{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T16:32:57Z","timestamp":1786725177939,"version":"build-2736575974"},"reference-count":29,"publisher":"MDPI AG","issue":"8","license":[{"start":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T00:00:00Z","timestamp":1786665600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Background\/Objectives: Isolated anti-HBc (IAHBc)\u2014anti-HBc reactivity without HBsAg or anti-HBs\u2014may indicate occult HBV infection (OBI) and confers reactivation risk under immunosuppression, yet most evidence derives from single specialties. We assessed the frequency, predictors, and diagnostic yield of detectable HBV DNA across multiple clinical specialties in a large real-world cohort to inform risk-based testing. Methods: In this 8-year, single-center retrospective study from an intermediate-endemic setting, 36,506 patients were screened for HBsAg, anti-HBs, and anti-HBc IgG. Patients with the IAHBc pattern who underwent HBV DNA testing formed the analytic cohort. Predictors of HBV DNA positivity were identified by multivariable logistic regression, and the number needed to screen (NNS) was calculated per specialty. Results: IAHBc prevalence was 4.16% (1517\/36,506); 1412 patients comprised the analytic cohort (median age 60 years; 55.2% male). HBV DNA was detectable in 117 patients (8.3% of the cohort; 0.32% of all screened). Positivity varied more than fifteen-fold across specialties, with NNS ranging from 4.3 in gastroenterology to 66 in other clinics. High-intensity immunosuppression was the strongest independent predictor (adjusted OR 14.5), alongside younger age and gastroenterology or infectious diseases referral; the model showed good discrimination (AUC 0.810), while male sex was not an independent predictor. Among positive patients, 47% had HBV DNA below 200 IU\/mL, consistent with low-level occult infection. Conclusions: These findings support guideline-recommended HBV DNA testing in all anti-HBc-positive patients before immunosuppression and, where universal testing is not feasible, provide local denominators for prioritizing it as an exercise in diagnostic stewardship. The proposed algorithm is institution-level rather than generalizable.<\/jats:p>","DOI":"10.3390\/v18080899","type":"journal-article","created":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T15:48:36Z","timestamp":1786722516000},"page":"899","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Hepatitis B in Isolated Anti-HBc Carriers: Predictors of Detectable HBV DNA and Implications for Risk-Stratified Screening"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9145-083X","authenticated-orcid":false,"given":"Hasan","family":"Zeybek","sequence":"first","affiliation":[{"name":"Department of Medical Microbiology, Gulhane Training and Research Hospital, 06010 Ankara, T\u00fcrkiye"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,8,14]]},"reference":[{"key":"ref_1","unstructured":"World Health Organization (2024). Global Hepatitis Report 2024: Action for Access in Low- and Middle-Income Countries, World Health Organization."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1038\/s41575-023-00760-9","article-title":"Global burden of hepatitis B virus: Current status, missed opportunities and a call for action","volume":"20","author":"Hsu","year":"2023","journal-title":"Nat. Rev. Gastroenterol. Hepatol."},{"key":"ref_3","first-page":"263","article-title":"Farkl\u0131 klinik yak\u0131nmal\u0131 hastalarda izole hepatit B kor antikoru (\u0130zole Anti-Hbc) pozitifli\u011finin retrospektif de\u011ferlendirilmesi","volume":"51","author":"Cihan","year":"2021","journal-title":"Turk. Mikrobiyol. Cemiy. Derg."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Hyun, C.S., Lee, S., and Ventura, W.R. (2019). The prevalence and significance of isolated hepatitis B core antibody (anti-HBc) in endemic population. BMC Res. Notes, 12.","DOI":"10.1186\/s13104-019-4287-z"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1255","DOI":"10.3748\/wjg.v12.i8.1255","article-title":"Serological pattern \u201canti-HBc alone\u201d: Characterization of 552 individuals and clinical significance","volume":"12","author":"Hartmann","year":"2006","journal-title":"World J. Gastroenterol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"450","DOI":"10.1002\/1096-9071(200012)62:4<450::AID-JMV9>3.0.CO;2-Y","article-title":"Serological pattern \u201canti-HBc alone\u201d: Report on a workshop","volume":"62","author":"Grob","year":"2000","journal-title":"J. Med. Virol."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Moretto, F., Catherine, F.X., Esteve, C., Blot, M., and Piroth, L. (2020). Isolated anti-HBc: Significance and management. J. Clin. Med., 9.","DOI":"10.3390\/jcm9010202"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Wang, C., Li, X., Zhang, C., Xiao, L., and Xian, J. (2024). Prevalence and influential factors of isolated hepatitis B core antibody positivity in a Chinese adult population. Sci. Rep., 14.","DOI":"10.1038\/s41598-023-50907-6"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1016\/S2468-1253(16)30076-0","article-title":"Significance of anti-HBc alone serological status in clinical practice","volume":"2","author":"Wang","year":"2017","journal-title":"Lancet Gastroenterol. Hepatol."},{"key":"ref_10","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_11","doi-asserted-by":"crossref","unstructured":"Wang, C., Xue, R., Wang, X., Xiao, L., and Xian, J. (2023). High-sensitivity HBV DNA test for the diagnosis of occult HBV infection: Commonly used but not reliable. Front. Cell. Infect. Microbiol., 13.","DOI":"10.3389\/fcimb.2023.1186877"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"721","DOI":"10.1111\/j.1365-2893.2011.01482.x","article-title":"High levels of serum hepatitis B virus DNA in patients with \u2018anti-HBc alone\u2019: Role of HBsAg mutants","volume":"18","author":"Launay","year":"2011","journal-title":"J. Viral Hepat."