{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T14:55:09Z","timestamp":1773068109056,"version":"3.50.1"},"reference-count":85,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2026,3,7]],"date-time":"2026-03-07T00:00:00Z","timestamp":1772841600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>In October 2020, the International Coalition to Eliminate Hepatitis B Virus (ICE-HBV) updated the biomarker framework; they underscored major advances in the understanding of viral and immunologic markers, yet highlighted persistent gaps in their clinical integration. This is particularly the case in low- and middle-income regions, where HBV remains a substantial public health problem, including in the pediatric population. To synthesize contemporary evidence, a structured literature search was performed across PubMed\/MEDLINE, Scopus, and Web of Science. Classical biomarkers\u2014including HBeAg, HBV DNA, and quantitative HBsAg\u2014remain central for disease staging and therapeutic monitoring, while emerging markers enhance precision in risk stratification: HBcrAg, which correlates strongly with intrahepatic cccDNA activity and virological rebound after NA discontinuation; serum HBV RNA, which offers additional insight into transcriptional activity, which is particularly relevant for RNA-targeted therapies; and quantitative anti-HBc (qAnti-HBc), which reflects stronger humoral imprinting and more competent HBV-specific immune memory, and is consistently associated with fewer ALT flares and reduced virological rebound at end of treatment. Despite these advances, assay standardization, genotype-related variability, and limited pediatric data constrain broad clinical application. Integrating classical and emerging biomarkers into personalized therapeutic algorithms offers substantial potential for refining treatment decisions, predicting post-treatment outcomes, and advancing HBV elimination strategies in diverse clinical settings.<\/jats:p>","DOI":"10.3390\/ijms27052464","type":"journal-article","created":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T10:16:12Z","timestamp":1773051372000},"page":"2464","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Accuracy of Diagnostic Investigations in Monitoring Hepatitis B Virus Infection: Strengths, Limitations, and Emerging Biomarkers"],"prefix":"10.3390","volume":"27","author":[{"given":"Laura Iulia","family":"Bozomitu","sequence":"first","affiliation":[{"name":"Grigore T. Popa University of Medicine and Pharmacy Iasi, 700115 Iasi, Romania"},{"name":"Pediatrics\u2014\u201cSf. Maria\u201d Clinical Emergency Children Hospital, 700309 Iasi, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8147-3632","authenticated-orcid":false,"given":"Ancuta","family":"Lupu","sequence":"additional","affiliation":[{"name":"Grigore T. Popa University of Medicine and Pharmacy Iasi, 700115 Iasi, Romania"},{"name":"Pediatrics\u2014\u201cSf. Maria\u201d Clinical Emergency Children Hospital, 700309 Iasi, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2640-8795","authenticated-orcid":false,"given":"Vasile Valeriu","family":"Lupu","sequence":"additional","affiliation":[{"name":"Grigore T. Popa University of Medicine and Pharmacy Iasi, 700115 Iasi, Romania"},{"name":"Pediatrics\u2014\u201cSf. Maria\u201d Clinical Emergency Children Hospital, 700309 Iasi, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8713-5367","authenticated-orcid":false,"given":"Nicoleta","family":"Gimiga","sequence":"additional","affiliation":[{"name":"Grigore T. Popa University of Medicine and Pharmacy Iasi, 700115 Iasi, Romania"},{"name":"Pediatrics\u2014\u201cSf. Maria\u201d Clinical Emergency Children Hospital, 700309 Iasi, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8657-378X","authenticated-orcid":false,"given":"Dana Teodora","family":"Anton Paduraru","sequence":"additional","affiliation":[{"name":"Grigore T. Popa University of Medicine and Pharmacy Iasi, 700115 Iasi, Romania"},{"name":"Pediatrics\u2014\u201cSf. Maria\u201d Clinical Emergency Children Hospital, 700309 Iasi, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dana Elena","family":"M\u00eendru","sequence":"additional","affiliation":[{"name":"Grigore T. Popa University of Medicine and Pharmacy Iasi, 700115 Iasi, Romania"},{"name":"Pediatrics\u2014\u201cSf. Maria\u201d Clinical Emergency Children Hospital, 700309 Iasi, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mihaela","family":"Mihai","sequence":"additional","affiliation":[{"name":"Grigore T. Popa University of Medicine and Pharmacy Iasi, 700115 Iasi, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7717-1738","authenticated-orcid":false,"given":"Carmen","family":"Anton","sequence":"additional","affiliation":[{"name":"Grigore