Analysis of immunological and genetic factors implicated in operational tolerance in liver transplant patients

Not Applicable

Completed

• Conditions: iver transplantation; Surgery

• Registration Number: ISRCTN15775356
• Lead Sponsor: FFIS-Región de Murcia

Brief Summary

2018 Results article in https://pubmed.ncbi.nlm.nih.gov/30019408/ (added 06/09/2023)

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Completion: 2016-12-30
• Study Start: 2017-07-25
• Last Update Posted: 18 September 2023

Recruitment & Eligibility

• Status: Completed
• Sex: All
• Target Recruitment: 17

Inclusion Criteria

1. Older than 18 years
2. Liver transplantation more than three years ago
3. Treatment with IS that includes cyclosporine or tacrolimus
4. Have a normal liver function in the last year (defined as normal transaminases and alkaline phosphatase in all laboratory controls performed during the last year)
5. Not acute rejection in the last year and not chronic rejection
6. Normal hepatic biopsy according the Banff Working Group criteria for IS withdrawal
7. Etiology of the underlying disease: cirrhosis (with or without hepatic tumour) of any cause (except autoimmune etiopathogeny diseases): alcoholic B virus, C virus cirrhosis, cryptogenetic, ..., metabolic diseases, familial amyloid polyneuropathy; biliary atresia, fulminant hepatitis no A, no B, no C
8. Patients who offer sufficient guarantees of adherence to the protocol; I. Patients who give written informed consent to participate in the study

Exclusion Criteria

1. Transplantation of another non-hepatic organ
2. Liver transplantation due to a disease of autoimmune etiopathogenesis (primary biliary cholangitis, primary sclerosing cholangitis or autoimmune hepatitis)
3. Patients with hepatic retransplantation
4. Active infection with hepatitis C virus or hepatitis B virus
5. Patients with chronic rejection, or acute rejection in the last year
6. Inability to understand informed consent; e: liver biopsy with significant portal or lobular inflammation
7. Patients with rheumatic/autoimmune disease requiring sustained immunosuppressive treatment

Study & Design

• Study Type: Interventional
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
PBMCs, plasma and mRNA will be collected every month during the IS withdrawal. Most of the outcomes will be measured at these five timepoints:<br>1. Immunophenotyping in peripheral blood of different cell subpopulations including regulatory T cells, NK, B, dendritic and other specific markers, using flow cytometry<br>2. Level of serum inflammatory cytokines, measured using multiplex ELISA<br>3. Gene expression pattern of a pre-established cohort of genes and miRNAs, measured using qPCR<br>4. The methylation level of the TSDR zone of the FOXP3 gene in peripheral blood, measured pyrosequencing<br>5. The concentration in plasma of ferritin, hepcidin-25 (measured by ELISA) ATP and adenosine (measured by UPLC-MS-UV)<br>6. Gene expression (mainly genes related to iron homeostasis), miRNAs, FOXP3 methylation and immunohistochemical analysis of Foxp3 at tissue level, measured using liver biopsies taken prior to the start of the IS withdrawal study and in the rejection episode

Secondary Outcome Measures

Name	Time	Method
The diagnostic accuracy of one or more of these biomarkers of tolerance in blood or hepatic tissue, together or separately, for predicting as accurately as possible the result of protocolized withdrawal of immunosuppressive medication