{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,21]],"date-time":"2026-08-21T11:35:51Z","timestamp":1787312151649,"version":"build-2736575974"},"reference-count":34,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,4,28]],"date-time":"2025-04-28T00:00:00Z","timestamp":1745798400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/100019180","name":"HORIZON EUROPE European Research Council","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100019180","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2025,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and Aims<\/jats:title>\n                    <jats:p>HDV exploits HBV surface\u2010protein (HBsAg) for entering into hepatocytes. HBsAg consists of 3 isoforms: Large\u2010 (L\u2010HBs, predominantly present in virions and mediating binding to NTCP\u2010receptor), Middle\u2010 (M\u2010HBs) and Small\u2010HBsAg (S\u2010HBs). Here, we investigated the kinetics of HBs isoforms under bulevirtide treatment (BLV).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>67 consecutive patients with HDV\u2010related compensated cirrhosis starting BLV 2\u2009mg\/day were enrolled. L\u2010HBs, M\u2010HBs and S\u2010HBs were quantified by ad\u2010hoc ELISAs in baseline and week 48 (W48) samples.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      At baseline, median (IQR) HDV\u2010RNA was 5.1 (4.3\u20135.7) log IU\/mL while median (IQR) S\u2010HBs, M\u2010HBs and L\u2010HBs levels were 3801 (1401\u20137462), 743 (211\u20131710) and 5 (1\u201313) ng\/mL. At W48, virological responses (VR) were observed in 72% (48\/67) of patients, while 25.4% (17\/67) achieved undetectable HDV\u2010RNA (11\/17 with ALT\u2010normalisation). A decline of S\u2010HBs, M\u2010HBs and L\u2010HBs levels was observed in 51%, 63% and 31% of patients (median [IQR] decline: 961 [461\u20131985], 258 [68\u2013626] and 4 [2\u201012] ng\/mL). Notably, patients with undetectable HDV\u2010RNA at W48 had baseline L\u2010HBs and S\u2010HBs levels lower than patients not achieving this end\u2010point (1 [0.3\u20137] vs. 6 [2\u201013] ng\/mL,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.04 and 1570 [369\u20135185] vs. 4015 [1646\u20138687] ng\/mL,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.002).\n                    <\/jats:p>\n                    <jats:p>\n                      By AUROC, patients with baseline L\u2010HBs &lt;\u20093\u2009ng\/mL or S\u2010HBs &lt;\u20093400\u2009ng\/mL were more likely to achieve HDV\u2010RNA undetectability at W48 (39.3% vs. 15.8%,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.04 and 38.7% vs. 13.9%,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.03).\n                    <\/jats:p>\n                    <jats:p>\n                      Furthermore, the combination of pre\u2010treatment L\u2010HBs &lt;\u20093\u2009ng\/mL\u2009+\u2009HDV\u2010RNA\u2009&lt;\u20095logIU\/mL and S\u2010HBs &lt;\u20093400\u2009ng\/mL\u2009+\u2009HDV\u2010RNA &lt;\u20095logIU\/mL was the best predictor for achieving undetectable HDV\u2010RNA at W48 (56.3% vs. 15.7%,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.002 and 60% vs. 11%,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u20090.001).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Quantification of L\u2010HBs and of S\u2010HBs, along with HDV\u2010RNA, may reflect the burden of circulating infectious virions in HBV\/HDV co\u2010infection, providing a promising tool to identify patients more likely to respond to BLV.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/liv.70094","type":"journal-article","created":{"date-parts":[[2025,4,28]],"date-time":"2025-04-28T05:54:13Z","timestamp":1745819653000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["<scp>HBsAg<\/scp>\n                    Isoforms as Innovative Biomarkers in Predicting Virological Response to Bulevirtide in Patients With Chronic Hepatitis D"],"prefix":"10.1111","volume":"45","author":[{"given":"Stefano","family":"D'Anna","sequence":"first","affiliation":[{"name":"Department of Biology University of Rome Tor Vergata  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Romina","family":"Salpini","sequence":"additional","affiliation":[{"name":"Department of Biology University of Rome Tor Vergata  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9899-4669","authenticated-orcid":false,"given":"Elisabetta","family":"Degasperi","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lorenzo","family":"Piermatteo","sequence":"additional","affiliation":[{"name":"Department of Biology University of Rome Tor Vergata  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Floriana","family":"Facchetti","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dana","family":"Sambarino","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giulia","family":"Torre","sequence":"additional","affiliation":[{"name":"Department of Biology University of Rome Tor Vergata  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marta","family":"Borghi","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria Paola","family":"Anolli","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sara","family":"Monico","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology Foundation IRCCS Ca' Granda Ospedale Maggiore Policlinico  Milan Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2377-504X","authenticated-orcid":false,"given":"Valentina","family":"Svicher","sequence":"additional","affiliation":[{"name":"Department of Biology University of Rome Tor Vergata  Rome Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1026-7476","authenticated-orcid":false,"given":"Pietro","family":"Lampertico","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology Foundation IRCCS Ca' 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"}]}],"member":"311","published-online":{"date-parts":[[2025,4,28]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1136\/gut.46.3.420"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2020.02.030"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1111\/jvh.13577"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2020-323888"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1128\/jvi.58.3.945-950.1986"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1055\/s-0033-1345717"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.79.15.9786-9798.2005"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.21112"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1038\/nbt1389"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1515\/hsz-2022-0345"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1007\/3-540-29802-9_6"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.00272-18"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1080\/21505594.2021.1999130"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.antiviral.2019.104553"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2017-313811"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.1097\/HC9.0000000000000027"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhepr.2023.100842"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2020.08.039"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.3390\/pathogens13010046"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2213429"},{"key":"e_1_2_11_22_1","unstructured":"European Medicines Agency \u201cHepcludex \u201dhttps:\/\/www.ema.europa.eu\/en\/medicines\/human\/EPAR\/hepcludex."},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2017.03.021"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.3390\/microorganisms9040752"},{"key":"e_1_2_11_25_1","volume-title":"Chronic HDV Coinfection (CHD) is Characterized by a More Elevated Production of Middle and Large HBsAg Than HBV Mono\u2010Infection, That Parallels HDV Replicative and Cytolytic Activity","author":"Piermatteo L.","year":"2024"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2022.07.016"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.3390\/v16060825"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1111\/liv.15417"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.dld.2024.01.047"},{"key":"e_1_2_11_30_1","unstructured":"O.Wasserman S.Cotler H.Dahari andP.Lampertico \u201cBulevirtide Monotherapy in Patients With Compensated Cirrhosis and CSPH: A 96\u2010Week Interim Kinetic Analysis of Real\u2010Life Setting \u201d The Liver Meeting 2024 San Diego CA 2024 661\u2013662."},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep4.1951"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2020-323300"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1111\/jvh.13804"},{"key":"e_1_2_11_34_1","doi-asserted-by":"crossref","unstructured":"E.Degasperi M. P.Anolli D.Sambarino et\u00a0al. \u201cKinetics of Hepatitis B Core Related Antigen in Patients With Compensated HDV Cirrhosis Treated With Bulevirtide Monotherapy for 72\u2009Weeks: A Single\u2010Center Study \u201d 2nd Delta Cure International Meeting 2023.","DOI":"10.1016\/S0168-8278(23)03314-7"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41575-022-00649-z"}],"container-title":["Liver International"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/liv.70094","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,8]],"date-time":"2025-10-08T21:24:01Z","timestamp":1759958641000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/liv.70094"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,4,28]]},"references-count":34,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2025,5]]}},"alternative-id":["10.1111\/liv.70094"],"URL":"https:\/\/doi.org\/10.1111\/liv.70094","archive":["Portico"],"relation":{},"ISSN":["1478-3223","1478-3231"],"issn-type":[{"value":"1478-3223","type":"print"},{"value":"1478-3231","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,4,28]]},"assertion":[{"value":"2024-05-31","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-04-02","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2025-04-28","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70094"}}