{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T02:41:21Z","timestamp":1784688081091,"version":"3.55.0"},"reference-count":88,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2023,5,3]],"date-time":"2023-05-03T00:00:00Z","timestamp":1683072000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["U1905205"],"award-info":[{"award-number":["U1905205"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>The hepatitis B virus core protein (HBcAg) is a highly immunogenic particulate antigen. Nearly all patients with persistent or resolved hepatitis B virus (HBV) infection show seropositivity for hepatitis B core antibody (anti-HBc), which appears in the early stage of infection and is mostly present for life. Traditionally, the anti-HBc is regarded as an evidential serological marker of HBV infections. In the last ten years, several studies revealed the predictive value of quantitative anti-HBc (qAnti-HBc) level in the treatment response and clinical outcome of chronic HBV infections, implying new insights into this classic marker. Overall, qAnti-HBc should be regarded as an indicator of the host\u2019s immune response specific to HBV, which correlates with HBV-related hepatitis activity and liver pathology. This review summarized the latest understanding of the clinical values of qAnti-HBc for differentiating the CHB phase, predicting treatment response, and providing disease prognosis. Moreover, we also discussed the possible mechanism of qAnti-HBc regulation during different courses of HBV infection.<\/jats:p>","DOI":"10.3390\/v15051111","type":"journal-article","created":{"date-parts":[[2023,5,4]],"date-time":"2023-05-04T01:33:36Z","timestamp":1683164016000},"page":"1111","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Hepatitis B Core Antibody Level: A Surrogate Marker for Host Antiviral Immunity in Chronic Hepatitis B Virus Infections"],"prefix":"10.3390","volume":"15","author":[{"given":"Yang","family":"Shi","sequence":"first","affiliation":[{"name":"State Key Laboratory of Infectious Disease Vaccine Development, Xiang An Biomedicine Laboratory, School of Public Health, Xiamen University, Xiamen 361102, China"},{"name":"NMPA Key Laboratory for Research and Evaluation of Infectious Disease Diagnostic Technology, National Institute of Diagnostics Vaccine Development in Infectious Diseases, School of Public Health, Xiamen 361102, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zihan","family":"Wang","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Infectious Disease Vaccine Development, Xiang An Biomedicine Laboratory, School of Public Health, Xiamen University, Xiamen 361102, China"},{"name":"NMPA Key Laboratory for Research and Evaluation of Infectious Disease Diagnostic Technology, National Institute of Diagnostics Vaccine Development in Infectious Diseases, School of Public Health, Xiamen 361102, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7165-3004","authenticated-orcid":false,"given":"Shengxiang","family":"Ge","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Infectious Disease Vaccine Development, Xiang An Biomedicine Laboratory, School of Public Health, Xiamen University, Xiamen 361102, China"},{"name":"NMPA Key Laboratory for Research and Evaluation of Infectious Disease Diagnostic Technology, National Institute of Diagnostics Vaccine Development in Infectious Diseases, School of Public Health, Xiamen 361102, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0179-5266","authenticated-orcid":false,"given":"Ningshao","family":"Xia","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Infectious Disease Vaccine Development, Xiang An Biomedicine Laboratory, School of Public Health, Xiamen University, Xiamen 361102, China"},{"name":"NMPA Key Laboratory for Research and Evaluation of Infectious Disease Diagnostic Technology, National Institute of Diagnostics Vaccine Development in Infectious Diseases, School of Public Health, Xiamen 361102, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quan","family":"Yuan","sequence":"additional","affiliation":[{"name":"State Key Laboratory of Infectious Disease Vaccine Development, Xiang An Biomedicine Laboratory, School of Public Health, Xiamen University, Xiamen 361102, China"},{"name":"NMPA Key Laboratory for Research and Evaluation of Infectious Disease Diagnostic Technology, National Institute of Diagnostics Vaccine Development in Infectious Diseases, School of Public Health, Xiamen 361102, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,5,3]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1017\/S0950268800001497","article-title":"Epidemiological patterns of hepatitis B virus (HBV) in highly endemic areas","volume":"117","author":"Edmunds","year":"1996","journal-title":"Epidemiol. Infect."