T. Popa University of Medicine and Pharmacy Iasi, 700115 Iasi, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8244-0522","authenticated-orcid":false,"given":"Emil","family":"Anton","sequence":"additional","affiliation":[{"name":"Grigore T. Popa University of Medicine and Pharmacy Iasi, 700115 Iasi, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mihaela","family":"Mitrea","sequence":"additional","affiliation":[{"name":"Grigore T. Popa University of Medicine and Pharmacy Iasi, 700115 Iasi, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1979-8174","authenticated-orcid":false,"given":"Anca","family":"Adam-Raileanu","sequence":"additional","affiliation":[{"name":"Grigore T. Popa University of Medicine and Pharmacy Iasi, 700115 Iasi, Romania"},{"name":"Pediatrics\u2014\u201cSf. Maria\u201d Clinical Emergency Children Hospital, 700309 Iasi, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0908-0495","authenticated-orcid":false,"given":"Lorenza","family":"Forna","sequence":"additional","affiliation":[{"name":"Grigore T. Popa University of Medicine and Pharmacy Iasi, 700115 Iasi, Romania"},{"name":"Pediatrics\u2014\u201cSf. Maria\u201d Clinical Emergency Children Hospital, 700309 Iasi, Romania"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1007\/s12072-008-9050-9","article-title":"Natural history and clinical management of chronic hepatitis B virus infection in children","volume":"2","author":"Chang","year":"2008","journal-title":"Hepatol. Int."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Forna, L., Bozomitu, L., Lupu, A., Lupu, V.V., Cojocariu, C., Anton, C., Girleanu, I., Singeap, A.M., Muzica, C.M., and Trifan, A. (2024). Insights into the Natural and Treatment Courses of Hepatitis B in Children: A Retrospective Study. Biomedicines, 12.","DOI":"10.3390\/biomedicines12071585"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e00046-19","DOI":"10.1128\/CMR.00046-19","article-title":"Hepatitis B Virus: Advances in Prevention, Diagnosis, and Therapy","volume":"33","author":"Nguyen","year":"2020","journal-title":"Clin. Microbiol. Rev."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"561","DOI":"10.1016\/j.semcancer.2013.08.006","article-title":"Possible origins and evolution of the hepatitis B virus (HBV)","volume":"23","author":"Locarnini","year":"2013","journal-title":"Semin. Cancer Biol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"583","DOI":"10.1016\/j.cgh.2024.07.036","article-title":"Predictors of Functional Cure of Chronic Hepatitis B Virus Infection: A Long-Term Follow-Up Study","volume":"23","author":"Wu","year":"2025","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1016\/j.jceh.2012.10.003","article-title":"Molecular biology of the hepatitis B virus for clinicians","volume":"2","author":"Datta","year":"2012","journal-title":"J. Clin. Exp. Hepatol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/S0076-6879(96)75013-9","article-title":"Expression and characterization of hepadnavirus reverse transcriptases","volume":"275","author":"Hu","year":"1996","journal-title":"Methods Enzymol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"199","DOI":"10.35772\/ghm.2023.01065","article-title":"Biology of the hepatitis B virus (HBV) core and capsid assembly modulators (CAMs) for chronic hepatitis B (CHB) cure","volume":"5","author":"McFadden","year":"2023","journal-title":"Glob. Health Med."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"19975","DOI":"10.1073\/pnas.0908365106","article-title":"Nuclear HBx binds the HBV minichromosome and modifies the epigenetic regulation of cccDNA function","volume":"106","author":"Belloni","year":"2009","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"2846","DOI":"10.1016\/j.celrep.2016.08.026","article-title":"Hepatitis B Virus X Protein Promotes Degradation of SMC5\/6 to Enhance HBV Replication","volume":"16","author":"Murphy","year":"2016","journal-title":"Cell Rep."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1491","DOI":"10.1128\/JVI.02500-12","article-title":"Role of transmembrane domains of hepatitis B virus small surface proteins in subviral-particle biogenesis","volume":"87","author":"Siegler","year":"2013","journal-title":"J. Virol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/j.antiviral.2015.06.008","article-title":"Chronic hepatitis B: Virology, natural history, current management and a glimpse at future opportunities","volume":"121","author":"Gish","year":"2015","journal-title":"Antivir. Res."