Aurélia Poujois1, Rodolphe Sobesky2, Wassilios G Meissner2, Anne-Sophie Brunet2, Emmanuel Broussolle2, Chloé Laurencin2, Laurence Lion-François2, Olivier Guillaud2, Alain Lachaux2, François Maillot2, Jérémie Belin2, Ephrem Salamé2, Claire Vanlemmens2, Bruno Heyd2, Céline Bellesme2, Dalila Habes2, Christophe Bureau2, Fabienne Ory-Magne2, Pascal Chaine2, Jean-Marc Trocello2, Daniel Cherqui2, Didier Samuel2, Victor de Ledinghen2, Jean-Charles Duclos-Vallée2, France Woimant2. 1. From the Neurology Department (A.P., P.C., J.-M.T., F.W.), AP-HP, Lariboisière University Hospital; National Reference Centre for Wilson's Disease (A.P., P.C., J.-M.T., F.W.), AP-HP, Lariboisière University Hospital, Paris; Hepatobiliary Centre (R.S., D.C., D.S., J.-C.D.-V.), DHU Hepatinov, UMR-1193, AP-HP, Paul Brousse Hospital, Villejuif; Service de Neurologie (W.G.M.), CHU Bordeaux; Université de Bordeaux (W.G.M.), Institut des Maladies Neurodégénératives, CNRS UMR 5393, France; Department of Medicine (W.G.M.), University of Otago and New Zealand Brain Research Institute (W.G.M.), Christchurch; Hepatology, Gastroenterology and Nutrition Department (A.-S.B., A.L.), Hôpital Femme Mère Enfant, Hospices Civils de Lyon; National Reference Centre for Wilson's Disease (A.-S.B., E.B., C.L., L.L.-F., O.G., A.L.), Hospices Civils de Lyon; Neurology Department (E.B., C.L.), Hôpital Neurologique Pierre-Wertheimer, Hospices Civils de Lyon; CNRS (E.B., C.L.), UMR 5229, Institut des Sciences Cognitives Marc-Jeannerod, Bron; Faculté de Médecine Lyon Sud Charles-Mérieux (E.B., C.L., A.L.), Université Claude-Bernard Lyon 1; Neurology and Paediatrics Department (L.L.-F.), Hôpital Femme Mère Enfant, Hospices Civils de Lyon, Bron; Hepatogastroenterology Department (O.G.), Edouard Herriot Hospital, Hospices Civils de Lyon; Internal Medicine Department (F.M.), National Reference Centre for Inborn Errors of Metabolism, Université François Rabelais; Neurology Department (J.B.), CHRU Bretonneau, Tours; Surgery, Oncology and Liver Transplantation Department (E.S.), CHRU Tours; Hepatology and Gastroenterology Department (C.V.) and Surgery and Liver Transplantation Department (B.H.), CHU Besançon; Neurology and Paediatrics Department (C. Bellesme), AP-HP, Bicêtre University Hospital, Kremlin-Bicetre; Pediatric Hepatology and Pediatric Liver Transplantation Unit (U.H) and National Reference Centre for Rare Pediatric Liver Diseases (U.H), Bicêtre University Hospital, Faculty of Medicine Paris-Sud, University of Paris-Sud 11, DHU Hepatinov, AP-HP, Le Kremlin Bicêtre; INSERM (D.H.), UMR-S1174, Hepatinov, University of Paris Sud 11, Orsay; Hepatology and Gastroenterology Department (C. Bureau) and Neurology Department (F.O.