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1335","DOI":"10.1016\/j.jhep.2021.07.030","article-title":"Infection courses, virological features and IFN-alpha responses of HBV genotypes in cell culture and animal models","volume":"75","author":"Zhang","year":"2021","journal-title":"J. Hepatol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"618","DOI":"10.1038\/s41575-020-0296-6","article-title":"The evolution and clinical impact of hepatitis B virus genome diversity","volume":"17","author":"Revill","year":"2020","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_4","unstructured":"World Health Organization (WHO) (2023, April 24). Hepatitis B. Available online: https:\/\/www.who.int\/news-room\/fact-sheets\/detail\/hepatitis-b."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2313","DOI":"10.1016\/S0140-6736(18)31865-8","article-title":"Chronic hepatitis B virus infection","volume":"392","author":"Seto","year":"2018","journal-title":"Lancet"},{"key":"ref_6","unstructured":"World Health Organization (WHO) (2016). Global Health Sector Strategy on Viral Hepatitis 2016\u20132021. Towards Ending Viral Hepatitis, World Health Organization."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/s12072-015-9675-4","article-title":"Asian-Pacific clinical practice guidelines on the management of hepatitis B: A 2015 update","volume":"10","author":"Sarin","year":"2016","journal-title":"Hepatol. Int."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"649","DOI":"10.1007\/s12072-019-09988-7","article-title":"APASL HCV guidelines of virus-eradicated patients by DAA on how to monitor HCC occurrence and HBV reactivation","volume":"13","author":"Kanda","year":"2019","journal-title":"Hepatol. Int."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"43","DOI":"10.1111\/apt.14376","article-title":"Review article: Hepatitis B core-related antigen (HBcrAg): An emerging marker for chronic hepatitis B virus infection","volume":"47","author":"Mak","year":"2018","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"700","DOI":"10.1016\/j.jhep.2016.05.029","article-title":"Serum hepatitis B virus RNA is encapsidated pregenome RNA that may be associated with persistence of viral infection and rebound","volume":"65","author":"Wang","year":"2016","journal-title":"J. Hepatol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1016\/j.cgh.2019.07.046","article-title":"Association Between Negative Results From Tests for HBV DNA and RNA and Durability of Response After Discontinuation of Nucles(t)ide Analogue Therapy","volume":"18","author":"Fan","year":"2020","journal-title":"Clin Gastroenterol Hepatol"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"727","DOI":"10.1038\/s41575-022-00649-z","article-title":"A roadmap for serum biomarkers for hepatitis B virus: Current status and future outlook","volume":"19","author":"Kramvis","year":"2022","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1080\/22221751.2022.2045874","article-title":"A standardized assay for the quantitative detection of serum HBV RNA in chronic hepatitis B patients","volume":"11","author":"Yu","year":"2022","journal-title":"Emerg. Microbes Infect."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1016\/j.jhep.2018.11.030","article-title":"Serum hepatitis B core-related antigen (HBcrAg) correlates with covalently closed circular DNA transcriptional activity in chronic hepatitis B patients","volume":"70","author":"Testoni","year":"2019","journal-title":"J. Hepatol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"745","DOI":"10.1111\/hepr.13761","article-title":"Management of hepatitis B virus (HBV) reactivation in patients with resolved HBV infection based on a highly sensitive HB core-related antigen assay","volume":"52","author":"Hagiwara","year":"2022","journal-title":"Hepatol. Res."