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Plasma Hepatitis E Virus Kinetics in Solid Organ Transplant Patients Receiving Ribavirin

1
National Reference Center for Hepatitis E, Department of Virology, Federative Institute of Biology, CHU Purpan, INSERM U1043, University Toulouse III-Paul Sabatier, 31300 Toulouse, France
2
The Program for Experimental & Theoretical Modeling, Division of Hepatology, Loyola University Medical Center, Maywood, IL 60153, USA
3
Department of Mathematics and Computational Science, University of South Carolina-Beaufort, Bluffton, SC 29909, USA
4
Department of Nephrology and Organ Transplantation, CHU Rangueil, INSERM U1043, University Toulouse III-Paul Sabatier, 31300 Toulouse, France
5
Department of Pharmacokinetics and Toxicology, Federative Institute of Biology, CHU Purpan, INTHERES, INRA, ENVT, University Toulouse III-Paul Sabatier, 31300 Toulouse, France
*
Authors to whom correspondence should be addressed.
Viruses 2019, 11(7), 630; https://doi.org/10.3390/v11070630
Received: 17 June 2019 / Revised: 6 July 2019 / Accepted: 8 July 2019 / Published: 9 July 2019
(This article belongs to the Special Issue Hepatitis E Virus)
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Abstract

Hepatitis E virus (HEV) infection causes chronic hepatitis in solid organ transplant (SOT) recipients. Antiviral therapy consists of three months of ribavirin, although response rates are not optimal. We characterized plasma HEV kinetic patterns in 41 SOT patients during ribavirin therapy. After a median pharmacological delay of three (range: 0–21) days, plasma HEV declined from a median baseline level of 6.12 (3.53–7.45) log copies/mL in four viral kinetic patterns: (i) monophasic (n = 18), (ii) biphasic (n = 13), (iii) triphasic (n = 8), and (iv) flat-partial response (n = 2). The mean plasma HEV half-life was estimated to be 2.0 ± 0.96 days. Twenty-five patients (61%) had a sustained virological response (SVR) 24 weeks after completion of therapy. Viral kinetic patterns (i)–(iii) were not associated with baseline characteristics or outcome of therapy. A flat-partial response was associated with treatment failure. All patients with a log concentration decrease of plasma HEV at day seven of >15% from baseline achieved SVR. In conclusion, viral kinetic modeling of plasma HEV under ribavirin therapy showed, for the first time, four distinct kinetic profiles, a median pharmacologic delay of three days, and an estimated HEV half-life of two days. Viral kinetic patterns were not associated with response to therapy, with the exception of a flat-partial response. View Full-Text
Keywords: hepatitis E virus; viral kinetics; ribavirin; chronic infection hepatitis E virus; viral kinetics; ribavirin; chronic infection
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MDPI and ACS Style

Lhomme, S.; DebRoy, S.; Kamar, N.; Abravanel, F.; Metsu, D.; Marion, O.; Dimeglio, C.; Cotler, S.J.; Izopet, J.; Dahari, H. Plasma Hepatitis E Virus Kinetics in Solid Organ Transplant Patients Receiving Ribavirin. Viruses 2019, 11, 630.

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