-M.), CHU Toulouse; Centre D'investigation de la Fibrose Hépatique (V.L.), Hôpital Haut-Lévêque, CHU Bordeaux; and INSERM U1053 (V.d.L.), Université de Bordeaux, France. A. Poujois is currently at Neurology Department, Rothschild Foundation Hospital, and National Reference Centre for Wilson's Disease, Rothschild Foundation Hospital, Paris. apoujois@for.paris. 2. From the Neurology Department (A.P., P.C., J.-M.T., F.W.), AP-HP, Lariboisière University Hospital; National Reference Centre for Wilson's Disease (A.P., P.C., J.-M.T., F.W.), AP-HP, Lariboisière University Hospital, Paris; Hepatobiliary Centre (R.S., D.C., D.S., J.-C.D.-V.), DHU Hepatinov, UMR-1193, AP-HP, Paul Brousse Hospital, Villejuif; Service de Neurologie (W.G.M.), CHU Bordeaux; Université de Bordeaux (W.G.M.), Institut des Maladies Neurodégénératives, CNRS UMR 5393, France; Department of Medicine (W.G.M.), University of Otago and New Zealand Brain Research Institute (W.G.M.), Christchurch; Hepatology, Gastroenterology and Nutrition Department (A.-S.B., A.L.), Hôpital Femme Mère Enfant, Hospices Civils de Lyon; National Reference Centre for Wilson's Disease (A.-S.B., E.B., C.L., L.L.-F., O.G., A.L.), Hospices Civils de Lyon; Neurology Department (E.B., C.L.), Hôpital Neurologique Pierre-Wertheimer, Hospices Civils de Lyon; CNRS (E.B., C.L.), UMR 5229, Institut des Sciences Cognitives Marc-Jeannerod, Bron; Faculté de Médecine Lyon Sud Charles-Mérieux (E.B., C.L., A.L.), Université Claude-Bernard Lyon 1; Neurology and Paediatrics Department (L.L.-F.), Hôpital Femme Mère Enfant, Hospices Civils de Lyon, Bron; Hepatogastroenterology Department (O.G.), Edouard Herriot Hospital, Hospices Civils de Lyon; Internal Medicine Department (F.M.), National Reference Centre for Inborn Errors of Metabolism, Université François Rabelais; Neurology Department (J.B.), CHRU Bretonneau, Tours; Surgery, Oncology and Liver Transplantation Department (E.S.), CHRU Tours; Hepatology and Gastroenterology Department (C.V.) and Surgery and Liver Transplantation Department (B.H.), CHU Besançon; Neurology and Paediatrics Department (C. Bellesme), AP-HP, Bicêtre University Hospital, Kremlin-Bicetre; Pediatric Hepatology and Pediatric Liver Transplantation Unit (U.H) and National Reference Centre for Rare Pediatric Liver Diseases (U.H), Bicêtre University Hospital, Faculty of Medicine Paris-Sud, University of Paris-Sud 11, DHU Hepatinov, AP-HP, Le Kremlin Bicêtre; INSERM (D.H.), UMR-S1174, Hepatinov, University of Paris Sud 11, Orsay; Hepatology and Gastroenterology Department (C. Bureau) and Neurology Department (F.O.-M.), CHU Toulouse; Centre D'investigation de la Fibrose Hépatique (V.L.), Hôpital Haut-Lévêque, CHU Bordeaux; and INSERM U1053 (V.d.L.), Université de Bordeaux, France. A. Poujois is currently at Neurology Department, Rothschild Foundation Hospital, and National Reference Centre for Wilson's Disease, Rothschild Foundation Hospital, Paris.
