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

Journal of Hepatology

 January 2022

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Loglio and colleagues, reported a unique hepatitis D virus (HDV) RNA kinetic case study under entry-inhibitor Bulevirtide (BLV) monotherapy in 3 patients. Historically, mathematical modeling of viral hepatitis kinetics predicts a monophasic viral decline under antiviral treatment that blocks virus infection. Modeling suggests that the monophasic decline is driven by the rate of virus productive-infected cells loss/death(parameter δ, Fig.1a). Indeed, assuming that BLV’s only mode of action(MOA) is blocking HDV entry/infection(assuming η∼100%, Fig.1a), the model(Fig.1a) fits well the measured HDV data in patients 2 and 3(Fig.S1), but not in patient 1 in whom a transient viral increase was seen during the first 4 weeks of treatment, consisting of a 0.4 log increase from pretreatment HDV-RNA level at week 2, followed by a monophasic HDV decline onwards(Fig.1b). Such a transient viral increase can also be noticed in several hepatitis B virus (HBV) mono-infected patients treated with BLV 10 mg/day, suggesting that this transient viral increase may occur in some patients treated with BLV for both HBV and HDV. The nature of this early transient viral increase phenomenon under BLV treatment is not known.

 Louis Shekhtman, Scott J. Cotler, Alexander Ploss, Harel Dahari