{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,6]],"date-time":"2026-11-06T11:19:31Z","timestamp":1793963971005,"version":"4.8.0"},"reference-count":26,"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>Hepatitis B virus (HBV) precore (PC) and dual basal core promoter (BCP) mutations halt and down\u2010regulate hepatitis B e antigen (HBeAg) production respectively. PC mutation is rarely associated with HBV genotype A. We sought to examine the association of these variants with HBV genotypes, age, and HBeAg status in a racially diverse population in North America. Prospective study included 1,036 (808 adults, 228 children) participants in the Hepatitis B Research Network. PC and BCP variants were determined by Sanger sequencing, and dominant HBV species (&gt;50%) were reported.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Approach and Results<\/jats:title>\n            <jats:p>Median age was 36.3\u00a0years (range, 2\u201080), 44.6% HBeAg(+), 74.2% Asians, 13.3% black, and 9.7% white. The dominant PC variant was present in 29.4% participants, including 20 with subgenotype A1 or A2. Seventeen of 20 participants with genotype A and PC had a compensatory C1858T mutation. In the HBeAg(+) cohort, the prevalence of PC and\/or BCP variants increased from 14.4% in the first two decades to 51% after 40\u00a0years of age. Among those aged 2\u201018, 52% and 83% with dominant PC and BCP variants were HBeAg(+) compared to 3.8% and 29% in the &gt;40\u00a0years age group. HBeAg clearance rates were significantly higher for those with dominant PC or BCP variants: 24.4 and 15.0 per 100 person\u2010years compared to 6.0 in wild\u2010type HBV (<jats:italic toggle=\"yes\">P<\/jats:italic>\u00a0&lt;\u00a00.0001).<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>PC variants can be present in HBV genotype A and are usually associated with C1858T, which preserves the pregenome encapsidation sequence. Selection of PC and BCP variants occurred at a young age, with increasing prevalence across age groups. HBeAg(+) participants with dominant PC and BCP variants progressed to the HBeAg(\u2212) phase of chronic HBV infection significantly faster. This finding has potential clinical and therapeutic implications.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1002\/hep.31506","type":"journal-article","created":{"date-parts":[[2020,8,29]],"date-time":"2020-08-29T05:12:01Z","timestamp":1598677921000},"page":"1637-1651","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":28,"title":["Precore and Basal Core Promoter Hepatitis B Virus (HBV) Variants Are Present From a Young Age and Differ Across HBV Genotypes"],"prefix":"10.1097","volume":"73","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4139-1987","authenticated-orcid":false,"given":"Daryl T.Y.","family":"Lau","sequence":"first","affiliation":[{"name":"Liver Center,Beth Israel Deaconess Medical Center,Harvard Medical School,Boston,MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lilia","family":"Ganova\u2010Raeva","sequence":"additional","affiliation":[{"name":"Division of Viral Hepatitis Laboratory Branch,Centers for Disease Control and Prevention,Atlanta,GA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junyao","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Biostatistics,Graduate School of Public Health,University of Pittsburgh,Pittsburgh,PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Douglas","family":"Mogul","sequence":"additional","affiliation":[{"name":"Department of Pediatrics,Johns Hopkins University School of Medicine,Baltimore,MD"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raymond T.","family":"Chung","sequence":"additional","affiliation":[{"name":"Liver Center,Massachusetts General Hospital,Harvard Medical School,Boston,MA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mauricio","family":"Lisker\u2010Melman","sequence":"additional","affiliation":[{"name":"Washington University School of Medicine,St. Louis,MO"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyong\u2010Mi","family":"Chang","sequence":"additional","affiliation":[{"name":"Medical Research,The Corporal Michael J. Crescenz VA Medical Center and Department of Medicine,University of Pennsylvania Perelman School of Medicine,Philadelphia,PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Obaid S.","family":"Shaikh","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology,VA Pittsburgh Healthcare System,Pittsburgh,PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harry L.A.","family":"Janssen","sequence":"additional","affiliation":[{"name":"Toronto Centre for Liver Disease,Toronto General Hospital,University of Toronto,Toronto,ON,Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Abdus S.","family":"Wahed","sequence":"additional","affiliation":[{"name":"Department of Biostatistics,Graduate School of Public Health,University of Pittsburgh,Pittsburgh,PA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna S.","family":"Lok","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine\u2010Gastroenterology,University of Michigan,Ann Arbor,MI"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"for the Hepatitis B Research Network","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2021,4,29]]},"reference":[{"key":"hep31506-bib-0001-20250824","article-title":"Hepatitis B virus genotypes and variants","volume":"5","year":"2015","journal-title":"Cold Spring Harb Perspect Med"},{"key":"hep31506-bib-0002-20250824","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1159\/000360947","article-title":"Genotypes and genetic variability of hepatitis B virus","volume":"57","year":"2014","journal-title":"Intervirology"},{"key":"hep31506-bib-0003-20250824","article-title":"Hepatitis B virus subgenotype A1: evolutionary relationships between Brazilian, African and Asian isolates","volume":"9","year":"2014","journal-title":"PLoS 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