{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T11:19:47Z","timestamp":1781090387562,"version":"3.54.1"},"reference-count":18,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2023,9,26]],"date-time":"2023-09-26T00:00:00Z","timestamp":1695686400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>Spontaneous HBsAg seroclearance has been mainly studied in populations from Asia, Australia, the Pacific Islands, and Polynesia. For the first time, we evaluated the spontaneous HBsAg seroclearance and its possible associated factors and the risk of disease progression in HBeAg-negative patients with inactive infection all coming from the same region in South Italy. In this multicenter retrospective study, 146 patients were selected after 18 months of observation and followed for a median of 82 months (IQR 60\u2013107). For our analyses, they were divided into three groups based on their HBsAg levels: &lt;100 IU\/mL, 100\u20131000 IU\/mL, and &gt;1000 IU\/mL. Crude and adjusted hazard ratios (HRs) for HBsAg seroclearance were determined. During the follow-up period, three patients (2.0%) showed a disease progression with an increased liver stiffness, whereas 17 (11.6%) cleared the HBsAg. Patients with HBsAg levels &lt;100 IU\/mL had the highest probability of HBsAg seroclearance compared to the other two groups (p = 0.009). In the multivariate analysis, the HBsAg level &lt;100 IU\/mL was the only parameter independently associated with HBsAg seroclearance (adjusted HR = 3.53; CI 1.29\u20139.69; p = 0.01). In patients with chronic HBV inactive infection, HBsAg levels &lt;100 IU\/mL predicted the highest probability of HBsAg seroclearance.<\/jats:p>","DOI":"10.3390\/pathogens12101198","type":"journal-article","created":{"date-parts":[[2023,9,27]],"date-time":"2023-09-27T03:04:18Z","timestamp":1695783858000},"page":"1198","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Natural History and Hepatitis B Virus Surface Antigen (HBsAg) Spontaneous Seroclearance in Hepatitis B Virus e-Antigen (HBeAg)-Negative Patients with Inactive Chronic Infection: A Multicenter Regional Study from South Italy"],"prefix":"10.3390","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-8284-5127","authenticated-orcid":false,"given":"Michele","family":"Barone","sequence":"first","affiliation":[{"name":"Gastroenterology Unit, Department of Precision and Regenerative Medicine\u2014Jonian Area\u2014(DiMePRe-J), University of Bari \u201cAldo Moro\u201d, Policlinic University Hospital, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"Iannone","sequence":"additional","affiliation":[{"name":"Gastroenterology Unit, Policlinic University Hospital, Piazza G. Cesare 11, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martino","family":"Mezzapesa","sequence":"additional","affiliation":[{"name":"Gastroenterology Unit, Policlinic University Hospital, Piazza G. Cesare 11, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele","family":"Milella","sequence":"additional","affiliation":[{"name":"Clinic of Infectious Diseases, Policlinic University Hospital, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3453-5647","authenticated-orcid":false,"given":"Francesco","family":"Di Gennaro","sequence":"additional","affiliation":[{"name":"Clinic of Infectious Diseases, Department of Precision and Regenerative Medicine\u2014Jonian Area\u2014(DiMePRe-J), University of Bari \u201cAldo Moro\u201d, Policlinic University Hospital, Piazza G. Cesare 11, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grazia","family":"Niro","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Endoscopy, Fondazione IRCCS \u2018Casa Sollievo della Sofferenza\u2019, Viale Cappuccini, snc, 71013 San Giovanni Rotondo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rosa","family":"Cotugno","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Endoscopy, Fondazione IRCCS \u2018Casa Sollievo della Sofferenza\u2019, Viale Cappuccini, snc, 71013 San Giovanni Rotondo, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Raffaele","family":"Cozzolongo","sequence":"additional","affiliation":[{"name":"Gastroenterology Unit, IRCCS \u201cS. De Bellis\u201d, Via Turi 27, 70013 Castellana Grotte, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Giuseppe","family":"Mennea","sequence":"additional","affiliation":[{"name":"Internal Medicine Unit, \u201cL. Bonomo\u201d Hospital, Viale Istria, 76123 Andria, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Rendina","sequence":"additional","affiliation":[{"name":"Gastroenterology Unit, Policlinic University Hospital, Piazza G. Cesare 11, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2026-1200","authenticated-orcid":false,"given":"Alfredo","family":"Di Leo","sequence":"additional","affiliation":[{"name":"Gastroenterology Unit, Department of Precision and Regenerative Medicine\u2014Jonian Area\u2014(DiMePRe-J), University of Bari \u201cAldo Moro\u201d, Policlinic University Hospital, 70124 Bari, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,9,26]]},"reference":[{"key":"ref_1","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_2","doi-asserted-by":"crossref","first-page":"133","DOI":"10.3851\/IMP1497","article-title":"Hepatitis B surface antigen seroclearance during chronic HBV infection","volume":"15","author":"Chu","year":"2010","journal-title":"Antivir. Ther."