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1136\/gutjnl-2012-302656","article-title":"Quantitative hepatitis B core antibody level may help predict treatment response in chronic hepatitis B patients","volume":"62","author":"Yuan","year":"2013","journal-title":"Gut"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"4215","DOI":"10.1128\/JVI.02844-06","article-title":"Characterization of hepatitis B virus (HBV)-specific T-cell dysfunction in chronic HBV infection","volume":"81","author":"Boni","year":"2007","journal-title":"J. Virol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"8623","DOI":"10.1073\/pnas.0809818106","article-title":"High antigen levels are the cause of T cell exhaustion during chronic viral infection","volume":"106","author":"Mueller","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"3617","DOI":"10.4049\/jimmunol.141.10.3617","article-title":"Comparative immunogenicity of hepatitis B virus core and E antigens","volume":"141","author":"Milich","year":"1988","journal-title":"J. Immunol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"6670","DOI":"10.4049\/jimmunol.0803683","article-title":"Interaction of the hepatitis B core antigen and the innate immune system","volume":"182","author":"Lee","year":"2009","journal-title":"J. Immunol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"467","DOI":"10.1089\/vim.2010.0042","article-title":"Hepatitis B virus e antigen downregulates cytokine production in human hepatoma cell lines","volume":"23","author":"Wu","year":"2010","journal-title":"Viral Immunol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"213","DOI":"10.3390\/diseases3030213","article-title":"HBV Core Protein Enhances Cytokine Production","volume":"3","author":"Kanda","year":"2015","journal-title":"Diseases"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1093\/infdis\/jis363","article-title":"Hepatitis B virus e antigen physically associates with receptor-interacting serine\/threonine protein kinase 2 and regulates IL-6 gene expression","volume":"206","author":"Wu","year":"2012","journal-title":"J. Infect. Dis."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"e793","DOI":"10.1002\/iid3.793","article-title":"Antibodies to Hepatitis B core antigen prevalence study in Kazakhstan","volume":"11","author":"Savchuk","year":"2023","journal-title":"Immun. Inflamm. Dis."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1","DOI":"10.15585\/mmwr.rr7201a1","article-title":"Contributors, Screening and Testing for Hepatitis B Virus Infection: CDC Recommendations\u2014United States, 2023","volume":"72","author":"Conners","year":"2023","journal-title":"MMWR Recomm. Rep."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e322","DOI":"10.1097\/MD.0000000000000322","article-title":"Antibody to hepatitis B core antigen levels in the natural history of chronic hepatitis B: A prospective observational study","volume":"93","author":"Jia","year":"2014","journal-title":"Medicine"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"3806","DOI":"10.1039\/C5NR90030A","article-title":"Dendritic polymers for smart drug delivery applications","volume":"7","author":"Khandare","year":"2015","journal-title":"Nanoscale"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"e4422","DOI":"10.1097\/MD.0000000000004422","article-title":"Quantitative hepatitis B core antibody level is associated with inflammatory activity in treatment-naive chronic hepatitis B patients","volume":"95","author":"Li","year":"2016","journal-title":"Medicine"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"E133","DOI":"10.1111\/hepr.12937","article-title":"Role of quantitative hepatitis B core antibody levels in predicting significant liver inflammation in chronic hepatitis B patients with normal or near-normal alanine aminotransferase levels","volume":"48","author":"Li","year":"2018","journal-title":"Hepatol. Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1806","DOI":"10.1111\/jgh.15881","article-title":"Serum qAnti-HBc combined with ALT and HBsAg predicts significant hepatic inflammation in HBeAg-positive immune active patients","volume":"37","author":"Wang","year":"2022","journal-title":"J. Gastroenterol. Hepatol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1016\/j.dld.2017.12.028","article-title":"A novel noninvasive index for the prediction of moderate to severe fibrosis in chronic hepatitis B patients","volume":"50","author":"Li","year":"2018","journal-title":"Dig. Liver Dis."