{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T02:33:30Z","timestamp":1760236410683,"version":"build-2065373602"},"reference-count":32,"publisher":"MDPI AG","issue":"12","license":[{"start":{"date-parts":[[2021,11,24]],"date-time":"2021-11-24T00:00:00Z","timestamp":1637712000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Diagnostics"],"abstract":"<jats:p>The reactivation of hepatitis B virus (HBVr) in patients undergoing pharmacological immunosuppression is a potentially fatal clinical event that may occur in patients with overt or occult HBV infection. The risk of HBVr is mainly determined by the type of immunosuppressive therapy and the HBV serologic profile, with a higher risk in patients positive for the hepatitis B surface antigen (HBsAg), and a lower risk in HBsAg-negative\/antibodies to core antigen-positive subjects. Notably, a considerable proportion of patients experiencing HBVr showed a high degree of variability of the HBV S gene, possibly leading to immune escape mutants. These mutations, usually in the \u201ca-determinant\u201d of the HBsAg, can cause diagnostic problems and consequently hamper the appropriate management strategy of patients at risk of HBVr. Here, we describe a case of HBVr in a patient with a diagnosis of chronic myeloid leukemia and a previous history of kidney transplant, providing evidence of the potential usefulness of hepatitis B core-related antigen measurement in patients with HBV immune-escape mutants at risk of viral reactivation.<\/jats:p>","DOI":"10.3390\/diagnostics11122185","type":"journal-article","created":{"date-parts":[[2021,11,29]],"date-time":"2021-11-29T01:49:58Z","timestamp":1638150598000},"page":"2185","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Hepatitis B Virus Reactivation upon Immunosuppression: Is There a Role for Hepatitis B Core-Related Antigen in Patients with Immune-Escape Mutants? A Case Report"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0529-9481","authenticated-orcid":false,"given":"Gian Paolo","family":"Caviglia","sequence":"first","affiliation":[{"name":"Department of Medical Sciences, University of Turin, 10126 Turin, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonella","family":"Zorzi","sequence":"additional","affiliation":[{"name":"Virology and Microbiology Unit, Department of Pathology and Diagnostics, Verona University Hospital, 37126 Verona, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mario","family":"Rizzetto","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences, University of Turin, 10126 Turin, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Massimo","family":"Mirandola","sequence":"additional","affiliation":[{"name":"Infectious Diseases Section, Department of Diagnostics and Public Health, University of Verona, 37134 Verona, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0327-3875","authenticated-orcid":false,"given":"Antonella","family":"Olivero","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences, University of Turin, 10126 Turin, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Giada","family":"Carolo","sequence":"additional","affiliation":[{"name":"Infectious Diseases Section, Department of Diagnostics and Public Health, University of Verona, 37134 Verona, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2021,11,24]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"917","DOI":"10.1080\/14712598.2016.1177017","article-title":"Reactivation of hepatitis B virus during targeted therapies for cancer and immune-mediated disorders","volume":"16","author":"Serra","year":"2016","journal-title":"Expert Opin. Biol. Ther."},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Svicher, V., Salpini, R., Malagnino, V., Piermatteo, L., Alkhatib, M., Cerva, C., and Sarmati, L. (2019). New Markers in Monitoring the Reactivation of Hepatitis B Virus Infection in Immunocompromised Hosts. Viruses, 11.","DOI":"10.3390\/v11090783"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1972","DOI":"10.1136\/gutjnl-2015-309809","article-title":"HBV cccDNA: Viral persistence reservoir and key obstacle for a cure of chronic hepatitis B","volume":"64","author":"Nassal","year":"2015","journal-title":"Gut"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Armandi, A., Rosso, C., Ribaldone, D.G., and