Liver Transplantation, Liver Transplantation in Long-term
Conditions
Keywords
liver transplantation, chimerism, immunosuppression
Brief summary
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.
Detailed 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 Therefore, the hypothesis of this study is that immunosuppressive agents can be withdrawn if the liver becomes chimeric.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 To determine whether immunosuppression can be withdrawn based on liver chimerism.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.
Interventions
DRUGImmunosuppression minimization
For patients with STR \> 15% but not reaching the 75% percentile cutoff, the immunosuppressive regimen is decreased by 1/3 at the first two months. If liver function is unaltered, it is further decreased to 1/2 of the original dose.
PROCEDUREliver biopsy
Liver tissue will be obtained to perform short tandem repeat (STR) analysis to determine the degree of parenchymal chimerism.
For patients with an STR $\\ge$ 75% percentile cutoff, half dose of the immunosuppressive regimen is decreased for the first two months. If liver function is unaltered, immunosuppression is totally withdrawn at the 3rd month.
Sponsors
Chang Gung Memorial Hospital
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
DIAGNOSTIC
Masking
NONE
Intervention model description
If the patients with \> 15% of chimerism of liver parenchyma, the immunosuppression will be taping, than withdrawn.
Eligibility
Sex/Gender
ALL
Age
20 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Percentage of Recipient Cells in the Liver Allograft | 1 year | Short tandem repeat (STR) analysis is used to calculate the chimeric percentage of recipient cells in the liver parenchyma. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants with Successful Complete Immunosuppression Withdrawal | up to 1 year | The number of enrolled patients who successfully complete the immunosuppression withdrawal protocol and remain immunosuppression-free without experiencing acute cell-mediated rejection. |
| AST Levels | up to 1 year | Aspartate aminotransferase (AST) levels will be monitored to evaluate liver allograft stability and function after immunosuppression withdrawal or minimization. |
| ALT Levels | up to 1 year | Alanine aminotransferase (ALT) levels will be monitored to evaluate liver allograft stability and function after immunosuppression withdrawal or minimization. |
| eGFR (Estimated Glomerular Filtration Rate) | At 3 months after immunosuppression withdrawal | eGFR will be measured to evaluate the improvement of immunosuppressant-related renal adverse effects following drug withdrawal or minimization. |
| HbA1c (Glycated Hemoglobin) | At 3 months after immunosuppression withdrawal | HbA1c will be measured to evaluate the improvement of immunosuppressant-related metabolic adverse effects following drug withdrawal or minimization. |
| Cholesterol Profiles | At 3 months after immunosuppression withdrawal | Cholesterol profiles will be measured to evaluate the improvement of immunosuppressant-related metabolic adverse effects following drug withdrawal or minimization. |
Countries
Taiwan
Outcome results
None listed