{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,5]],"date-time":"2026-02-05T18:26:35Z","timestamp":1770315995872,"version":"3.49.0"},"reference-count":37,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2020,6,17]],"date-time":"2020-06-17T00:00:00Z","timestamp":1592352000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"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":["Journal of Viral Hepatitis"],"published-print":{"date-parts":[[2020,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Nucleos(t)ide analogues (NUC) treatment prevents progression of liver fibrosis in subjects with chronic hepatitis B (CHB). However, risk of hepatocellular carcinoma (HCC) persists despite viral suppression. Specific HBV variants have been associated with adverse outcomes, including HCC; however, the frequency of these variants during the seemingly benign immunotolerant (IT) phase is unknown. Next\u2010generation sequencing and detailed virological characterization on a cohort of treatment\u2010na\u00efve IT subjects were performed to determine the frequency of clinically relevant viral variants. Samples from 97 subjects (genotype B\/C 55%\/45%, median HBV\u2010DNA 8.5\u00a0log<jats:sub>10<\/jats:sub> IU\/mL, median HBsAg 4.8 log<jats:sub>10<\/jats:sub>\u00a0IU\/mL, median HBeAg 3.6 log<jats:sub>10<\/jats:sub>\u00a0PEIU\/mL) were analysed. Despite subjects being in the IT phase, clinically relevant HBV variants were common at baseline, particularly in the basal core promoter (BCP, overlaps the hepatitis B X (HBx) gene), precore and PreS regions. BCP\/HBx variants were independently associated with lower baseline HBeAg, HBsAg and HBV\u2010DNA titres. Precore variants were independently associated with higher baseline ALT. Increased viral diversity was associated with increased age and lower HBV\u2010DNA, HBsAg and HBeAg levels. Low\u2010level (&lt;5%) drug resistance\u2013associated amino acid substitutions in the HBV reverse transcriptase were detected in 9 (9%) subjects at pre\u2010treatment but were not associated with reduced antiviral activity. Future studies should evaluate whether the detection of HBV variant during IT CHB is predictive of progression to immune clearance and poor prognosis, and whether early initiation of antiviral therapy during IT CHB to prevent the selection of HBV variants is clinically beneficial.<\/jats:p>","DOI":"10.1111\/jvh.13318","type":"journal-article","created":{"date-parts":[[2020,5,8]],"date-time":"2020-05-08T20:29:41Z","timestamp":1588969781000},"page":"1061-1070","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["HBV variants are common in the \u2018immune\u2010tolerant\u2019 phase of chronic hepatitis B"],"prefix":"10.1111","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2934-0167","authenticated-orcid":false,"given":"Lilly","family":"Yuen","sequence":"first","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":"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 Microbiology and Immunology University of Melbourne Parkville Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gillian","family":"Rosenberg","sequence":"additional","affiliation":[{"name":"National Cancer Research Institute London UK"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Josef","family":"Wagner","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":"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":"Julianne","family":"Bayliss","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":"Susanna K.","family":"Tan","sequence":"additional","affiliation":[{"name":"Gilead Sciences, Inc Foster City CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anuj","family":"Gaggar","sequence":"additional","affiliation":[{"name":"Gilead Sciences, Inc Foster City CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kathryn","family":"Kitrinos","sequence":"additional","affiliation":[{"name":"Gilead Sciences, Inc Foster City CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mani","family":"Subramanian","sequence":"additional","affiliation":[{"name":"Gilead Sciences, Inc Foster City CA USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ed","family":"Gane","sequence":"additional","affiliation":[{"name":"New Zealand Transplant Unit Auckland New Zealand"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7790-1611","authenticated-orcid":false,"given":"Henry L. Y.","family":"Chan","sequence":"additional","affiliation":[{"name":"Department of Medicine and Therapeutics The Chinese University of Hong Kong Hong Kong Hong Kong SAR"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xin","family":"Li","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":"Scott","family":"Bowden","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":"Stephen","family":"Locarnini","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":"Alexander","family":"Thompson","sequence":"additional","affiliation":[{"name":"St Vincent's Hospital Melbourne Victoria Australia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,6,17]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cld.2010.05.007"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/jvh.12370"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2012.02.010"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.23190"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12072-012-9365-4"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2011-300937"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2016.07.012"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2012.06.009"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.21992"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2014-306977"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2014.01.044"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(12)61425-1"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2015-309300"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1128\/CVI.05122-11"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.69.9.5437-5444.1995"},{"key":"e_1_2_8_17_1","first-page":"125","article-title":"HBV genotyping and analysis for unique mutations","volume":"95","author":"Ayres A","year":"2004","journal-title":"Methods Mol Med"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.antiviral.2006.11.014"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btu170"},{"key":"e_1_2_8_20_1","article-title":"CliqueSNV: Scalable reconstruction of Intra\u2010host viral populations from NGS reads","author":"Knyazev S","year":"2018","journal-title":"BioRxiv"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1093\/molbev\/msw054"},{"key":"e_1_2_8_22_1","unstructured":"Mu\u2010MInBK.Multi\u2010model inference. R Package Version. 0.12.2\/r18.2009.http:\/\/R\u2010Forge.R\u2010project.org\/projects\/mumin\/. Accessed August 16 2019."},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2009.08.063"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2019.02.006"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.7150\/ijms.2.2"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0038394"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.29320"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2017.03.021"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2014.04.030"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1002\/jmv.21208"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.25592"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1002\/jmv.10458"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2180-12-307"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrgastro.2009.107"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/0140-6736(90)91874-A"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0021856"},{"key":"e_1_2_8_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2011.11.012"},{"key":"e_1_2_8_38_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12072-008-9048-3"}],"container-title":["Journal of Viral Hepatitis"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fjvh.13318","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jvh.13318","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/jvh.13318","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/jvh.13318","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,5]],"date-time":"2023-09-05T02:56:52Z","timestamp":1693882612000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/jvh.13318"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,6,17]]},"references-count":37,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2020,10]]}},"alternative-id":["10.1111\/jvh.13318"],"URL":"https:\/\/doi.org\/10.1111\/jvh.13318","archive":["Portico"],"relation":{},"ISSN":["1352-0504","1365-2893"],"issn-type":[{"value":"1352-0504","type":"print"},{"value":"1365-2893","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,6,17]]},"assertion":[{"value":"2020-01-08","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-04-23","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-06-17","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}