Caviglia, G.P. (2020). Moving towards core antigen for the management of patients with overt and occult HBV infection. Panminerva Med., in press.","DOI":"10.23736\/S0031-0808.20.04163-4"},{"key":"ref_5","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_6","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_7","doi-asserted-by":"crossref","unstructured":"Zannella, A., Marignani, M., and Begini, P. (2019). Hematological Malignancies and HBV Reactivation Risk: Suggestions for Clinical Management. Viruses, 11.","DOI":"10.20944\/preprints201907.0282.v1"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Inoue, J., Nakamura, T., and Masamune, A. (2019). Roles of Hepatitis B Virus Mutations in the Viral Reactivation after Immunosuppression Therapies. Viruses, 11.","DOI":"10.3390\/v11050457"},{"key":"ref_9","doi-asserted-by":"crossref","unstructured":"Konopleva, M.V., Belenikin, M.S., Shanko, A.V., Bazhenov, A.I., Kiryanov, S.A., Tupoleva, T.A., Sokolova, M.V., Pronin, A.V., Semenenko, T.A., and Suslov, A.P. (2021). Detection of S-HBsAg Mutations in Patients with Hematologic Malignancies. Diagnostics, 11.","DOI":"10.3390\/diagnostics11060969"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1788","DOI":"10.1038\/ajg.2016.436","article-title":"Association of Hepatitis B Core-Related Antigen with Hepatitis B Virus Reactivation in Occult Viral Carriers Undergoing High-Risk Immunosuppressive Therapy","volume":"111","author":"Seto","year":"2016","journal-title":"Am. J. Gastroenterol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1002\/hep4.1022","article-title":"Resistance mutations of hepatitis B virus in entecavir-refractory patients","volume":"1","author":"Yamada","year":"2017","journal-title":"Hepatol. Commun."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"114985","DOI":"10.1016\/j.diagmicrobio.2020.114985","article-title":"Analytical and clinical evaluation of a novel assay for anti-HBc IgG measurement in serum of subjects with overt and occult HBV infection","volume":"96","author":"Caviglia","year":"2020","journal-title":"Diagn. Microbiol. Infect. Dis."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1020","DOI":"10.1016\/j.dld.2014.07.172","article-title":"Prediction of occult hepatitis B virus infection in liver transplant donors through hepatitis B virus blood markers","volume":"46","author":"Tandoi","year":"2014","journal-title":"Dig. Liver Dis."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1111\/hepr.12811","article-title":"Hepatitis B core-related antigen kinetics in chronic hepatitis B virus genotype D-infected patients treated with nucleos(t)ide analogues or pegylated-interferon-\u03b1","volume":"47","author":"Caviglia","year":"2017","journal-title":"Hepatol. Res."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"e22334","DOI":"10.1002\/jcla.22334","article-title":"Evaluation of the highly sensitive chemiluminescent enzyme immunoassay \u201cLumipulse HBsAg-HQ\u201d for hepatitis B virus screening","volume":"32","author":"Deguchi","year":"2018","journal-title":"J. Clin. Lab. Anal."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"1297","DOI":"10.1053\/j.gastro.2017.02.009","article-title":"Hepatitis B Reactivation Associated with Immune Suppressive and Biological Modifier Therapies: Current Concepts, Management Strategies, and Future Directions","volume":"152","author":"Loomba","year":"2017","journal-title":"Gastroenterology"},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"European Association for the Study of the Liver (2017). EASL 2017 Clinical Practice Guidelines on the management of hepatitis B virus infection. J. Hepatol., 67, 370\u2013398.","DOI":"10.1016\/j.jhep.2017.03.021"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"155","DOI":"10.1080\/14639230500236818","article-title":"Fatal hepatitis B virus reactivation in a chronic myeloid leukemia patient during imatinib mesylate treatment","volume":"47","author":"Ikeda","year":"2006","journal-title":"Leuk. Lymphoma"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1016\/j.transproceed.2010.02.038","article-title":"Living donor liver transplantation for acute hepatic failure caused by reactivation of hepatitis B virus infection after chemotherapy for hematologic malignancy: Case reports","volume":"42","author":"Kim","year":"2010","journal-title":"Transplant. Proc."