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"2765","DOI":"10.1200\/JCO.2012.48.5938","article-title":"Randomized controlled trial of entecavir prophylaxis for rituximab-associated hepatitis B virus reactivation in patients with lymphoma and resolved hepatitis B","volume":"31","author":"Huang","year":"2013","journal-title":"J. Clin. Oncol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1053\/j.gastro.2024.11.008","article-title":"AGA Clinical Practice Guideline on the Prevention and Treatment of Hepatitis B Virus Reactivation in At-Risk Individuals","volume":"168","author":"Ali","year":"2025","journal-title":"Gastroenterology"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Buti, M., Manzano, M.L., Morillas, R.M., Garc\u00eda-Retortillo, M., Mart\u00edn, L., Prieto, M., Guti\u00e9rrez, M.L., Su\u00e1rez, E., G\u00f3mez Rubio, M., and L\u00f3pez, J. (2017). Randomized prospective study evaluating tenofovir disoproxil fumarate prophylaxis against hepatitis B virus reactivation in anti-HBc-positive patients with rituximab-based regimens to treat hematologic malignancies: The Preblin study. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0184550"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1670","DOI":"10.1016\/j.jhep.2022.07.003","article-title":"Hepatitis B virus reactivation associated with new classes of immunosuppressants and immunomodulators: A systematic review, meta-analysis, and expert opinion","volume":"77","author":"Papatheodoridis","year":"2022","journal-title":"J. Hepatol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"2447","DOI":"10.1111\/jgh.16725","article-title":"Rituximab carries high risks of hepatitis B virus reactivation in hematologic and rheumatic patients with chronic or resolved hepatitis B","volume":"39","author":"Hou","year":"2024","journal-title":"J. Gastroenterol. Hepatol."},{"key":"ref_18","first-page":"480","article-title":"Hepatitis B virus reactivation in HBsAg-negative, anti-HBc-positive patients receiving immunosuppressive therapy: A systematic review","volume":"31","author":"Cholongitas","year":"2018","journal-title":"Ann. Gastroenterol."},{"key":"ref_19","unstructured":"European Association for the Study of the Liver (2025). EASL Clinical Practice Guidelines on the management of hepatitis B virus infection. J. Hepatol., 83, 502\u2013583."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"806","DOI":"10.1136\/bmj.39335.541782.AD","article-title":"Strengthening the Reporting of Observational Studies in Epidemiology (STROBE) statement: Guidelines for reporting observational studies","volume":"335","author":"Altman","year":"2007","journal-title":"BMJ"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Toy, M., \u00d6nder, F.O., W\u00f6rmann, T., Bozdayi, A.M., Schalm, S.W., Borsboom, G.J., van Rosmalen, J., Richardus, J.H., and Yurdaydin, C. (2011). Age- and region-specific hepatitis B prevalence in Turkey estimated using generalized linear mixed models: A systematic review. BMC Infect. Dis., 11.","DOI":"10.1186\/1471-2334-11-337"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1020","DOI":"10.1016\/j.cmi.2015.06.028","article-title":"Seroprevalence of hepatitis B and C virus infections and risk factors in Turkey: A fieldwork TURHEP study","volume":"21","author":"Karasu","year":"2015","journal-title":"Clin. Microbiol. Infect."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Davarc\u0131, I., and Guducuo\u011flu, H. (2024). Evaluation of Isolated Anti-HBc Positivity in Patients Considered for Hepatitis B Diagnosis: 8.5 Years of Data. Jundishapur J. Microbiol., 17.","DOI":"10.5812\/jjm-154441"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"1560","DOI":"10.1002\/hep.29800","article-title":"Update on prevention, diagnosis, and treatment of chronic hepatitis B: AASLD 2018 hepatitis B guidance","volume":"67","author":"Terrault","year":"2018","journal-title":"Hepatology"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1007\/s00415-023-11973-y","article-title":"Hepatitis B reactivation is a rare event among patients with resolved infection undergoing anti-CD20 antibodies in monotherapy without antiviral prophylaxis: Results from the HEBEM study","volume":"271","author":"Marzo","year":"2024","journal-title":"J. Neurol."},{"key":"ref_26","doi-asserted-by":"crossref","unstructured":"Fu, M.X., Simmonds, P., and Harvala, H. (2024). A need for confirmatory testing of isolated HBcAb-positive results in screening programs. Hepatol. Commun., 8.","DOI":"10.1097\/HC9.0000000000000554"},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Cai, J., Wu, W., Wu, J., Chen, Z., Wu, Z., Tang, Y., and Hu, M. (2022). Prevalence and clinical characteristics of hepatitis B surface antigen-negative\/hepatitis B core antibody-positive patients with detectable serum hepatitis B virus DNA. Ann. Transl. Med., 10.","DOI":"10.21037\/atm-21-6272"},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Caviglia, G.P., Olivero, A., Ciancio, A., Tandoi, F., Troshina, G., Rosso, C., Abate, M.L., Younes, R., Ribaldone, D.G., and Smedile, A. (2020). Analytical and clinical evaluation of a novel assay for anti-HBc IgG measurement in serum of subjects with overt and occult HBV infection. Diagn. Microbiol. Infect. Dis., 96.","DOI":"10.1016\/j.diagmicrobio.2020.114985"},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Karimi, G., Zadsar, M., Vafaei, N., Sharifi, Z., and FalahTafti, M. (2016). Prevalence of antibody to Hepatitis B core antigen and Hepatitis B virus DNA in HBsAg negative healthy blood donors. Virol. J., 13.","DOI":"10.1186\/s12985-016-0492-8"}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/18\/8\/899\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T15:50:27Z","timestamp":1786722627000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/18\/8\/899"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,14]]},"references-count":29,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2026,8]]}},"alternative-id":["v18080899"],"URL":"https:\/\/doi.org\/10.3390\/v18080899","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,14]]}}}