Role of Human Leukocyte Antigen Matching in Liver Transplantation and Its Relation to Outcomes

Study Overview
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Brief Summary
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The study aimed to assess HLA compatibility, HLA antibodies and cross matching in liver transplantation recipients and their relation to acute rejection, CMV infection, and recurrence of HCV.

Detailed Description
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This was a cohort study conducted in patients who had undergone LDLT between January 2015 and January 2016 at in Ain Shams Center for Organ Transplantation (ASCOT) . HLA Typing and Mismatch: Preoperative blood samples from all recipients and donors were collected. The serological tissue typing for HLA was performed by a SSP-PCR (sequence-specific- primer). HLA-A, HLA- B, and HLA-DR loci were examined and used to calculate mismatch scores. The locus-specific type of HLA mismatch, as well as the degree of HLA mismatch, was then assessed. For each locus individually, the mismatch number was scored as 0, 1, or 2, on the basis of the number of donor alleles not shared with the respective recipient. Each patient was assigned an overall total score depending on the total number of mismatches at the 3 loci, ranging from 0 (no mismatches at any loci) to 6 (mismatches at all loci) Cross matching (total and autocross): Crossmatch involves placing recipient serum (potentially containing donor-specific anti-HLA antibodies) onto donor lymphocytes (containing HLA antigens).A cytotoxic reaction (deemed 'positive') suggests the presence of preformed DSAbs (donor specific antibodies). Autoantibodies are generally IgM rather than IgG antibodies. To establish if autoantibodies are responsible for the result an auto-crossmatch should be performed. In this assay, recipient serum is crossmatched against recipient (rather than donor) lymphocytes. Second, the original crossmatch should be repeated with the addition of the agent Dithiothreitol (DTT). DTT reduces the disulfide bonds in IgM thereby preventing IgM antibodies from generating a positive result. IgM antibodies are generally regarded as having no pathological significance in transplantation.

Official Title
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Role of Human Leukocyte Antigen Matching in Liver Transplantation and Its Relation to Outcomes

Conditions
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Liver Transplantation

Intervention / Treatment
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* Diagnostic Test: HLA cross matching


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Recipient selection: Adult recipients who are candidate for LDLT due to HCV related ESLD and meeting the transplantation criteria of the Ain Shams Center of Organ Transplantation (Child Pugh score ≥ 7and MELD score ≥15). Donor selection: Living donors are usually close family members or spouses, although unrelated living donors can be accepted according to the legal registration of MOH (ministry of health) ABO blood type compatibility Age is between 18-50 Absence of previous significant abdominal surgery and/or medical problems Exclusion Criteria: Adult recipients who underwent LDLT due to other causes rather than HCV. Cardiopulmonary disease that cannot be corrected and is a prohibitive risk for surgery Acquired immunodeficiency syndrome (AIDS) Malignancy outside of the liver not meeting oncologic criteria for cure Hepatocellular carcinoma with metastatic spread Anatomic abnormalities that preclude liver transplantation Uncontrolled sepsis Acute liver failure with a sustained intracranial pressure >50 mmHg or a cerebral perfusion pressure <40 mmH Persistent non adherence with medical care and Lack of adequate social support Advanced age older than 65y.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Liver transplantation receipients<br>All patients underwent Living donor liver transplantation at Ain Shams center for organ transplantation (ASCOT) during the designed study period | Diagnostic Test: HLA cross matching<br>* HLA Typing and Mismatch Cross matching (total and autocross): Cross match involves placing recipient serum onto donor lymphocytes and a cytotoxic reaction (deemed 'positive') suggests the presence of preformed donor specific antibodies (DSAs),Second, the original crossmatch should be repeated with the addition of the agent Dithiothreitol (DTT). DTT reduces the disulfide bonds in IgM thereby preventing IgM antibodies from generating a positive result.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Relation between HLA cross matching and post transplantation outcome | We o investigated the post transplantation laboratory data, incidence of acute rejection, recurrence of hepatitis C virus (HCV) infection and CMV infection as outcome parameters. | 1 year |