Immunosuppressant Withdrawal Based on Parenchymal Chimerism in the Liver Transplantation

Chang Gung Medical Foundation

Status: Invitation-only

Conditions: Liver Transplantation; Liver Transplantation in Long-term

Treatments: Drug: Immunosuppression withdrawal; Procedure: liver biopsy; Drug: Immunosuppression minimization

Study type: Interventional

Funder types: Other

Identifiers

NCT07735650

202402038A3

Details and patient eligibility

About

The goal of this clinical trial is to learn whether liver parenchyma chimerism can represent a chievement of operational tolerance in liver transplantation recipients. The researchers will examine the degree of parenchyma chimerism. The participants will withdraw or minimize their immunosuppression to avoid the adverse effects of immunosuppressants.

Full description

After liver transplantation, immunosuppression should be induced or maintained to prevent acute cell-mediated rejection or chronic antibody-mediated rejection.All these immunosuppressive agents have various adverse effects including nephrotoxicity, neurotoxicity, hyperglycemia, hypertension, bone marrow suppression, gastrointestinal disturbance, etc. We examine the liver specimen from long-term liver transplant recipients with stable liver function. The liver showed chimeric change of the liver. Therefore, the hypothesis of this study is that immunosuppressive agents can be withdrawn if the liver becomes chimeric. The specific aims of this study are:

1. To determine whether the liver allografts become chimeric in long-term liver transplant recipients.
2. To determine the degree of liver chimerism in long-term liver transplant recipients.
3. To determine whether immunosuppression can be withdrawn based on liver chimerism.

Based on the degree of chimeric change of the liver grafts, immunosuppression withdrawal can be conducted in this study and find out the indicator of immunosuppression withdrawal in liver transplantation setting.

Enrollment: 60 estimated patients

Sex: All

Ages: 20+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• a. The patients had liver transplantation, either deceased liver or liver donor, for ≥ 5 years.

  b. Age ≥ 20 years old. c. The patients have stable liver function, and do not have clinical suspicious of acute cell-mediated rejection within 1 year.

  d. Sign the informed consent. e. Platelet ≥ 80000/mm3. f. INR ≤ 1.4 g. AST and ALT ≤ 1.5X h. Albumin ≥ 3.5gm/dl. i. Total bilirubin < 1.5mg/dl. j. ECOG ≤ 2

Exclusion criteria

• a. Liver transplantation less than 5 years b. Abnormal liver function AST and ALT > 1.5X c. Severe infection d. De novo malignancy e. Disagree to have liver biopsy. f. ECOG > 2

Trial design

Primary purpose: Diagnostic

Allocation: N/A

Interventional model: Single Group Assignment

Masking: None (Open label)

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60 participants in 1 patient group

liver parenchyma chimerism in liver transplant recipient

Experimental group

Description:

All enrolled liver transplant recipients will undergo a liver biopsy for STR analysis. Based on the degree of chimerism found, patients will proceed to either an immunosuppression withdrawal protocol (if STR $\\ge$ 75% percentile cutoff) or an immunosuppression minimization protocol (if STR \> 15% but \< 75% percentile).

Treatment:

Drug: Immunosuppression minimization

Procedure: liver biopsy

Drug: Immunosuppression withdrawal