Abstract
Purpose of Review: Hepatitis D virus (HDV) infection is the most severe form of chronic viral hepatitis, with no FDA-approved therapy. Progress in the development of effective HDV treatments is accelerating. This review highlights how mathematical modeling is improving understanding of HDV-HBsAg-host dynamics during antiviral therapy and generating insights into the efficacy and modes of action (MOA) of new antiviral agents. Recent Findings: Clinical trials with pegylated-interferon-λ, bulevertide, nucleic acid polymers, and/or lonafarnib against various steps of the HDV-life cycle have revealed new viral-kinetic patterns that were not observed under standard treatment with pegylated-interferon-α. Modeling indicated that the half-lives of circulating HDV and HBsAg are ~ 1.7 d and ~ 1.3 d, respectively, estimated the relative response of HDV and HBsAg during different antiviral therapies, and provided insights into the efficacy and MOA of drugs in development for treating HDV, which can inform response-guided therapy to individualize treatment duration. Summary: Mathematical modeling of HDV and HBsAg kinetics provides a window into the HDV virus lifecycle, HDV-HBsAg-host dynamics during antiviral therapy, and the MOA of new drugs for HDV.
Original language | English |
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Pages (from-to) | 401-412 |
Number of pages | 12 |
Journal | Current Gastroenterology Reports |
Volume | 25 |
Issue number | 12 |
Early online date | 11 Oct 2023 |
DOIs | |
State | Published - Dec 2023 |
Bibliographical note
Publisher Copyright:© 2023, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
Funding
The current study was supported by NIH grants R01AI144112 and R01AI146917. The funders had no role in the study design, and analysis, the decision to publish, or preparation of the manuscript.
Funders | Funder number |
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National Institutes of Health | |
Office of Research Infrastructure Programs, National Institutes of Health | R01AI146917, R01AI144112 |
Keywords
- Bulevertide
- Hepatitis D virus
- Lonafarnib
- Mathematical modeling
- Nucleic acid polymers
- Pegylated-interferon-α
- Pegylated-interferon-λ
- Response-guided therapy