Clinical and Pathophysiological Considerations Related to the Impact of Bulevirtide, a New Entry Inhibitor, in HBV-HDV Infection.

Raisa Eloise Barbu, Mariana Daniela Ignat, Roxana Elena Bogdan Goroftei, Alexia Anastasia Ștefania Baltă, Valerii Lutenco, Valentin Bulza, Valerian Ionuț Stoian, Simona Claudia Cambrea, Elena Dumea, Liliana Baroiu

Journal: Viruses 2026;18(4):

PMID: 42043266

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Abstract

This review critically examines the inhibition of viral entry as an emerging disease-modifying strategy in chronic hepatitis B (HBV) and delta (HDV) virus infection, with particular emphasis on bulevirtide, the first-in-class of the sodium taurocholate cotransporting polypeptide entry inhibitor. This paper summarizes the analysis of 7 clinical trials that either underpinned the registration of bulevirtide or are important European real-life trials. We synthesize virological, pathophysiological and clinical evidence, highlighting the impact of this novel bulevirtide-based therapy on virological control, liver inflammation, fibrosis dynamics and long-term prognosis, as well as the limitations of this therapy. The observation of these trials is a greater than 2 log decrease from baseline in hepatitis D virus ribonucleic acid (HDV RNA) in 54-92% of patients and normalization of alanine transaminase (ALT) in 48.8-74% of patients after 23-144 weeks of treatment, and a significant decrease in liver fibrosis, as quantified by Fibroscan, at 12 months of treatment. The conclusion of the study is that this therapy represents an important leap in the etiological approach to chronic HDV infection and in improving the prognosis of these patients, but future clinical studies are needed to define the criteria for discontinuation of therapy, the long-term impact, as well as studies targeting new therapies that can intervene in other stages of the HDV and HBV life cycle not only to achieve HDV RNA negativity but also HBsAg clearance.

Address: Doctoral School of Biomedical Sciences, 'Dunărea de Jos' University of Galați, 800008 Galați, Romania.; Faculty of Medicine and Pharmacy, Research Centre in the Medical-Pharmaceutical Field, 'Dunărea de Jos' University of Galați, 800008 Galați, Romania.; Clinical Medical Department, Faculty of Medicine and Pharmacy, 'Dunărea de Jos' University of Galați, 800008 Galați, Romania.; 'Sf. Ioan' Clinical Hospital for Children, 800487 Galați, Romania.; Doctoral School of Biomedical Sciences, 'Dunărea de Jos' University of Galați, 800008 Galați, Romania.; Faculty of Medicine and Pharmacy, Research Centre in the Medical-Pharmaceutical Field, 'Dunărea de Jos' University of Galați, 800008 Galați, Romania.; Clinical Medical Department, Faculty of Medicine and Pharmacy, 'Dunărea de Jos' University of Galați, 800008 Galați, Romania.; 'Sf. Cuv. Parascheva' Clinical Hospital of Infectious Diseases, 800179 Galați, Romania.; Faculty of Medicine and Pharmacy, Research Centre in the Medical-Pharmaceutical Field, 'Dunărea de Jos' University of Galați, 800008 Galați, Romania.; 'Sf. Ioan' Clinical Hospital for Children, 800487 Galați, Romania.; Depatment of Morphofunctional Science, Faculty of Medicine and Pharmacy, 'Dunărea de Jos' University of Galați, 800008 Galați, Romania.; Doctoral School of Biomedical Sciences, 'Dunărea de Jos' University of Galați, 800008 Galați, Romania.; Faculty of Medicine and Pharmacy, Research Centre in the Medical-Pharmaceutical Field, 'Dunărea de Jos' University of Galați, 800008 Galați, Romania.; 'Sf. Apostol Andrei' Clinical Emergency County Hospital, 800578 Galați, Romania.; Medical Department, Faculty of Medicine and Pharmacy, 'Dunărea de Jos' University of Galați, 800008 Galați, Romania.; Doctoral School of Biomedical Sciences, 'Dunărea de Jos' University of Galați, 800008 Galați, Romania.; Faculty of Medicine and Pharmacy, Research Centre in the Medical-Pharmaceutical Field, 'Dunărea de Jos' University of Galați, 800008 Galați, Romania.; 'Sf. Apostol Andrei' Clinical Emergency County Hospital, 800578 Galați, Romania.; Clinical Surgical Department, Faculty of Medicine and Pharmacy, 'Dunărea de Jos' University of Galați, 800008 Galați, Romania.; Doctoral School of Biomedical Sciences, 'Dunărea de Jos' University of Galați, 800008 Galați, Romania.; Faculty of Medicine and Pharmacy, Research Centre in the Medical-Pharmaceutical Field, 'Dunărea de Jos' University of Galați, 800008 Galați, Romania.; Galați Railways General Hospital, 800223 Galați, Romania.; Doctoral School of Biomedical Sciences, 'Dunărea de Jos' University of Galați, 800008 Galați, Romania.; Faculty of Medicine and Pharmacy, Research Centre in the Medical-Pharmaceutical Field, 'Dunărea de Jos' University of Galați, 800008 Galați, Romania.; National Institute for Public Health, 050463 Bucharest, Romania.; Faculty of Medicine, 'Ovidius' University, 900470 Constanta, Romania.; Clinical Hospital of Infectious Diseases, 900178 Constanta, Romania.; Faculty of Medicine and Pharmacy, Research Centre in the Medical-Pharmaceutical Field, 'Dunărea de Jos' University of Galați, 800008 Galați, Romania.; Clinical Medical Department, Faculty of Medicine and Pharmacy, 'Dunărea de Jos' University of Galați, 800008 Galați, Romania.; 'Sf. Cuv. Parascheva' Clinical Hospital of Infectious Diseases, 800179 Galați, Romania.

DOI: 10.3390/v18040477

MeSH Terms: Humans, Antiviral Agents, Hepatitis Delta Virus, Hepatitis B virus, Hepatitis B, Chronic, Virus Internalization, Clinical Trials as Topic, Hepatitis D, Chronic, Peptides, Nucleic Acids, Polymers