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

被引：84

作者：

Kamar, Nassim ^{[1
]}

Abravanel, Florence ^{[2
]}

Behrendt, Patrick ^{[3
,4
]}

Hofmann, Jorg ^{[5
,6
]}

Pageaux, Georges Phillippe ^{[7
]}

Barbet, Christelle ^{[8
]}

Moal, Valerie ^{[9
]}

Couzi, Lionel ^{[10
]}

Horvatits, Thomas ^{[11
]}

De Man, Robert A. ^{[12
,13
]}

Cassuto, Elisabeth ^{[14
]}

Elsharkawy, Ahmed M. ^{[15
]}

Riezebos-Brilman, Annelies ^{[16
,37
]}

Scemla, Anne ^{[17
,18
]}

Hillaire, Sophie ^{[19
]}

Donnelly, Mhairi C. ^{[20
,21
]}

Radenne, Sylvie ^{[22
]}

Sayegh, Johnny ^{[23
]}

Garrouste, Cyril ^{[24
]}

Dumortier, Jerome ^{[25
]}

Glowaki, Francois ^{[26
]}

Matignon, Marie ^{[27
]}

Coilly, Audrey ^{[28
]}

Figueres, Lucile ^{[29
]}

Mousson, Christiane ^{[30
]}

Minello, Anne ^{[31
]}

Dharancy, Sebastien ^{[32
]}

Rerolle, Jean Philippe ^{[33
]}

Lebray, Pascal ^{[34
]}

Etienne, Isabelle ^{[35
]}

Perrin, Peggy ^{[36
]}

Choi, Mira ^{[5
,6
]}

Marion, Olivier ^{[2
]}

Izopet, Jacques ^{[2
]}

机构：

[1] Univ Paul Sabatier, Ctr Hosp Univ CHU Languor, INSERM,Dept Nephrol Dialysis & Organ Transplantat, U1043,Inst Federatif Rech Biomed Toulouse IFR BMT, Toulouse, France

[2] Univ Paul Sabatier, Dept Virol, IFR BMT, INSERM U1043, Toulouse, France

[3] Hannover Med Sch, Dept Gastroenterol Hepatol & Endocrinol, Hannover, Germany

[4] German Ctr Infect Res, Ctr Expt & Clin Infect Res, Inst Expt Virol, TWINCORE, Hannover, Germany

[5] Charite Univ Med Berlin, Dept Nephrol & Intens Care, Berlin, Germany

[6] Lab Berlin Charite Vivantes GmbH, Inst Virol, Berlin, Germany

[7] St Eloi Hosp, Dept Hepatol, Montpellier, France

[8] Univ Hosp, Bretonneau Hosp, Dept Nephrol & Clin Immunol, Tours, France

[9] Aix Marseille Univ, Hop Conception, AP HM,Ctr Nephrol & Transplantat Renate, Inst Hosp Univ Mediterranee Infect,Inst Rech Dev, Marseille, France

[10] CHU Bordeaux, Dept Nephrol & Transplantat, Bordeaux, France

[11] Univ Med Ctr Hamburg Eppendorf, Dept Med 1, Hamburg, Germany

[12] Erasmus MC, Dept Gastroenterol, Rotterdam, Netherlands

[13] Erasmus MC, Dept Hepatol, Rotterdam, Netherlands

[14] CHU Nice, Dept Nephrol & Transplantat, Chu Nice, France

[15] Univ Hosp Birmingham, Liver Unit, Birmingham, W Midlands, England

[16] Univ Groningen, Univ Med Ctr Groningen, Dept Med Microbiol, Groningen, Netherlands

[17] Hop Necker Enfants Malad, AP HP, Serv Nephrol Transplantat, Paris, France

[18] Univ Paris 05, Paris, France

[19] Hop Foch, Dept Hepatol, Suresnes, France

[20] Royal Infirm Edinburgh NHS Trust, Dept Hepatol, Edinburgh, Midlothian, Scotland

[21] Royal Infirm Edinburgh NHS Trust, Scottish Liver Transplant Unit, Edinburgh, Midlothian, Scotland

[22] CHU Croix Rousse, Dept Hepatol & Liver Transplantat, Lyon, France

[23] CHU Angers, Dept Nephrol & Transplantat, Angers, France

[24] CHU Clermont Ferrand, Dept Nephrol, Clermont Ferrand, France

[25] CHU Lyon, Edouard Herriot Hosp, Dept Hepatol, Lyon, France

[26] CHU Lille, Dept Nephrol, Lille, France

[27] Univ Paris Est Creteil, Grp Hosp Henri Mondor Albert Chenevier, AP HP,Dept Hosp Univ Virus Immunite Canc,Inst Mon, Nephrol & Renal Transplantat Dept,Equipe 21,INSER, Creteil, France

[28] Univ Paris Sud Paris Saclay, Hop Paul Brousse, AP HP, Ctr Hepatobiliaire,INSERM U1193, Villejuif, France

[29] CHU Nantes, Dept Nephrol & Clin Immunol, Nantes, France

[30] CHU Francois Mitterrand, Dept Nephrol, Dijon, France

[31] CHU Francois Mitterrand, Dept Hepatogastroenterol & Digest Oncol, Dijon, France

