Ribavirin for Hepatitis E Virus Infection After Organ Transplantation

Nassim Kamar (1, 2) , Florence Legrand-Abravanel (3, 4) , Patrick Behrendt (5) , Jörg Hofmann (6) , Georges Phillippe Pageaux (7) , Christelle Barbet (8) , Valerie Moal (9, 10, 11) , Lionel Couzi (12) , Thomas Horvatits (13) , Robert de Man (14) , Elisabeth Cassuto (15) , Ahmed Elsharkawy (16) , Annelies Riezebos-Brilman (17) , Anne Scemla (18) , Sophie Hillaire (19) , Mhairi Donnelly (20) , Sylvie Radenne (21) , Johnny Sayegh (22) , Cyril Garrouste (23) , Jérôme Dumortier (24) , François Glowaki (25) , Marie Matignon (26) , Audrey Coilly (27) , Lucile Figueres (28) , Christiane Mousson (29) , Anne Minello (30) , Sébastien Dharancy (31) , Jean Philippe Rerolle (32) , Pascal Lebray (33) , Isabelle Etienne (34) , Peggy Perrin (35) , Mira Choi (6) , Marion Olivier (2) , Jacques Izopet (2) , J Bellière , O. Cointault (1) , Arnaud del Bello (36) , L Espostio , A Hebral , L Lavayssière , S Lhomme , J Mansuy , H Wedemeyer , P Nickel , M. Bismuth (7) , K Stefic , M. Buchler (8) , L D’alteroche , P. Colson (9, 11) , S Bufton , C Ramière , P. Trimoulet (37) , S Pischke , E Todesco , R Sberro Soussan , C Legendre , V. Mallet , I Johannessen , K Simpson

1 Service de Néphrologie - Hypertension Artérielle Dialyse - Transplantation
2 CPTP - Centre de Physiopathologie Toulouse Purpan
3 CHU Toulouse - Centre Hospitalier Universitaire de Toulouse
4 UT3 - Université Toulouse III - Paul Sabatier
5 MHH - Hannover Medical School [Hannover]
6 Charité - UniversitätsMedizin = Charité - University Hospital [Berlin]
7 Département d'Hépato-Gastroentérologie et de Transplantation Hépatique [CHU Saint-Eloi]
8 Service de néphrologie et immunologie clinique [CHRU Tours]
9 MEPHI - Microbes évolution phylogénie et infections
10 APHM - Assistance Publique - Hôpitaux de Marseille
11 IHU Marseille - Institut Hospitalier Universitaire Méditerranée Infection
12 CHU Bordeaux [Bordeaux]
13 UKE - Universitaetsklinikum Hamburg-Eppendorf = University Medical Center Hamburg-Eppendorf [Hamburg]
14 Erasmus MC - Erasmus University Medical Center [Rotterdam]
15 CHU Nice - Centre Hospitalier Universitaire de Nice
16 University Hospitals Birmingham [Birmingham, Royaume-Uni]
17 UMCG - University Medical Center Groningen [Groningen]
18 Réseau CENTAURE
19 Hôpital Foch [Suresnes]
20 Royal Infirmary of Edinburgh
21 Service d'Hépatologie [Hôpital de la Croix-Rousse - HCL]
22 CHU Angers - Centre Hospitalier Universitaire d'Angers
23 CHU Clermont-Ferrand
24 Hôpital Edouard Herriot [CHU - HCL]
25 CHRU Lille - Centre Hospitalier Régional Universitaire [Lille]
26 IMRB - Institut Mondor de Recherche Biomédicale
27 Hôpital Paul Brousse
28 CHU Nantes - Centre hospitalier universitaire de Nantes
29 Service de néphrologie (CHU de Dijon)
30 Service d'Hépato-Gastro-Entérologie (CHU de Dijon)
31 Hôpital Claude Huriez [Lille]
32 Service de Néphrologie, Dialyse, Transplantations [CHU Limoges]
33 Service d'Hépato-Gastro-Entérologie [CHU Pitié-Salpêtrière]
34 CHU Rouen
35 CHU Strasbourg
36 Département de Néphrologie et Transplantation d'organes [CHU Toulouse]
37 Service de virologie et d'immunologie biologique

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.

Keywords: Anemia; Hepatitis E virus; Organ transplantation; Ribavirin; Sustained virological response

Domains: Life Sciences [q-bio]; Microbiology and Parasitology; Virology; Life Sciences [q-bio]; Human health and pathology; Infectious diseases; Life Sciences [q-bio]; Human health and pathology; Hépatology and Gastroenterology; Life Sciences [q-bio]; Pharmaceutical sciences

Nassim Kamar, Florence Legrand-Abravanel, Patrick Behrendt, Jörg Hofmann, Georges Phillippe Pageaux, et al.. Ribavirin for Hepatitis E Virus Infection After Organ Transplantation: A Large European Retrospective Multicenter Study. Clinical Infectious Diseases, 2020, 71 (5), pp.1204-1211. ⟨10.1093/cid/ciz953⟩. ⟨hal-02465266⟩