ArticleHepatology (Baltimore, Md.)2021
Efficacy and Safety of Immunosuppression Withdrawal in Pediatric Liver Transplant Recipients: Moving Toward Personalized Management.
Article in Hepatology (Baltimore, Md.), 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 89 citations in OpenAlex.
- Immunosuppression Withdrawal in Pediatric Liver Transplant Recipients With Posttransplant Lymphoproliferative Disorder: A Single-Center Retrospective Study.Annals of transplantation · 2026Article
- Induction of Clinical Operational Tolerance Through Immunosuppression Minimization: Less Is More?Liver international : official journal of the International Association for the Study of the Liver · 2026Review
- Defining the Society of Pediatric Liver Transplantation (SPLIT) research agenda: A Delphi consensus project.Hepatology communications · 2026Article
- MicroRNA Profiling as a Novel Predictive Tool for Operational Tolerance in Pediatric Liver Transplantation: A Single-center Study.Transplantation direct · 2026Article
- Neutrophil-associated plasma proteomics identifies HDAC1 as a baseline biomarker of immune tolerance during immunosuppressant withdrawal after pediatric liver transplantation: a single-center cohort study.Frontiers in immunology · 2026Article
- Immunometabolic remodeling: new perspectives and strategies for liver transplantation.Frontiers in immunology · 2026Review
- Review
- Assessment of Donor-Specific Human Leukocyte Antigen Antibodies Following Pediatric Liver Transplantation: Predictors, Protectors, and Clinical Relevance.Clinical transplantation · 2025Article
- Single-cell transcriptional landscape of liver transplant rejection reveals tissue persistence of clonally expanded, treatment-resistant T cells.American journal of transplantation : official journal of the American Society of Transplantation and the American Society of Transplant Surgeons · 2025Article
- Evaluating the Efficacy of Levetiracetam on Non-Cognitive Symptoms and Pathology in a Tau Mouse Model.Biomedicines · 2024Article
- Proceedings of the 28th Annual Congress of the International Liver Transplantation Society.Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society · 2024Article
- Cellular strategies to induce immune tolerance after liver transplantation: Clinical perspectives.World journal of gastroenterology · 2024Article
- Defining the T cell transcriptional landscape in pediatric liver transplant rejection at single cell resolution.bioRxiv : the preprint server for biology · 2024Article
- Revisiting transplant immunology through the lens of single-cell technologies.Seminars in immunopathology · 2023Review
- Genotype-guided model significantly improves accuracy of tacrolimus initial dosing after liver transplantation.EClinicalMedicine · 2023Article
- Combination of everolimus and low-dose tacrolimus controls histological liver allograft injury as sufficiently as high-dose tacrolimus.Frontiers in transplantation · 2023Article
- Post-transplant donor-specific anti-HLA antibodies with a higher mean fluorescence intensity are associated with graft fibrosis in pediatric living donor liver transplantation.Frontiers in pediatrics · 2023Article
- Linked sensitization by memory CD4+ T cells prevents costimulation blockade-induced transplantation tolerance.JCI insight · 2022Article
- Donor and recipient polygenic risk scores influence the risk of post-transplant diabetes.Nature medicine · 2022Article
- Immunologic benefits of maternal living donor allografts in pediatric liver transplantation: fewer rejection episodes and no evidence of de novo allosensitization.Pediatric transplantation · 2022Article
Corrections and comments
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Authors and funding
28 authors at 20 institutions in 4 countries.
Funding
Abstract
BACKGROUND AND
aimsTolerance is transplantation's holy grail, as it denotes allograft health without immunosuppression and its toxicities. Our aim was to determine, among stable long-term pediatric liver transplant recipients, the efficacy and safety of immunosuppression withdrawal to identify operational tolerance. APPROACH AND
resultsWe conducted a multicenter, single-arm trial of immunosuppression withdrawal over 36-48 weeks. Liver tests were monitored biweekly (year 1), monthly (year 2), and bimonthly (years 3-4). For-cause biopsies were done at investigators' discretion but mandated when alanine aminotransferase or gamma glutamyltransferase exceeded 100 U/L. All subjects underwent final liver biopsy at trial end. The primary efficacy endpoint was operational tolerance, defined by strict biochemical and histological criteria 1 year after stopping immunosuppression. Among 88 subjects (median age 11 years; 39 boys; 57 deceased donor grafts), 33 (37.5%; 95% confidence interval [CI] 27.4%, 48.5%) were operationally tolerant, 16 were nontolerant by histology (met biochemical but failed histological criteria), and 39 were nontolerant by rejection. Rejection, predicted by subtle liver inflammation in trial entry biopsies, typically (n = 32) occurred at ≤32% of the trial-entry immunosuppression dose and was treated with corticosteroids (n = 32) and/or tacrolimus (n = 38) with resolution (liver tests within 1.5 times the baseline) for all but 1 subject. No death, graft loss, or chronic, severe, or refractory rejection occurred. Neither fibrosis stage nor the expression level of a rejection gene set increased over 4 years for either tolerant or nontolerant subjects.
conclusionsImmunosuppression withdrawal showed that 37.5% of selected pediatric liver-transplant recipients were operationally tolerant. Allograft histology did not deteriorate for either tolerant or nontolerant subjects. The timing and reversibility of failed withdrawal justifies future trials exploring the efficacy, safety, and potential benefits of immunosuppression minimization.
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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 OpenQuestion graph.