{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T18:23:35Z","timestamp":1789669415226,"version":"4.0.1"},"reference-count":40,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2021,7,27]],"date-time":"2021-07-27T00:00:00Z","timestamp":1627344000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>In patients with chronic hepatitis B (CHB) under long-term treatment with nucleso(t)ide analogues (NAs), the loss of hepatitis B surface antigen (HBsAg) is a rare event. A growing body of evidence supports the use of quantitative HBsAg for the prediction of functional cure, although these results are mainly derived from studies performed on Asian patients with hepatitis B e antigen (HBeAg)-positive CHB. Here, we investigated the clinical role of quantitative HBsAg in a real-life cohort of CHB patients under treatment with NAs in a tertiary care center from North-West Italy. A total of 101 CHB patients (HBeAg-negative, n = 86) undergoing NAs treatment were retrospectively enrolled. HBsAg was measured at baseline (T0), 6 months (T1), 12 months (T2) and at the last follow-up (FU). Median FU was 5.5 (3.2\u20138.3) years; at the end of FU, 11 patients lost the HBsAg (annual incidence rate = 1.8%). Baseline HBsAg levels were significantly different between patients with no HBsAg loss and those achieving a functional cure (3.46, 2.91\u20133.97 vs. 1.11, 0.45\u20131.98 Log IU\/mL, p &lt; 0.001). Similarly, the HBsAg decline (\u0394) from T0 to T2 was significantly different between the two groups of patients (0.05, \u22120.04\u20130.13, vs. 0.38, 0.11\u20130.80 Log IU\/mL, p = 0.002). By stratified cross-validation analysis, the combination of baseline HBsAg and \u0394HBsAg T0\u2013T2 showed an excellent accuracy for the prediction of HBsAg loss (C statistic = 0.966). These results corroborate the usefulness of quantitative HBsAg in Caucasian CHB patients treated with antivirals for the prediction of HBsAg seroclearance.<\/jats:p>","DOI":"10.3390\/jcm10153308","type":"journal-article","created":{"date-parts":[[2021,7,27]],"date-time":"2021-07-27T12:18:31Z","timestamp":1627388311000},"page":"3308","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Usefulness of a Hepatitis B Surface Antigen-Based Model for the Prediction of Functional Cure in Patients with Chronic Hepatitis B Virus Infection Treated with Nucleos(t)ide Analogues: A Real-World Study"],"prefix":"10.3390","volume":"10","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 Torino, 10123 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yulia","family":"Troshina","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences, University of Torino, 10123 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Enrico","family":"Garro","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences, University of Torino, 10123 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcantonio","family":"Gesualdo","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences, University of Torino, 10123 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4303-2507","authenticated-orcid":false,"given":"Serena","family":"Aneli","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences, University of Torino, 10123 Turin, Italy"},{"name":"Department of Biology, University of Padua, 35122 Padova, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0160-9312","authenticated-orcid":false,"given":"Giovanni","family":"Birolo","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences, University of Torino, 10123 Turin, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabrizia","family":"Pittaluga","sequence":"additional","affiliation":[{"name":"Microbiology Unit, A.O.U. Citt\u00e0 della Salute e della Scienza, 10126 Torino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rossana","family":"Cavallo","sequence":"additional","affiliation":[{"name":"Microbiology Unit, A.O.U. Citt\u00e0 della Salute e della Scienza, 10126 Torino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5310-4143","authenticated-orcid":false,"given":"Giorgio Maria","family":"Saracco","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences, University of Torino, 10123 Turin, Italy"},{"name":"Gastroenterology Unit, A.O.U. Citt\u00e0 della Salute e della Scienza, 10126 Torino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alessia","family":"Ciancio","sequence":"additional","affiliation":[{"name":"Department of Medical Sciences, University of Torino, 10123 Turin, Italy"},{"name":"Gastroenterology Unit, A.O.U. Citt\u00e0 della Salute e della Scienza, 10126 Torino, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,7,27]]},"reference":[{"key":"ref_1","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_2","unstructured":"World Health Organization (2017). Global Hepatitis Report 2017, Global Hepatitis Programme. Available online: http:\/\/www.who.int\/hepatitis\/publications\/global-hepatitis-report2017\/en\/."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1007\/s12072-018-9884-8","article-title":"Global HBV burden: Guesstimates and facts","volume":"12","author":"Ginzberg","year":"2018","journal-title":"Hepatol. Int."