No diffuse intrahepatic biliary stricture after ABO-incompatible adult living donor liver transplantation using tailored rituximab-based desensitization protocol

Abstract

Background: Rituximab (RTx) desensitization protocol offered good outcome in ABO-incompatible (ABOi) living donor liver transplantation (LDLT). However, diffuse intrahepatic biliary stricture (DIHBS) is still inevitable hurdle. We selectively added postoperative high dose intravenous immunoglobulin (IVIG) and/or simultaneous splenectomy if ABO isoagglutinin titer just before liver transplantation after plasma exchange (PE) was higher than 1/16. Herein, we reported the excellent outcome of ABOi LDLT without DIHBS using tailored desensitization protocol and compared it with that of ABO-compatible (ABOc) LDLT.Methods: Sixty-five cases (14.8%) of ABOi LDLTs were performed among 438 primary adult LDLTs in our center between March 2012 and June 2017. We performed 1-to-2 propensity score matching (PSM) to extract 60 cases of ABOi LDLTs and 120 cases of ABOc LDLTs.Results: There were no significant differences in clinical characteristics between ABOi and ABOc recipients. There were no significant differences in complications and rejection. There was no DIHBS in both groups. The 1-, 3-, and 5-year overall survival rates were 98.3%, 86.7%, and 82.9% in ABOi group and 96.7%, 86.7%, and 85.4% in ABOc group, respectively (P=0.88). Most common cause of deaths of both groups was hepatocellular recurrence. The 1-, 3-, and 5-year biliary complication (anastomosis leakage or stricture) free survival rates were 81.4%, 69.5%, and 67.5% in ABOi group and 83.0%, 81.3%, and 80.0% in ABOc group, with no significant differences (P=0.11).Conclusions: RTx-based tailored (optional IVIG + splenectomy) desensitization protocol for ABOi LDLT was feasible and acceptable.

Pretransplant mycophenolate mofetil may be associated with reduced intrahepatic cholangiopathy in ABO-incompatible liver transplantation

“…In recent years, there have been reports that ABOi LDLT is related to antibody-mediated rejection and biliary complications, particularly ischemic-type diffuse biliary stricture 2,12 . A review of our data on ABOi LDLT revealed that this type of biliary complication occurred predominantly in patients who received liver grafts from donors with a laparoscopic donor hepatectomy.…”

“…[11] In recent years, there have been reports that ABOi LDLT is related to antibody-mediated rejection and biliary complications, particularly ischemic-type diffuse biliary stricture. [2,12] A review of our data on ABOi LDLT revealed that this type of biliary complication occurred predominantly in patients who received liver grafts from donors with a laparoscopic donor hepatectomy. As a preventive measure, our center changed our protocol to lower the immunologic risk by prescribing pretransplant mycophenolate mofetil (MMF) to patients scheduled for LT.…”

The fate of donor‐type ABO blood group antigen expression in liver grafts in ABO‐incompatible adult living donor liver transplantation

“…Desensitization protocols at our center involved the routine administration of rituximab, a monoclonal antibody targeting CD20, and plasmapheresis exchanges prior to transplantation. Rituximab (300 mg/m 2 body surface area) was administered 3–4 weeks before transplantation, followed by 1–6 plasmapheresis exchanges 1 week before transplantation to achieve target anti‐A or anti‐B IgG isoagglutinin titers of less than 1:32 7 . In recipients whose post‐desensitization anti‐A or anti‐B IgG isoagglutinin titers were greater than 1:32, preoperative intravenous immunoglobulin (IVIG) therapy or combined splenectomy was performed 7 .…”

“…Although liver transplantation across the ABO blood type barrier yield unfavorable outcomes, effective desensitization protocols using rituximab and plasmapheresis have significantly improved recipient and graft survival. ABOi ALDLT is no longer a contraindication and has gained recognition in recent years 3–7 …”

Current Status of ABO-incompatible Liver Transplantation

“…In one counterstrategy, when the ABO isoagglutinin titer exceeded 1:16 just before LT and after plasma exchange, high-dose IVIG (0.8 g/kg daily) was administered for 5 d beginning on postoperative day 1; concurrent splenectomy was added selectively. 35 However, in the era of rituximab desensitization, the value of the preoperative isoagglutinin titer has become unclear, 34 and a prospective study is warranted.…”