{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T21:04:34Z","timestamp":1790975074640,"version":"4.1.0"},"reference-count":31,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T00:00:00Z","timestamp":1779235200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Patients with low HBsAg levels, HBeAg-negative status and undetectable HBV DNA are recognized as the advantaged population for pegylated interferon \u03b1-2b (Peg-IFN\u03b1-2b) therapy. However, there are limited reports on the sustainability of HBsAg loss in this population. This study aims to explore the patterns of sustained response following HBsAg clearance in low HBsAg level patients treated with Peg-IFN\u03b1-2b through long-term follow-up, providing guidance for clinical practice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This retrospective study analyzed patients with baseline HBsAg &amp;lt; 200 IU\/mL, HBeAg negativity and undetectable baseline HBV DNA, who achieved HBsAg clearance and received either Peg-IFN\u03b1-2b monotherapy or nucleos(t)ide analog (NA) combination therapy. HBV biomarkers and clinical biochemical indicators were assessed during follow-up.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>We evaluated sustained HBsAg loss and investigated the risk factors of HBsAg reversion. A total of 203 patients with baseline HBsAg&amp;lt;200IU\/ml, HBeAg-negativity and undetectable HBV DNA were enrolled in this study. The median follow-up duration was 96 weeks (range:72 to 120 weeks). 44 (21.67%) patients were observed HBsAg reversion during follow-up, 91.36% (40\/44) of which occurred within 96 weeks. Kaplan-Meier stratification analysis revealed that higher end-of-treatment (EOT) HBsAb levels and longer consolidation therapy duration were independently associated with higher sustained HBsAg clearance rates (P&amp;lt; 0.001). Specifically, patients with EOT HBsAb &amp;gt;1000 IU\/mL achieved a 100% sustained clearance rate (no reversion observed). Cox regression analysis identified EOT HBsAb levels \u2265100 IU\/mL (HR\u00a0=\u00a00.238, P\u00a0=\u00a00.003)) and consolidation therapy \u226512 weeks (HR\u00a0=\u00a00.492, P\u00a0=\u00a00.027) as independent predictor against HBsAg reversion. No ALT flares and adverse events were observed in these HBsAg reverted patients during follow-up, while six patients had detectable HBV DNA.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Low HBsAg and HBeAg negative patients exhibited favorable long-term persistence of HBsAg clearance induced by Peg-IFN\u03b1-2b. We identified the EOT HBsAb levels (with levels &amp;gt;1000 IU\/mL predicting 100% sustained clearance) and the duration of consolidation therapy as key determinants of long-term treatment success, and proposed 96 weeks as the optimal follow-up time point for these patients.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fcimb.2026.1803818","type":"journal-article","created":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T10:52:25Z","timestamp":1779274345000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Sustained HBsAg clearance induced by pegylated interferon \u03b1-2b in HBeAg-negative patients with low baseline HBsAg"],"prefix":"10.3389","volume":"16","author":[{"given":"Chaojing","family":"Wen","sequence":"first","affiliation":[{"name":"Department of Infectious Diseases, Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, the Second Affiliated Hospital, Chongqing Medical University","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taiyu","family":"He","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, the Second Affiliated Hospital, Chongqing Medical University","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guanhua","family":"Zha","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, the Second Affiliated Hospital, Chongqing Medical University","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Aoyi","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, the Second Affiliated Hospital, Chongqing Medical University","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhiyi","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, the Second Affiliated Hospital, Chongqing Medical University","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhi","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, the Second Affiliated Hospital, Chongqing Medical University","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dachuan","family":"Cai","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, the Second Affiliated Hospital, Chongqing Medical University","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dazhi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, the Second Affiliated Hospital, Chongqing Medical University","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingli","family":"Peng","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, the Second Affiliated Hospital, Chongqing Medical University","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaofeng","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, the Second Affiliated Hospital, Chongqing Medical University","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Ren","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Key Laboratory of Molecular Biology for Infectious Diseases (Ministry of Education), Institute for Viral Hepatitis, the Second Affiliated Hospital, Chongqing Medical University","place":["Chongqing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,5,20]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"953","DOI":"10.1093\/infdis\/jiaf198","article-title":"Predictors of durable hepatitis B surface antigen loss after pegylated interferon\u2013based therapy in patients with hepatitis B e antigen\u2013negative chronic hepatitis B: A multicenter real-world study","volume":"232","author":"Chen","year":"2025","journal-title":"J. Infect. Dis."