},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"Coppola, N., Corvino, A.R., De Pascalis, S., Signoriello, G., Di Fiore, E., Nienhaus, A., Sagnelli, E., and Lamberti, M. (2015). The Long-Term Immunogenicity of Recombinant Hepatitis B Virus (HBV) Vaccine: Contribution of Universal HBV Vaccination in Italy. BMC Infect. Dis., 15.","DOI":"10.1186\/s12879-015-0874-3"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"521","DOI":"10.1016\/0264-410X(93)90222-J","article-title":"Vaccination against hepatitis B: The Italian strategy","volume":"11","author":"Zanetti","year":"1993","journal-title":"Vaccine"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"11941","DOI":"10.3748\/wjg.v21.i42.11941","article-title":"Hepatitis B virus burden in developing countries","volume":"21","author":"Zampino","year":"2015","journal-title":"World J. Gastroenterol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"8187","DOI":"10.3748\/wjg.v22.i36.8187","article-title":"Etiology of chronic liver diseases in the Northwest of Italy, 1998 through 2014","volume":"22","author":"Saracco","year":"2016","journal-title":"World J. Gastroenterol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2138","DOI":"10.1002\/jmv.24873","article-title":"Influence of universal HBV vaccination on chronic HBV infection in Italy: Results of a cross-sectional multicenter study","volume":"89","author":"Sagnelli","year":"2017","journal-title":"J. Med. Virol."},{"key":"ref_9","first-page":"61","article-title":"Chronic hepatitis B therapy: Available drugs and treatment guidelines","volume":"61","author":"Caviglia","year":"2015","journal-title":"Minerva Gastroenterol. Dietol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"201","DOI":"10.23736\/S1121-421X.18.02470-4","article-title":"Efficacy and safety of long-term entecavir therapy in a European population","volume":"64","author":"Collo","year":"2018","journal-title":"Minerva Gastroenterol. Dietol."},{"key":"ref_11","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_12","doi-asserted-by":"crossref","first-page":"e124","DOI":"10.1016\/j.ejim.2012.03.018","article-title":"Current practice of chronic hepatitis B treatment in Southern Italy","volume":"23","author":"Stroffolini","year":"2012","journal-title":"Eur. J. Intern. Med."},{"key":"ref_13","first-page":"150","article-title":"What to start with in first line treatment of chronic hepatitis B patients: An Italian multicentre observational cohort, HBV-RER study group","volume":"25","author":"Cuomo","year":"2017","journal-title":"Infez. Med."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"77","DOI":"10.23736\/S1121-421X.18.02517-5","article-title":"Long-term results of chronic hepatitis B antiviral treatment with nucleos(t)ide analogues: A single center experience","volume":"65","author":"Caviglia","year":"2019","journal-title":"Minerva Gastroenterol. Dietol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1016\/j.jhep.2016.08.009","article-title":"The role of quantitative hepatitis B surface antigen revisited","volume":"66","author":"Cornberg","year":"2017","journal-title":"J. Hepatol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"S82","DOI":"10.1111\/liv.12735","article-title":"HBsAg quantification to optimize treatment monitoring in chronic hepatitis B patients","volume":"35","author":"Asselah","year":"2015","journal-title":"Liver Int."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"409","DOI":"10.3350\/cmh.2013.19.4.409","article-title":"HBsAg level and clinical course in patients with chronic hepatitis B treated with nucleoside analogue: Five years of follow-up data","volume":"19","author":"Kim","year":"2013","journal-title":"Clin. Mol. Hepatol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"42879","DOI":"10.1038\/srep42879","article-title":"Early hepatitis B surface antigen decline predicts treatment response to entecavir in patients with chronic hepatitis B","volume":"7","author":"Peng","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"725","DOI":"10.3748\/wjg.v24.i6.725","article-title":"Clinical utility of hepatitis B surface antigen kinetics in treatment-naive chronic hepatitis B patients during long-term entecavir therapy","volume":"24","author":"Lin","year":"2018","journal-title":"World J. Gastroenterol."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Broquetas, T., Garcia-Retortillo, M., Hernandez, J.J., Puigveh\u00ed, M., Ca\u00f1ete, N., Coll, S., Cabrero, B., Gim\u00e9nez, M.D., Sol\u00e0, R., and Carri\u00f3n, J.A. (2017). Quantification of HBsAg to predict low levels and seroclearance in HBeAg-negative patients receiving nucleos(t)ide analogues. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0188303"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1178","DOI":"10.1002\/jmv.22089","article-title":"Correlation of serum hepatitis B surface antigen level with response to entecavir in naive patients with chronic hepatitis B","volume":"83","author":"Lee","year":"2011","journal-title":"J. Med. Virol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"329","DOI":"10.20452\/pamw.2301","article-title":"Noninvasive assessment of liver fibrosis: Key messages for clinicians","volume":"124","author":"Caviglia","year":"2014","journal-title":"Pol. Arch. Med. Wewn."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"341","DOI":"10.1016\/j.jcv.2014.05.013","article-title":"Quantification of hepatitis B surface antigen with the novel DiaSorin LIAISON XL Murex HBsAg Quant: Correlation with the ARCHITECT quantitative assays","volume":"60","author":"Burdino","year":"2014","journal-title":"J. Clin. Virol."