{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,5]],"date-time":"2025-11-05T14:35:03Z","timestamp":1762353303818,"version":"3.40.5"},"reference-count":36,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2022,11,25]],"date-time":"2022-11-25T00:00:00Z","timestamp":1669334400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100005564","name":"Gilead Sciences","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100005564","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Aliment Pharmacol Ther"],"published-print":{"date-parts":[[2023,3]]},"abstract":"<jats:title>Summary<\/jats:title><jats:sec><jats:title>Backgrounds and Aims<\/jats:title><jats:p>We investigated associations between hepatitis B virus (HBV) genome\u2010length haplotype number (HN) at baseline in subjects with HBeAg\u2010positive chronic hepatitis B (CHB), and the likelihood of achieving functional cure during direct\u2010acting antiviral therapy<\/jats:p><\/jats:sec><jats:sec><jats:title>Method<\/jats:title><jats:p>We analysed 86 HBeAg\u2010positive baseline samples from patients with HBV genotypes A and D who were enrolled in a Phase II trial of tenofovir disoproxil fumarate (TDF) to determine if HN was a biomarker of HBsAg loss during therapy. Findings were validated using baseline samples from 181 patients with HBV genotypes A and D from an independent clinical trial utilising TDF or tenofovir alafenamide therapy in HBeAg\u2010positive CHB.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>In the HBeAg\u2010positive test cohort, patients with genotypes A or D and \u22642 haplotypes had a minimum of 21\u2010fold higher likelihood of achieving HBsAg loss on TDF. Baseline HN (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.0001) was a stronger predictor of HBsAg loss on therapy than HBsAg titre (<jats:italic>p<\/jats:italic>\u00a0=\u00a00.03), HBeAg titre (<jats:italic>p<\/jats:italic>\u00a0=\u00a00.0002), or the presence of HBV basal core promoter (A1762T, <jats:italic>p<\/jats:italic>\u00a0=\u00a00.0379 and G1764A, <jats:italic>p<\/jats:italic>\u00a0=\u00a00.0176) or G1896A precore mutations (<jats:italic>p<\/jats:italic>\u00a0=\u20090.0218). This finding was validated in the independent validation cohort. HN was statistically higher in patients with HBV genotypes B or C infection compared to genotypes A and D.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Baseline HN \u22642 predicts which patients with HBV genotypes A or D will more likely progress to functional cure on current direct\u2010acting antiviral therapy, with greater accuracy than current biomarkers including baseline HBsAg and HBeAg titre.<\/jats:p><\/jats:sec>","DOI":"10.1111\/apt.17299","type":"journal-article","created":{"date-parts":[[2022,11,26]],"date-time":"2022-11-26T00:49:24Z","timestamp":1669423764000},"page":"509-523","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Hepatitis B virus haplotype number at baseline is a predictive marker of functional cure during antiviral therapy for patients with genotypes A and D <scp>HBeAg<\/scp>\u2010positive chronic hepatitis B"],"prefix":"10.1111","volume":"57","author":[{"given":"Josef","family":"Wagner","sequence":"first","affiliation":[{"name":"Victorian Infectious Diseases Reference Laboratory Royal Melbourne Hospital at the Peter Doherty Institute for Infection and Immunity  Melbourne Victoria Australia"},{"name":"Department of Paediatrics University of Melbourne  Melbourne Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lilly","family":"Yuen","sequence":"additional","affiliation":[{"name":"Victorian Infectious Diseases Reference Laboratory Royal Melbourne Hospital at the Peter Doherty Institute for Infection and Immunity  Melbourne Victoria Australia"},{"name":"Department of Infectious Diseases University of Melbourne at the Peter Doherty Institute for Infection and Immunity  Melbourne Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Margaret","family":"Littlejohn","sequence":"additional","affiliation":[{"name":"Victorian Infectious Diseases Reference Laboratory Royal Melbourne Hospital at the Peter Doherty Institute for Infection and Immunity  Melbourne Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vitina","family":"Sozzi","sequence":"additional","affiliation":[{"name":"Victorian Infectious Diseases Reference Laboratory Royal Melbourne Hospital at the Peter Doherty Institute for Infection and Immunity  Melbourne Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kathy","family":"Jackson","sequence":"additional","affiliation":[{"name":"Victorian Infectious Diseases Reference Laboratory Royal Melbourne Hospital at the Peter Doherty Institute for Infection and Immunity  Melbourne Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ross","family":"Martin","sequence":"additional","affiliation":[{"name":"Gilead Sciences  Foster City California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Aeschbacher","sequence":"additional","affiliation":[{"name":"Gilead Sciences  Foster City California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vithika","family":"Suri","sequence":"additional","affiliation":[{"name":"Gilead Sciences  Foster City California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susanna K.","family":"Tan","sequence":"additional","affiliation":[{"name":"Gilead Sciences  Foster City California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Becket","family":"Feierbach","sequence":"additional","affiliation":[{"name":"Gilead Sciences  Foster City California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anuj","family":"Gaggar","sequence":"additional","affiliation":[{"name":"Gilead Sciences  Foster City California USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patrick","family":"Marcellin","sequence":"additional","affiliation":[{"name":"H\u00f4pital Beaujon University of Paris  Clichy France"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Buti Ferret","sequence":"additional","affiliation":[{"name":"Liver Unit Valle d'Hebron (Ciberehd) University Hospital  Barcelona Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Harry L. A.","family":"Janssen","sequence":"additional","affiliation":[{"name":"Toronto Center for Liver Diseases, Toronto General Hospital, University: Health Network University of Toronto  Toronto Ontario Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ed","family":"Gane","sequence":"additional","affiliation":[{"name":"New Zealand Liver Transplant Unit Auckland City Hospital  Auckland New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Niamh","family":"Meagher","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases University of Melbourne at the Peter Doherty Institute for Infection and Immunity  Melbourne Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David J.","family":"Price","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases University of Melbourne at the Peter Doherty Institute for Infection and Immunity  Melbourne Victoria Australia"},{"name":"Centre for Epidemiology and Biostatistics, Melbourne School of Population and Global Health The University of Melbourne  Melbourne Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Darren","family":"Wong","sequence":"additional","affiliation":[{"name":"Victorian Infectious Diseases Reference Laboratory Royal Melbourne Hospital at the Peter Doherty Institute for Infection and Immunity  Melbourne Victoria Australia"},{"name":"Department of Gastroenterology St. Vincent's Hospital  Melbourne Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexander T.","family":"Thompson","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology St. Vincent's Hospital  Melbourne Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2715-2541","authenticated-orcid":false,"given":"Peter A.","family":"Revill","sequence":"additional","affiliation":[{"name":"Victorian Infectious Diseases Reference Laboratory Royal Melbourne Hospital at the Peter Doherty Institute for Infection and Immunity  Melbourne Victoria Australia"},{"name":"Department of Infectious Diseases University of Melbourne at the Peter Doherty Institute for Infection and Immunity  Melbourne Victoria Australia"},{"name":"Department of Microbiology and Immunology University of Melbourne at the Peter Doherty Institute for Infection and Immunity  Melbourne Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2022,11,25]]},"reference":[{"key":"e_1_2_12_2_1","unstructured":"World Health Organization.Progress report on HIV viral hepatitis and sexually transmitted infections 2021: accountability for the global health sector strategies 2016\u20132021: actions for impact [Internet].2021. 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