De novo donor-specific anti-HLA antibodies are a risk factor for graft loss in DCD liver transplantation
Oya Andacoglu, Thomas Ellis, Anthony M. D'Alessandro, David Foley, Amy Powell, Glen E. Leverson, Michael R. Lucey, Alexandru I.Musat
University of Wisconsin School of Medicine and Public Health, Madison, WI
Donor shortage has led to an increasing use of liver grafts recovered from donors after circulatory death (DCD). In contrast to donation after brain death (DBD) grafts, DCD livers have inferior graft survival related mainly to ischemic cholangiopathy. Aim: In this study we explored the possible impact of humoral alloreactivity directed against donor HLA on the survival of DCD liver grafts. Methods: For this purpose we studied 20 consecutive ABO compatible, primary liver transplant recipients of DCD grafts transplanted between 5/1/2009 and 2/5/2012.Donor-specific antibodies (DSA) against HLA class I (A, B, C) and II (DR, DQ, DP) were determined pretransplant and at 3, 6, 12 months post-transplant using single antigen beads on a Luminex platform. Results: The patient follow-up was 6 months to 3.2 years. During the study period there were 4 graft losses, all due to ischemic cholangiopathy. None had hepatic artery thrombosis. There was no statistically significant difference between patients with or without preformed/pretransplant DSA in terms of patient and donor demographics, model for endstage liver disease (MELD) score, warm-, or cold ischemia times, or donor risk index. Cox proportional hazards model showed that patients who developed de novo anti-HLA DSA (i. e. as a direct consequence of sensitization to the graft) had a 10 times higher risk of ischemic cholangiopathy (p=0.003), the leading cause of DCD graft loss. Most de novo DSAs were directed against class II histocompatibility antigens. Conclusions: To our knowledge this is the first study to suggest that development of de novo humoral alloreactivity to the DCD liver contributes to graft loss, presumably due to ischemia caused by peribiliary plexus injury. Our observations raise the possibility that addressing ischemia-related generation of DSA, a potentially modifiable risk factor, may improve the DCD graft survival.
Michael R. Lucey - Grant/Research Support: Vertex, Abbvie, Gilead, Salix; Speaking and Teaching: Roche
The following people have nothing to disclose: Oya Andacoglu, Thomas Ellis, Anthony M. D'Alessandro, David Foley, Amy Powell, Glen E. Leverson, Alexandru I. Musat