Evidence map›Paper›PMID 41359656›Full record

Trial reportPloS one2025

Longitudinal biomarker progression and validation for predicting operational tolerance in a prospective multicenter liver transplantation immunosuppression withdrawal trial.

Gloria López-Díaz, María Isabel Sánchez-Lorencio, Mercedes Iñarrairaegui, María Luisa González-Diéguez, Valle Cadahía, Alejandra Otero-Ferreiro, María Ángeles Vázquez-Millán, Mario Romero-Cristóbal, Magdalena Salcedo, Sara Lorente-Pérez and 7 more

Abstract readMulticenter StudyRandomized Controlled Trial
In one paragraph

Trial report in PloS one, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

2 citing papers in PubMed.

  1. Review
  2. Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

17 authors.

Gloria López-DíazHepatology and Liver Transplant Unit, University Clinical Hospital Virgen de la Arrixaca, Biomedical Research Institute of Murcia (IMIB-Pascual Parrilla), Murcia, Spain.
María Isabel Sánchez-LorencioMolecular Inflammation Group, University Clinical Hospital Virgen de la Arrixaca, Biomedical Research Institute of Murcia (IMIB-Pascual Parrilla), Murcia, Spain.
Mercedes IñarrairaeguiLiver Unit, Clínica Universidad de Navarra, Pamplona, Spain.
María Luisa González-DiéguezLiver Unit, Hospital Universitario Central de Asturias, Oviedo, Asturias, Spain.
Valle CadahíaLiver Unit, Hospital Universitario Central de Asturias, Oviedo, Asturias, Spain.
Alejandra Otero-FerreiroLiver Transplant Unit, Complejo Hospitalario A Coruña, A Coruña, Spain.
María Ángeles Vázquez-MillánLiver Transplant Unit, Complejo Hospitalario A Coruña, A Coruña, Spain.
Mario Romero-CristóbalLiver Unit, H.G.U. Gregorio Marañón, Madrid, Spain.
Magdalena SalcedoLiver Unit, H.G.U. Gregorio Marañón, Madrid, Spain.
Sara Lorente-PérezLiver Transplant Unit, Hospital Clínico Universitario Lozano Blesa, Universitiy of Zaragoza and ISS Aragón, Zaragoza, Spain.
Gloria Sánchez-AntolínHepatology and Liver Transplant Unit, Hospital Universitario Río Hortega, Valladolid, Spain.
Jesús de la PeñaPathological Anatomy Unit, University Clinical Hospital Virgen de la Arrixaca, Murcia, Spain.
Pablo RamírezGeneral Surgery Unit, University Clinical Hospital Virgen de la Arrixaca, Biomedical Research Institute of Murcia (IMIB-Pascual Parrilla), Murcia, Spain.
María P PataBiostatech Advice, Training and Innovation in Biostatistics S.L., Santiago de Compostela, Spain.
Alberto Baroja-MazoMolecular Inflammation Group, University Clinical Hospital Virgen de la Arrixaca, Biomedical Research Institute of Murcia (IMIB-Pascual Parrilla), Murcia, Spain.
José I HerreroLiver Unit, Clínica Universidad de Navarra, Pamplona, Spain.ORCID https://orcid.org/0000-0002-9076-6717
José Antonio PonsHepatology and Liver Transplant Unit, University Clinical Hospital Virgen de la Arrixaca, Biomedical Research Institute of Murcia (IMIB-Pascual Parrilla), Murcia, Spain.ORCID https://orcid.org/0000-0001-5017-7240

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Liver transplantation (LT) is a life-saving treatment for end-stage liver disease, but long-term immunosuppression (IS) is associated with significant side effects. Achieving operational tolerance (OT), where the graft is accepted without IS, remains a critical goal. Biomarkers play a pivotal role in understanding the complex mechanisms of OT, enabling personalized treatment strategies and improving patient outcomes. Additionally, machine learning techniques offer powerful tools for identifying predictive biomarkers and optimizing IS withdrawal protocols. This multicenter trial aimed to investigate the longitudinal evolution of genetic biomarkers during IS withdrawal and validate their predictive value for OT in LT recipients. A prospective, multicenter IS withdrawal trial was conducted with 91 LT patients. Tolerant (TOL) and non-tolerant (non-TOL) patients were compared, and longitudinal blood and liver samples were collected to analyze biomarkers. Generalized Additive Mixed Models (GAMMs) and logistic algorithms were employed to assess biomarker associations and predict OT. Of the 45 patients who completed the trial, 17 (37.8%) achieved OT. Molecular biomarker analysis revealed significant differences between TOL and non-TOL groups. Non-TOL patients exhibited higher baseline methylation of the FOXP3 regulatory T cell-specific demethylated region (TSDR) in whole blood. Longitudinal analysis showed distinct patterns in FOXP3, SENP6, miR31, and miR95 expression between groups. Notably, FOXP3 expression followed a U-shaped trajectory in TOL patients, decreasing during IS withdrawal and increasing post-withdrawal. Machine learning identified several key predictive biomarkers for OT. This study confirms the association between FOXP3 TSDR methylation and OT in LT patients and identifies FEM1C, miR31 and TFRC as promising predictive biomarkers. These findings highlight the potential for personalized IS withdrawal strategies, though further validation in larger cohorts is needed before clinical application.

Indexed as

BiomarkersImmunosuppression TherapyLiver TransplantationAdultFemaleForkhead Transcription FactorsHumansLongitudinal StudiesMaleMiddle AgedProspective StudiesBiomarkersForkhead Transcription FactorsFOXP3 protein, human

Identifiers

PMID41359656
PMCPMC12685220

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.