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"11063","DOI":"10.18632\/oncotarget.14323","article-title":"Serum hepatitis B core antibody titer use in screening for significant fibrosis in treatment-naive patients with chronic hepatitis B","volume":"8","author":"Li","year":"2017","journal-title":"Oncotarget"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1052","DOI":"10.1016\/j.jcma.2018.05.007","article-title":"Correlations between serum hepatitis B surface antigen and hepatitis B core antibody titers and liver fibrosis in treatment-naive CHB patients","volume":"81","author":"Li","year":"2018","journal-title":"J. Chin. Med. Assoc."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"52","DOI":"10.1016\/j.jhep.2020.01.024","article-title":"Hepatitis B core-specific memory B cell responses associate with clinical parameters in patients with chronic HBV","volume":"73","author":"Vanwolleghem","year":"2020","journal-title":"J. Hepatol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1398","DOI":"10.1126\/science.3491425","article-title":"The nucleocapsid of hepatitis B virus is both a T-cell-independent and a T-cell-dependent antigen","volume":"234","author":"Milich","year":"1986","journal-title":"Science"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"6359","DOI":"10.1128\/JVI.75.14.6359-6366.2001","article-title":"Hepatitis B virus core antigen binds and activates naive human B cells in vivo: Studies with a human PBL-NOD\/SCID mouse model","volume":"75","author":"Cao","year":"2001","journal-title":"J. Virol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1038\/329547a0","article-title":"Antibody production to the nucleocapsid and envelope of the hepatitis B virus primed by a single synthetic T cell site","volume":"329","author":"Milich","year":"1987","journal-title":"Nature"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"3358","DOI":"10.1128\/jvi.69.6.3358-3368.1995","article-title":"Activation of a heterogeneous hepatitis B (HB) core and e antigen-specific CD4+ T-cell population during seroconversion to anti-HBe and anti-HBs in hepatitis B virus infection","volume":"69","author":"Jung","year":"1995","journal-title":"J. Virol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"14648","DOI":"10.1073\/pnas.94.26.14648","article-title":"Role of B cells in antigen presentation of the hepatitis B core","volume":"94","author":"Milich","year":"1997","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2747","DOI":"10.1038\/s41598-017-03102-3","article-title":"Serum hepatitis B core antibody as a biomarker of hepatic inflammation in chronic hepatitis B patients with normal alanine aminotransferase","volume":"7","author":"Zhou","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"3911","DOI":"10.1002\/jmv.27779","article-title":"Dose-response relationship between qAnti-HBc and liver inflammation in chronic hepatitis B with normal or mildly elevated alanine transaminase based on liver biopsy","volume":"94","author":"Zhang","year":"2022","journal-title":"J. Med. Virol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"101563","DOI":"10.1016\/j.clinre.2020.10.008","article-title":"Combination of quantitative hepatitis B core antibody (qHBcAb) and aspartate aminotransferase (AST) can accurately diagnose immune tolerance of chronic hepatitis B virus infection based on liver biopsy","volume":"45","author":"Chi","year":"2021","journal-title":"Clin. Res. Hepatol. Gastroenterol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"105315","DOI":"10.1016\/j.antiviral.2022.105315","article-title":"A novel model based on qAnti-HBc and conventional biomarkers for identifying significant liver injury among CHB patients with ALT <\/= ULN","volume":"202","author":"Feng","year":"2022","journal-title":"Antivir. Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"659","DOI":"10.1002\/jmv.27327","article-title":"Association of anti-HBc and liver inflammation in HBeAg-negative chronic hepatitis B virus-infected patients with normal ALT and detectable HBV DNA","volume":"94","author":"Yao","year":"2022","journal-title":"J. Med. Virol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"1903","DOI":"10.1002\/hep.30788","article-title":"Baseline Level of Hepatitis B Core Antibody Predicts Spontaneous Hepatitis B e Antigen (HBeAg) Seroconversion in HBeAg-Positive Children With a Normal Alanine Aminotransferase Level","volume":"70","author":"Chen","year":"2019","journal-title":"Hepatology"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1016\/j.cmi.2014.10.002","article-title":"Quantitative