failure or severely decompensated end-stage disease, intubated and/or in the intensive care unit, were grouped as ABO-In (n ¼ 14), ABO-compatible (n ¼ 29, ABO-C) and ABO-identical (n ¼ 65, ABO-Id). ABO-In received quadruple immunosuppression with antibody-depleting induction agents (except two), calcineurin inhibitors, antimetabolites and steroids. No significant difference of patient and graft survivals was observed among ABO-In, ABO-C and ABO-Id: graft survivals were 64%, 62% and 67%, respectively, in 1 year and 56%, 54% and 60%, respectively, in 5 years; patient survivals 86%, 69% and 67%, respectively, in 1 year and 77%, 61% and 62%, respectively, in 5 years. Three ABO-In grafts were lost (one hyper-acute rejection and two hepatic artery thrombosis). Surgical and infectious complications were similarly distributed between groups, except the hepatic artery thrombosis, more frequent in ABO-In (2, 14%) than ABO-I (1, 1.5%, P < 0.05). In contrast to previous studies, no significant difference of patient and graft survivals could be observed among all ABO-compatibility settings. Our results suggest that ABO-incompatible transplants should be viewed as an important therapeutic option in adult patients with acute liver failure awaiting an emergency procedure.

ABO-Incompatible Liver Transplantation in Acute Liver Failure: A Single Portuguese Center Study

“…12,14 These observations reinforce the need for close monitoring of isoagglutinin levels, especially during the first month and argue for prophylactic institution of immunosuppression when levels increase. 4,11,13,28 We cannot confirm that AMR was directly associated with a higher titer of anti-ABO antibodies. Patients 4 and 5 with elevated titers showed no evidence of AMR or other complications, possibly as a consequence of effective interventions.…”

“…8 -10 Recently, Toso et al did not observe a significant difference regarding patient and graft survival when comparing 1-and 5-year data from ABOi, ABO compatible and ABO identical livers. 11 The main complication of ABOi LT is AMR, closely related to high levels of anti-donor ABO antibodies present perioperative and posttransplant. As a result, most efforts to improve ABOi LT outcome have been directed to reducing anti-blood type antibodies.…”

“…2,5 ABOi transplantation remains a high-risk procedure performed only in cases lacking an available/compatible organ donor 6 or as a rescue option in emergency situations with the unavailability of a compatible graft. [7][8][9][10][11] Early results with adult ABOi LT were disappointing; patient and graft survivals were significantly worse than adult compatible OLT. 2,9,10 In 1988, Demetris et al reported a 46% graft failure rate during the first 30 days after primary ABOi LT compared with 11% with ABO compatibility.…”

“…7 The worse outcomes related to the potential for antibody-mediated rejection (AMR) associated with the presence of agglutinin antibodies. [12][13][14][15] Vascular thrombosis, acute liver necrosis, [11][12][13][14] intrahepatic biliary complications, 16 -18 and sepsis caused by over-immunosuppression have been recognized to be causes of the poor outcomes. 5,14 Recently, some authors have reported similar patient and graft survivals for ABOi LT compared with compatible OLT among all age groups.…”

“…5,14 Recently, some authors have reported similar patient and graft survivals for ABOi LT compared with compatible OLT among all age groups. 4,5,11,19 Two-year adult recipient survival after ABOi LT was reported to be nearly 70%, whereas before 2002, it was approximately 40%. 5 Similar data have also been reported in a review of the Organ Procurement and Transplantation Network (OPTN) in 2009.…”