{"doi":"10.1002/hep.31506","title":"Precore and Basal Core Promoter Hepatitis B Virus (HBV) Variants Are Present From a Young Age and Differ Across HBV Genotypes","abstract":"BACKGROUND AND AIMS: 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. APPROACH AND RESULTS: 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). CONCLUSIONS: 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","year":2020,"id":105673,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":23,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9617,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2020-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":511282,"name":"Lilia Ganova‐Raeva","orcid":"0000-0001-6698-256X","position":1,"is_corresponding":false},{"id":449598,"name":"Junyao Wang","orcid":"0000-0002-1567-6447","position":2,"is_corresponding":false},{"id":286709,"name":"Douglas Mogul","orcid":"0000-0002-6486-3302","position":3,"is_corresponding":false},{"id":270866,"name":"Raymond T. Chung","orcid":"0000-0001-7587-718X","position":4,"is_corresponding":false},{"id":404033,"name":"Mauricio Lisker‐Melman","orcid":"0000-0001-7929-6841","position":5,"is_corresponding":false},{"id":11255,"name":"Kyong-Mi Chang","orcid":"0000-0001-6811-9364","position":6,"is_corresponding":false},{"id":511283,"name":"Obaid S. Shaikh","orcid":"0000-0002-4955-9222","position":7,"is_corresponding":false},{"id":270563,"name":"Harry L.A. Janssen","orcid":"0000-0003-2398-8392","position":8,"is_corresponding":false},{"id":449597,"name":"Abdus S. Wahed","orcid":"0000-0001-6911-7221","position":9,"is_corresponding":false},{"id":262768,"name":"Anna S. Lok","orcid":"0000-0002-5811-6845","position":10,"is_corresponding":false},{"id":464998,"name":"Daryl Lau","orcid":"0000-0003-4139-1987","position":0,"is_corresponding":true}],"reference_count":26,"raw_metadata":null,"created_at":"2026-07-18T23:12:21.275494Z","pmid":"32860463","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}