1. Ribavirin for Hepatitis E Virus Infection After Organ Transplantation
- Author
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Kamar, Nassim, Legrand-Abravanel, Florence, Behrendt, Patrick, Hofmann, Jörg, Pageaux, Georges Phillippe, Barbet, Christelle, Moal, Valerie, Couzi, Lionel, Horvatits, Thomas, de Man, Robert, Cassuto, Elisabeth, Elsharkawy, Ahmed, Riezebos-Brilman, Annelies, Scemla, Anne, Hillaire, Sophie, Donnelly, Mhairi, Radenne, Sylvie, Sayegh, Johnny, Garrouste, Cyril, Dumortier, Jérôme, Glowaki, François, Matignon, Marie, Coilly, Audrey, Figueres, Lucile, Mousson, Christiane, Minello, Anne, Dharancy, Sébastien, Rerolle, Jean Philippe, Lebray, Pascal, Etienne, Isabelle, Perrin, Peggy, Choi, Mira, Olivier, Marion, Izopet, Jacques, Bellière, J, Cointault, O., del Bello, Arnaud, Espostio, L, Hebral, A, Lavayssière, L, Lhomme, S, Mansuy, J, Wedemeyer, H, Nickel, P, Bismuth, M., Stefic, K, Buchler, M., D’alteroche, L, Colson, P., Bufton, S, Ramière, C, Trimoulet, P., Pischke, S, Todesco, E, Sberro Soussan, R, Legendre, C, Mallet, V., Johannessen, I, Simpson, K, Service de Néphrologie - Hypertension Artérielle Dialyse - Transplantation, Centre de Physiopathologie Toulouse Purpan (CPTP), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Toulouse [Toulouse], Université Fédérale Toulouse Midi-Pyrénées, Hannover Medical School [Hannover] (MHH), Charité - UniversitätsMedizin = Charité - University Hospital [Berlin], Département d'Hépato-Gastroentérologie et de Transplantation Hépatique [CHU Saint-Eloi], Hôpital Saint Eloi (CHRU Montpellier), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université de Montpellier (UM), Service de néphrologie et immunologie clinique [CHRU Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours (UT), Microbes évolution phylogénie et infections (MEPHI), Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS), Assistance Publique - Hôpitaux de Marseille (APHM), Institut Hospitalier Universitaire Méditerranée Infection (IHU Marseille), CHU Bordeaux [Bordeaux], Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg] (UKE), Erasmus University Medical Center [Rotterdam] (Erasmus MC), Centre Hospitalier Universitaire de Nice (CHU Nice), University Hospitals Birmingham [Birmingham, Royaume-Uni], University Medical Center Groningen [Groningen] (UMCG), Réseau CENTAURE, Hôpital Foch [Suresnes], Royal Infirmary of Edinburgh, Service d'Hépatologie [Hôpital de la Croix-Rousse - HCL], Hôpital de la Croix-Rousse [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM), CHU Clermont-Ferrand, Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Institut Mondor de Recherche Biomédicale (IMRB), Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Hôpital Paul Brousse, Centre hospitalier universitaire de Nantes (CHU Nantes), Service de néphrologie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Service d'Hépato-Gastro-Entérologie (CHU de Dijon), Hôpital Claude Huriez [Lille], CHU Lille, Service de Néphrologie, Dialyse, Transplantations [CHU Limoges], CHU Limoges, Service d'Hépato-Gastro-Entérologie [CHU Pitié-Salpêtrière], CHU Pitié-Salpêtrière [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), CHU Rouen, Normandie Université (NU), CHU Strasbourg, Département de Néphrologie et Transplantation d'organes [Toulouse], Service de virologie et d'immunologie biologique, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Gastroenterology & Hepatology, CHU Toulouse [Toulouse]-Hôpital de Rangueil, Université de Montpellier (UM)-CHU Saint-Eloi, Service de néphrologie et immunologie clinique [CHRU Tours] (EA4245 UT), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours, Département de Néphrologie et Transplantation d'organes, Hôpital de Rangueil, CHU Toulouse [Toulouse]-CHU Toulouse [Toulouse], Service de néphrologie et immunologie clinique, Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université de Toulouse (UT), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Département de Néphrologie et Transplantation d'organes [CHU Toulouse], Pôle Urologie - Néphrologie - Dialyse - Transplantations - Brûlés - Chirurgie plastique - Explorations fonctionnelles et physiologiques [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Aix Marseille Université (AMU), and Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-IFR10
