Hepatitis D Virus and HBsAg Dynamics in the era of new Antiviral Treatments.

Q1 Medicine Current Gastroenterology Reports Pub Date : 2023-12-01 Epub Date: 2023-10-11 DOI:10.1007/s11894-023-00901-9

Louis Shekhtman, Sarah Duehren, Ohad Etzion, Scott J Cotler, Harel Dahari

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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. 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.

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新抗病毒治疗时代的丁型肝炎病毒和HBsAg动态。

综述目的：丁型肝炎病毒（HDV）感染是最严重的慢性病毒性肝炎，没有美国食品药品监督管理局批准的治疗方法。开发有效的HDV治疗方法的进展正在加快。这篇综述强调了数学建模如何提高对抗病毒治疗过程中HDV-HBsAg宿主动力学的理解，并深入了解新抗病毒药物的疗效和作用模式（MOA）。最近的发现：聚乙二醇化干扰素-λ、博韦肽、核酸聚合物和/或洛那法尼对抗HDV生命周期各个阶段的临床试验揭示了新的病毒动力学模式，这些模式在聚乙二醇化干扰素α的标准治疗下没有观察到。模型显示循环HDV和HBsAg的半衰期分别为 ~ 1.7 d和 ~ 1.3天，分别估计了HDV和HBsAg在不同抗病毒治疗期间的相对反应，并深入了解了正在开发的治疗HDV的药物的疗效和MOA，这可以为反应指导治疗提供个性化治疗持续时间的信息。HDV和HBsAg动力学的数学建模为了解HDV病毒的生命周期、抗病毒治疗期间的HDV-HBsAg宿主动力学以及HDV新药的MOA提供了一个窗口。

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来源期刊

Current Gastroenterology Reports Medicine-Gastroenterology

CiteScore

7.80

自引率

0.00%

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期刊介绍： As the field of gastroenterology and hepatology rapidly evolves, the wealth of published literature can be overwhelming. The aim of the journal is to help readers stay abreast of such advances by offering authoritative, systematic reviews by leading experts. We accomplish this aim by appointing Section Editors who invite international experts to contribute review articles that highlight recent developments and important papers published in the past year. Major topics in gastroenterology are covered, including pediatric gastroenterology, neuromuscular disorders, infections, nutrition, and inflammatory bowel disease. These reviews provide clear, insightful summaries of expert perspectives relevant to clinical practice. An Editorial Board of internationally diverse members suggests topics of special interest to their country/region and ensures that topics are current and include emerging research. We also provide commentaries from well-known figures in the field.

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