{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T00:14:02Z","timestamp":1779236042773,"version":"3.51.4"},"reference-count":38,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","license":[{"start":{"date-parts":[[2021,4,29]],"date-time":"2021-04-29T00:00:00Z","timestamp":1619654400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2021,4,29]],"date-time":"2021-04-29T00:00:00Z","timestamp":1619654400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2021,5]]},"abstract":"<jats:sec>\n            <jats:title>Background and Aims<\/jats:title>\n            <jats:p>We conducted haplotype analysis of complete hepatitis B virus (HBV) genomes following deep sequencing from 368 patients across multiple phases of chronic hepatitis B (CHB) infection from four major genotypes (A\u2010D),\u00a0analyzing 4,110 haplotypes to identify viral variants associated with treatment outcome and disease progression.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Approach and Results<\/jats:title>\n            <jats:p>Between 18.2% and 41.8% of nucleotides and between 5.9% and 34.3% of amino acids were 100% conserved in all genotypes and phases examined, depending on the region analyzed. Hepatitis B e antigen (HBeAg) loss by week 192 was associated with different haplotype populations at baseline. Haplotype populations differed across the HBV genome and CHB history, this being most pronounced in the precore\/core gene. Mean number of haplotypes (frequency) per patient was higher in immune\u2010active, HBeAg\u2010positive chronic hepatitis phase 2 (11.8) and HBeAg\u2010negative chronic hepatitis phase 4 (16.2) compared to subjects in the \u201cimmune\u2010tolerant,\u201d HBeAg\u2010positive chronic infection phase 1 (4.3, <jats:italic toggle=\"yes\">P<\/jats:italic>&lt; 0.0001). Haplotype frequency was lowest in genotype B (6.2, <jats:italic toggle=\"yes\">P<\/jats:italic>&lt; 0.0001) compared to the other genotypes (A = 11.8, C = 11.8, D = 13.6). Haplotype genetic diversity increased over the course of CHB history, being lowest in phase 1, increasing in phase 2, and highest in phase 4 in all genotypes except genotype C. HBeAg loss by week 192 of tenofovir therapy was associated with different haplotype populations at baseline.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>Despite a degree of HBV haplotype diversity and heterogeneity across the phases of CHB natural history, highly conserved sequences in key genes and regulatory regions were identified in multiple HBV genotypes that should be further investigated as targets for antiviral therapies and predictors of treatment response.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1002\/hep.31516","type":"journal-article","created":{"date-parts":[[2020,8,11]],"date-time":"2020-08-11T22:56:43Z","timestamp":1597186603000},"page":"1652-1670","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":10,"title":["Analysis of Hepatitis B Virus Haplotype Diversity Detects Striking Sequence Conservation Across Genotypes and Chronic Disease Phase"],"prefix":"10.1097","volume":"73","author":[{"given":"Josef","family":"Wagner","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lilly","family":"Yuen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Margaret","family":"Littlejohn","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vitina","family":"Sozzi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kathy","family":"Jackson","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vithika","family":"Suri","sequence":"additional","affiliation":[{"name":"Gilead Sciences,Foster City,CA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susanna","family":"Tan","sequence":"additional","affiliation":[{"name":"Gilead Sciences,Foster 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Hospital,University Health Network,University of Toronto,Toronto,ON,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":"Henry L.Y.","family":"Chan","sequence":"additional","affiliation":[{"name":"Department of Medicine and Therapeutics,The Chinese University of Hong Kong,Hong Kong"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Danni","family":"Colledge","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gillian","family":"Rosenberg","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Julianne","family":"Bayliss","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Benjamin P","family":"Howden","sequence":"additional","affiliation":[{"name":"Microbiological Diagnostic Unit Public Health Laboratory,The University of Melbourne,Peter Doherty Institute for Infection and Immunity,Melbourne,VIC,Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stephen A.","family":"Locarnini","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Darren","family":"Wong","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology,St. Vincent\u2019s Hospital,Melbourne,VIC,Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexander T.","family":"Thompson","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology,St. Vincent\u2019s Hospital,Melbourne,VIC,Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter 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