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1045","DOI":"10.1002\/hep.30474","article-title":"The Role of Hepatitis B Surface Antigen in Nucleos(t)ide Analogues Cessation Among Asian Patients With Chronic Hepatitis B: A Systematic Review","volume":"70","author":"Liu","year":"2019","journal-title":"Hepatology"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"17","DOI":"10.3350\/cmh.2021.0093","article-title":"Toward a complete cure for chronic hepatitis B: Novel therapeutic targets for hepatitis B virus","volume":"28","author":"Kim","year":"2022","journal-title":"Clin. Mol. Hepatol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"153","DOI":"10.1111\/jvh.12222","article-title":"Occult hepatitis B virus infection and hepatocellular carcinoma: A systematic review","volume":"21","author":"Huang","year":"2014","journal-title":"J. Viral Hepat."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"474","DOI":"10.1055\/a-2448-4157","article-title":"HBV Biomarkers and Their Role in Guiding Treatment Decisions","volume":"44","author":"Mak","year":"2024","journal-title":"Semin. Liver Dis."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1016\/j.jhep.2012.03.036","article-title":"Chronic hepatitis B in children and adolescents","volume":"57","author":"Paganelli","year":"2012","journal-title":"J. Hepatol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1002\/hep.28156","article-title":"AASLD guidelines for treatment of chronic hepatitis B","volume":"63","author":"Terrault","year":"2016","journal-title":"Hepatology"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1520","DOI":"10.1002\/hep.32479","article-title":"Circulating HBV RNA: From biology to clinical applications","volume":"76","author":"Deng","year":"2022","journal-title":"Hepatology"},{"key":"ref_20","unstructured":"Seto, W.-K., and Eslam, M. (2023). Chapter 7\u2014Hepatitis B: Epidemiology, Natural History, and Diagnosis. Comprehensive Guide 403 to Hepatitis Advances, Academic Press."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1111\/liv.14364","article-title":"Can we cure hepatitis B virus with novel direct-acting antivirals?","volume":"40","author":"Martinez","year":"2020","journal-title":"Liver Int."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"6979","DOI":"10.12998\/wjcc.v9.i24.6979","article-title":"Discontinuation of antiviral therapy in chronic hepatitis B patients","volume":"9","author":"Medas","year":"2021","journal-title":"World J. Clin. Cases"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1111\/apt.13272","article-title":"Systematic review: Cessation of long-term nucleos(t)ide analogue therapy in patients with hepatitis B e antigen-negative chronic hepatitis B","volume":"42","author":"Chang","year":"2015","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1007\/s11262-020-01733-9","article-title":"Peculiarities in the designations of hepatitis B virus genes, their products, and their antigenic specificities: A potential source of misunderstandings","volume":"56","author":"Gerlich","year":"2020","journal-title":"Virus Genes"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"S4","DOI":"10.1016\/j.jhep.2016.01.027","article-title":"Overview of hepatitis B viral replication and genetic variability","volume":"64","author":"Tong","year":"2016","journal-title":"J. Hepatol."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Niklasch, M., Zimmermann, P., and Nassal, M. (2021). The Hepatitis B Virus Nucleocapsid-Dynamic Compartment for Infectious Virus Production and New Antiviral Target. Biomedicines, 9.","DOI":"10.3390\/biomedicines9111577"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"936","DOI":"10.1111\/jvh.13091","article-title":"Can we stop nucleoside analogues before HBsAg loss?","volume":"26","author":"Papatheodoridi","year":"2019","journal-title":"J. Viral Hepat."},{"key":"ref_28","first-page":"e19152","article-title":"Critical Updates on Chronic Hepatitis B Virus Infection in 2021","volume":"13","author":"Philips","year":"2021","journal-title":"Cureus"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"257","DOI":"10.1021\/acsinfecdis.7b00144","article-title":"Discovery of Small Molecule Therapeutics for Treatment of Chronic HBV Infection","volume":"4","author":"Feng","year":"2018","journal-title":"ACS Infect. Dis."