ABO-Incompatible Adult Living Donor Liver Transplantation Under the Desensitization Protocol With Rituximab

Abstract

ABO incompatibility is no longer considered a contraindication for adult living donor liver transplantation (ALDLT) due to various strategies to overcome the ABO blood group barrier. We report the largest singlecenter experience of ABO-incompatible (ABOi) ALDLT in 235 adult patients. The desensitization protocol included a single dose of rituximab and total plasma exchange. In addition, local graft infusion therapy, cyclophosphamide, or splenectomy was used for a certain time period, but these treatments were eventually discontinued due to adverse events. There were three cases (1.3%) of in-hospital mortality. The cumulative 3-year graft and patient survival rates were 89.2% and 92.3%, respectively, and were comparable to those of the ABO-compatible group (n ¼ 1301). Despite promising survival outcomes, 17 patients (7.2%) experienced antibody-mediated rejection that manifested as diffuse intrahepatic biliary stricture; six cases required retransplantation, and three patients died. ABOi ALDLT is a feasible method for expanding a living liver donor pool, but the efficacy of the desensitization protocol in targeting B cell immunity should be optimized.

Endoscopic management of biliary strictures after living donor liver transplantation

“…Immunological factors (e.g., ABO blood type incompatibility [37,38] and cytomegalovirus infection [39]) are also associated with non-BAS formation. Because cholangiocytes play an important role in mucosal immunity in the biliary system [40,41], they are the primary targets of immune attack, which leads to stricture formation.…”

Single-Center Experience of ABO-Incompatible Living-Donor Liver Transplantation With a New Simplified Intravenous Immunoglobulin Protocol: A Propensity Score-Matching Analysis

“…Basically, damage to ABO-I liver grafts is initiated by preformed IA and is potentiated by B-cell proliferation, which is activated by ABO antigens in the donor graft [9]. The main targets are endothelial cells in the graft vasculature and the epithelial cells in the bile duct [3,9]. Therefore, several different DSZ protocols have been introduced to prevent these IA-mediated graft injuries [9].…”

“…However, various strategies in B cell desensitization (DSZ), aimed at preventing antibody-mediated rejection (AMR), including rituximab and local infusion therapy (LIT), have improved the outcomes of ABO-I liver transplantation (LT) so that it is now similar to that of ABO-compatible LT [2,3]. As a result, ABO-I LDLT has become a feasible option for end-stage liver disease in countries with an extreme scarcity of deceased-donor organs [4].…”

Evading antigens—ABO-incompatible liver transplantation

“…Despite all these efforts, graft options continue to be limited in many instances. One avenue that has been explored since the initial development of liver transplantation by Starzl is transplantation across ABO blood groups, which has been addressed again in the current series published by Song et al 1 The status of the liver as a 'privileged organ' that is resistant to rejection led to the breaching of the blood group barrier early during the history of liver transplantation.…”

“…1 Firstly, and most importantly, Song et al 1 have arrived at an ABOi liver transplantation immunosuppression protocol with rates of overall and graft survival that are comparable to the ABOc group. The ABOi group did have more biliary complications and more antibody-mediated rejection (defined as periportal oedema and necrosis or haemorrhagic oedema associated with an increase in IA titres, in addition to ≥50% stromal-positive portal tracts staining for C4d, a degradation product of the complement pathway).…”