Non-invasive alloimmune risk stratification of long-term liver transplant recipients
Rattachement africain : gb, ch, ca, es, be, de, us. Niveau de preuve : code pays fourni par la source.
Le résumé fourni par la source
BACKGROUND & AIMS: Management of long-term immunosuppression following liver transplantation (LT) remains empirical. Surveillance liver biopsies in combination with transcriptional profiling could overcome this challenge by identifying recipients with active alloimmune-mediated liver damage despite normal liver tests, but this approach lacks applicability. Our aim was to investigate the utility of non-invasive tools for the stratification of stable long-term survivors of LT, according to their immunological risk and need for immunosuppression. METHODS: We conducted a cross-sectional multicentre study of 190 adult LT recipients assessed to determine their eligibility to participate in an immunosuppression withdrawal trial. Patients had stable liver allograft function and had been transplanted for non-autoimmune non-replicative viral liver disease >3 years before inclusion. We performed histological, immunogenetic and serological studies and measured the intrahepatic transcript levels of an 11-gene classifier highly specific for T cell-mediated rejection (TCMR). RESULTS: In this cohort, 35.8% of patients harboured clinically silent fibro-inflammatory liver lesions (13.7% had mild damage and 22.1% had moderate-to-severe damage). The severity of liver allograft damage was positively associated with TCMR-related transcripts, class II donor-specific antibodies (DSAs), ALT, AST, and liver stiffness measurement (LSM), and negatively correlated with serum creatinine and tacrolimus trough levels. Liver biopsies were stratified according to their TCMR transcript levels using a cut-off derived from biopsies with clinically significant TCMR. Two multivariable prediction models, integrating ALT+LSM or ALT+class II DSAs, had a high discriminative capacity for classifying patients with or without alloimmune damage. The latter model performed well in an independent cohort of 156 liver biopsies obtained from paediatric liver recipients with similar inclusion/exclusion criteria. CONCLUSION: ALT, class II DSAs and LSM are valuable tools to non-invasively identify stable LT recipients without significant underlying alloimmunity who could benefit from minimisation of immunosuppression. LAY SUMMARY: A large proportion of liver transplant patients with normal liver tests have inflammatory liver lesions, which in 17% of cases are molecularly indistinguishable from those seen at the time of rejection. ALT, class II donor-specific antibodies and liver stiffness are useful in identifying patients with this form of subclinical rejection. We propose these markers as a useful tool to help clinicians determine if the immunosuppression administered is adequate.
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Le contrôle bibliographique ouvert
DOI retrouvé dans Crossref DOI retrouvé ; titre concordant.
- Titre Crossref
- Non-invasive alloimmune risk stratification of long-term liver transplant recipients
- Date Crossref
- 01/12/2021
- Éditeur
- Elsevier BV
- Type
- journal-article
Ce recoupement confirme des métadonnées liées au DOI. Il ne confirme ni la méthode ni les conclusions de l’étude, et il ne compte pas comme une seconde source scientifique indépendante.
Où se fait cette recherche
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King's College London Institute of Liver Studies pays non établi dans la noticeUniversité ou école supérieure
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Centre Hospitalier Universitaire Vaudois pays non établi dans la noticeÉtablissement de santé
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King's College Hospital Liver Histopathology Laboratory pays non établi dans la noticeÉtablissement de santé
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University College London pays non établi dans la noticeUniversité ou école supérieure
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University of Alberta Centre of Excellence for Gastrointestinal Inflammation and Immunity Research pays non établi dans la noticeUniversité ou école supérieure
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Instituto de Salud Carlos III pays non établi dans la noticeOrganisation à but non lucratif
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Hospital Clínic de Barcelona pays non établi dans la noticeÉtablissement de santé
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The Royal Free Hospital pays non établi dans la noticeÉtablissement de santé
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KU Leuven pays non établi dans la noticeUniversité ou école supérieure
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Addenbrooke's Hospital pays non établi dans la noticeÉtablissement de santé
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Newcastle upon Tyne Hospitals NHS Foundation Trust pays non établi dans la noticeÉtablissement de santé
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Medizinische Hochschule Hannover pays non établi dans la noticeUniversité ou école supérieure
Institute of Liver Studies — King's College London, Centre Hospitalier Universitaire Vaudois et Liver Histopathology Laboratory — King's College Hospital, avec 9 autres affiliations.
Une affiliation ne permet pas de déduire la nationalité d’un auteur.