Antibodies and Liver Retransplantation

Active, not recruiting

• Conditions: Antibody-mediated Rejection; Liver Transplant Failure
• Interventions: Diagnostic Test: Luminex-based solid phase assay of banked sera for anti-HLA antibodies directed against the donor of a second liver transplantation

• Registration Number: NCT03815864
• Lead Sponsor: London Health Sciences Centre

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.

Study Timeline

• Study Start: 1977-01-01
• Status Verified: 2019-01
• Study First Submitted: 2019-01-20
• Study First Submitted QC: 2019-01-22
• Study First Posted: 2019-01-24
• Last Update Submitted: 2019-01-24
• Last Update Posted: 2019-01-28
• Primary Completion: 2021-01-01
• Study Completion: 2026-01-01

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 200

Inclusion Criteria

• Recipients of a second liver transplantation performed at LHSC

Exclusion Criteria

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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
D2SA+	Luminex-based solid phase assay of banked sera for anti-HLA antibodies directed against the donor of a second liver transplantation	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-	Luminex-based solid phase assay of banked sera for anti-HLA antibodies directed against the donor of a second liver transplantation	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

Primary Outcome Measures

Name	Time	Method
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 Outcome Measures

Name	Time	Method
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