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Mathematical/Computational Virology & Medicine
Plasma hepatitis E virus kinetics in solid organ transplant patients receiving ribavirin
Sebastien Lhomme, Swati Debroy, Nassim Kamar, Florence Abravanel, David Metsu, Olivier Marion, Chloé Dimeglio, Scott Cotler, Jacques Izopet, Harel Dahari
Hepatitis E virus (HEV) infection causes chronic hepatitis in solid organ transplant (SOT) recipients. Antiviral therapy consists of 3 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 3 [range:0-21] days, plasma HEV declined from a median baseline level of 6.12 [3.53-7.45] log copies/ml in 4 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. 25 (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 7 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 3 days, and an estimated HEV half-life of 2 days. Viral kinetic patterns were not associated with response to therapy, with the exception of a flat partial response.
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