Clinical Outcome of Liver Transplant Patients With Tacrolimus-based Immunosuppression

Study Overview
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Brief Summary
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Genetic polymorphism and numerous clinical factors could influence tacrolimus pharmacokinetics, which led to large inter-and intra-individual variability.Since its narrow therapeutic range,predicting therapeutic outcome and individualized dosage remains to be a challenge. The study's objective is to identify the genetic and clinical factors that can influence clinical outcome in liver transplant.

Detailed Description
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A great number of studies had found significant correlation between tacrolimus pharmacokinetics and gene polymorphism. However, previous studies on the correlation between genetic factors and clinical outcome were controversial. Furthermore, most studies focused on single genetic polymorphism and clinical outcome, and very limited studies took multiple genetic factors and clinical factors into account. This is a retrospective study. Eligible patients were those who had signed informed consent for genetic study in previous research projects ( IRB approval number：201512005RINC and 201612023RIND ). The present study will collect laboratory data, concurrent medications, and therapeutic drug monitoring (TDM) data. Patient survival, graft survival, acute rejection and tacrolimus-associated adverse events will be assessed.

Official Title
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The Influence of Genetic and Clinical Factors on Clinical Outcome of Liver Transplant Patients With Tacrolimus-based Immunosuppression

Conditions
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Liver Transplantation

Participation Criteria
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Eligibility Criteria
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Eligible patients were those who had signed informed consent for genetic study in our previous research projects. Inclusion Criteria of the Previous Study: patients who underwent living-donor liver transplantation during January 2008 to December 2017 at the age of 20-65 with tacrolimus-based immunosuppression after liver transplant for at least 6 months. Exclusion Criteria of the Previous Study : retransplantation multi-organ transplantation human immunodeficiency virus (HIV) positive.

Ages Eligible for Study
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Minimum Age: 20 Years
Maximum Age: 65 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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What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of patients with biopsy proven acute rejection (BPAR) | Incidence of BPAR will be estimated with Kaplan-Meier analysis | up to 12 months after liver transplantation | 
| Graft survival | incidence of graft loss will be estimated Kaplan-Meier analysis | up to 9 years after liver transplantation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of patients with tacrolimus-associated adverse events | Common adverse events of tacrolimus such as nephrotoxicity, post-transplant diabetes mellitus, hypertension, infection, hyperlipidemia and malignancy. nephrotoxicity：decreased renal function estimated by glomerular filtration rate(GFR) using MDRD 4-Variable Equation Post-transplant diabetes mellitus：defined by diagnosis and the use of antihyperglycemic agents, laboratory data including blood sugar(mg/dL) and hemoglobin A1c (percentage) hypertension：defined by diagnosis and the use of antihypertensive agents, laboratory data including blood pressure(mmHg) infection：defined by diagnosis of infection and the use of antiinfective agents Hyperlipidemia：defined by diagnosis and the use of lipid-lowering agents, laboratory data including LDL (mg/dL), HDL (mg/dL) and total cholesterol (mg/dL) malignancy：incidence of cancer | up to 9 years after liver transplantation | 
| Patient survival | incidence of death | up to 9 years after liver transplantation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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immunosuppressant, tacrolimus, liver transplant, gene polymorphism