Blood-Bile Ratio Tacrolimus After Liver Transplantation

Study Overview
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Brief Summary
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Tacrolimus is the most widely used immunosuppressive drug in the prevention of rejection after solid organ transplantation. Pharmacokinetic studies in healthy volunteers and in transplanted patients have shown that this molecule is rapidly absorbed after oral administration (maximum plasma concentration after 1-2 hours), is found in the circulation bound mainly to erythrocytes and, after being metabolized by CYP3A4, is eliminated through the bile. The importance of the tacrolimus blood dosage is now widely recognized for detecting the immunosuppressive capacity reached in the individual patient or the eventual overdose of the drug. In the use of Tacrolimus after Liver Transplantation, however, it is interesting to note that the biochemical pathway for metabolism and excretion of the drug is present in the transplanted organ, the main object of immunological and functional surveillance. The excretory capacity of Tacrolimus by the liver through the bile, therefore, could be a useful tool for recognizing the early liver failure from a functional point of view, before the onset of hepatoecrosis.

Detailed Description
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Prospective monocentric randomized study comparing two parallel groups: liver transplanted patients with early (10 POD) organ rejection (experimental arm); liver transplanted patients without early (10 POD) organ rejection (control arm) Primary Objective: Evaluation of a correlation between the reduction of Tacrolimus biliary excretion and the early liver failure Primary Endpoint: Increase of Tacrolimus blood-bile ratio measured before the onset of laboratory hepatonecrosis Secondary Objective: Analysis of the cause of any drug-related toxicity Secondary Endpoint: correlation study between drug dosage and biliary excretion level in case of blood overdose or clinical evidence of pharmacological toxicity

Official Title
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Use of Tacrolimus Blood-bile Ratio for the Detection of Early Liver Failure After Liver Transplantation

Conditions
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Liver Transplant; Complications, Immunosuppression, Transplant Failure, Transplant; Complication, Rejection

Intervention / Treatment
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* Diagnostic Test: Blood-Bile Ratio of Tacrolimus


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age ≥18 years History of recent liver transplant (less than 10 days) Placement of kehr tube in the biliary tract during liver transplant Immunosuppressive therapy with Tacrolimus Functioning of kehr tube Exclusion Criteria: Age - Age ≥18 years History of liver transplant for more than 10 days Liver transplant without positioning of kehr tube Immunosuppressive therapy with a drug different from Tacrolimus No functioning of kehr tube18 years History of liver transplant for more than 10 days Liver transplant without positioning of kehr tube Immunosuppressive therapy with a drug different from Tacrolimus No functioning of kehr tube

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 |
| --- | --- |
| Rejection<br>Patient undergone liver transplant with diagnosis of rejection within 10 days | Diagnostic Test: Blood-Bile Ratio of Tacrolimus<br>* Diagnosis of early transplanted liver dysfunction to adjust Tacrolimus dose adminstered<br>|
| No-Rejection<br>Patient undergone liver transplant wothout diagnosis of rejection within 10 days | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Analysis of early liver rejection | Evaluation of early liver rejection throught creation of a Tacrolimus blood-bile ratio | 10 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Analysis of Tacrolimus toxicity | Evaluation of Tacrolimus toxicity throught blood dosage of the drug | 10 days | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Liver transplant;, Immunosuppression;, Transplant rejection;