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Comment
. 2022 May;76(5):1229-1231.
doi: 10.1016/j.jhep.2021.12.030. Epub 2022 Jan 5.

Mathematical modeling suggests that entry-inhibitor bulevirtide may interfere with hepatitis D virus clearance from circulation

Louis Shekhtman  1 , Scott J Cotler  2 , Alexander Ploss  3 , Harel Dahari  4
Affiliations
Comment

Mathematical modeling suggests that entry-inhibitor bulevirtide may interfere with hepatitis D virus clearance from circulation

Louis Shekhtman et al. J Hepatol. 2022 May.
No abstract available

Keywords: HDV kinetics; bulevirtide; mathematical modeling.

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Conflict of interest statement

Conflicts of interest The authors declare no conflicts of interest that pertain to this work. Please refer to the accompanying ICMJE disclosure forms for further details.

Figures

Fig. 1.
Fig. 1.
(a) Schematic and model equations (Eq. 1) of HDV infection and treatment. Target cells, T0, become HDV-infected cells, I, at rate β. Infected cells are then lost or die at rate δ. Infected cells also produce virions, V, at rate p. Virions in circulation are cleared at rate c. Bulevirtide (BLV) known mode of action (MOA) in blocking entry/infection is shown using solid green line (parameter η) and theoretical MOA are shown using dashed green lines (parameters θ representing reduced viral clearance and κp representing increase of viral production). Blocking HDV production by interferon-α (IFN), lonafarnib (LNF) or nucleic acid polymer (NAP) is shown using red symbols (parameter ε). (b) Model fitting, using Python version 3.7.4 and Scipy version 1.3.1, with measured HDV kinetics from patient 1 in [1] (symbols) assuming BLV MOA is blocking only viral infection (η~100%) does not fit the data well (dotted line). Assuming that in additional to BLV η~100%, viral clearance decreases (θ=66%, dashed line) or viral production increases (κp=3.5, solid line) fits the data well. Fixed parameters were c=0.42 day−1, p=10 virions/infected cell/day, and β=1e-7 mL ·virions−1·day−1. Initial conditions were set such that V0 equaled its value at the first data point, and I0 and T0 were set by steady state conditions as done in [6]. (c) Model simulations of HDV decline under antivirals that block HDV production (ε=95%, solid line) alone or in combination with BLV (ε=95%, η~100%) assuming a BLV-induced decrease in viral clearance of θ=66% (dashed line). We fixed δ=0.042 day−1 with other model parameters fixed as described in (b). (d) Same as (c) but with ε=50%.
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Comment on

References

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