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1053\/j.gastro.2018.11.037","article-title":"New and old biomarkers for diagnosis and management of chronic hepatitis B virus infection","volume":"156","author":"Coffin","year":"2019","journal-title":"Gastroenterology"},{"key":"ref_31","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_32","doi-asserted-by":"crossref","first-page":"706","DOI":"10.1016\/j.jhep.2021.05.013","article-title":"Covalently closed circular DNA: The ultimate therapeutic target for curing HBV infections","volume":"75","author":"Martinez","year":"2021","journal-title":"J. Hepatol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1016\/j.ymeth.2021.05.011","article-title":"Droplet digital PCR assay as an innovative and promising highly sensitive assay to unveil residual and cryptic HBV replication in peripheral compartment","volume":"201","author":"Piermatteo","year":"2022","journal-title":"Methods"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2972","DOI":"10.1128\/JCM.00760-17","article-title":"Serum hepatitis B virus DNA, RNA, and HBsAg: Which correlated better with intrahepatic covalently closed circular DNA before and after nucleos(t)ide analogue treatment?","volume":"55","author":"Gao","year":"2017","journal-title":"J. Clin. Microbiol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"2106","DOI":"10.1002\/hep.30082","article-title":"Hepatitis B virus serum DNA and RNA levels in nucleos(t)ide analog-treated or untreated patients during chronic and acute infection","volume":"68","author":"Butler","year":"2018","journal-title":"Hepatology"},{"key":"ref_36","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_37","doi-asserted-by":"crossref","first-page":"1720","DOI":"10.1111\/apt.14684","article-title":"Letter: Serum HBcrAg is a useful marker for disease monitoring, predicting treatment response and disease outcome of chronic hepatitis B virus infection-authors\u2019 reply","volume":"47","author":"Mak","year":"2018","journal-title":"Aliment. Pharmacol. Ther."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"e01695-20","DOI":"10.1128\/JVI.01695-20","article-title":"Characterization of hepatitis B precore\/core-related antigens","volume":"95","author":"Hong","year":"2021","journal-title":"J. Virol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"436","DOI":"10.1093\/jac\/dkac409","article-title":"Combined baseline HBcrAg and end-of-treatment HBsAg predict HBV relapse after entecavir or tenofovir cessation","volume":"78","author":"Tseng","year":"2023","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1002\/hep.31026","article-title":"Pregenomic HBV RNA and Hepatitis B Core-Related Antigen Predict Outcomes in Hepatitis B e Antigen-Negative Chronic Hepatitis B Patients Suppressed on Nucleos(T)ide Analogue Therapy","volume":"72","author":"Carey","year":"2020","journal-title":"Hepatology"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"731","DOI":"10.1016\/j.jhep.2022.12.017","article-title":"A critique and systematic review of the clinical utility of hepatitis B core-related antigen","volume":"78","author":"Adraneda","year":"2023","journal-title":"J. Hepatol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"S343","DOI":"10.1093\/infdis\/jiaa668","article-title":"Hepatitis B Vaccines","volume":"224","author":"Pattyn","year":"2021","journal-title":"J. Infect. Dis."},{"key":"ref_43","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_44","doi-asserted-by":"crossref","first-page":"13293","DOI":"10.3748\/wjg.v20.i37.13293","article-title":"Update on hepatitis B virus infection","volume":"20","author":"You","year":"2014","journal-title":"World J. Gastroenterol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"501","DOI":"10.1111\/jgh.14534","article-title":"Okuda lecture: Challenges of hepatitis B in the era of antiviral therapy","volume":"34","author":"Chan","year":"2019","journal-title":"J. Gastroenterol. Hepatol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"36","DOI":"10.1007\/s11901-025-00710-w","article-title":"Strategies to Achieve Functional Cure in HBV: Focus on siRNA","volume":"24","author":"Karthikeyan","year":"2025","journal-title":"Curr. Hepatol. Rep."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1007\/s11684-017-0590-z","article-title":"Potential use of serum HBV RNA in antiviral therapy for chronic hepatitis B in the era of nucleos(t)ide analogs","volume":"11","author":"Lu","year":"2017","journal-title":"Front. Med."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Hall, S., Howell, J., Visvanathan, K., and Thompson, A. (2020). The Yin and the Yang of Treatment for Chronic Hepatitis B-When to Start, When to Stop Nucleos(t)ide Analogue Therapy. Viruses, 12.","DOI":"10.3390\/v12090934"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1320","DOI":"10.1007\/s12072-025-10907-2","article-title":"Do the therapeutic vaccines hold hope for the treatment of hepatitis B?","volume":"19","author":"Yan","year":"2025","journal-title":"Hepatol. Int."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1093\/infdis\/jiv397","article-title":"Hepatitis B virus pregenomic RNA is present in virions in plasma and is associated with a response to pegylated interferon Alfa-2a and nucleos(t)ide analogues","volume":"213","author":"Jansen","year":"2016","journal-title":"J. Infect. Dis."