Antibody-mediated Rejection, Liver Transplant Failure
Conditions
Keywords
donor specific antibody, autoantibody, human leucocyte antigen
Brief summary
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
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.
Interventions
DIAGNOSTIC_TESTLuminex-based solid phase assay of banked sera for anti-HLA antibodies directed against the donor of a second liver transplantation
Anti-AT1R antibodies were tested on pre-transplantation sera using ELISA kit (Lot #30, One Lambda, Canoga Park, CA)
Sponsors
London Health Sciences Centre
Study design
Observational model
COHORT
Time perspective
RETROSPECTIVE
Eligibility
Sex/Gender
ALL
Healthy volunteers
No
Inclusion criteria
* Recipients of a second liver transplantation performed at LHSC
Exclusion criteria
* Recipients of ABO incompatible second liver transplantation * Recipients of multiple organs
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Retransplant graft survival | 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 | Average length of time the second liver graft remains in a living recipient regardless of function |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Patient survival | From date of transplantation until the date of death from any cause assessed up to 240 months | Average length of time a recipient is alive regardless of presence of the second liver transplant |
Other
| Measure | Time frame | Description |
|---|---|---|
| Acute rejection | From date of transplantation until the date of first documented acute rejection assessed up to 240 months | number of participants with a clinically diagnosed and treated episode of rejection (either acute cellular or humoral) |
Outcome results
None listed