Withdrawal of Immunosuppression in Long Term Stable Liver Transplant Recipients

Study Overview
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Brief Summary
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Long-term immunosuppression carries potential adverse effects such as risk of infection, malignancy, renal insufficiency, diabetes and hypertension. In clinical liver transplantation, some liver transplant recipients maintain allograft function without immunosuppressive drugs. This is called as operational tolerance. Many attempts have been made to identify immunological biomarkers predicting operational tolerant patients. Therefore, the investigators aimed to identify patients who have the potential to be operationally tolerant using biomarkers, withdraw immunosuppressant gradually and stop ultimately with monitoring of biomarkers.

Detailed Description
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Among long term stable liver transplant recipients, we will select some proportion of patients who have the high potential for obtaining operational tolerance using biomarkers. Then, we will gradually reduce immunosuppressants and monitor biomarkers as well as biochemical tests. The course of tapering off immunosuppressant will take about 1 year. During withdrawal of immunosuppression, participants will be closely monitored for liver enzyme, immunological profile. If there are some signs of rejection, liver biopsy will be undertaken and participants will be treated using immunosuppressant. After complete withdrawal of immunosuppressant, participants will be followed for at least of 1 year.

Official Title
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Gradual Withdrawal of Immunosuppression in Long Term Stable Liver Transplant Recipients Using Immunologic Profile Predicting Operational Tolerance

Conditions
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Liver Transplantation

Intervention / Treatment
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* Procedure: immunosuppression withdrawal
* Procedure: continue of taking immunosuppressant


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: long term stable liver transplant recipients Exclusion Criteria: liver transplant due to autoimmune disease liver transplant due to hepatitis C virus (HCV) history of graft rejection history of biliary infection or stricture

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: LT, withdrawal of immunosuppression<br> | Procedure: immunosuppression withdrawal<br>* tapering off immunosuppressant<br>* Other names: WIS;|
| Active Comparator: LT, maintenance of immunosuppression<br> | Procedure: continue of taking immunosuppressant<br>* maintain immunosuppression<br>* Other names: MIS;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| number of participants who have the potential for the operational tolerance | measure number of patients who can be weaned off immunosuppression completely | in the 2 years fololowing study enrollment | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Tolerance biomarker | find out biomarkers which can predict operational tolerance | 1 year following immunosuppression withdrawal | 
| immunologic profile related to rejection | observe immunologic profile changes which are related to rejection | up to 2 years following withdrawal of immunosuppression | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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long term, stable, recipients