Introduction: Though human leukocyte antigen (HLA) matching between donor and recipient affects both graft and patient survival after kidney and heart transplantation, prior analysis has failed to produce a definitive conclusion as to whether HLA matching has a similar effect after liver transplantation. This is the first study to address this question using the Scientific Registry of Transplant Recipients (SRTR) database.

Methods: The study population consisted of all adult subjects in the SRTR database who received a liver graft between 2002-2012. Separate Cox proportional hazard models were constructed to analyze all-cause death and all-cause graft failure censoring at 5 years of follow up. The association between mismatch and acute early rejection before hospital discharge was analyzed using logistic regression.

Results: Of 53,686 total patients, 41.2% had information about both donor and recipient HLA A, B, and DR types. Patients were grouped into those with 0 mismatches (0.42%), low (1-2) mismatches (4.38%), and high (3-6) mismatches (95.2%). There were no significant differences in patient or graft survival in univariate analysis. Controlling for age, gender, race, primary liver disease type, ABO blood type, MELD, donor type (living vs. deceased), and post-transplant immunosuppression, patients with 0 HLA mismatches had a higher risk of all-cause death compared to both patients with low HLA mismatches (HR=1.8, p=0.003) and high HLA mismatches (HR=1.71, p=0.005) and a higher risk of all-cause graft failure compared to patients with HLA mismatches (HR=1.8, p=0.032). Conversely, patients with high HLA mismatches had higher risk of early (during initial hospitalization) rejection episodes compared to those with low HLA mismatches (OR=1.85, p<0.001) with a strong trend towards higher incidence compared to those with 0 HLA mismatches (OR=4, p=0.053).

Conclusions: In the largest analysis to date, and the only analysis to use SRTR data, we show that HLA matching affects both patient and graft survival and incidence of early rejection episodes. It is possible that the same HLA mismatch factors associated with early acute rejection episodes may also correlate with later graft failure or patient death. Exploring these possibilities, which include decreased tolerance or more graft-versus-host response with zero mismatches, will be the subject of future work.

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