Clinical trial NCT03815864: Antibodies and Liver Retransplantation
Official title: Role of Donor Specific Antibodies, Other Anti-human Leucocyte Antibodies and Autoantibodies in the Outcome of Liver Retransplantation
Study type: OBSERVATIONAL
Overall status: ACTIVE_NOT_RECRUITING
Conditions: Liver Transplant Failure
Antibody-mediated Rejection
Keywords: donor specific antibody
autoantibody
human leucocyte antigen
Lead sponsor: London Health Sciences Centre
Sponsor class: OTHER
First posted: 2019-01-24
Enrollment: 200
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: RETROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: all patients who have undergone a repeat transplantation of the liver at LHSC.

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.

Eligibility criteria: Inclusion Criteria:

* Recipients of a second liver transplantation performed at LHSC

Exclusion Criteria:

* Recipients of ABO incompatible second liver transplantation
* Recipients of multiple organs

Primary outcomes:
measure: Retransplant graft survival
timeFrame: 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 outcomes:
measure: Patient survival
timeFrame: From date of transplantation until the date of death from any cause assessed up to 240 months
Other outcomes:
measure: Acute rejection
timeFrame: From date of transplantation until the date of first documented acute rejection assessed up to 240 months
Locations:
Study officials:
affiliation: London Health Sciences Center
name: Vivian McAlister
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.