{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T10:44:47Z","timestamp":1776681887052,"version":"3.51.2"},"reference-count":95,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,4,19]],"date-time":"2026-04-19T00:00:00Z","timestamp":1776556800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>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\u201392% of patients and normalization of alanine transaminase (ALT) in 48.8\u201374% of patients after 23\u2013144 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.<\/jats:p>","DOI":"10.3390\/v18040477","type":"journal-article","created":{"date-parts":[[2026,4,20]],"date-time":"2026-04-20T09:37:42Z","timestamp":1776677862000},"page":"477","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Clinical and Pathophysiological Considerations Related to the Impact of Bulevirtide, a New Entry Inhibitor, in HBV-HDV Infection"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0009-0008-3466-4717","authenticated-orcid":false,"given":"Raisa Eloise","family":"Barbu","sequence":"first","affiliation":[{"name":"Doctoral School of Biomedical Sciences, \u2018Dun\u0103rea de Jos\u2019 University of Gala\u021bi, 800008 Gala\u021bi, Romania"},{"name":"Faculty of Medicine and Pharmacy, Research Centre in the Medical-Pharmaceutical Field, \u2018Dun\u0103rea de Jos\u2019 University of Gala\u021bi, 800008 Gala\u021bi, Romania"},{"name":"Clinical Medical Department, Faculty of Medicine and Pharmacy, \u2018Dun\u0103rea de Jos\u2019 University of Gala\u021bi, 800008 Gala\u021bi, Romania"},{"name":"\u2018Sf. Ioan\u2019 Clinical Hospital for Children, 800487 Gala\u021bi, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mariana Daniela","family":"Ignat","sequence":"additional","affiliation":[{"name":"Doctoral School of Biomedical Sciences, \u2018Dun\u0103rea de Jos\u2019 University of Gala\u021bi, 800008 Gala\u021bi, Romania"},{"name":"Faculty of Medicine and Pharmacy, Research Centre in the Medical-Pharmaceutical Field, \u2018Dun\u0103rea de Jos\u2019 University of Gala\u021bi, 800008 Gala\u021bi, Romania"},{"name":"Clinical Medical Department, Faculty of Medicine and Pharmacy, \u2018Dun\u0103rea de Jos\u2019 University of Gala\u021bi, 800008 Gala\u021bi, Romania"},{"name":"\u2018Sf. Cuv. Parascheva\u2019 Clinical Hospital of Infectious Diseases, 800179 Gala\u021bi, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1125-8774","authenticated-orcid":false,"given":"Roxana Elena","family":"Bogdan Goroftei","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Pharmacy, Research Centre in the Medical-Pharmaceutical Field, \u2018Dun\u0103rea de Jos\u2019 University of Gala\u021bi, 800008 Gala\u021bi, Romania"},{"name":"\u2018Sf. Ioan\u2019 Clinical Hospital for Children, 800487 Gala\u021bi, Romania"},{"name":"Depatment of Morphofunctional Science, Faculty of Medicine and Pharmacy, \u2018Dun\u0103rea de Jos\u2019 University of Gala\u021bi, 800008 Gala\u021bi, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexia Anastasia \u0218tefania","family":"Balt\u0103","sequence":"additional","affiliation":[{"name":"Doctoral School of Biomedical Sciences, \u2018Dun\u0103rea de Jos\u2019 University of Gala\u021bi, 800008 Gala\u021bi, Romania"},{"name":"Faculty of Medicine and Pharmacy, Research Centre in the Medical-Pharmaceutical Field, \u2018Dun\u0103rea de Jos\u2019 University of Gala\u021bi, 800008 Gala\u021bi, Romania"},{"name":"\u2018Sf. Apostol Andrei\u2019 Clinical Emergency County Hospital, 800578 Gala\u021bi, Romania"},{"name":"Medical Department, Faculty of Medicine and Pharmacy, \u2018Dun\u0103rea de Jos\u2019 University of Gala\u021bi, 800008 Gala\u021bi, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-6620-7851","authenticated-orcid":false,"given":"Valerii","family":"Lutenco","sequence":"additional","affiliation":[{"name":"Doctoral School of Biomedical Sciences, \u2018Dun\u0103rea de Jos\u2019 University of Gala\u021bi, 800008 Gala\u021bi, Romania"},{"name":"Faculty of Medicine and Pharmacy, Research Centre in the Medical-Pharmaceutical Field, \u2018Dun\u0103rea de Jos\u2019 University of Gala\u021bi, 800008 Gala\u021bi, Romania"},{"name":"\u2018Sf. Apostol Andrei\u2019 Clinical Emergency County Hospital, 800578 Gala\u021bi, Romania"},{"name":"Clinical Surgical Department, Faculty of Medicine and Pharmacy, \u2018Dun\u0103rea de Jos\u2019 University of Gala\u021bi, 800008 Gala\u021bi, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valentin","family":"Bulza","sequence":"additional","affiliation":[{"name":"Doctoral School of Biomedical Sciences, \u2018Dun\u0103rea de Jos\u2019 University of Gala\u021bi, 800008 Gala\u021bi, Romania"},{"name":"Faculty of Medicine and Pharmacy, Research Centre in the Medical-Pharmaceutical Field, \u2018Dun\u0103rea de Jos\u2019 University of Gala\u021bi, 800008 Gala\u021bi, Romania"},{"name":"Gala\u021bi Railways General Hospital, 800223 Gala\u021bi, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Valerian Ionu\u021b","family":"Stoian","sequence":"additional","affiliation":[{"name":"Doctoral School of Biomedical Sciences, \u2018Dun\u0103rea de Jos\u2019 University of Gala\u021bi, 800008 Gala\u021bi, Romania"},{"name":"Faculty of Medicine and Pharmacy, Research Centre in the Medical-Pharmaceutical Field, \u2018Dun\u0103rea de Jos\u2019 University of Gala\u021bi, 800008 Gala\u021bi, Romania"},{"name":"National Institute for Public Health, 050463 Bucharest, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Simona Claudia","family":"Cambrea","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, \u2018Ovidius\u2019 University, 900470 Constanta, Romania"},{"name":"Clinical Hospital of Infectious Diseases, 900178 Constanta, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4679-899X","authenticated-orcid":false,"given":"Elena","family":"Dumea","sequence":"additional","affiliation":[{"name":"Faculty of Medicine, \u2018Ovidius\u2019 University, 900470 Constanta, Romania"},{"name":"Clinical Hospital of Infectious Diseases, 900178 Constanta, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7602-8435","authenticated-orcid":false,"given":"Liliana","family":"Baroiu","sequence":"additional","affiliation":[{"name":"Faculty of Medicine and Pharmacy, Research Centre in the Medical-Pharmaceutical Field, \u2018Dun\u0103rea de Jos\u2019 University of Gala\u021bi, 800008 Gala\u021bi, Romania"},{"name":"Clinical Medical Department, Faculty of Medicine and Pharmacy, \u2018Dun\u0103rea de Jos\u2019 University of Gala\u021bi, 800008 Gala\u021bi, Romania"},{"name":"\u2018Sf. Cuv. Parascheva\u2019 Clinical Hospital of Infectious Diseases, 800179 Gala\u021bi, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,4,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"87","DOI":"10.3350\/kjhep.2011.17.2.87","article-title":"Epidemiology and prevention of hepatitis B virus infection","volume":"17","author":"Kwon","year":"2011","journal-title":"Korean J. Hepatol."},{"key":"ref_2","unstructured":"World Health Organization (2026, March 02). Hepatitis, B. 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