{"doi":"10.1093/infdis/jiad124","title":"Hepatitis B e Antigen-Negative Single Hepatocyte Analysis Shows Transcriptional Silencing and Slow Decay of Infected Cells With Treatment","abstract":"BACKGROUND: Nucleos(t)ide analogues (NUCs) rarely cure chronic hepatitis B (CHB) because they do not eliminate covalently closed circular deoxyribonucleic acid, the stable replication template. In hepatitis B e antigen (HBeAg)-positive CHB during NUCs, HBV-infected cells decline slowly and are transcriptionally silenced. Whether these occur in HBeAg-negative CHB is unknown. METHODS: Using paired liver biopsies separated by 2.7-3.7 years in 4 males with HIV and HBeAg-negative CHB at both biopsies and 1 male with HIV who underwent HBeAg seroconversion between biopsies, we quantified amounts of viral nucleic acids in hundreds of individual hepatocytes. RESULTS: In the 4 persistently HBeAg-negative participants, HBV-infected hepatocytes ranged from 6.2% to 17.7% (biopsy 1) and significantly declined in 3 of 4 by biopsy 2. In the HBeAg seroconverter, the proportion was 97.4% (biopsy 1) and declined to 81.9% at biopsy 2 (P < .05). We extrapolated that HBV eradication with NUCs would take >100 years. At biopsy 1 in the persistently HBeAg-negative participants, 23%-56.8% of infected hepatocytes were transcriptionally inactive-higher than we observed in HBeAg-positive CHB-and significantly declined in 1 of 4 at biopsy 2. CONCLUSIONS: In HBeAg-negative CHB on NUCs, the negligible decline in infected hepatocytes is similar to HBeAg-positive CHB, supporting the need for more potent therapeutics to achieve functional cure.","journal":"The Journal of Infectious Diseases","year":2023,"id":362111,"datarank":0.4844841894653864,"base_score":2.1972245773362196,"endowment":2.1972245773362196,"self_citation_contribution":0.32958368660043297,"citation_network_contribution":0.15490050286495347,"self_endowment_contribution":0.32958368660043297,"citer_contribution":0.15490050286495347,"corpus_percentile":null,"corpus_rank":null,"citation_count":8,"citer_count":5,"citers_with_citation_signal":3,"citers_with_endowment":3,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.9595,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":1115239,"name":"Maraake Taddese","orcid":"0000-0001-8148-8738","position":1,"is_corresponding":false},{"id":479141,"name":"Yasmeen S. Saad","orcid":"0000-0001-6612-7985","position":2,"is_corresponding":false},{"id":1115240,"name":"Kristina Diana A. Zambo","orcid":"0000-0003-2247-8104","position":3,"is_corresponding":false},{"id":56058,"name":"Ruy M. Ribeiro","orcid":"0000-0002-3988-8241","position":4,"is_corresponding":false},{"id":479140,"name":"Tanner Grudda","orcid":"0000-0001-9045-2753","position":5,"is_corresponding":false},{"id":315359,"name":"Mark Sulkowski","orcid":"0000-0002-2145-6352","position":6,"is_corresponding":false},{"id":325248,"name":"Richard K. Sterling","orcid":"0000-0002-8637-2475","position":7,"is_corresponding":false},{"id":237547,"name":"Yang Zhang","orcid":"0000-0001-7462-2935","position":8,"is_corresponding":false},{"id":1115241,"name":"Eric D. Young","orcid":"0000-0002-0014-1482","position":9,"is_corresponding":false},{"id":479142,"name":"Hyon S. Hwang","orcid":"0000-0001-8117-0199","position":10,"is_corresponding":false},{"id":434568,"name":"Ashwin Balagopal","orcid":"0000-0002-6143-3104","position":11,"is_corresponding":false},{"id":414209,"name":"Chloe L. Thio","orcid":"0000-0002-8851-8319","position":0,"is_corresponding":true}],"reference_count":16,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T01:14:19.266946Z","pmid":"37129258","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":[]}