The clinical impact of donor against recipient HLA one way mismatch on the occurrence of graft versus host disease in liver transplantation

Abstract

Graft versus host disease (GVHD) after liver transplantation (LT) is a rare, fatal disease. This study aimed to evaluate the risk factors of GVHD after LT including the human leukocyte antigen (HLA) donor-recipient relationship after LT. LT recipients, who underwent HLA typing together with donors, were included in the study. The donor against recipient (D → R) one-way mismatch of HLA loci was evaluated. HLA relationships, along with basic characteristics, were analyzed as variable factors of GVHD, graft survival, and patient survival. A total of 994 living donor LT (LDLT) and 393 deceased donor LT (DDLT) patients were included. Nine patients had suffered GVHD, four LDLT with D → R one-way at three loci, one LDLT without D → R one-way at three loci, and four DDLT without D → R one-way at three loci. Four (57.1%) of seven LDLT patients, with D → R one-way mismatch at three loci, developed GVHD. D → R one-way mismatch at three loci was related to high GVHD incidence (HR 787, p < 0.001, multivariate). D → R one-way mismatch at three loci was related to graft failure and patient death (HR 9.90, p = 0.020 and HR 12.8, p < 0.001, respectively, multivariate). Only one GVHD without D → R one-way mismatch at three loci, survived despite receiving multiple modalities including tumor necrosis factor-alpha inhibitors. D → R one-way mismatch at three loci was significantly related to GVHD incidence after LT.

One-way donor-to-recipient human leukocyte antigen mismatch and graft-versus-host disease in liver transplantation: an observational study of a single-center experience in Korea

“…Previous studies have reported that the incidence of GVHD in LDLT patients with OWMM at three loci is >50%, and the 5-year patient survival rate is only 15%–20% [ 12 - 15 ]. Nevertheless, the incidence of GVHD in patients with LDLT in this study was 16.7% (both HLA-OWMM at one to two loci and at three loci), corresponding to approximately one-third of the rates reported in previous studies.…”

“…HCC was also numerically more frequent in the HLA-OWMM group, but without statistical significance (64.5% vs. 41.4%, P=0.379). The pretransplant MELD score was significantly lower in the HLA-OW-MM group than in the control group(11 [IQR,(8)(9)(10)(11)(12)(13)(14)(15) vs. 15 [IQR, 10-25]; P=0.013]. In the HLA-OWMM group, 14.3% of donors were deceased, compared to 32.9% in the control group (P=0.057).…”

“…Previous literature has indicated a significantly higher risk of GVHD when there is a one-way mismatch (OWMM) between the donor, who is human leukocyte antigen (HLA)-homozygous, and the recipient, who is HLA-heterozygous [ 12 - 15 ]. This risk is particularly pronounced in the case of three-loci OWMM in living donor LT (LDLT) [ 15 ].…”

“…It is theorized that when HLA-OWMM is present, the recipient is less likely to reject passenger hematopoietic cells, which allows donor T cells to interact with the host antigen-presenting cell [ 16 ]. The incidence of GVHD in LDLT with three-loci HLA-OWMM has been reported to be as high as 57.1%, with a 5-year patient survival rate of only 15%–20% [ 12 , 13 ]. However, various studies have reported differing incidences of GVHD and risks of posttransplant mortality [ 5 , 13 , 15 ].…”

Development of graft-versus-host disease in a liver recipient. Clinical observations and literature review

“…В первом наблюдении нам было доступно исследование HLA донора и реципиента. Донор нашей пациентки был гомозиготен по трем аллелям, по которым реципиент был гетерозиготен, что считается одним из наиболее значимых факторов риска развития РТПХ [29]. Поскольку во втором случае ТП была проведена от посмертного донора, подобное исследование было недоступно.…”