Ribavirin for Hepatitis E Virus Infection After Organ Transplantation: A Large European Retrospective Multicenter Study

Author:

Kamar Nassim1,Abravanel Florence2,Behrendt Patrick3,Hofmann Jörg4,Pageaux Georges Phillippe5,Barbet Christelle6,Moal Valérie7,Couzi Lionel8,Horvatits Thomas9,De Man Robert A10,Cassuto Elisabeth11,Elsharkawy Ahmed M12,Riezebos-Brilman Annelies13,Scemla Anne14,Hillaire Sophie15,Donnelly Mhairi C16,Radenne Sylvie17,Sayegh Johnny18,Garrouste Cyril19,Dumortier Jérôme20,Glowaki François21,Matignon Marie22,Coilly Audrey23,Figueres Lucile24,Mousson Christiane25,Minello Anne26,Dharancy Sébastien27,Rerolle Jean Philippe28,Lebray Pascal29,Etienne Isabelle30,Perrin Peggy31,Choi Mira4,Marion Olivier2,Izopet Jacques2,Bellière J,Cointault O,Del Bello A,Espostio L,Hebral A L,Lavayssière L,Lhomme S,Mansuy J M,Wedemeyer H,Nickel P,Bismuth M,Stefic K,Büchler 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,

Affiliation:

1. Department of Nephrology, Dialysis and Organ Transplantation, Centre Hospitalier Universitaire (CHU) Rangueil, Institut National de la Santé et de la Recherche Médicale (INSERM) U1043, Institut Fédératif de Recherche Bio-médicale de Toulouse (IFR–BMT), University Paul Sabatier, Toulouse, France

2. Department of Virology, INSERM U1043, IFR–BMT, University Paul Sabatier, Toulouse, France

3. Department of Gastroenterology, Hepatology, and Endocrinology, Hannover Medical School, and Institute of Experimental Virology, TWINCORE, Centre for Experimental and Clinical Infection Research, a joint venture between the Medical School Hannover and the Helmholtz Centre for Infection Research, German Centre for Infection Research, Hannover, Germany

4. Charité Universitätsmedizin Berlin, Department of Nephrology and Intensive Care and Institute of Virology, Labor Berlin Charité-Vivantes-GmbH, Berlin, Germany

5. Department of Hepatology, Saint Eloi Hospital, Montpellier, France

6. Department of Nephrology and Clinical Immunology, Bretonneau Hospital, University Hospital, Tours, France

7. Aix Marseille Université, Asistance Publique Hôpitaux de Marseille, Institut Pour la Recherche Pour le Développement, Microbes, Evolution, Phylogénie et Infection, Institut Hospitalo-Universitaire–Méditerranée Infection, Hôpital Conception, Centre de Néphrologie et Transplantation Rénale, Marseille, France

8. Department of Nephrology and Transplantation, CHU Bordeaux, Bordeaux, France

9. Department of Medicine I, University Medical Center Hamburg-Eppendorf, Hamburg, Germany

10. Departments of Gastroenterology and Hepatology, Erasmus Medical Center, Rotterdam, The Netherlands

11. Department of Nephrology and Transplantation, CHU Nice, France

12. Liver Unit, University Hospitals Birmingham, Birmingham, United Kingdom

13. Department of Medical Microbiology, University of Groningen, University Medical Centre Groningen, Groningen, The Netherlands

14. Service de néphrologie-transplantation, Hôpital Necker, Assitance publique- Hôpitaux de Paris (AP-HP), Paris et Université Paris Descartes, Paris, France

15. Department of Hepatology, Hôpital Foch, Suresnes, France

16. Department of Hepatology and Scottish Liver Transplant Unit, Royal Infirmary of Edinburgh, Edinburgh, United Kingdom

17. Department of Hepatology and Liver Transplantation, CHU de la Croix Rousse, Lyon, France

18. Department of Nephrology and Transplantation, CHU Angers, Angers, France

19. Department of Nephrology, CHU Clermont-Ferrand, Clermont-Ferrand, France

20. Department of Hepatology, Edouard Herriot Hospital, CHU Lyon, Lyon, France

21. Department of Nephrology, CHU Lille, Lille, France

22. Assistance Publique-Hôpitaux de Paris, Nephrology and Renal Transplantation Department, Groupe Hospitalier Henri-Mondor/Albert-Chenevier, Université Paris-Est-Créteil, Département Hospitalo-Universitaire Virus-Immunité-Cancer, Institut Mondor de Recherche Biomédicale, Equipe 21, INSERM U 955, Créteil, France

23. Centre Hépato-Biliaire, Hôpital Paul Brousse, AP-HP, INSERM U1193, Université Paris-Sud Paris-Saclay, Villejuif, France

24. Department of Nephrology and Clinical Immunology, CHU Nantes, Nantes, France

25. Department of Nephrology, CHU François Mitterrand, Dijon, France

26. Department of Hepatogastroenterology and Digestive Oncology, CHU François Mitterrand, Dijon, France

27. Hôpital Claude Huriez, Services Maladies de l’Appareil Digestif, INSERM Unité 995, Lille, France

28. Department of Nephrology, CHU Limoges, Limoges, France

29. Department of Hepatology, Pitié Salpétrière Hospital, Paris, France

30. Department of Nephrology, CHU Rouen, Rouen, France

31. Department of Nephrology, CHU Strasbourg, Strasbourg, France

Abstract

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.

Publisher

Oxford University Press (OUP)

Subject

Infectious Diseases,Microbiology (medical)

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