Antibody-Mediated Rejection after Adult ABO-Incompatible Liver Transplantation Remedied by Gamma-Globulin Bolus Infusion Combined with Plasmapheresis

Abstract

Adult ABO-incompatible liver transplantation has been known to be associated with markedly desperate outcomes. Antibody-mediated rejection (AMR) has been recognized as one of the primary causes of these desperate outcomes, but its clinical features and significance have not been well understood. Recently, some clinicians have succeeded in improving the outcome of adult ABO-incompatible liver transplantation. However, in some transplant patients undergoing these treatments, AMR has still led to graft losses. We recently encountered two patients suffering from AMR after adult ABO-incompatible liver transplantation and remedied their conditions with various therapeutic modalities including direct hepatic infusion therapy and gamma-globulin bolus infusion therapy combined with plasmapheresis. In this article, we describe the clinical features of these patients and the therapeutic strategies we applied. Furthermore, we show the histologic course of the recovery from AMR in the second patient, from whom we were able to extract serial liver biopsies.

Preformed antibody, not primed T cells, is the initial and major barrier to bone marrow engraftment in allosensitized recipients

“…2,[4][5][6] Preformed antibody present at the time of BM infusion is unaffected by standard transplantation conditioning regimens or T-or B-cell immunosuppressive or modulatory strategies given in the peritransplantation period. Although plasmapheresis, high-dose intravenous immunoglobulin, splenectomy, and immunoadsorption are commonly used in solid organ transplantation for the abrogation of alloantibody-mediated rejection, [8][9][10][11]13,14,[24][25][26][27] these strategies generally are not part of the BMT conditioning regimen.…”

“…[1][2][3][4][5][6][7] Despite the well-recognized hazard of antibody-mediated rejection in solid organ transplantation, [8][9][10][11][12][13][14][15] donor BM rejection is generally attributed to cytolytic host antidonor T and natural killer (NK) cells that survive the conditioning regimen. [16][17][18][19][20][21][22][23] However, antibody-mediated BM failure after allogeneic bone marrow transplantation (BMT) can occur either by antibody-dependent cell-mediated cytotoxicity or complement-mediated cytotoxicity.…”

Intravenous immunoglobulins in liver transplant patients: Perspectives of clinical immune modulation

“…It would be very important that future investigations include appropriate risk stratifications, in order to identify subsets that particularly benefit from IVIg. Apart from that, adequate Morioka et al [167] LDLT n = 2; post-LDLT; treatment of AMR Plasmapheresis Normalization of liver function; survived Urbani et al [170] LT n = 1; post-LT; treatment of AMR Plasmapheresis Normalization of liver function; survived Ikegami et al [168] LDLT n = 1; post-LDLT; treatment of AMR Rituximab, plasma exchange, splenectomy Normalization of liver function; survived Testa et al [169] LDLT n = 5; pre-LDLT Plasmapheresis, splenectomy Patient and graft survival 80% at mean of 43 mo post-LDLT Urbani et al [172] LT n = 8; pre-and post-LT Plasma exchange Patient and graft survival 87.5% at 18 mo; no case of acute or chronic rejection, no ITBL Ikegami et al [161] LDLT n = 4; post-LDLT Rituximab, plasma exchange, splenectomy Survival rate 100% (28,8,6, 5 mo post-LDLT) Takeda et al [173] LDLT n = 3; post-LDLT; treatment of AMR Plasma exchange Normalization liver function; survived Mendes et al [174] LT n = 10; pre-and post-LT Rituximab, plasmapheresis Survival rate 50%; death mainly related to MOF and sepsis Kim et al [175] LDLT n = 14; post-LDLT Rituximab, plasma exchange Survival 100%; no case of acute or chronic rejection Lee et al [176] LDLT n = 15; post-LT Rituximab, plasma exchange Survival 100%; no case of bacterial or fungal infection; 3 cases of biliary strictures Shen et al [177] LT n = 35; pre-and post-LT Rituximab Survival rate 83.1% at 3-yr; one case of acute celluar rejection; two cases of AMR …”

“…Apart from that, the interpretation of previous studies are hampered by differences regarding indications, transplant techniques, recipients' characteristics, immunosuppressive treatments and immune modulation protocols (Table 5). Nonetheless, current available data suggest that the implementation of IVIg and its immuno-modulatory properties contributed significantly to recent outcome improvement in ABO-I LT [165][166][167][168][169][170][171][172][173][174][175][176][177] .…”

“…The implementation of beneficial immuno-regulatory properties by IVIg encouraged many transplant groups to perform ABO-I LT without complicating local graft catheterization and/or splenectomy [161,[165][166][167][168][169][170][171][172][173][174][175][176][177] . Testa et al [169] reported in 2008 on survival of 4 of 5 patients at mean of 43 mo after ABO-I LDLT following a combination of pretransplant IVIg, pre-and post-LT plasmapheresis and splenectomy.…”