Abstract
OBJECTIVE: To evaluate the effect of liver transplantation (LT) in patients with Wilson disease (WD) with severe neurologic worsening resistant to active chelation. METHODS: French patients with WD who underwent LT for pure neurologic indication were retrospectively studied. Before LT and at the last follow-up, neurologic impairment was evaluated with the Unified Wilson's Disease Rating Scale (UWDRS) score, disability with the modified Rankin Scale (mRS) score, and hepatic function with the Model for End-stage Liver Disease score, together with the presence of a Kayser-Fleischer ring (KFR), brain MRI scores, and copper balance. The survival rate and disability at the last follow-up were the coprimary outcomes; evolution of KFR and brain MRI were the secondary outcomes. Prognosis factors were further assessed. RESULTS: Eighteen patients had LT. All were highly dependent before LT (median mRS score 5). Neurologic symptoms were severe (median UWDRS score 105), dominated by dystonia and parkinsonism. The cumulated survival rate was 88.8% at 1 year and 72.2% at 3 and 5 years. At the last follow-up, 14 patients were alive. Their mRS and UWDRS scores improved (p < 0.0001 and p = 0.0003). Eight patients had a major improvement (78% decrease of the UWDRS score), 4 a moderate one (41% decrease), and 2 a stable status. KFR and brain MRI scores improved (p = 0.0007). Severe sepsis (p = 0.011) and intensive care unit admission (p = 0.001) before LT were significantly associated with death. CONCLUSIONS: LT is a rescue therapeutic option that should be carefully discussed in selected patients with neurologic WD resistant to anticopper therapies (chelators or zinc salts) as it might allow patients to gain physical independency with a reasonable risk. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that for patients with WD with severe neurologic worsening resistant to active pharmacologic therapy, LT might decrease neurologic impairment.
OBJECTIVE: To evaluate the effect of liver transplantation (LT) in patients with Wilson disease (WD) with severe neurologic worsening resistant to active chelation. METHODS: French patients with WD who underwent LT for pure neurologic indication were retrospectively studied. Before LT and at the last follow-up, neurologic impairment was evaluated with the Unified Wilson's Disease Rating Scale (UWDRS) score, disability with the modified Rankin Scale (mRS) score, and hepatic function with the Model for End-stage Liver Disease score, together with the presence of a Kayser-Fleischer ring (KFR), brain MRI scores, and copper balance. The survival rate and disability at the last follow-up were the coprimary outcomes; evolution of KFR and brain MRI were the secondary outcomes. Prognosis factors were further assessed. RESULTS: Eighteen patients had LT. All were highly dependent before LT (median mRS score 5). Neurologic symptoms were severe (median UWDRS score 105), dominated by dystonia and parkinsonism. The cumulated survival rate was 88.8% at 1 year and 72.2% at 3 and 5 years. At the last follow-up, 14 patients were alive. Their mRS and UWDRS scores improved (p < 0.0001 and p = 0.0003). Eight patients had a major improvement (78% decrease of the UWDRS score), 4 a moderate one (41% decrease), and 2 a stable status. KFR and brain MRI scores improved (p = 0.0007). Severe sepsis (p = 0.011) and intensive care unit admission (p = 0.001) before LT were significantly associated with death. CONCLUSIONS: LT is a rescue therapeutic option that should be carefully discussed in selected patients with neurologic WD resistant to anticopper therapies (chelators or zinc salts) as it might allow patients to gain physical independency with a reasonable risk. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that for patients with WD with severe neurologic worsening resistant to active pharmacologic therapy, LT might decrease neurologic impairment.
Authors: Marta Ruiz-Lopez; Ana Moreno Estébanez; Beatriz Tijero; Tamara Fernandez; Alba Rebollo-Perez; Iñigo Gabilondo; Nuria Lopez-Osle; Leticia Ceberio-Hualde; Juan Jose Zarranz; Juan Carlos Gomez-Esteban Journal: Neurology Date: 2022-06-13 Impact factor: 11.800
Authors: Tomasz Litwin; Jan Bembenek; Agnieszka Antos; Adam Przybyłkowski; Marta Skowrońska; Iwona Kurkowska-Jastrzębska; Anna Członkowska Journal: Acta Neurol Belg Date: 2022-01-26 Impact factor: 2.396
Authors: Peter Ott; Aurélia Poujois; Thomas Damgaard Sandahl; Karl Heinz Weiss; Peter Ferenci; Michael L Schilsky; Aftab Ala; Frederick K Askari; Anna Czlonkowska; Ralf-Dieter Hilgers; Eve A Roberts Journal: Hepatology Date: 2021-10-05 Impact factor: 17.298