- Subjects
0301 basic medicine ,MESH: Antiviral Agents / therapeutic use ,Sofosbuvir ,viruses ,medicine.disease_cause ,Gastroenterology ,THERAPY ,Organ transplantation ,Hepatitis E virus / genetics ,Hepatitis E / drug therapy ,Humans ,chemistry.chemical_compound ,0302 clinical medicine ,Hepatitis E virus ,[SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases ,Medicine ,MUTATION ,MESH: Hepatitis E* / drug therapy ,POLYMERASE ,organ transplantation ,virus diseases ,MESH: Ribavirin / therapeutic use ,Anemia ,[SDV.SP]Life Sciences [q-bio]/Pharmaceutical sciences ,Hepatitis E ,anemia ,3. Good health ,PREDICTS ,Sustained virological response ,Infectious Diseases ,MESH: RNA, Viral ,[SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology ,RNA, Viral ,030211 gastroenterology & hepatology ,sustained virological response ,medicine.drug ,Microbiology (medical) ,medicine.medical_specialty ,ribavirin ,MESH: Organ Transplantation / adverse effects ,RNA, Viral Retrospective Studies ,Ribavirin / therapeutic use ,Alpha interferon ,MESH: Organ Transplantation* / adverse effects ,hepatitis E virus ,Antiviral Agents ,Virus ,03 medical and health sciences ,SDG 3 - Good Health and Well-being ,Internal medicine ,Ribavirin ,Retrospective Studies ,MESH: Hepatitis E virus* / genetics ,MESH: Humans ,business.industry ,Retrospective cohort study ,MESH: Retrospective Studies ,[SDV.MHEP.HEG]Life Sciences [q-bio]/Human health and pathology/Hépatology and Gastroenterology ,IN-VITRO ,medicine.disease ,digestive system diseases ,030104 developmental biology ,chemistry ,SOFOSBUVIR ,HEV ,REPLICATION ,INTERFERON-ALPHA ,business - Abstract
Background Ribavirin is currently recommended for treating chronic hepatitis E virus (HEV) infection. This retrospective European multicenter study aimed to assess the sustained virological response (SVR) in a large cohort of solid organ transplant (SOT) recipients with chronic HEV infection treated with ribavirin monotherapy (N = 255), to identify the predictive factors for SVR, and to evaluate the impact of HEV RNA mutations on virological response. Methods Data from 255 SOT recipients with chronic HEV infection from 30 European centers were analyzed. Ribavirin was given at the median dose of 600 (range, 29–1200) mg/day (mean, 8.6 ± 3.6 mg/kg/day) for a median duration of 3 (range, 0.25–18) months. Results After a first course of ribavirin, the SVR rate was 81.2%. It increased to 89.8% when some patients were offered a second course of ribavirin. An increased lymphocyte count at the initiation of therapy was a predictive factor for SVR, while poor hematological tolerance of ribavirin requiring its dose reduction (28%) and blood transfusion (15.7%) were associated with more relapse after ribavirin cessation. Pretreatment HEV polymerase mutations and de novo mutations under ribavirin did not have a negative impact on HEV clearance. Anemia was the main adverse event. Conclusions This large-scale retrospective study confirms that ribavirin is highly efficient for treating chronic HEV infection in SOT recipients and shows that the predominant HEV RNA polymerase mutations found in this study do not affect the rate of HEV clearance. This large-scale retrospective study that included 255 solid organ transplant recipients confirms that ribavirin is highly efficient for treating chronic hepatitis E virus (HEV) infection and shows that HEV RNA polymerase mutations do not play a role in HEV clearance.
- Published
- 2020