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"100112","DOI":"10.1016\/j.jhepr.2020.100112","article-title":"Rebound of HBV DNA after cessation of nucleos\/tide analogues in chronic hepatitis B patients with undetectable covalently closed","volume":"2","author":"Lai","year":"2020","journal-title":"JHEP Rep."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1007\/s12072-023-10631-9","article-title":"Functional cure is associated with younger age in children undergoing antiviral treatment for active chronic hepatitis B","volume":"18","author":"Zhang","year":"2024","journal-title":"Hepatol. Int."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"704","DOI":"10.1007\/s12072-025-10828-0","article-title":"Emerging therapies for HBsAg seroclearance: Spotlight on novel combination strategies","volume":"19","author":"Hui","year":"2025","journal-title":"Hepatol. Int."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"775","DOI":"10.1136\/gutjnl-2020-321116","article-title":"Role of serum HBV RNA and hepatitis B surface antigen levels in identifying Asian patients with chronic hepatitis B suitable for entecavir cessation","volume":"70","author":"Seto","year":"2021","journal-title":"Gut"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1016\/j.jhep.2017.08.021","article-title":"Relationship between serum HBV-RNA levels and intrahepatic viral as well as histologic activity markers in entecavir-treated patients","volume":"68","author":"Wang","year":"2018","journal-title":"J. Hepatol."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1016\/j.jhep.2018.05.004","article-title":"Hepatitis B virus-specific T cell responses after stopping nucleos(t)ide analogue therapy in HBeAg-negative chronic hepatitis B","volume":"69","author":"Rinker","year":"2018","journal-title":"J. Hepatol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"2605","DOI":"10.1111\/liv.16029","article-title":"High end-of-treatment hepatitis B core-related antigen levels predict hepatitis flare after stopping nucleot(s)ide analogue therapy","volume":"44","author":"Hume","year":"2024","journal-title":"Liver Int."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1093\/infdis\/jiaa136","article-title":"Combining Hepatitis B Virus RNA and Hepatitis B Core-Related Antigen: Guidance for Safely Stopping Nucleos(t)ide Analogues in Hepatitis B e Antigen-Positive Patients With Chronic Hepatitis B","volume":"222","author":"Fan","year":"2020","journal-title":"J. Infect. Dis."},{"key":"ref_59","first-page":"37","article-title":"Pediatric Hepatitis B Treatment","volume":"5","author":"Komatsu","year":"2017","journal-title":"Ann. Transl. Med."},{"key":"ref_60","first-page":"649","article-title":"96-Week Treatment of Tenofovir Amibufenamide and Tenofovir Disoproxil Fumarate in Chronic Hepatitis B Patients","volume":"11","author":"Liu","year":"2023","journal-title":"J. Clin. Transl. Hepatol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"238","DOI":"10.1038\/s41575-022-00724-5","article-title":"The scientific basis of combination therapy for chronic hepatitis B functional cure","volume":"20","author":"Lim","year":"2023","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"502","DOI":"10.1016\/j.jhep.2025.03.018","article-title":"EASL Clinical Practice Guidelines on the management of hepatitis B virus infection","volume":"83","author":"Cornberg","year":"2025","journal-title":"J. Hepatol."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"e145421","DOI":"10.5812\/hepatmon-145421","article-title":"Relationship Between Serum HBV-RNA Levels, Sero-biochemical Indices, and Clinicopathological Parameters in Patients with Hepatitis B Virus","volume":"24","author":"Liang","year":"2024","journal-title":"Hepat. Mon."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"e144239","DOI":"10.5812\/hepatmon-144239","article-title":"Unraveling the Mechanisms of MicroRNA in Suppressing Hepatitis B Virus Progression: A Comprehensive Review for Designing Treatment Strategies","volume":"24","author":"Song","year":"2024","journal-title":"Hepat. Mon."},{"key":"ref_65","first-page":"e0656","article-title":"Serum levels of hepatitis B core antibodies and hepatitis B core-related antigen at the time of nucleos(t)ide analog cessation and risk of severe flares in patients with chronic hepatitis B","volume":"9","author":"Verbinnen","year":"2025","journal-title":"Hepatol. Commun."},{"key":"ref_66","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_67","doi-asserted-by":"crossref","first-page":"2674","DOI":"10.1111\/liv.15433","article-title":"Low anti-HBc levels are associated with lower risk of virological relapse after nucleos(t)ide analogue cessation in HBe antigen-negative patients","volume":"42","author":"Ohlendorf","year":"2022","journal-title":"Liver Int."