{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Lau DTY"],"funding":["NCATS NIH HHS","NIDDK NIH HHS","NCRR NIH HHS","National Institute of Diabetes and Digestive and Kidney Diseases"],"pagination":["1637-1651"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC8570313"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["73(5)"],"pubmed_abstract":["<h4>Background and aims</h4>Hepatitis B virus (HBV) precore (PC) and dual basal core promoter (BCP) mutations halt and down-regulate 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 (>50%) were reported.<h4>Approach and results</h4>Median age was 36.3 years (range, 2-80), 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 years of age. Among those aged 2-18, 52% and 83% with dominant PC and BCP variants were HBeAg(+) compared to 3.8% and 29% in the >40 years age group. HBeAg clearance rates were significantly higher for those with dominant PC or BCP variants: 24.4 and 15.0 per 100 person-years compared to 6.0 in wild-type HBV (P < 0.0001).<h4>Conclusions</h4>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(-) phase of chronic HBV infection significantly faster. This finding has potential clinical and therapeutic implications."],"journal":["Hepatology (Baltimore, Md.)"],"pubmed_title":["Precore and Basal Core Promoter Hepatitis B Virus (HBV) Variants Are Present From a Young Age and Differ Across HBV Genotypes."],"pmcid":["PMC8570313"],"funding_grant_id":["M01 RR000040","UL1 TR000058","UL1 TR001111","U01 DK082872","UL1 TR000004","UL1 TR000423","U01 DK082871","U01 DK082843","U01 DK082866","U01 DK082943","UL1 TR002319","U01 DK082874","U01 DK082863","U01 DK082864","U01 DK082867","U01 DK082944","U01 DK082923","U01‐DK082919","UL1 RR024986","U01 DK082916","U01 DK082927","U01 DK082919","P30 DK050306"],"pubmed_authors":["Sherker AH","Averbach F","Vladutu D","Jake Liang T","King WC","Reyes KJC","Hassan MA","Nasser I","Di Bisceglie AM","Murakami CS","DeVole N","Chang KM","Oshima K","Moran I","Torrance RJ","Cooper SL","Patel K","Lake J","Rushing K","Kowdley KV","Chung RT","Levine D","Norman-Wheeler J","Cooper KL","Murray KF","Lisker-Melman M","Rowan D","Terrault NA","Riggs SM","von Bakonyi A","Feld J","Yim C","Kaznowski D","Do S","Feier N","Wolfstone A","Anders R","Lee P","Feier J","Peacock V","Zadorozny E","Ghany MG","Stahler AC","Mooney J","Cerkoski J","Zhao Q","Montanye S","Shobe A","Ling SC","La D","Kelley S","Choudhry S","Bass S","Podolskaya V","Imteyaz H","Cardona D","Valiga ME","Klebert MK","Wong R","Schwarz KB","Ganova-Raeva L","Younoszai B","Lalama C","McKenna B","Weiner M","Shaikh OS","Kleiner D","Rivera E","Lau DTY","Kafka K","Stadheim L","Montaner LJ","Wang CC","Hofmann C","Janssen HLA","Metheny V","Huang F","Kuras R","Stoliker D","Foley C","Carithers RC","Sidney Barritt A","Keith J","Haller T","Donovan A","Davis R","Wang J","Betts M","Hepatitis B Research Network","Shah PA","Fryzek N","Ayala C","Kaza S","Smith PG","Huang A","Peters M","Li H","Wahed AS","Nadal C","Nagy RA","Chen J","Hoofnagle J","Fontana RJ","Cerocchi O","Haynes-Williams V","Oberhelman K","Tsai N","Schwarzenberg SJ","Roberts LR","Lin HS","Wong DK","Lombardero M","Lacher P","Hau A","Rodriguez-Baez N","Rodgers-Augustyniak LA","Doo E","Han SB","Islam N","Cardona-Gonzalez L","Huddleston L","French S","Liu L","Marsh T","Hardison R","Choi K","Sterling RK","Lawlor S","Torrey K","Pelesko A","Noureldin S","Morris N","Muir A","Lok AS","Niu J","Darling JM","Rosenthal P","Rusibamayila N","Belle SH","Khalili M","Lee WM","Evon D","Park JJ","Juan J","Tran TT","Langlois C","Mogul D","Hall SR","Fried MW","Luketic VA","Shuhart M","Kessels L","Hoofnagle JH","Teckman J","Lilly B","Lau I","Perrillo R","Shaw DD"],"additional_accession":[]},"is_claimable":false,"name":"Precore and Basal Core Promoter Hepatitis B Virus (HBV) Variants Are Present From a Young Age and Differ Across HBV Genotypes.","description":"<h4>Background and aims</h4>Hepatitis B virus (HBV) precore (PC) and dual basal core promoter (BCP) mutations halt and down-regulate 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 (>50%) were reported.<h4>Approach and results</h4>Median age was 36.3 years (range, 2-80), 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 years of age. Among those aged 2-18, 52% and 83% with dominant PC and BCP variants were HBeAg(+) compared to 3.8% and 29% in the >40 years age group. HBeAg clearance rates were significantly higher for those with dominant PC or BCP variants: 24.4 and 15.0 per 100 person-years compared to 6.0 in wild-type HBV (P < 0.0001).<h4>Conclusions</h4>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(-) phase of chronic HBV infection significantly faster. This finding has potential clinical and therapeutic implications.","dates":{"release":"2021-01-01T00:00:00Z","publication":"2021 May","modification":"2025-04-05T14:04:59.215Z","creation":"2025-04-05T14:04:59.215Z"},"accession":"S-EPMC8570313","cross_references":{"pubmed":["32860463"],"doi":["10.1002/hep.31506"]}}