Reduced-Dose Tacrolimus with Mycophenolate Mofetil vs. Standard-Dose Tacrolimus in Liver Transplantation: A Randomized Study

Authors

  • K. Boudjema,

    Corresponding author
    1. Service de Chirurgie Hépatobiliaire et Digestive, Hôpital de Pontchaillou, Centre Hospitalier Universitaire, Université de Rennes 1, Rennes, France
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  • C. Camus,

    1. Service de Maladies Infectieuses et Réanimation Médicale, Hôpital de Pontchaillou, Centre Hospitalier Universitaire, Université de Rennes 1, Rennes, France
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  • F. Saliba,

    1. Centre Hépato-biliaire, Service d’Hépato-gastro-entérologie, Hôpital Paul Brousse, Assistance Publique Hôpitaux de Paris, Université Paris XI, Villejuif, France
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  • Y. Calmus,

    1. Pôle Médico-chirurgical d’Hépato-gastro-entérologie, Unité Fonctionnelle de Transplantation Hépatique, Hôpital Cochin, Assistance Publique Hôpitaux de Paris, Université Paris 5, Paris, France
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  • E. Salamé,

    1. Département de Chirurgie Digestive et de Transplantation Hépatique, Hôpital de la Côte de Nacre, Centre Hospitalier Universitaire, Université de Caen, Caen, France
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  • G. Pageaux,

    1. Service d’Hépato-gastro-entérologie et Transplantation Hépatique, Hôpital St Eloi, Centre Hospitalier Universitaire, Université de Montpellier 1, Montpellier, France
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  • C. Ducerf,

    1. Service de Chirurgie Digestive et Transplantation, Hôpital de la Croix Rousse, Hospices Civils de Lyon, Université de Lyon 1, Lyon, France
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  • C. Duvoux,

    1. Service d’Hépato-gastro-entérologie, Hôpital Henri Mondor, Assistance Publique Hôpitaux de Paris, Université Paris 12, Créteil, France
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  • C. Mouchel,

    1. Service de Pharmacologie Clinique, Hôpital de Pontchaillou, Centre Hospitalier Universitaire, Université de Rennes 1, Rennes, France
    2. Centre d’Investigation Clinique INSERM 0203, Hôpital de Pontchaillou, Centre Hospitalier Universitaire, Université de Rennes 1, Rennes, France
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  • A. Renault,

    1. Service de Pharmacologie Clinique, Hôpital de Pontchaillou, Centre Hospitalier Universitaire, Université de Rennes 1, Rennes, France
    2. Centre d’Investigation Clinique INSERM 0203, Hôpital de Pontchaillou, Centre Hospitalier Universitaire, Université de Rennes 1, Rennes, France
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  • P. Compagnon,

    1. Service de Chirurgie Hépatobiliaire et Digestive, Hôpital de Pontchaillou, Centre Hospitalier Universitaire, Université de Rennes 1, Rennes, France
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  • R. Lorho,

    1. Service des Maladies du Foie, Hôpital de Pontchaillou, Centre Hospitalier Universitaire, Université de Rennes 1, Rennes, France
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  • E. Bellissant

    1. Service de Pharmacologie Clinique, Hôpital de Pontchaillou, Centre Hospitalier Universitaire, Université de Rennes 1, Rennes, France
    2. Centre d’Investigation Clinique INSERM 0203, Hôpital de Pontchaillou, Centre Hospitalier Universitaire, Université de Rennes 1, Rennes, France
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Corresponding author: Karim Boudjema, karim.boudjema@chu-rennes.fr

Abstract

We conducted a multicenter randomized study in liver transplantation to compare standard-dose tacrolimus to reduced-dose tacrolimus with mycophenolate mofetil to reduce the occurrence of tacrolimus side effects. Two primary outcomes (censored criteria) were monitored during 48 weeks post-transplantation: occurrence of renal dysfunction or arterial hypertension or diabetes (evaluating benefit) and occurrence of acute graft rejection (evaluating risk). Interim analyses were performed every 40 patients to stop the study in the case of increased risk of graft rejection. One hundred and ninety-five patients (control: 100; experimental: 95) had been included when the study was stopped. Acute graft rejection occurred in 46 (46%) and 28 (30%) patients in control and experimental groups, respectively (HR = 0.59; 95% CI: [0.37–0.94]; p = 0.024). Renal dysfunction or arterial hypertension or diabetes occurred in 80 (80%) and 61 (64%) patients in control and experimental groups, respectively (HR = 0.68; 95% CI: [0.49–0.95]; p = 0.021). Renal dysfunction occurred in 42 (42%) and 23 (24%) patients in control and experimental groups, respectively (HR = 0.49; 95% CI: [0.29–0.81]; p = 0.004). Leucopoenia (p = 0.001), thrombocytopenia (p = 0.017) and diarrhea (p = 0.002) occurred more frequently in the experimental group. Reduced-dose tacrolimus with mycophenolate mofetil reduces the occurrence of renal dysfunction and the risk of graft rejection. This immunosuppressive regimen could replace full-dose tacrolimus in adult liver transplantation.

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