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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
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| D2SA+ | 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 |
| |
| D2SA- | 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 |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Luminex-based solid phase assay of banked sera for anti-HLA antibodies directed against the donor of a second liver transplantation | Diagnostic Test | Anti-AT1R antibodies were tested on pre-transplantation sera using ELISA kit (Lot #30, One Lambda, Canoga Park, CA) |
| 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 |
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| Acute rejection | number of participants with a clinically diagnosed and treated episode of rejection (either acute cellular or humoral) | From date of transplantation until the date of first documented acute rejection assessed up to 240 months |
Inclusion Criteria:
Exclusion Criteria:
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all patients who have undergone a repeat transplantation of the liver at LHSC.
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| Name | Affiliation | Role |
|---|---|---|
| Vivian McAlister | London Health Sciences Center | Principal Investigator |
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| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 33871888 | Derived | Xu Q, McAlister VC, House AA, Molinari M, Leckie S, Zeevi A. Autoantibodies to LG3 are associated with poor long-term survival after liver retransplantation. Clin Transplant. 2021 Jul;35(7):e14318. doi: 10.1111/ctr.14318. Epub 2021 Apr 25. | |
| 31419065 | Derived | Xu Q, McAlister VC, Leckie S, House AA, Skaro A, Marotta P. Angiotensin II type I receptor agonistic autoantibodies are associated with poor allograft survival in liver retransplantation. Am J Transplant. 2020 Jan;20(1):282-288. doi: 10.1111/ajt.15571. Epub 2019 Sep 6. |
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Study mechanisms and de-identified subject level data will be shared with researchers who contact the principal investigator.
From publication until 5 years later
De-identified subject level data will be shared with researchers who contact the principal investigator, submit a research plan and sign an agreement. Approval by Western Research Ethics may be required depending on the request.
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| Type | Date | Date Unknown |
|---|---|---|
| Release | Apr 4, 2022 | |
| Reset | Oct 18, 2022 | |
| Release | Oct 18, 2022 | |
| Reset | Aug 29, 2023 |
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| Release Date | Unrelease Date | Unrelease Date Unknown | Reset Date | MCP Release Number |
|---|---|---|---|---|
| Apr 4, 2022 | Oct 18, 2022 | |||
| Oct 18, 2022 |
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Blood and tissue samples stored for clinical use by the Transplant Laboratory since the beginning of liver transplantation at our facility in 1977
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| Aug 29, 2023 |