Impact of Rituximab Desensitization on Blood-Type-Incompatible Adult Living Donor Liver Transplantation: A Japanese Multicenter Study

Abstract

We evaluated the effects of rituximab prophylaxis on outcomes of ABO‐blood‐type‐incompatible living donor liver transplantation (ABO‐I LDLT) in 381 adult patients in the Japanese registry of ABO‐I LDLT. Patients underwent dual or triple immunosuppression with or without B cell desensitization therapies such as plasmapheresis, splenectomy, local infusion, intravenous immunoglobulin and rituximab. Era before 2005, intensive care unit‐bound status, high Model for End‐Stage Liver Disease score and absence of rituximab prophylaxis were significant risk factors for overall survival and antibody‐mediated rejection (AMR) in the univariate analysis. After adjustment for era effects in the multivariate analysis, only absence of rituximab prophylaxis was a significant risk factor for AMR, and there were no significant risk factors for survival. Rituximab prophylaxis significantly decreased the incidence of AMR, especially hepatic necrosis (p < 0.001). In the rituximab group, other B cell desensitization therapies had no add‐on effects. Multiple or large rituximab doses significantly increased the incidence of infection, and early administration had no advantage. In conclusion, outcomes in adult ABO‐I LDLT have significantly improved in the latest era coincident with the introduction of rituximab.

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

“…A Japanese nationwide survey revealed that the 3-year survival rate increased from 30% to 80% after the introduction of RIT (17). A recent Japanese multicenter study revealed that the only risk factor for AMR was a DSZ protocol without RIT (5). In that study, the incidence of AMR decreased from 23.5% to 6.2% after the introduction of RIT.…”

“…Several previous studies revealed that the effect of RIT on B cells in peripheral blood was very rapid, eliminating cells within 48-72 hours, and persisted for several months in transplant recipients (25). Furthermore, most data indicate that a single dose of RIT, as opposed to repeated doses, is sufficient for sustained suppression of B cells in peripheral blood (5,9,25,26). Consequently, repeated dosing of RIT may be unnecessary and may increase the risk of serious infection due to prolonged hypogammaglobulinemia.…”

“…Even though the role of the ABO antibody titer is still not well defined, the general belief is that a higher IA titer may result in a higher risk of AMR (4)(5)(6)17,26).The role of IA titers in the AMR of ABOi LT has been controversial. Mor et al (38) showed a possible link between a high IA titer and AMR, in particular, in A-to-O transplants, whereas Skogsberg et al (39) showed no correlation between a high IA titer and AMR.…”

“…Consequently, ABOi LT became unpopular and was reserved for urgent LT, particularly for pediatric patients (4). Since the introduction of desensitization (DSZ) with the anti-CD20 monoclonal antibody rituximab (RIT), the risk of hepatic necrosis caused by full-blown AMR has almost disappeared, and overimmunosuppression aimed at avoiding AMR is no longer required (5,6). Nonetheless, most reports on the clinical outcomes of ABOi ALDLT in the literature still include unfavorable outcome data from before the RIT era, leading to overestimation of the morbidity rate and underestimation of the survival rate of current ABOi ALDLT (7).…”

Current management of hepatocellular carcinoma: An Eastern perspective

“…Despite this method, the donor pool has not significantly expanded because of the technical complexity of the surgery and ethical concerns. To further overcome organ shortage, ABO-incompatible LDLT was attempted and became successful after the implementation of rituximab, which decreased antibody-mediated rejection rates from 23.5% to 6.3%, as shown in a Japanese multicenter study [15] . The Milan criteria (solitary tumor < 5 cm, 2 or 3 tumors < 3 cm each, and absence of vascular invasion and extrahepatic metastasis) have been applied for the selection of candidates for liver transplantation [16][17][18] .…”