biostudies-literatureLau DTYNCATS NIH HHSNIDDK NIH HHSNCRR NIH HHSNational Institute of Diabetes and Digestive and Kidney Diseases1637-1651https://www.ebi.ac.uk/biostudies/studies/S-EPMC8570313biostudies-literatureUnknown73(5)<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.Hepatology (Baltimore, Md.)Precore and Basal Core Promoter Hepatitis B Virus (HBV) Variants Are Present From a Young Age and Differ Across HBV Genotypes.PMC8570313M01 RR000040UL1 TR000058UL1 TR001111U01 DK082872UL1 TR000004UL1 TR000423U01 DK082871U01 DK082843U01 DK082866U01 DK082943UL1 TR002319U01 DK082874U01 DK082863U01 DK082864U01 DK082867U01 DK082944U01 DK082923U01‐DK082919UL1 RR024986U01 DK082916U01 DK082927U01 DK082919P30 DK050306Sherker AHAverbach FVladutu DJake Liang TKing WCReyes KJCHassan MANasser IDi Bisceglie AMMurakami CSDeVole NChang KMOshima KMoran ITorrance RJCooper SLPatel KLake JRushing KKowdley KVChung RTLevine DNorman-Wheeler JCooper KLMurray KFLisker-Melman MRowan DTerrault NARiggs SMvon Bakonyi AFeld JYim CKaznowski DDo SFeier NWolfstone AAnders RLee PFeier JPeacock VZadorozny EGhany MGStahler ACMooney JCerkoski JZhao QMontanye SShobe ALing SCLa DKelley SChoudhry SBass SPodolskaya VImteyaz HCardona DValiga MEKlebert MKWong RSchwarz KBGanova-Raeva LYounoszai BLalama CMcKenna BWeiner MShaikh OSKleiner DRivera ELau DTYKafka KStadheim LMontaner LJWang CCHofmann CJanssen HLAMetheny VHuang FKuras RStoliker DFoley CCarithers RCSidney Barritt AKeith JHaller TDonovan ADavis RWang JBetts MHepatitis B Research NetworkShah PAFryzek NAyala CKaza SSmith PGHuang APeters MLi HWahed ASNadal CNagy RAChen JHoofnagle JFontana RJCerocchi OHaynes-Williams VOberhelman KTsai NSchwarzenberg SJRoberts LRLin HSWong DKLombardero MLacher PHau ARodriguez-Baez NRodgers-Augustyniak LADoo EHan SBIslam NCardona-Gonzalez LHuddleston LFrench SLiu LMarsh THardison RChoi KSterling RKLawlor STorrey KPelesko ANoureldin SMorris NMuir ALok ASNiu JDarling JMRosenthal PRusibamayila NBelle SHKhalili MLee WMEvon DPark JJJuan JTran TTLanglois CMogul DHall SRFried MWLuketic VAShuhart MKessels LHoofnagle JHTeckman JLilly BLau IPerrillo RShaw DDfalsePrecore and Basal Core Promoter Hepatitis B Virus (HBV) Variants Are Present From a Young Age and Differ Across HBV Genotypes.<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.2021-01-01T00:00:00Z2021 May2025-04-05T14:04:59.215Z2025-04-05T14:04:59.215ZS-EPMC85703133286046310.1002/hep.31506