Donor-Specific HLA Antibodies in Living Versus Deceased Donor Liver Transplant Recipients

Abstract

With less ischemia, improved donor selection and controlled procedures, living donor liver transplantation (LDLT) might lead to less HLA donor-specific antibody (DSA) formation or fewer adverse outcomes than deceased donor liver transplantation (DDLT). Using the multicenter A2ALL (Adult-to-Adult Living Donor Liver Transplantation Cohort Study) biorepository, we compared the incidence and outcomes of preformed and de novo DSAs between LDLT and DDLT. In total, 129 LDLT and 66 DDLT recipients were identified as having serial samples. The prevalence of preformed and de novo DSAs was not different between DDLT and LDLT recipients (p = 0.93). There was no association between patient survival and the timing (preformed vs. de novo), class (I vs. II) and relative levels of DSA between the groups; however, preformed DSA was associated with higher graft failure only in DDLT recipients (p = 0.01). De novo DSA was associated with graft failure regardless of liver transplant type (p = 0.005) but with rejection only in DDLT (p = 0.0001). On multivariate analysis, DSA was an independent risk factor for graft failure regardless of liver transplant type (p = 0.017, preformed; p = 0.002, de novo). In conclusion, although similar in prevalence, DSA may have more impact in DDLT than LDLT recipients. Although our findings need further validation, future research should more robustly test the effect of donor type and strategies to mitigate the impact of DSA.

Prevalence and Impact of De Novo Donor‐Specific Antibodies During a Multicenter Immunosuppression Withdrawal Trial in Adult Liver Transplant Recipients

“…This suggests that while CNI therapy may participate in the clearance of pfDSA, these antibodies did not appear to have an impact on outcomes. Together, these results add to the controversy about pfDSA as some reports have shown associations with liver allograft failure and early rejection when pfDSA are against HLA‐II antigens …”

Acute Rejection Increases Risk of Graft Failure and Death in Recent Liver Transplant Recipients

“…These corroborative findings, which are consistent with results in other organs, may help to explain recent data demonstrating higher survival and less impact of donor specific antibodies in LDLT vs. DDLT recipients. 5, 6, 23 In regard to immune-mediated diseases, higher rejection rates in autoimmune hepatitis have led to recommendations for augmented immunosuppression. 7, 15, 22, 24 However, in A2ALL and SRTR cohorts, LT recipients with other immune-mediated liver disease (primary biliary cirrhosis, primary sclerosing cholangitis) had significantly increased risks, suggesting the need to maintain a higher level of immunosuppression in all immune-mediated diseases.…”

Preformed donor‐specific antibodies are associated with 90‐day mortality in living‐donor liver transplantation

“…Levitsky et al . examined the association between DSAs and survival after DDLT and LDLT, and reported that preformed DSAs were associated with a higher graft failure rate only after DDLT . However, there was survival selection bias as the vast majority of the post‐transplant samples were available only at or after 3 months.…”