},{"key":"B2","doi-asserted-by":"publisher","first-page":"1839","DOI":"10.1016\/j.intimp.2005.06.004","article-title":"Impaired function of hepatic natural killer cells from murine chronic HBsAg carriers","volume":"5","author":"Chen","year":"2005","journal-title":"Int. Immunopharmacol."},{"key":"B3","doi-asserted-by":"publisher","first-page":"680","DOI":"10.1093\/cid\/cix353","article-title":"Durability of response after hepatitis B surface antigen seroclearance during nucleos(t)ide analogue treatment in a multiethnic cohort of chronic hepatitis B patients: Results after treatment cessation","volume":"65","author":"Chi","year":"2017","journal-title":"Clin. Infect. Dis."},{"key":"B4","doi-asserted-by":"publisher","first-page":"202","DOI":"10.1016\/j.jhep.2020.03.039","article-title":"A new definition for metabolic dysfunction-associated fatty liver disease: An international expert consensus statement","volume":"73","author":"Eslam","year":"2020","journal-title":"J. Hepatol."},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1016\/j.cgh.2025.09.009","article-title":"Novel HBV biomarkers-guided NAs withdrawal strategy promotes HBsAg clearance in Asian CHB patients: A randomized controlled trial","author":"Fan","year":"2025","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"1086","DOI":"10.1111\/apt.17670","article-title":"Integrated HBV DNA and cccDNA maintain transcriptional activity in intrahepatic HBsAg-positive patients with functional cure following PEG-IFN-based therapy","volume":"58","author":"Gao","year":"2023","journal-title":"Aliment. Pharmacol. Ther."},{"key":"B7","doi-asserted-by":"publisher","first-page":"944","DOI":"10.1016\/j.imbio.2014.07.020","article-title":"Hepatitis B virus e antigen (HBeAg) may have a negative effect on dendritic cell generation","volume":"219","author":"Hatipoglu","year":"2014","journal-title":"Immunobiology"},{"key":"B8","doi-asserted-by":"publisher","first-page":"25","DOI":"10.14218\/JCTH.2017.00072","article-title":"HBsAg loss with peg-interferon alfa-2a in hepatitis B patients with partial response to nucleos(t)ide analog: New switch study","volume":"6","author":"Hu","year":"2018","journal-title":"J. Clin. Transl. Hepatol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"42","DOI":"10.1016\/j.jhep.2022.01.021","article-title":"End-of-treatment HBcrAg and HBsAb levels identify durable functional cure after Peg-IFN-based therapy in patients with CHB","volume":"77","author":"Huang","year":"2022","journal-title":"J. Hepatol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"425","DOI":"10.1002\/hep.29640","article-title":"Incidence and predictors of hepatitis B surface antigen seroclearance after cessation of nucleos(t)ide analogue therapy in hepatitis B e antigen-negative chronic hepatitis B","volume":"68","author":"Jeng","year":"2018","journal-title":"Hepatology"},{"key":"B11","doi-asserted-by":"publisher","first-page":"275","DOI":"10.1016\/j.jhep.2016.08.022","article-title":"Reduction of covalently closed circular DNA with long-term nucleos(t)ide analogue treatment in chronic hepatitis B","volume":"66","author":"Lai","year":"2017","journal-title":"J. Hepatol."},{"key":"B12","doi-asserted-by":"publisher","first-page":"314","DOI":"10.1186\/s12985-024-02589-3","article-title":"Mechanisms underlying the compromised clinical efficacy of interferon in clearing HBV","volume":"21","author":"Lei","year":"2024","journal-title":"Virol. J."},{"key":"B13","doi-asserted-by":"publisher","first-page":"32","DOI":"10.1111\/jvh.13151","article-title":"Predictors of sustained functional cure in hepatitis B envelope antigen-negative patients achieving hepatitis B surface antigen seroclearance with interferon-alpha-based therapy","author":"Li","year":"2019","journal-title":"J. Viral Hepat"},{"key":"B14","doi-asserted-by":"publisher","first-page":"231","DOI":"10.1186\/s12985-024-02512-w","article-title":"Efficacy of short-term Peg-IFN \u03b1-2b treatment in chronic hepatitis B patients with ultra-low HBsAg levels: a retrospective cohort study","volume":"21","author":"Li","year":"2024","journal-title":"Virol. J."},{"key":"B15","doi-asserted-by":"publisher","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":"B16","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1002\/hep4.1436","article-title":"Durability of hepatitis B surface antigen loss with nucleotide analogue and peginterferon therapy in patients with chronic hepatitis B","volume":"4","author":"Lok","year":"2020","journal-title":"Hepatol. Commun."