title: Mutation in the Hepatitis E Virus Polymerase and Outcome of Ribavirin Therapy.
abstract: Hepatitis E virus (HEV) can lead to chronic infection in solid-organ transplant patients. Ribavirin is efficient for treatment of chronically infected patients. Recently, the1634R mutation in the HEV polymerase has been associated with treatment failure. However, it is unclear if this mutation can be used as a prognostic marker of treatment outcome. We studied the prevalence of the 1634R mutation in the HEV polymerase of patients starting ribavirin therapy, the influence of the 1634R variants on the viral response, the frequency of the 1634R mutation in patients whose treatment failed, and its impact on ribavirin retreatment. We analyzed pretreatment samples from 63 solid-organ transplant patients with chronic hepatitis E using deep sequencing; 42 patients had a sustained virologic response (SVR), and 21 were non-SVR patients. We detected the 1634R variant by deep sequencing in 36.5% (23/63) of the patients (proportions, 1.3 to 100%). The 1634R variant was detected in 31.0% (13/42) of baseline plasma samples from patients with SVR and in 47.6% (10/21) in the other patients (P = 0.2). The presence of this mutation did not influence the initial decrease in viral RNA. Lastly, a second prolonged ribavirin treatment led to SVR in 70% of the patients who initially did not have SVR, despite the presence of the 1634R variant. We conclude that the presence of the 1634R variant at ribavirin initiation does not lead to absolute ribavirin resistance. Although its proportion increased in patients whose treatment failed, the presence of the 1634R variant did not compromise the response to a second ribavirin treatment.
authors.affiliation: INSERM, UMR1043, Toulouse, France Department of Virology, CHU Purpan, Toulouse, France Université Paul Sabatier, Toulouse, France.
authors.forename: Sebastien
authors.initials: S
authors.lastname: Lhomme
authors.affiliation: INSERM, UMR1043, Toulouse, France Université Paul Sabatier, Toulouse, France Department of Nephrology, Dialysis and Organ Transplantation, CHU Rangueil, Toulouse, France.
authors.forename: Nassim
authors.initials: N
authors.lastname: Kamar
authors.affiliation: Department of Virology, CHU Purpan, Toulouse, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Nicot
authors.affiliation: Department of Virology, CHU Lapeyronie, Montpellier, France.
authors.forename: Jacques
authors.initials: J
authors.lastname: Ducos
authors.affiliation: Department of Gastroenterology, CHU Saint Eloi, Montpellier, France.
authors.forename: Michael
authors.initials: M
authors.lastname: Bismuth
authors.affiliation: Department of Nephrology, Dialysis and Organ Transplantation, CHU Lapeyronie, Montpellier, France.
authors.forename: Valerie
authors.initials: V
authors.lastname: Garrigue
authors.affiliation: Department of Virology, University Hospital, Caen, France.
authors.forename: Joelle
authors.initials: J
authors.lastname: Petitjean-Lecherbonnier
authors.affiliation: Department of Gastroenterology, University Hospital, Caen, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Ollivier
authors.affiliation: Department of Virology, University Hospital, Rouen, France.
authors.forename: Elodie
authors.initials: E
authors.lastname: Alessandri-Gradt
authors.affiliation: Department of Gastroenterology, University Hospital, Rouen, France.
authors.forename: Odile
authors.initials: O
authors.lastname: Goria
authors.affiliation: Department of Virology, University Hospital, Strasbourg, France.
authors.forename: Heidi
authors.initials: H
authors.lastname: Barth
authors.affiliation: Department of Nephrology-Transplantation, University Hospital, Strasbourg, France.
authors.forename: Peggy
authors.initials: P
authors.lastname: Perrin
authors.affiliation: INSERM, UMR1043, Toulouse, France Department of Virology, CHU Purpan, Toulouse, France Université Paul Sabatier, Toulouse, France.
authors.forename: Karine
authors.initials: K
authors.lastname: Saune
authors.affiliation: INSERM, UMR1043, Toulouse, France Department of Virology, CHU Purpan, Toulouse, France Université Paul Sabatier, Toulouse, France.
authors.forename: Martine
authors.initials: M
authors.lastname: Dubois
authors.affiliation: Department of Virology, CHU Purpan, Toulouse, France.
authors.forename: Romain
authors.initials: R
authors.lastname: Carcenac
authors.affiliation: Department of Virology, CHU Purpan, Toulouse, France.
authors.forename: Caroline
authors.initials: C
authors.lastname: Lefebvre
authors.affiliation: Department of Virology, CHU Purpan, Toulouse, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Jeanne
authors.affiliation: INSERM, UMR1043, Toulouse, France Department of Virology, CHU Purpan, Toulouse, France Université Paul Sabatier, Toulouse, France.
authors.forename: Florence
authors.initials: F
authors.lastname: Abravanel
authors.affiliation: INSERM, UMR1043, Toulouse, France Department of Virology, CHU Purpan, Toulouse, France Université Paul Sabatier, Toulouse, France izopet.j@chu-toulouse.fr.
authors.forename: Jacques
authors.initials: J
authors.lastname: Izopet
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000998:Antiviral Agents / Q000627:therapeutic use*; D001483:Base Sequence; D002648:Child; D005260:Female; D005819:Genetic Markers; D016751:Hepatitis E / Q000188:drug therapy* / Q000821:virology; D016752:Hepatitis E virus / Q000187:drug effects* / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics; D012367:RNA, Viral / Q000235:genetics; D012324:RNA-Dependent RNA Polymerase / Q000235:genetics*; D012254:Ribavirin / Q000627:therapeutic use*; D017423:Sequence Analysis, RNA; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D005819:Genetic Markers; D012367:RNA, Viral; D012254:Ribavirin; D012324:RNA-Dependent RNA Polymerase