Fatal graft-versus-host disease after living donor liver transplantation: Differential impact of donor-dominant one-way HLA matching

Abstract

Graft-versus-host disease (GVHD) is an uncommon but potentially devastating complication following liver transplantation. Recently, it was shown that use of a human leukocyte antigen (HLA)-homozygous donor leading to one-way HLA matching significantly increases the risk of GVHD after living donor liver transplantation (LDLT). However, the precise impact of HLA matching between donor and recipient on the risk of GVHD is not yet clear. We surveyed instances of fatal GVHD following LDLT in Japan and reviewed all 8 cases in detail, especially with respect to HLA matching. Serological typing showed that 7 of those cases had donor-dominant one-way HLA matching in the 3 loci of HLA-A, -B, and -DR, while one had donor-dominant one-way HLA matching in the 2 loci of HLA-A and -DR and identical alleles in the B locus. However, DNA typing revealed that the latter case had 1-way HLA matching in the 3 loci. Further, we analyzed HLA typing of 906 donor-recipient pairs who underwent LDLT. There were 5 cases with donor-dominant one-way matching in 2 loci and 2 with donor-dominant one-way matching in 1 locus. All of those cases except 1, who died from an unrelated cause, are alive without an obvious presentation of GVHD. In conclusion, our results suggest that the total number of loci with donor-dominant one-way HLA matching is important for determining the risk of fatal GVHD following LDLT, and that DNA typing of HLA alleles is indispensable in some cases to identify the true risk of donor-dominant 1-way HLA matching.