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Abstract
Background
Antibody mediated rejection (AMR) is an area of great importance in solid organ transplantation. Donor-specific antibodies (DSA) have emerged as relevant biomarkers in predicting graft function and survival. DSA detected post-transplant may either be preformed or de novo and emerging evidence suggests de novo DSA, in particular, is associated with inferior graft outcomes. In contrast to the clear role that AMR plays in renal and thoracic organ transplantation, its importance in liver transplants remains controversial.
Aims
The aim of this study was to determine the risk factors associated with de novo DSA formation and to evaluate its role in determining clinical outcomes after liver transplantation.
Methods
This single-center retrospective study compiled data on liver transplants performed between 2005 and 2019 in Edmonton, Canada. Data collected from medical charts included gender, age at transplant, reason for transplant, and immunosuppressive regimens, among several others. The presence of DSA was determined by single antigen flow beads until 2009 and by Luminex thereafter. Potential predictors of DSA formation were evaluated using Cox proportional hazard models. Graft survival estimates were obtained using the Kaplan-Meier method and comparisons between patient groups were conducted using the log-rank test.
Results
Between 2005–2019, 131 patients had measurements of DSA both before and after liver transplantation. In this cohort, 17 patients (13%) tested negative on DSA screening before transplant but developed new antibodies against either Class I or Class II molecules post-transplant. Risk factor analysis revealed transplants performed in the setting of autoimmune liver disease (PSC, PBC, and autoimmune hepatitis) had higher risks of developing de novo DSA post-transplant (p=0.002. See Table 1). Graft survival probability at 5- and 10-years was 72% and 61% in those with de novo DSA formation, compared to 93% and 89% in patients without de novo DSA formation (p=0.04. See Figure 1). Overall patient survival was similar between the two groups.
Conclusions
In this single-center study, a transplant done in the setting of autoimmune liver disease had a higher risk of de novo DSA formation. Furthermore, de novo DSA formation lead to a decreased graft survival time in liver transplant patients but overall patient survival was not significantly decreased. A standard approach to DSA monitoring, especially in high risk populations, is required to better understand its prevalence and impact in liver transplantation.
Table 1: Risk of de novo DSA formation related as a function of reason for transplantation
| DSA status | % de novo | p-value | ||
| Preformed | De novo | |||
| Autoimmune liver disease (PSC, PBC, autoimmune hepatitis) | 34 | 12 | 35% | 0.002 |
| Other cause for transplant | 80 | 5 | 6% | |
Funding Agencies
None
Details
1 University of Alberta Faculty of Medicine and Dentistry, Edmonton, AB, Canada