{"doi":"10.1172/jci161818","title":"Integrated hepatitis B virus DNA maintains surface antigen production during antiviral treatment","abstract":null,"journal":"Journal of Clinical Investigation","year":2022,"id":590027,"datarank":2.459423249791172,"base_score":4.343805421853684,"endowment":4.343805421853684,"self_citation_contribution":0.6515708132780527,"citation_network_contribution":1.807852436513119,"self_endowment_contribution":0.6515708132780527,"citer_contribution":1.807852436513119,"corpus_percentile":null,"corpus_rank":null,"citation_count":76,"citer_count":67,"citers_with_citation_signal":46,"citers_with_endowment":46,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":null,"is_data_producer":false,"deposit_databanks":null,"is_oa":false,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":null,"fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":479142,"name":"Hyon S. Hwang","orcid":"0000-0001-8117-0199","position":1,"is_corresponding":false},{"id":1115239,"name":"Maraake Taddese","orcid":"0000-0001-8148-8738","position":2,"is_corresponding":false},{"id":434570,"name":"Jeffrey Quinn","orcid":"0000-0002-4734-5108","position":3,"is_corresponding":false},{"id":315359,"name":"Mark Sulkowski","orcid":"0000-0002-2145-6352","position":4,"is_corresponding":false},{"id":325248,"name":"Richard K. Sterling","orcid":"0000-0002-8637-2475","position":5,"is_corresponding":false},{"id":434568,"name":"Ashwin Balagopal","orcid":"0000-0002-6143-3104","position":6,"is_corresponding":false},{"id":414209,"name":"Chloe L. Thio","orcid":"0000-0002-8851-8319","position":7,"is_corresponding":false},{"id":479140,"name":"Tanner Grudda","orcid":"0000-0001-9045-2753","position":0,"is_corresponding":false}],"reference_count":0,"raw_metadata":{"has_enrichment":true,"resolved":true,"title":"Integrated hepatitis B virus DNA maintains surface antigen production during antiviral treatment","abstract":"The focus of hepatitis B functional cure, defined as sustained loss of hepatitis B virus (HBV) surface antigen (HBsAg) and HBV DNA from blood, is on eliminating or silencing the intranuclear template for HBV replication, covalently closed circular DNA (cccDNA). However, HBsAg also derives from HBV DNA integrated into the host genome (iDNA). Little is known about the contribution of iDNA to circulating HBsAg with current therapeutics. We applied a multiplex droplet digital PCR assay to demonstrate that iDNA is responsible for maintaining HBsAg quantities in some individuals. Using paired bulk liver tissue from 16 HIV/HBV-coinfected persons on nucleos(t)ide analog (NUC) therapy, we demonstrate that people with larger HBsAg declines between biopsies derive HBsAg from cccDNA, whereas people with stable HBsAg levels derive predominantly from iDNA. We applied our assay to individual hepatocytes in paired tissues from 3 people and demonstrated that the individual with significant HBsAg decline had a commensurate loss of infected cells with transcriptionally active cccDNA, while individuals without HBsAg decline had stable or increasing numbers of cells producing HBsAg from iDNA. We demonstrate that while NUC therapy may be effective at controlling cccDNA replication and transcription, innovative treatments are required to address iDNA transcription that sustains HBsAg production.","is_dataset_classified":null,"base_score":4.330733340286331,"endowment":4.330733340286331,"datacite_reuse_total":0,"file_count":0,"downloads":0,"views":0,"has_version_chain":false,"is_dataset":false,"is_oa":false,"pmid":"35797115","pmcid":"PMC9473722","openalex_id":"https://openalex.org/W4284680923","authors":[],"funders":[{"funder_name":"National Institute of Allergy and Infectious Diseases","grant_id":"AI138810","title":null},{"funder_name":"National Institute of Allergy and Infectious Diseases","grant_id":"AI116269","title":null},{"funder_name":"National