[32] Hop Claude Huriez, Serv Malad Appareil Digestif, INSERM Unite 995, Lille, France

[33] CHU Limoges, Dept Nephrol, Limoges, France

[34] Hop La Pitie Salpetriere, Dept Hepatol, Paris, France

[35] CHU Rouen, Dept Nephrol, Rouen, France

[36] CHU Strasbourg, Dept Nephrol, Strasbourg, France

[37] Univ Med Ctr Utrecht, Dept Med Microbiol, Utrecht, Netherlands

来源：

CLINICAL INFECTIOUS DISEASES | 2020年 / 71卷 / 05期

关键词：

organ transplantation; hepatitis E virus; ribavirin; sustained virological response; anemia; INTERFERON-ALPHA; IN-VITRO; REPLICATION; THERAPY; HEV; SOFOSBUVIR; POLYMERASE; MUTATION; PREDICTS;

D O I：

10.1093/cid/ciz953

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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.

引用

页码：1204 / 1211

页数：8

共 30 条

[1] Protracted Fecal Shedding of HEV During Ribavirin Therapy Predicts Treatment Relapse [J].

Abravanel, Florence ;

Lhomme, Sebastien ;

Rostaing, Lionel ;

Kamar, Nassim ;

Izopet, Jacques .

CLINICAL INFECTIOUS DISEASES, 2015, 60 (01) :96-99

[2] Genotype 3 Diversity and Quantification of Hepatitis E Virus RNA [J].

Abravanel, Florence ;

Sandres-Saune, Karine ;

Lhomme, Sebastien ;

Dubois, Martine ;

Mansuy, Jean-Michel ;

Izopet, Jacques .

JOURNAL OF CLINICAL MICROBIOLOGY, 2012, 50 (03) :897-902

[3]

Debing Y, 2016, J HEPATOL, V147, P1008

[4] A Mutation in the Hepatitis E Virus RNA Polymerase Promotes Its Replication and Associates With Ribavirin Treatment Failure in Organ Transplant Recipients [J].

Debing, Yannick ;

Gisa, Anett ;

Dallmeier, Kai ;

Pischke, Sven ;

Bremer, Birgit ;

Manns, Michael ;

Wedemeyer, Heiner ;

Suneetha, Pothakamuri Venkata ;

Neyts, Johan .

GASTROENTEROLOGY, 2014, 147 (05) :1008-+

[5] Ribavirin Inhibits In Vitro Hepatitis E Virus Replication through Depletion of Cellular GTP Pools and Is Moderately Synergistic with Alpha Interferon [J].

Debing, Yannick ;

Emerson, Suzanne U. ;

Wang, Yijin ;

Pan, Qiuwei ;

Balzarini, Jan ;

Dallmeier, Kai ;

Neyts, Johan .

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY, 2014, 58 (01) :267-273

[6] Sofosbuvir and Daclatasvir Anti-Viral Therapy Fails to Clear HEV Viremia and Restore Reactive T Cells in a HEV/HCV Co-Infected Liver Transplant Recipient [J].

Donnelly, Mhairi C. ;

Imlach, Stuart N. ;

Abravanel, Florence ;

Ramalingam, Sandeep ;

Johannessen, Ingolfur ;

Petrik, Juraj ;

Fraser, Alistair R. ;

Campbell, John D. M. ;

Bramley, Peter ;

Dalton, Harry R. ;

Hayes, Peter C. ;

Kamar, Nassim ;

Simpson, Kenneth J. .

GASTROENTEROLOGY, 2017, 152 (01) :300-301

[7] EASL Clinical Practice Guidelines on hepatitis E virus infection [J].

Dalton H.R. ;

Kamar N. ;

Baylis S.A. ;

Moradpour D. ;

Wedemeyer H. ;

Negro F. .

JOURNAL OF HEPATOLOGY, 2018, 68 (06) :1256-1271

[8] Prevalence of active hepatitis E virus infection and efficacy of ribavirin treatment in renal allograft recipients [J].

Friebus-Kardash, Justa ;

Eisenberger, Ute ;

Ackermann, Jessica ;

Kribben, Andreas ;

Witzke, Oliver ;

Wenzel, Juergen ;

Rohn, Hana ;

Fiedler, Melanie .

TRANSPLANT INFECTIOUS DISEASE, 2019, 21 (03)

[9] Hepatitis E virus and chronic hepatitis in organ-transplant recipients. [J].

Kamar, Nassim ;

Selves, Janick ;

Mansuy, Jean-Michel ;

Ouezzani, Leila ;

Peron, Jean-Marie ;

Guitard, Joelle ;

Cointault, Olivier ;

Esposito, Laure ;

Abravanel, Florence ;

Danjoux, Marie ;

Durand, Dominique ;

Vinel, Jean-Pierre ;

Izopet, Jacques ;

Rostaing, Lionel .

NEW ENGLAND JOURNAL OF MEDICINE, 2008, 358 (08) :811-817

[10] Hepatitis E virus infection [J].

Kamar, Nassim ;

Izopet, Jacques ;

Pavio, Nicole ;

Aggarwal, Rakesh ;

Labrique, Alain ;

Wedemeyer, Heiner ;

Dalton, Harry R. .

NATURE REVIEWS DISEASE PRIMERS, 2017, 3

← 1 2 3 →