Evaluation of human leukocyte antigen histocompatibility and its impact on liver transplant graft outcomes

Background: The impact of human leukocyte antigen (HLA) histocompatibility on graft survival is well established in kidney and haematopoietic stem cell transplantation; however, its role in liver transplantation (LT) remains uncertain. Prior studies have reported inconsistent associations between HLA mismatching and LT graft outcomes. Given emerging evidence linking HLA mismatch to post-transplant complications, this relationship warrants reassessment. Objectives: To investigate the effect of HLA Class I (A, B, C) and Class II (DRB1, DQA, DQB) mismatching on LT graft survival in a single-centre retrospective analysis. Design: A retrospective, single-centre cohort study. Methods: 610 patients who underwent their first deceased donor LT between January 2010 and March 2021 were included. The primary outcome was graft failure. Donor and recipient HLA typing was available at HLA-A, HLA-B and HLA-DRB1 loci in 610 patients, HLA-C in 38 patients, HLA-DQA in 63 patients and HLA-DQB in 63 patients. Graft survival was assessed using Kaplan–Meier analysis and predictors identified using Cox regression. Results: HLA-C mismatching was associated with reduced graft survival on Kaplan–Meier analysis ( p = 0.02); however, this was based on a small subgroup ( n = 38), and the univariate Cox estimate was imprecise (HR 9.24, 95% CI 1.01–83.48, p = 0.047). HLA-DRB1 mismatching was associated with improved graft survival ( p = 0.047) and reduced graft failure risk on multivariate Cox regression (aHR 0.34, 95% CI 0.14–0.87, p = 0.02), although limited by the small number of matched transplants ( n = 9). There was no association between mismatches at other loci and graft survival. Hepatic artery thrombosis worsened graft survival (aHR 3.42, 95% CI 2.44–4.80, p < 0.001) but was not associated with HLA mismatch. Conclusion: These results suggest that the effect of HLA histocompatibility in LT may be locus-specific. Associations were observed for differential graft outcomes at the HLA-C and HLA-DRB1 loci; however, given the small sample sizes and imprecision of estimates, these findings should be considered hypothesis-generating and require validation in larger prospective cohorts.