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1007\/s12185-009-0386-2","article-title":"Chronic myeloid leukemia patient manifesting fatal hepatitis B virus reactivation during treatment with imatinib rescued by liver transplantation: Case report and literature review","volume":"90","author":"Kang","year":"2009","journal-title":"Int. J. Hematol."},{"key":"ref_21","first-page":"2636","article-title":"Hepatitis B virus reactivation in a chronic myeloid leukemia patient treated with imatinib mesylate","volume":"125","author":"Wang","year":"2012","journal-title":"Chin. Med. J."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1318","DOI":"10.3748\/wjg.v19.i8.1318","article-title":"Hepatitis B reactivation in chronic myeloid leukemia patients receiving tyrosine kinase inhibitor","volume":"19","author":"Lai","year":"2013","journal-title":"World J. Gastroenterol."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Lazarevic, I., Banko, A., Miljanovic, D., and Cupic, M. (2019). Immune-Escape Hepatitis B Virus Mutations Associated with Viral Reactivation upon Immunosuppression. Viruses, 11.","DOI":"10.3390\/v11090778"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"823","DOI":"10.1002\/hep.27604","article-title":"Hepatitis B surface antigen genetic elements critical for immune escape correlate with hepatitis B virus reactivation upon immunosuppression","volume":"61","author":"Salpini","year":"2015","journal-title":"Hepatology"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1111\/j.1582-4934.2002.tb00317.x","article-title":"Molecular, immunological and clinical properties of mutated hepatitis B viruses","volume":"6","author":"Kreutz","year":"2002","journal-title":"J. Cell. Mol. Med."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"3484","DOI":"10.1128\/JCM.00726-13","article-title":"Application of a newly developed high-sensitivity HBsAg chemiluminescent enzyme immunoassay for hepatitis B patients with HBsAg seroclearance","volume":"51","author":"Shinkai","year":"2013","journal-title":"J. Clin. Microbiol."},{"key":"ref_27","unstructured":"Marzano, A., Bruno, R., Fagiuoli, S., Marignani, M., Madonia, S., Toniutto, P., and Vigan\u00f2, M. (2020, October 29). Gestione Clinica Della Epatite B Negli Immunocompromessi: Aggiornamento Italiano 2017. Available online: https:\/\/www.webaisf.org\/wpcontent\/uploads\/2019\/02\/gestione_clinica_della_epatite_b_negli_immunocompromessi.2017.pdf."},{"key":"ref_28","first-page":"29","article-title":"Role of serum hepatitis B core-related antigen in chronic hepatitis B infection","volume":"30","author":"Caviglia","year":"2018","journal-title":"Minerva Biotecnol."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Hadziyannis, E., and Laras, A. (2018). Viral Biomarkers in Chronic HBeAg Negative HBV Infection. Genes, 9.","DOI":"10.3390\/genes9100469"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"21713","DOI":"10.1074\/jbc.M501564200","article-title":"Hepatitis B virus DNA-negative dane particles lack core protein but contain a 22-kDa precore protein without C-terminal arginine-rich domain","volume":"280","author":"Kimura","year":"2005","journal-title":"J. Biol. Chem."},{"key":"ref_31","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_32","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1016\/j.cgh.2020.04.045","article-title":"Assay for Hepatitis B Core-related Antigen Identify Patients with High Viral Load: Systematic Review and Meta-analysis of Individual Participant Data","volume":"19","author":"Yoshida","year":"2021","journal-title":"Clin. Gastroenterol. Hepatol."}],"container-title":["Diagnostics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2075-4418\/11\/12\/2185\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:35:19Z","timestamp":1760168119000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2075-4418\/11\/12\/2185"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,11,24]]},"references-count":32,"journal-issue":{"issue":"12","published-online":{"date-parts":[[2021,12]]}},"alternative-id":["diagnostics11122185"],"URL":"https:\/\/doi.org\/10.3390\/diagnostics11122185","relation":{},"ISSN":["2075-4418"],"issn-type":[{"type":"electronic","value":"2075-4418"}],"subject":[],"published":{"date-parts":[[2021,11,24]]}}}