{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T16:26:26Z","timestamp":1782491186788,"version":"3.54.5"},"reference-count":23,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2025,1,24]],"date-time":"2025-01-24T00:00:00Z","timestamp":1737676800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100009139","name":"Deutsches Zentrum f\u00fcr Infektionsforschung","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009139","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background and Aim<\/jats:title><jats:p>Bulevirtide (BLV) leads to beneficial virologic and biochemical responses when given alone to treat hepatitis delta virus (HDV) infection, which causes the most severe form of chronic viral hepatitis. We evaluated 48\u2009weeks of BLV monotherapy, BLV\u2009+\u2009tenofovir disoproxil fumarate (TDF) and BLV\u2009+\u2009pegylated interferon alfa\u20102a (Peg\u2010IFN\u03b1\u20102a), with 24\u2010week follow\u2010up.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Ninety patients were enrolled into six arms of 15 each (A\u2013F); 60 patients were included in the main randomisation (arms A\u2013D), and 30 patients (arms E\u2013F) were randomised to the extension phase: (A) Peg\u2010IFN\u03b1\u20102a 180\u2009\u03bcg once weekly (QW); (B) BLV 2\u2009mg once daily (QD)\u2009+\u2009Peg\u2010IFN\u03b1\u20102a 180\u2009\u03bcg QW; (C) BLV 5\u2009mg QD\u2009+\u2009Peg\u2010IFN\u03b1\u20102a 180\u2009\u03bcg QW; (D) BLV 2\u2009mg QD; (E) BLV 10\u2009mg QD\u2009+\u2009Peg\u2010IFN\u03b1\u20102a 180\u2009\u03bcg QW and (F) BLV 10\u2009mg (5\u2009mg twice daily)\u2009+\u2009TDF QD. The primary endpoint was undetectable HDV RNA at week (W)72.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>At W72, 53%, 27%, 7%, 7% and 33% of patients achieved undetectable HDV RNA in arms B, C, D, E and F, respectively, versus 0% in arm A. More arm B versus A patients had a &gt;\u20091 log<jats:sub>10<\/jats:sub> IU\/mL decline in or loss of hepatitis B surface antigen (HBsAg) at W72 (<jats:italic>p<\/jats:italic>\u2009=\u20090.017), including four patients with loss of HBsAg. Bile acid elevations were dose\u2010dependent and reversible following the completion of BLV treatment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>BLV combined with Peg\u2010IFN\u03b1\u20102a was well tolerated and resulted in high rates of HDV RNA undetectability off\u2010treatment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Trial Registration<\/jats:title><jats:p>NCT02888106<\/jats:p><\/jats:sec>","DOI":"10.1111\/liv.70008","type":"journal-article","created":{"date-parts":[[2025,1,24]],"date-time":"2025-01-24T12:48:56Z","timestamp":1737722936000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Phase 2 Randomised Study of Bulevirtide as Monotherapy or Combined With Peg\u2010<scp>IFN\u03b1<\/scp>\u20102a as Treatment for Chronic Hepatitis Delta"],"prefix":"10.1111","volume":"45","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-1026-7476","authenticated-orcid":false,"given":"Pietro","family":"Lampertico","sequence":"first","affiliation":[{"name":"Division of Gastroenterology and Hepatology Foundation IRCCS Ca\u2019 Granda Ospedale Maggiore Policlinico  Milan Italy"},{"name":"CRC \u201cA. M. And A. Migliavacca\u201d Center for Liver Disease, Department of Pathophysiology and Transplantation University of Milan  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pavel O.","family":"Bogomolov","sequence":"additional","affiliation":[{"name":"State Budgetary Institution of Health Care of Moscow Region Moscow Regional Research Clinical Institute n.a. M.F. Vladimirsky, Moscow  Moscow Russian Federation"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vladimir","family":"Chulanov","sequence":"additional","affiliation":[{"name":"National Medical Research Center of Tuberculosis and Infectious Diseases  Moscow Russian Federation"},{"name":"Sechenov First Moscow State Medical University  Moscow Russian Federation"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatiana","family":"Stepanova","sequence":"additional","affiliation":[{"name":"Limited Liability Company \u201cClinic of Modern Medicine,\u201d Moscow  Moscow Russian Federation"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Viacheslav","family":"Morozov","sequence":"additional","affiliation":[{"name":"LLC Medical Company Hepatolog  Samara Russian Federation"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lena","family":"Allweiss","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine University Medical Center Hamburg\u2010Eppendorf  Hamburg Germany"},{"name":"German Center for Infection Research (DZIF), Hamburg\u2010L\u00fcbeck\u2010Borstel\u2010Riems  Borstel Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0073-6689","authenticated-orcid":false,"given":"Maura","family":"Dandri","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine University Medical Center Hamburg\u2010Eppendorf  Hamburg Germany"},{"name":"German Center for Infection Research (DZIF), Hamburg\u2010L\u00fcbeck\u2010Borstel\u2010Riems  Borstel Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J\u00fcrgen","family":"Burhenne","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology and Pharmacoepidemiology Heidelberg University Hospital  Heidelberg Germany"},{"name":"German Center for Infection Research (DZIF)  Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antje","family":"Blank","sequence":"additional","affiliation":[{"name":"Department of Clinical Pharmacology and Pharmacoepidemiology Heidelberg University Hospital  Heidelberg Germany"},{"name":"German Center for Infection Research (DZIF)  Heidelberg Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandra","family":"Ciesek","sequence":"additional","affiliation":[{"name":"Institute for Medical Virology University Hospital Frankfurt, Goethe University Frankfurt  Frankfurt Germany"},{"name":"German Centre for Infection Research External Partner Site  Frankfurt Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carina","family":"Elsner","sequence":"additional","affiliation":[{"name":"Institute for Virology University Hospital Essen, University of Duisburg\u2010Essen  Essen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulf","family":"Dittmer","sequence":"additional","affiliation":[{"name":"Institute for Virology University Hospital Essen, University of Duisburg\u2010Essen  Essen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"An","sequence":"additional","affiliation":[{"name":"Gilead Sciences Inc.  Foster City California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-3873-096X","authenticated-orcid":false,"given":"Dmitry","family":"Manuilov","sequence":"additional","affiliation":[{"name":"Gilead Sciences Inc.  Foster City California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ben L.","family":"Da","sequence":"additional","affiliation":[{"name":"Gilead Sciences Inc.  Foster City California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John F.","family":"Flaherty","sequence":"additional","affiliation":[{"name":"Gilead Sciences Inc.  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