Institute of Allergy and Infectious Diseases","grant_id":"AI165166","title":null},{"funder_name":"National Institute of Allergy and Infectious Diseases","grant_id":"AI157760","title":null},{"funder_name":"National Institute of Diabetes and Digestive and Kidney Diseases","grant_id":"DK094818","title":null},{"funder_name":"NIAID NIH HHS","grant_id":"R01 AI138810","title":null},{"funder_name":"NIAID NIH HHS","grant_id":"R56 AI138810","title":null},{"funder_name":"NIAID NIH HHS","grant_id":"R21 AI157760","title":null},{"funder_name":"NIAID NIH HHS","grant_id":"R01 AI116269","title":null},{"funder_name":"NIDDK NIH HHS","grant_id":"R01 DK094818","title":null},{"funder_name":"NIDA NIH HHS","grant_id":"K24 DA034621","title":null},{"funder_name":"NIAID NIH HHS","grant_id":"R21 AI165166","title":null},{"funder_name":"National Institutes of Health","grant_id":"5R21AI157760-02","title":"Unraveling sources of hepatitis B surface antigen before and after nucleos(t)ide analogue treatment in People with HIV"},{"funder_name":"National Institutes of Health","grant_id":"5R21AI165166-02","title":"Identifying the source of hepatitis B surface antigen in people with hepatitis B-HIV co-infection"},{"funder_name":"National Institutes of Health","grant_id":"1R01AI138810-01A1","title":"Characterization of silently HBV-infected hepatocytes in HIV co-infection"},{"funder_name":"National Institutes of Health","grant_id":"5K24DA034621-10","title":"Midcareer Investigator Award in Patient-Oriented Research (Parent K24)"},{"funder_name":"National Institutes of Health","grant_id":"5R01AI116269-02","title":"Immune correlates of acute HBV recovery with and without HIV"},{"funder_name":"National Institutes of Health","grant_id":"5R01DK094818-03","title":"HBV HIV Coinfection Research Network"}],"total_grants":18,"fwci":8.948,"citation_percentile":0.98753001,"influential_citations":0,"citation_trend":[{"year":2022,"count":3},{"year":2023,"count":15},{"year":2024,"count":24},{"year":2025,"count":19},{"year":2026,"count":14}],"oa_status":"gold","license":"cc-by","oa_locations":[{"url":"http://www.jci.org/articles/view/161818/files/pdf","host_type":"journal"},{"url":"http://www.jci.org/articles/view/161818/files/pdf","host_type":"publisher"},{"url":"https://www.jci.org/articles/view/161818/files/pdf","host_type":"publisher"},{"url":"https://doi.org/10.1172/jci161818","host_type":"journal"},{"url":"https://pubmed.ncbi.nlm.nih.gov/35797115","host_type":"repository"},{"url":"https://doaj.org/article/4ae31255e99b4eb3a92cbb60ecbdf52f","host_type":"repository"},{"url":"https://www.ncbi.nlm.nih.gov/pmc/articles/9473722","host_type":"repository"},{"url":"https://europepmc.org/articles/PMC9473722","host_type":"Europe_PMC"},{"url":"https://europepmc.org/articles/PMC9473722?pdf=render","host_type":"Europe_PMC"},{"url":"http://dx.doi.org/10.1172/JCI161818","host_type":""}],"fields_of_study":["Hepatitis B Virus Studies","Hepatitis C virus research","HIV Research and Treatment","0301 basic medicine","0303 health sciences","03 medical and health sciences","Antigens, Surface","Antiviral Agents","DNA, Circular","DNA, Viral","Hepatitis B","Hepatitis B Surface Antigens","Hepatitis B virus","Hepatitis B, Chronic","Humans","Liver"],"mesh_terms":["Antigens, Surface","Antiviral Agents","DNA, Circular","DNA, Viral","Hepatitis B","Hepatitis B Surface Antigens","Hepatitis B virus","Humans","Liver","Hepatitis B, Chronic"],"keywords":["cccDNA","HBsAg","Hepatitis B virus","Virology","Biology","Hepatitis B","Antigen","Immunology","Virus","Medicine","Molecular biology","Hepatitis","Infectious disease","Hepatitis B Surface Antigens","R","Antiviral Agents","Hepatitis B, Chronic","Liver","Antigens, Surface","DNA, Viral","Humans","DNA, Circular","Research Article"],"sdg_mappings":[{"sdg_number":3,"sdg_label":"3. 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