Discovery and Validation of Proteogenomic Biomarker Panels in Liver Transplant Recipients

Study Overview
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Brief Summary
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The main focus of this study is to develop blood and/or urine tests that will help to detect early signs of rejection in people who have had a liver transplant. Researchers will examine blood, urine, and tissue samples and try to identify markers for certain conditions such as rejection, response to therapy, and scarring of the liver. Additionally, researchers would like to identify biomarkers that can detect damage to the native kidneys before blood levels of creatinine rises. By studying gene expression, researchers hope to be able to diagnose these conditions earlier and improve liver survival.

Official Title
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Discovery and Validation of Proteogenomic Biomarker Panels in a Prospective Serial Blood and Urine Monitoring Study of Liver Transplant Recipients - Transplant Proteogenomics

Conditions
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Liver Transplant Recipients, Liver Transplantation

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Subjects undergoing primary deceased-donor or living donor liver transplantation; Subject must be able to understand and provide informed consent. Exclusion Criteria: Need for combined organ transplantation; Previous solid organ and/or islet cell transplantation; Infection with HIV; Allergy to iodine; Inability or unwillingness of a participant to comply with study protocol; Any condition that, in the opinion of the investigator, would interfere with the participant's ability to comply with study requirements.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Liver Transplant Recipients<br> | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Acute Rejection | The primary endpoint is the incidence of biopsy proven AR at 3, 12 and 24 months after LT. | 3 months after liver transplant | 
| Acute Rejection |  | 12 months after liver transplant | 
| Acute Rejection |  | 24 months after liver transplant | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Severity of acute rejection | Severity (initial grade, steroid-responsive vs. refractory by biopsy) and clinical/biochemical resolution following treatment of AR | Baseline (Visit 1) to Month 24 (Visit 12): | 
| Recurrent Hepatitis-C Virus (HCV-R) | Incidence, severity (grade, stage), and treatment (requirement for, response rates) of HCV-R | Baseline (Visit 1) to Month 24 (Visit 12) | 
| Chronic Kidney Disease(CKD) | Incidence, severity (stage, need for renal replacement therapy or kidney transplantation), and response to treatment (CNI reduction/withdrawal ± MPA or mTOR) of CKD | Baseline (Visit 1) to Month 24 (Visit 12) | 
| Incidence of death, graft loss, and need for liver retransplantation |  | Baseline (Visit 1) to Month 24 (Visit 12) | 
| Incidence of opportunistic infections, malignancy, and cardiovascular complications |  | Baseline (Visit 1) to Month 24 (Visit 12) | 
| mRNA expression profiles of peripheral blood (AR, HCV-R, CKD) |  | Baseline (Visit 1) to Month 24 (Visit 12) | 
| mRNA expression profiles of liver biopsies (AR, HCV-R) |  | Baseline (Visit 1) to Month 24 (Visit 12) | 
| Protein expression profiles of plasma ( AR, HCV-R, CKD) |  | Baseline (Visit 1) to Month 24 (Visit 12) | 
| Protein expression profiles of urine (CKD) |  | Baseline (Visit 1) to Month 24 (visit 12) | 
| microRNA Profiling Plasma & Cells |  | Baseline (Visit 1) to Month 24 (Visit 12) | 
| Multiparameter Flow Cytometry - Viral Pathogens |  | Baseline (Visit 1) to Month 24 (Visit 12) | 
| Viral Monitoring - EBV & CMV |  | Baseline (Visit 1) to Month 24 (Visit 12) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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proteogenomic biomarker panels