Division of Hepato-Biliary-Pancreatic Surgery and Transplantation, Department of Surgery, Graduate School of Medicine Kyoto University Kyoto Japan Department of Clinical Laboratory Medicine Kyoto University Hospital Kyoto Japan Department of Pediatric Surgery Kanazawa Medical University Kanazawa Japan Department of Diagnostic Pathology Kyoto University Hospital Kyoto Japan Shiga University of Medical Science Japan.
Liver Transpl. 2022 Oct;28(10):1588-1602. doi: 10.1002/lt.26511. Epub 2022 Jul 4.
Donor-recipient human leukocyte antigen (HLA) compatibility has not been considered to significantly affect liver transplantation (LT) outcomes; however, its significance in living-donor LT (LDLT), which is mostly performed between blood relatives, remains unclear. This retrospective cohort study included 1954 LDLTs at our institution (1990-2020). The primary and secondary endpoints were recipient survival and the incidence of T cell-mediated rejection (TCMR) after LDLT, respectively, according to the number of HLA mismatches at all five loci: HLA-A, HLA-B, HLA-C, HLA-DR, and HLA-DQ. Subgroup analyses were also performed in between-siblings that characteristically have widely distributed 0-10 HLA mismatches. A total of 1304 cases of primary LDLTs were finally enrolled, including 631 adults (recipient age at LT ≥18 years) and 673 children (<18 years). In adult-to-adult LDLT, the more HLA mismatches at each locus, the significantly worse the recipient survival was (p = 0.03, 0.01, 0.03, 0.001, and <0.001 for HLA-A, HLA-B, HLA-C, HLA-DR, and HLA-DQ, respectively). This trend was more pronounced when multiple loci were combined (all p < 0.001 for A + B + DR, A + B + C, DR + DQ, and A + B + C + DR + DQ). Notably, a total of three or more HLA-B + DR mismatches was an independent risk factor for both TCMR (hazard ratio [HR] 2.66, 95% confidence interval [CI] 1.21-5.87; p = 0.02) and recipient survival (HR 2.44, 95% CI 1.11-5.35; p = 0.03) in between-siblings. By contrast, HLA mismatch did not affect pediatric LDLT outcomes at any locus or in any combinations; however, it should be noted that all donor-recipient relationships are parent-to-child that characteristically possesses one or less HLA mismatch at each locus and maximally five or less mismatches in total. In conclusion, HLA mismatch significantly affects not only TCMR development but also recipient survival in adult LDLT, but not in children.
供者-受者人类白细胞抗原（HLA）相容性尚未被认为显著影响肝移植（LT）结局；然而，其在主要在血缘亲属间进行的活体供者 LT（LDLT）中的意义仍不清楚。这项回顾性队列研究纳入了我院 1954 例 LDLT（1990-2020 年）。根据所有五个 HLA 位点（HLA-A、HLA-B、HLA-C、HLA-DR 和 HLA-DQ）的 HLA 错配数量，将主要终点定义为 LT 后受者存活率，次要终点定义为 T 细胞介导的排斥反应（TCMR）发生率。还对同胞间供受者（特征为 HLA 错配广泛分布于 0-10 个位点）进行了亚组分析。最终共纳入 1304 例原发性 LDLT，包括 631 例成人（LT 时受者年龄≥18 岁）和 673 例儿童（<18 岁）。在成人对成人 LDLT 中，每个 HLA 位点的 HLA 错配数量越多，受者存活率越低（p=0.03、0.01、0.03、0.001 和 <0.001，分别对应 HLA-A、HLA-B、HLA-C、HLA-DR 和 HLA-DQ）。当多个 HLA 位点组合时，这种趋势更为明显（所有 A+B+DR、A+B+C、DR+DQ 和 A+B+C+DR+DQ 位点 p<0.001）。值得注意的是，HLA-B+DR 错配总数达到或超过 3 个是同胞间发生 TCMR（风险比[HR]2.66，95%置信区间[CI]1.21-5.87；p=0.02）和受者存活率（HR 2.44，95%CI 1.11-5.35；p=0.03）的独立危险因素。相比之下，在任何 HLA 位点或任何组合中，HLA 错配均不影响儿科 LDLT 结局；但应注意，所有供受者关系均为父母与子女，其特征为每个 HLA 位点存在 1 个或更少的错配，且总错配数最多为 5 个。总之，HLA 错配不仅显著影响成人 LDLT 中的 TCMR 发生，还影响受者存活率，但对儿童无影响。