hepatitis B core antibody levels in the natural history of hepatitis B virus infection","volume":"21","author":"Song","year":"2015","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"301","DOI":"10.1016\/j.jhep.2018.03.021","article-title":"Quantitation of HBV cccDNA in anti-HBc-positive liver donors by droplet digital PCR: A new tool to detect occult infection","volume":"69","author":"Caviglia","year":"2018","journal-title":"J. Hepatol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1016\/j.jhep.2018.02.033","article-title":"Quantification of HBV core antibodies may help predict HBV reactivation in patients with lymphoma and resolved HBV infection","volume":"69","author":"Yang","year":"2018","journal-title":"J. Hepatol."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Liu, Y.-Q., Nuersulitan, R., Zhang, C., Na, H., Li, J., Song, Y.-Q., Zhu, J., Wang, G.-Q., Liu, W.-P., and Zhao, H. (2023). Steadily Decline of HBV DNA Load under NAs in Lymphoma Patients and Higher Level of qAnti-HBc Predict HBV Reactivation, Research Square.","DOI":"10.21203\/rs.3.rs-2596830\/v1"},{"key":"ref_50","doi-asserted-by":"crossref","unstructured":"Yuan, Q., Song, L.W., Cavallone, D., Moriconi, F., Cherubini, B., Colombatto, P., Oliveri, F., Coco, B.A., Ricco, G., and Bonino, F. (2015). Total Hepatitis B Core Antigen Antibody, a Quantitative Non-Invasive Marker of Hepatitis B Virus Induced Liver Disease. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0130209"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1111\/jvh.12895","article-title":"Quantification of serum markers of hepatitis B (HBV) and Delta virus (HDV) infections in patients with chronic HDV infection","volume":"25","author":"Ricco","year":"2018","journal-title":"J. Viral Hepat."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"283","DOI":"10.1111\/jvh.13804","article-title":"Kinetics and predictive value of HBcrAg, HBV RNA and anti-HBc during bulevirtide treatment of chronic HDV-infected patients","volume":"30","author":"Sandmann","year":"2023","journal-title":"J. Viral Hepat."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"556","DOI":"10.1002\/hep.21077","article-title":"Chronic hepatitis B in children after e antigen seroclearance: Final report of a 29-year longitudinal study","volume":"43","author":"Bortolotti","year":"2006","journal-title":"Hepatology"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1136\/gut.52.3.416","article-title":"A large population study of spontaneous HBeAg seroconversion and acute exacerbation of chronic hepatitis B infection: Implications for antiviral therapy","volume":"52","author":"Yuen","year":"2003","journal-title":"Gut"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"425","DOI":"10.1007\/s12072-009-9140-3","article-title":"HBeAg seroconversion as an important end point in the treatment of chronic hepatitis B","volume":"3","author":"Liaw","year":"2009","journal-title":"Hepatol. Int."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1136\/gutjnl-2014-308546","article-title":"Baseline quantitative hepatitis B core antibody titre alone strongly predicts HBeAg seroconversion across chronic hepatitis B patients treated with peginterferon or nucleos(t)ide analogues","volume":"65","author":"Fan","year":"2016","journal-title":"Gut"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"218","DOI":"10.7150\/thno.10636","article-title":"Quantitative hepatitis B core antibody level is a new predictor for treatment response in HBeAg-positive chronic hepatitis B patients receiving peginterferon","volume":"5","author":"Hou","year":"2015","journal-title":"Theranostics"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1111\/jvh.12626","article-title":"Baseline hepatitis B core antibody predicts treatment response in chronic hepatitis B patients receiving long-term entecavir","volume":"24","author":"Xu","year":"2017","journal-title":"J. Viral Hepat."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"469","DOI":"10.2147\/IDR.S163038","article-title":"Serum hepatitis B core antibody levels predict HBeAg seroconversion in chronic hepatitis B patients with high viral load treated with nucleos(t)ide analogs","volume":"11","author":"Cai","year":"2018","journal-title":"Infect. Drug Resist."