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"e00196","DOI":"10.14309\/ctg.0000000000000196","article-title":"Incidence, Factors, and Patient-Level Data for Spontaneous HBsAg Seroclearance: A Cohort Study of 11,264 Patients","volume":"11","author":"Yeo","year":"2020","journal-title":"Clin. Transl. Gastroenterol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1053\/j.gastro.2010.04.052","article-title":"Hepatitis B surface antigen serum levels help to distinguish active from inactive hepatitis B virus genotype D carriers","volume":"139","author":"Brunetto","year":"2010","journal-title":"Gastroenterology"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"1481","DOI":"10.1016\/j.cgh.2016.01.019","article-title":"Good Practice in using HBsAg in Chronic Hepatitis B Study Group (GPs-CHB Study Group). Repeated Measurements of Hepatitis B Surface Antigen Identify Carriers of Inactive HBV During Long-term Follow-up","volume":"14","author":"Brouwer","year":"2016","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"829","DOI":"10.1016\/j.amjmed.2003.12.040","article-title":"Natural history of hepatitis B e antigen to antibody seroconversion in patients with normal serum aminotransferase levels","volume":"116","author":"Chu","year":"2004","journal-title":"Am. J. Med."},{"key":"ref_7","doi-asserted-by":"crossref","unstructured":"Yoshida, K., Enomoto, M., Tamori, A., Nishiguchi, S., and Kawada, N. (2021). Combination of Entecavir or Tenofovir with Pegylated Interferon-\u03b1 for Long-Term Reduction in Hepatitis B Surface Antigen Levels: Simultaneous, Sequential, or Add-on Combination Therapy. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22031456"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"European Association for the Study of the Liver (2012). EASL clinical practice guidelines: Management of chronic hepatitis B virus infection. J. Hepatol., 57, 167\u2013185.","DOI":"10.1016\/j.jhep.2012.02.010"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1029","DOI":"10.15585\/mmwr.mm7030a1","article-title":"Progress Toward Hepatitis B Control\u2014World Health Organization European Region, 2016\u20132019","volume":"70","author":"Khetsuriani","year":"2021","journal-title":"MMWR Morb. Mortal. Wkly. Rep."},{"key":"ref_10","first-page":"236","article-title":"Outcome of HBV screening and vaccination in a migrant population in southern Italy","volume":"29","author":"Mazzitelli","year":"2021","journal-title":"Infez. Med."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"130","DOI":"10.1055\/s-2006-939751","article-title":"Hepatitis B e antigen-negative chronic hepatitis: Natural history and treatment","volume":"26","author":"Hadziyannis","year":"2006","journal-title":"Semin. Liver Dis."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1016\/j.jhep.2006.03.007","article-title":"Characteristics of patients with chronic hepatitis B in France: Predominant frequency of HBe antigen negative cases","volume":"45","author":"Zarski","year":"2006","journal-title":"J. Hepatol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1093\/infdis\/jit209","article-title":"Risk stratification of hepatocellular carcinoma in hepatitis B virus e antigen-negative carriers by combining viral biomarkers","volume":"208","author":"Tseng","year":"2013","journal-title":"J. Infect. Dis."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1002\/jmv.24311","article-title":"HBsAg spontaneous seroclearance in a cohort of HBeAg-seronegative patients with chronic hepatitis B virus infection","volume":"88","author":"Han","year":"2016","journal-title":"J Med Virol."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Chien, T.L., Wang, J.H., Kee, K.M., Chen, C.H., Hung, C.H., and Lu, S.N. (2016). Factors Predicting HBsAg Seroclearance and Alanine Transaminase Elevation in HBeAg-Negative Hepatitis B Virus-Infected Patients with Persistently Normal Liver Function. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0166543"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1159\/000080872","article-title":"Genetic diversity of Hepatitis B virus strains derived worldwide: Genotypes, subgenotypes and HBsAg subtypes","volume":"47","author":"Norder","year":"2004","journal-title":"Intervirology"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"191","DOI":"10.7326\/0003-4819-118-3-199302010-00006","article-title":"The natural history of asymptomatic hepatitis B surface antigen carriers","volume":"118","author":"Meucci","year":"1993","journal-title":"Ann. Intern. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"756","DOI":"10.1053\/j.gastro.2004.06.021","article-title":"Natural history of chronic HBV carriers in Northern Italy: Morbidity and mortality after 30 years","volume":"127","author":"Manno","year":"2004","journal-title":"Gastroenterology"}],"container-title":["Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-0817\/12\/10\/1198\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:58:55Z","timestamp":1760129935000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-0817\/12\/10\/1198"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,9,26]]},"references-count":18,"journal-issue":{"issue":"10","published-online":{"date-parts":[[2023,10]]}},"alternative-id":["pathogens12101198"],"URL":"https:\/\/doi.org\/10.3390\/pathogens12101198","relation":{},"ISSN":["2076-0817"],"issn-type":[{"value":"2076-0817","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,9,26]]}}}