ArticleHepatology (Baltimore, Md.)2014
Understanding early serum hepatitis D virus and hepatitis B surface antigen kinetics during pegylated interferon-alpha therapy via mathematical modeling.
Article in Hepatology (Baltimore, Md.), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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35 citing papers in PubMed, 65 citations in OpenAlex.
- Durable virological response and functional cure of chronic hepatitis D after long-term peginterferon therapy.Alimentary pharmacology & therapeutics · 2021Trial
- Oral prenylation inhibition with lonafarnib in chronic hepatitis D infection: a proof-of-concept randomised, double-blind, placebo-controlled phase 2A trial.The Lancet. Infectious diseases · 2015Trial
- Long-term therapy of chronic delta hepatitis with peginterferon alfa.Alimentary pharmacology & therapeutics · 2014Trial
- Topological Stability and Transcritical Bifurcations in a Target-Cell-Limited Model of HBV-HDV Viral Interference.Viruses · 2026Article
- Clinical trial simulation of antiviral drugs.Journal of virology · 2026Review
- Interferon alpha induces a stronger antiviral effect than interferon lambda in HBV/HDV infected humanized mice.Virus research · 2024Article
- Effect of Peg-IFN on the viral kinetics of patients with HDV infection treated with bulevirtide.JHEP reports : innovation in hepatology · 2024Article
- Incorporating Intracellular Processes in Virus Dynamics Models.Microorganisms · 2024Review
- Multiscale modeling of HBV infection integrating intra- and intercellular viral propagation to analyze extracellular viral markers.PLoS computational biology · 2024Article
- Modelling HDV kinetics under the entry inhibitor bulevirtide suggests the existence of two HDV-infected cell populations.JHEP reports : innovation in hepatology · 2024Article
- Advances and Challenges in Managing Hepatitis D Virus: Evolving Strategies.Current hepatology reports · 2024Article
- Hepatitis D Virus and HBsAg Dynamics in the era of new Antiviral Treatments.Current gastroenterology reports · 2023Review
- Hepatitis B and Hepatitis D Viruses: A Comprehensive Update with an Immunological Focus.International journal of molecular sciences · 2022Review
- Modeling the Interplay between HDV and HBV in Chronic HDV/HBV Patients.Mathematics (Basel, Switzerland) · 2022Article
- Hepatitis D virus (HDV): investigational therapeutic agents in clinical trials.Expert opinion on investigational drugs · 2022Review
- Advances in Parameter Estimation and Learning from Data for Mathematical Models of Hepatitis C Viral Kinetics.Mathematics (Basel, Switzerland) · 2022Article
- Mathematical modeling suggests that entry-inhibitor bulevirtide may interfere with hepatitis D virus clearance from circulation.Journal of hepatology · 2022Article
- A Mathematical Analysis of HDV Genotypes: From Molecules to Cells.Mathematics (Basel, Switzerland) · 2021Article
- HBV/HDV Co-Infection: Epidemiological and Clinical Changes, Recent Knowledge and Future Challenges.Life (Basel, Switzerland) · 2021Review
- A Mathematical Model for early HBV and -HDV Kinetics during Anti-HDV Treatment.Mathematics (Basel, Switzerland) · 2021Article
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11 authors at 4 institutions in 2 countries.
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Abstract
unlabelledThere is little information on the early kinetics of hepatitis delta virus (HDV) and hepatitis B surface antigen (HBsAg) during interferon-α therapy. Here a mathematical model was developed and fitted to frequent HDV and HBsAg kinetic data from 10 patients during the first 28 weeks of pegylated-interferon-α2a (peg-IFN) therapy. Three patients achieved a complete virological response (CVR), defined as undetectable HDV 6 months after treatment stopped with loss of HBsAg and anti-HBsAg seroconversion. After initiation of therapy, a median delay of 9 days (interquartile range [IQR]: 5-15) was observed with no significant changes in HDV level. Thereafter, HDV declined in a biphasic manner, where a rapid first phase lasting for 25 days (IQR: 23-58) was followed by a slower or plateau second phase. The model predicts that the main effect of peg-IFN is to reduce HDV production/release with a median effectiveness of 96% (IQR: 93-99.8). Median serum HDV half-life (t1/2 ) was estimated as 2.9 days (IQR: 1.5-5.3) corresponding to a pretreatment production and clearance of about 10(10) (IQR: 10(9.7) -10(10.7) ) virions/day. None of the patients with flat second phase in HDV achieved CVR. HBsAg kinetics of decline paralleled the second phase of HDV decline consistent with HBsAg-productive-infected cells being the main source of production of HDV, with a median t1/2 of 135 days (IQR: 20-460). The interferon lambda-3 polymorphism (rs12979860) was not associated with kinetic parameters.
conclusionModeling results provide insights into HDV-host dynamics, the relationship between serum HBsAg levels and HBsAg-infected cells, IFN's mode of action, and its effectiveness. The observation that a flat second phase in HDV and HBsAg kinetics was associated with failure to achieve CVR provides the basis to develop early stopping rules during peg-IFN treatment in HDV-infected patients.
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