ArticleJHEP reports : innovation in hepatology2024
Modelling HDV kinetics under the entry inhibitor bulevirtide suggests the existence of two HDV-infected cell populations.
Article in JHEP reports : innovation in hepatology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.
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Who cites it
5 citing papers in PubMed, 8 citations in OpenAlex.
- Phase 2 Randomised Study of Bulevirtide as Monotherapy or Combined With Peg-IFNα-2a as Treatment for Chronic Hepatitis Delta.Liver international : official journal of the International Association for the Study of the Liver · 2025Trial
- Modeling challenges of hepatitis D virus kinetics during bulevirtide-based therapy.JHEP reports : innovation in hepatology · 2025Article
- Exploring Predictive Factors for Bulevirtide Treatment Response in Hepatitis Delta-Positive Patients.Biomedicines · 2025Article
- Effect of Peg-IFN on the viral kinetics of patients with HDV infection treated with bulevirtide.JHEP reports : innovation in hepatology · 2024Article
- Hepatitis D Virus and HBsAg Dynamics in the era of new Antiviral Treatments.Current gastroenterology reports · 2023Review
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Authors and funding
12 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Background & Aims: Bulevirtide (BLV) was approved for the treatment of compensated chronic hepatitis D virus (HDV) infection in Europe in 2020. However, research into the effects of the entry inhibitor BLV on HDV-host dynamics is in its infancy. Methods: Eighteen patients with HDV under nucleos(t)ide analogue treatment for hepatitis B, with compensated cirrhosis and clinically significant portal hypertension, received BLV 2 mg/day. HDV RNA, alanine aminotransferase (ALT), and hepatitis B surface antigen (HBsAg) were measured at baseline, weeks 4, 8 and every 8 weeks thereafter. A mathematical model was developed to account for HDV, HBsAg and ALT dynamics during BLV treatment. Results: Median baseline HDV RNA, HBsAg, and ALT were 4.9 log IU/ml [IQR: 4.4-5.8], 3.7 log IU/ml [IQR: 3.4-3.9] and 106 U/L [IQR: 81-142], respectively. During therapy, patients fit into four main HDV kinetic patterns: monophasic (n = 2), biphasic (n = 10), flat-partial response (n = 4), and non-responder (n = 2). ALT normalization was achieved in 14 (78%) patients at a median of 8 weeks (range: 4-16). HBsAg remained at pre-treatment levels. Assuming that BLV completely (∼100%) blocks HDV entry, modeling indicated that two HDV-infected cell populations exist: fast HDV clearing (median t Conclusion: The entry inhibitor BLV provides a unique opportunity to understand HDV, HBsAg, ALT, and host dynamics. Impact and implications: Mathematical modeling of hepatitis D virus (HDV) treatment with the entry inhibitor bulevirtide (BLV) provides a novel window into the dynamics of HDV RNA and alanine aminotransferase. Kinetic data from patients treated with BLV monotherapy can be explained by hepatocyte populations with different basal HDV clearance rates and non-cytolytic clearance of infected cells. While further studies are needed to test and refine the kinetic characterization described here, this study provides a new perspective on viral dynamics, which could inform evolving treatment strategies for HDV.
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