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Antimicrob Agents Chemother. 2015 Dec 28;60(3):1608-14. doi: 10.1128/AAC.02496-15.

Mutation in the Hepatitis E Virus Polymerase and Outcome of Ribavirin Therapy.

Author information

1
INSERM, UMR1043, Toulouse, France Department of Virology, CHU Purpan, Toulouse, France Université Paul Sabatier, Toulouse, France.
2
INSERM, UMR1043, Toulouse, France Université Paul Sabatier, Toulouse, France Department of Nephrology, Dialysis and Organ Transplantation, CHU Rangueil, Toulouse, France.
3
Department of Virology, CHU Purpan, Toulouse, France.
4
Department of Virology, CHU Lapeyronie, Montpellier, France.
5
Department of Gastroenterology, CHU Saint Eloi, Montpellier, France.
6
Department of Nephrology, Dialysis and Organ Transplantation, CHU Lapeyronie, Montpellier, France.
7
Department of Virology, University Hospital, Caen, France.
8
Department of Gastroenterology, University Hospital, Caen, France.
9
Department of Virology, University Hospital, Rouen, France.
10
Department of Gastroenterology, University Hospital, Rouen, France.
11
Department of Virology, University Hospital, Strasbourg, France.
12
Department of Nephrology-Transplantation, University Hospital, Strasbourg, France.
13
INSERM, UMR1043, Toulouse, France Department of Virology, CHU Purpan, Toulouse, France Université Paul Sabatier, Toulouse, France izopet.j@chu-toulouse.fr.

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.

PMID:
26711757
PMCID:
PMC4775994
DOI:
10.1128/AAC.02496-15
[Indexed for MEDLINE]
Free PMC Article

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