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1206","DOI":"10.1002\/jmv.25628","article-title":"Development and validation of a model for hepatitis B e antigen seroconversion in entecavir-treated patients with chronic hepatitis B","volume":"92","author":"Shen","year":"2020","journal-title":"J. Med. Virol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"105146","DOI":"10.1016\/j.antiviral.2021.105146","article-title":"Baseline serum hepatitis B core antibody level predicts HBeAg seroconversion in patients with HBeAg-positive chronic hepatitis B after antiviral treatment","volume":"193","author":"Zhao","year":"2021","journal-title":"Antivir. Res."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"126","DOI":"10.1177\/13596535211059895","article-title":"A baseline model including quantitative anti-HBc to predict response of peginterferon in HBeAg-positive chronic hepatitis B patients","volume":"26","author":"Fang","year":"2021","journal-title":"Antivir. Ther."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1093\/infdis\/jiac210","article-title":"Levels of Antibodies to Hepatitis B Core Antigen Are Associated With Liver Inflammation and Response to Peginterferon in Patients With Chronic Hepatitis B","volume":"227","author":"Brakenhoff","year":"2022","journal-title":"J. Infect. Dis."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"1413","DOI":"10.1016\/j.cgh.2018.09.037","article-title":"Association Between High Levels of Hepatitis B Core Antibody and Seroclearance of Hepatitis B e Antigen in Individuals With Chronic Hepatitis B Virus Infection","volume":"17","author":"Liu","year":"2019","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"172","DOI":"10.1016\/j.cgh.2018.04.064","article-title":"Level of Hepatitis B (HB) Core Antibody Associates With Seroclearance of HBV DNA and HB Surface Antigen in HB e Antigen-Seronegative Patients","volume":"17","author":"Hu","year":"2019","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1007\/s10620-021-06845-2","article-title":"Anti-HBc IgG Levels: A Predictor of HBsAg Seroclearance in Chronic Hepatitis B Patients with Nucleos(t)ide Analogue-Induced HBeAg Seroclearance","volume":"67","author":"Kim","year":"2022","journal-title":"Dig. Dis. Sci."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"894410","DOI":"10.3389\/fimmu.2022.894410","article-title":"Quantitative anti-HBc combined with quantitative HBsAg can predict HBsAg clearance in sequential combination therapy with PEG-IFN-alpha in NA-suppressed chronic hepatitis B patients","volume":"13","author":"Wang","year":"2022","journal-title":"Front. Immunol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1016\/j.cgh.2018.05.047","article-title":"Serum Level of Antibodies Against Hepatitis B Core Protein Is Associated with Clinical Relapse after Discontinuation of Nucleos(t)ide Analogue Therapy","volume":"17","author":"Chi","year":"2019","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"915","DOI":"10.1016\/j.jfma.2017.11.012","article-title":"Quantification of serum hepatitis B core antibody to predict off-entecavir relapse in patients with chronic hepatitis B","volume":"117","author":"Tseng","year":"2018","journal-title":"J. Formos. Med. Assoc."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"406","DOI":"10.1016\/S2468-1253(19)30344-9","article-title":"Serum alanine aminotransferase flares in chronic hepatitis B infection: The good and the bad","volume":"5","author":"Ghany","year":"2020","journal-title":"Lancet Gastroenterol. Hepatol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1016\/j.cgh.2018.08.003","article-title":"Quantification of Antibody to Hepatitis B Core Antigen to Predict Outcomes of Patients With HBV Infection","volume":"17","author":"Lim","year":"2019","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1291","DOI":"10.1111\/jgh.15310","article-title":"Prognostic value of anti-HBc quantification in hepatitis B virus related acute-on-chronic liver failure","volume":"36","author":"Li","year":"2021","journal-title":"J. Gastroenterol. Hepatol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"710528","DOI":"10.3389\/fimmu.2021.710528","article-title":"Baseline Quantitative Hepatitis B Core Antibody Titer Is a Predictor for Hepatitis B Virus Infection Recurrence After Orthotopic Liver Transplantation","volume":"12","author":"Lou","year":"2021","journal-title":"Front. Immunol."