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1004","DOI":"10.1016\/j.cgh.2013.01.026","article-title":"Reduction of hepatitis B surface antigen and covalently closed circular DNA by nucleos(t)ide analogues of different potency","volume":"11","author":"Wong","year":"2013","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"557","DOI":"10.1016\/j.jhep.2018.10.003","article-title":"Over-gap PCR amplification to identify presence of replication-competent HBV DNA from integrated HBV DNA: An updated occult HBV infection definition","volume":"70","author":"Liu","year":"2019","journal-title":"J. Hepatol."},{"key":"ref_70","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_71","doi-asserted-by":"crossref","first-page":"397","DOI":"10.1016\/j.jhep.2019.03.034","article-title":"Update of the statements on biology and clinical impact of occult hepatitis B virus infection","volume":"71","author":"Raimondo","year":"2019","journal-title":"J. Hepatol."},{"key":"ref_72","doi-asserted-by":"crossref","unstructured":"Sosa-Jurado, F., Mel\u00e9ndez-Mena, D., Rosas-Murrieta, N.H., Guzm\u00e1n-Flores, B., Mendoza-Torres, M.A., Barcenas-Villalobos, R., M\u00e1rquez-Dom\u00ednguez, L., Cort\u00e9s-Hern\u00e1ndez, P., Reyes-Leyva, J., and Vallejo-Ruiz, V. (2018). Effectiveness of PCR primers for the detection of occult hepatitis B virus infection in Mexican patients. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0205356"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"e70023","DOI":"10.1111\/jvh.70023","article-title":"Development and Validation of a High-Sensitivity Droplet Digital PCR Assay for Serum Hepatitis B Virus DNA Detection","volume":"32","author":"Hui","year":"2025","journal-title":"J. Viral Hepat."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"187","DOI":"10.3851\/IMP3288","article-title":"Behaviour of Occult HBV Infection in HCV-Infected Patients under Treatment with Direct-Acting Antivirals","volume":"24","author":"Musolino","year":"2018","journal-title":"Antivir. Ther."},{"key":"ref_75","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_76","doi-asserted-by":"crossref","unstructured":"Zuccaro, V., Asperges, E., Colaneri, M., Marvulli, L.N., and Bruno, R. (2021). HBV and HDV: New Treatments on the Horizon. J. Clin. Med., 10.","DOI":"10.3390\/jcm10184054"},{"key":"ref_77","doi-asserted-by":"crossref","unstructured":"Saitta, C., Pollicino, T., and Raimondo, G. (2022). Occult Hepatitis B Virus Infection: An Update. Viruses, 14.","DOI":"10.3390\/v14071504"},{"key":"ref_78","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_79","doi-asserted-by":"crossref","unstructured":"Chien, R.N., and Liaw, Y.F. (2022). Current Trend in Antiviral Therapy for Chronic Hepatitis B. Viruses, 14.","DOI":"10.3390\/v14020434"},{"key":"ref_80","first-page":"92","article-title":"Hepatitis B Virus Infection during Pregnancy: Transmission and Prevention","volume":"3","author":"Navabakhsh","year":"2011","journal-title":"Middle East. J. Dig. Dis."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1016\/j.jcv.2016.02.003","article-title":"Management of mother-to-child transmission of hepatitis B virus: Propositions and challenges","volume":"77","author":"Yi","year":"2016","journal-title":"J. Clin. Virol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1007\/s12072-025-10888-2","article-title":"Combination therapies for chronic hepatitis B in the era of emerging novel drugs","volume":"20","author":"Weng","year":"2025","journal-title":"Hepatol. Int."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"2098","DOI":"10.1056\/NEJMoa2405485","article-title":"Xalnesiran with or without an Immunomodulator in Chronic Hepatitis B","volume":"391","author":"Hou","year":"2024","journal-title":"N. Engl. J. Med."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"497","DOI":"10.5009\/gnl17233","article-title":"Immunotherapy for Chronic Hepatitis B Virus Infection","volume":"12","author":"Bertoletti","year":"2018","journal-title":"Gut Liver"},{"key":"ref_85","first-page":"88","article-title":"Latest developments in the treatment of hepatitis B","volume":"62","author":"Dandri","year":"2016","journal-title":"Minerva Gastroenterol. E Dietol."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/5\/2464\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,3,9]],"date-time":"2026-03-09T10:18:44Z","timestamp":1773051524000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/27\/5\/2464"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,3,7]]},"references-count":85,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2026,3]]}},"alternative-id":["ijms27052464"],"URL":"https:\/\/doi.org\/10.3390\/ijms27052464","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,3,7]]}}}