},{"key":"B17","doi-asserted-by":"publisher","first-page":"225","DOI":"10.1016\/j.jhep.2012.09.029","article-title":"Differential boosting of innate and adaptive antiviral responses during pegylated-interferon-alpha therapy of chronic hepatitis B","volume":"58","author":"Micco","year":"2013","journal-title":"J. Hepatol."},{"key":"B18","doi-asserted-by":"publisher","first-page":"777","DOI":"10.1016\/j.jhep.2014.05.044","article-title":"Switching from entecavir to PegIFN alfa-2a in patients with HBeAg-positive chronic hepatitis B: a randomised open-label trial (OSST trial)","volume":"61","author":"Ning","year":"2014","journal-title":"J. Hepatol."},{"key":"B19","doi-asserted-by":"publisher","first-page":"1802","DOI":"10.1001\/jama.2018.3795","article-title":"Chronic hepatitis B infection: A review","volume":"319","author":"Tang","year":"2018","journal-title":"JAMA"},{"key":"B20","doi-asserted-by":"publisher","first-page":"9","DOI":"10.1007\/s12072-014-9571-3","article-title":"How to achieve immune control in chronic hepatitis B","volume":"9","author":"van Campenhout","year":"2015","journal-title":"Hepatol. Int."},{"key":"B21","doi-asserted-by":"publisher","first-page":"8","DOI":"10.1111\/apt.16659","article-title":"Systematic review with meta-analysis: the impact of functional cure on clinical outcomes in patients with chronic hepatitis B","volume":"55","author":"Vittal","year":"2022","journal-title":"Aliment. Pharmacol. Ther."},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2025.1518048","article-title":"Discussion on the duration of response following HBsAg clearance in patients with chronic hepatitis B treated with PegIFN\u03b1-2b","volume":"16","author":"Wang","year":"2025","journal-title":"Front. Immunol."},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.3389\/fcimb.2023.1332232","article-title":"Clinical cure induced by pegylated interferon \u03b1-2b in the advantaged population of chronic hepatitis B virus infection: a retrospective cohort study","volume":"13","author":"Wen","year":"2023","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"B24","doi-asserted-by":"publisher","first-page":"514","DOI":"10.1016\/j.cgh.2019.04.020","article-title":"Durability of interferon-induced hepatitis B surface antigen seroclearance","volume":"18","author":"Wu","year":"2020","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"B25","doi-asserted-by":"publisher","first-page":"1525","DOI":"10.3748\/wjg.v26.i13.1525","article-title":"Add-on pegylated interferon augments hepatitis B surface antigen clearance vs continuous nucleos(t)ide analog monotherapy in Chinese patients with chronic hepatitis B and hepatitis B surface antigen \u2264 1500 IU\/mL: An observational study","volume":"26","author":"Wu","year":"2020","journal-title":"World J. Gastroenterol."},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2015.42","article-title":"T-cell exhaustion in chronic hepatitis B infection: current knowledge and clinical significance","volume":"6","author":"Ye","year":"2015","journal-title":"Cell Death Dis."},{"key":"B27","doi-asserted-by":"publisher","first-page":"548","DOI":"10.1016\/j.cgh.2019.08.033","article-title":"How do we determine whether a functional cure for HBV infection has been achieved","volume":"18","author":"Yip","year":"2020","journal-title":"Clin. Gastroenterol. Hepatol."},{"key":"B28","doi-asserted-by":"publisher","first-page":"361","DOI":"10.1016\/j.jhep.2018.10.014","article-title":"HBsAg seroclearance further reduces hepatocellular carcinoma risk after complete viral suppression with nucleos(t)ide analogues","volume":"70","author":"Yip","year":"2019","journal-title":"J. Hepatol."},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2017.09.018","article-title":"Durability of hepatitis B surface antigen seroclearance in untreated and nucleos(t)ide analogue-treated patients","author":"Yip","year":"2017","journal-title":"J. Hepatol."},{"key":"B30","doi-asserted-by":"publisher","first-page":"2080","DOI":"10.1099\/vir.0.020552-0","article-title":"Hepatitis B virus polymerase inhibits RIG-I- and Toll-like receptor 3-mediated beta interferon induction in human hepatocytes through interference with interferon regulatory factor 3 activation and dampening of the interaction between TBK1\/IKKepsilon and DDX3","volume":"91","author":"Yu","year":"2010","journal-title":"J. Gen. Virol."},{"key":"B31","doi-asserted-by":"publisher","first-page":"1957","DOI":"10.1056\/NEJMoa2210027","article-title":"Efficacy and safety of bepirovirsen in chronic hepatitis B infection","volume":"387","author":"Yuen","year":"2022","journal-title":"N. Engl. J. Med."}],"container-title":["Frontiers in Cellular and Infection Microbiology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2026.1803818\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,20]],"date-time":"2026-05-20T10:52:26Z","timestamp":1779274346000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fcimb.2026.1803818\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,5,20]]},"references-count":31,"alternative-id":["10.3389\/fcimb.2026.1803818"],"URL":"https:\/\/doi.org\/10.3389\/fcimb.2026.1803818","relation":{},"ISSN":["2235-2988"],"issn-type":[{"value":"2235-2988","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,5,20]]},"article-number":"1803818"}}