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"1204","DOI":"10.1016\/j.immuni.2016.04.008","article-title":"Maternal-Derived Hepatitis B Virus e Antigen Alters Macrophage Function in Offspring to Drive Viral Persistence after Vertical Transmission","volume":"44","author":"Tian","year":"2016","journal-title":"Immunity"},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"Yang, F., Yu, X., Zhou, C., Mao, R., Zhu, M., Zhu, H., Ma, Z., Mitra, B., Zhao, G., and Huang, Y. (2019). Hepatitis B e antigen induces the expansion of monocytic myeloid-derived suppressor cells to dampen T-cell function in chronic hepatitis B virus infection. PLoS Pathog., 15.","DOI":"10.1371\/journal.ppat.1007690"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"762","DOI":"10.1016\/j.jhep.2010.12.042","article-title":"The hepatitis B e antigen (HBeAg) targets and suppresses activation of the toll-like receptor signaling pathway","volume":"55","author":"Lang","year":"2011","journal-title":"J. Hepatol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"455","DOI":"10.1002\/JLB.5MA0620-023RR","article-title":"Identification of the association between HBcAg-specific T cell and viral control in chronic HBV infection using a cultured ELISPOT assay","volume":"109","author":"Chen","year":"2021","journal-title":"J. Leukoc. Biol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"8766","DOI":"10.1073\/pnas.1003854107","article-title":"B cell gene signature with massive intrahepatic production of antibodies to hepatitis B core antigen in hepatitis B virus-associated acute liver failure","volume":"107","author":"Farci","year":"2010","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"407","DOI":"10.1002\/jmv.24067","article-title":"Direct role of antibody-secreting B cells in the severity of chronic hepatitis B","volume":"87","author":"Zgair","year":"2015","journal-title":"J. Med. Virol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"E11369","DOI":"10.1073\/pnas.1809028115","article-title":"Role of humoral immunity against hepatitis B virus core antigen in the pathogenesis of acute liver failure","volume":"115","author":"Chen","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"4573","DOI":"10.1172\/JCI121957","article-title":"PD-1 blockade partially recovers dysfunctional virus-specific B cells in chronic hepatitis B infection","volume":"128","author":"Salimzadeh","year":"2018","journal-title":"J. Clin. Investig."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"34","DOI":"10.1016\/j.jhep.2019.07.015","article-title":"Comparative characterization of B cells specific for HBV nucleocapsid and envelope proteins in patients with chronic hepatitis B","volume":"72","author":"Salimzadeh","year":"2020","journal-title":"J. Hepatol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"e00798-18","DOI":"10.1128\/JVI.00798-18","article-title":"Extracellular Hepatitis B Virus RNAs Are Heterogeneous in Length and Circulate as Capsid-Antibody Complexes in Addition to Virions in Chronic Hepatitis B Patients","volume":"92","author":"Bai","year":"2018","journal-title":"J. Virol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1111\/j.1462-5822.2010.01557.x","article-title":"Alix regulates egress of hepatitis B virus naked capsid particles in an ESCRT-independent manner","volume":"13","author":"Bardens","year":"2011","journal-title":"Cell. Microbiol."},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Zhang, X., Tang, Y., Wu, M., Wang, C., Hu, L., and Zhang, Z. (2022). The Origin of Capsid-Derived Immune Complexes and Their Impact on HBV-Induced Liver Diseases. Viruses, 14.","DOI":"10.3390\/v14122766"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"001733","DOI":"10.1099\/jgv.0.001733","article-title":"The role of hepatitis B virus surface proteins in regulating the maturation and secretion of complete and incomplete virions","volume":"103","author":"Xu","year":"2022","journal-title":"J. Gen. Virol."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1186\/s12929-022-00827-w","article-title":"Hepatitis B virus virion secretion is a CRM1-spike-mediated late event","volume":"29","author":"Su","year":"2022","journal-title":"J. Biomed. Sci."},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Lazarevic, I., Banko, A., Miljanovic, D., and Cupic, M. (2023). Clinical Utility of Quantitative HBV Core Antibodies for Solving Diagnostic Dilemmas. 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