},{"key":"ref_24","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_25","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1016\/j.dld.2010.10.014","article-title":"Treatment of chronic hepatitis B: Update of the recommendations from the 2007 Italian Workshop","volume":"43","author":"Carosi","year":"2011","journal-title":"Dig. Liver Dis."},{"key":"ref_26","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_27","doi-asserted-by":"crossref","first-page":"923","DOI":"10.1002\/hep.26376","article-title":"Reduction of hepatitis B surface antigen levels and hepatitis B surface antigen seroclearance in chronic hepatitis B patients receiving 10 years of nucleoside analogue therapy","volume":"58","author":"Seto","year":"2013","journal-title":"Hepatology"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1764","DOI":"10.1038\/ajg.2014.301","article-title":"Hepatitis B surface antigen seroclearance: Relationship to hepatitis B e-antigen seroclearance and hepatitis B e-antigen-negative hepatitis","volume":"109","author":"Fung","year":"2014","journal-title":"Am. J. Gastroenterol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"517","DOI":"10.1053\/j.gastro.2011.04.046","article-title":"Serum hepatitis B surface antigen levels predict surface antigen loss in hepatitis B e antigen seroconverters","volume":"141","author":"Tseng","year":"2011","journal-title":"Gastroenterology"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1642","DOI":"10.1111\/liv.13432","article-title":"Hepatitis B s antigen kinetics during treatment with nucleos(t)ides analogues in patients with hepatitis B e antigen-negative chronic hepatitis B","volume":"37","author":"Striki","year":"2017","journal-title":"Liver Int."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1420","DOI":"10.1080\/00365521.2017.1374450","article-title":"Pronounced decline of serum HBsAg in chronic hepatitis B patients with long-term effective nucleos(t)ide analogs therapy","volume":"52","author":"Wang","year":"2017","journal-title":"Scand. J. Gastroenterol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"449","DOI":"10.1016\/j.jhep.2010.07.046","article-title":"Kinetics of hepatitis B surface antigen differ between treatment with peginterferon and entecavir","volume":"54","author":"Reijnders","year":"2011","journal-title":"J. Hepatol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"676","DOI":"10.1016\/j.jhep.2012.11.039","article-title":"Long-term hepatitis B surface antigen (HBsAg) kinetics during nucleoside\/nucleotide analogue therapy: Finite treatment duration unlikely","volume":"58","author":"Chevaliez","year":"2013","journal-title":"J. Hepatol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"7686","DOI":"10.3748\/wjg.v20.i24.7686","article-title":"Serum hepatitis B surface antigen levels predict treatment response to nucleos(t)ide analogues","volume":"20","author":"Chen","year":"2014","journal-title":"World J. Gastroenterol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1228","DOI":"10.1016\/j.jhep.2014.07.019","article-title":"Kinetics of hepatitis B surface antigen loss in patients with HBeAg-positive chronic hepatitis B treated with tenofovir disoproxil fumarate","volume":"61","author":"Marcellin","year":"2014","journal-title":"J. Hepatol."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"915","DOI":"10.3851\/IMP1866","article-title":"Hepatitis B surface antigen (HBsAg) decrease and serum interferon-inducible protein-10 levels as predictive markers for HBsAg loss during treatment with nucleoside\/nucleotide analogues","volume":"16","author":"Jaroszewicz","year":"2011","journal-title":"Antivir. Ther."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"415","DOI":"10.1093\/infdis\/jir282","article-title":"Serum HBsAg decline during long-term potent nucleos(t)ide analogue therapy for chronic hepatitis B and prediction of HBsAg loss","volume":"204","author":"Zoutendijk","year":"2011","journal-title":"J. Infect. Dis."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1136\/gutjnl-2014-307237","article-title":"Treatment cessation of entecavir in Asian patients with hepatitis B e antigen negative chronic hepatitis B: A multicentre prospective study","volume":"64","author":"Seto","year":"2015","journal-title":"Gut"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.jhep.2014.08.031","article-title":"Quantification of HBsAg in nucleos(t)ide-na\u00efve patients treated for chronic hepatitis B with entecavir with or without tenofovir in the BE-LOW study","volume":"62","author":"Zoulim","year":"2015","journal-title":"J. Hepatol."},{"key":"ref_40","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"}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/10\/15\/3308\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T06:35:39Z","timestamp":1760164539000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/10\/15\/3308"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,7,27]]},"references-count":40,"journal-issue":{"issue":"15","published-online":{"date-parts":[[2021,8]]}},"alternative-id":["jcm10153308"],"URL":"https:\/\/doi.org\/10.3390\/jcm10153308","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,7,27]]}}}