O6 HLA-A matching influences clinical liver transplant graft survival in an indication specific fashion

<h3>Introduction</h3> The influence of human leukocyte antigen (HLA) matching between liver transplant donors and recipients on graft survival remains unclear and is not a clinical consideration in liver transplantation. This study aimed to determine the relationship between HLA matching and liver graft survival using a large-scale multi-center database (UNOS/OPTN) and multivariate logistic analysis. The secondary aim was to determine whether this relationship was influenced by transplant indication. <h3>Methods</h3> This retrospective observational analysis was performed using 22,702 liver transplant recipients from the UNOS/OPTN database. Patients were divided into groups based on number of HLA mismatches (0 vs 1 vs 2) at HLA-A, HLA-B and HLA-DR loci. Patients were then subcategorized by indication. Risk-adjusted outcomes were assessed by multivariate Cox analysis adjusting for donor and recipient characteristics and visualized using Kaplan-Meier survival curves. <h3>Results</h3> Log-rank testing revealed an association between graft survival and HLA-A mismatch, demonstrating increased graft loss with increased HLA-A mismatch (p=0.028). This association between graft survival and HLA mismatch was not seen in HLA-B (p=0.35) or HLA-DR (p=0.45) (figure 1). When the cohort was subdivided by indication for transplant, the final adjusted model demonstrated that 2 mismatches at the HLA-A locus was associated with a statistically significant increase in graft loss at 5 years in both non-alcoholic steatohepatitis (HR 1.6, CI (1.1–2.3), p=0.01) and alcohol related liver disease (HR 1.3, CI (1–1.7), p=0.004). There were no other statistically significant changes in graft loss hazard across HLA-A, HLA-B and HLA-DR in hepatitis-related, alcohol-related, cancer-related, autoimmune, non-alcoholic steatohepatitis (NASH), congenital, metabolic, and other indications for liver transplant. <h3>Conclusion</h3> The present study demonstrated that HLA-A mismatching was significantly associated with graft loss at 5 years in both NASH and alcoholic liver disease at 5 years. This is the largest study to explore the indication specific relationship between individual HLA Loci and graft survival liver transplantation. These findings are of potential clinical relevance to organ allocation, allograft matching algorithms, immunosuppression protocols and transplant surveillance. Further cohort studies are required to elucidate the underlying mechanisms driving the importance of HLA-A matching specifically in graft survival.