Antibodies and Liver Retransplantation

Study Overview
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Brief Summary
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Despite reports that associate donor specific antibody (DSA) with rejection after liver transplantation, grafts are still allocated according to blood group (ABO) but not human leukocyte antigen (HLA) compatibility, possibly due to the absence of an easily discernible clinical association between adverse recipient outcome and DSA. Re-transplantation provides a test environment where the presence of preformed DSA or other antibodies is prevalent and events (graft loss) more common so that the effect of these antibodies on outcome should be apparent. This is an observational study of routine clinical care to determine these effects on our own patients. The goal is to perfect donor-recipient matching to attain the best outcome. In addition, we may develop hypotheses and potential treatments that would be tested in further clinical trials

Detailed Description
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Despite reports that associate donor specific antibody (DSA) with rejection after liver transplantation, grafts are still allocated according to blood group (ABO) but not human leukocyte antigen (HLA) compatibility, possibly due to the absence of an easily discernible clinical association between adverse recipient outcome and DSA. Re-transplantation provides a test environment where the presence of preformed DSA or other antibodies is prevalent and events (graft loss) more common so that the effect of these antibodies on outcome should be apparent. This is an observational study of routine clinical care to determine these effects on our own patients. In phase 1, we will examine the effect of antibodies specifically directed against the second donor in liver retransplantation. Other factors known to effect the outcome will be checked to allow for risk adjustment. In phase 2, we will examine the role played by specific auto-antibodies such as angiotensin II receptor type 1 antibodies and endothelin-1 type A receptor antibodies on the outcome of liver retransplantation. The goal of these observational study is to perfect donor-recipient matching to attain the best outcome. In addition, we may develop hypotheses and potential treatments that would be tested in further clinical trials.

Official Title
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Role of Donor Specific Antibodies, Other Anti-human Leucocyte Antibodies and Autoantibodies in the Outcome of Liver Retransplantation

Conditions
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Liver Transplant Failure, Antibody-mediated Rejection

Intervention / Treatment
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* Diagnostic Test: Luminex-based solid phase assay of banked sera for anti-HLA antibodies directed against the donor of a second liver transplantation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Recipients of a second liver transplantation performed at LHSC Exclusion Criteria: Recipients of ABO incompatible second liver transplantation Recipients of multiple organs
Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| D2SA+<br>Median fluoresce intensity > or = 1000 on Luminex-based solid phase assay of banked sera for anti-HLA antibodies directed against the donor of a second liver transplantation | Diagnostic Test: Luminex-based solid phase assay of banked sera for anti-HLA antibodies directed against the donor of a second liver transplantation<br>* Anti-AT1R antibodies were tested on pre-transplantation sera using ELISA kit (Lot #30, One Lambda, Canoga Park, CA)<br>* Other names: AT1R antibody;|
| D2SA-<br>Median fluoresce intensity < 1000 on Luminex-based solid phase assay of banked sera for anti-HLA antibodies directed against the donor of a second liver transplantation | Diagnostic Test: Luminex-based solid phase assay of banked sera for anti-HLA antibodies directed against the donor of a second liver transplantation<br>* Anti-AT1R antibodies were tested on pre-transplantation sera using ELISA kit (Lot #30, One Lambda, Canoga Park, CA)<br>* Other names: AT1R antibody;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Retransplant graft survival | Average length of time the second liver graft remains in a living recipient regardless of function | From date of transplantation until the date of next transplantation or date of death from any cause, whichever came first, assessed up to 240 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Patient survival | Average length of time a recipient is alive regardless of presence of the second liver transplant | From date of transplantation until the date of death from any cause assessed up to 240 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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donor specific antibody, autoantibody, human leucocyte antigen