{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T22:21:20Z","timestamp":1793053280774,"version":"4.5.0"},"reference-count":36,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,1,8]],"date-time":"2025-01-08T00:00:00Z","timestamp":1736294400000},"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. Med."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>The minority of the chronic hepatitis B (CHB) patients received polyethylene glycol interferon (PEG-IFN) combined with nucleotide analogs (NAs) can obtain hepatitis B surface antigen (HBsAg) clearance.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In order to find out the advantaged population, we retrospectively collected 122 CHB patients treated with NAs alone or NAs plus PEG-IFN for 48\u202fweeks, who were admitted to Sun Yat-sen Memorial Hospital from 2019 to 2024.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>We found HBsAg clearance rate in NAs plus PEG-IFN group was 40.98%, which was significantly higher than that in the NAs group. Thus, NAs plus PEG-IFN therapy served as a relatively ideal regimen and the patients received combined treatment were then incorporated for further analysis for searching efficacy predictors. Through using univariate and multivariate analysis, we confirmed the predictive value of HBsAg, alanine aminotransferase (ALT) at week 24, and ALT change values from baseline to week 24. The area under the receiver operating characteristic (ROC) curve of each indicators ranged from 0.663 to 0.982.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>In conclusion, our study verified the clinical value of NAs plus PEG-IFN for treating CHB patients. Moreover, for the first time, we found ALT change values from baseline to week 24 (dALT2) could act as a novel independent clinical efficacy predictors in the forementioned population.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fmed.2024.1510230","type":"journal-article","created":{"date-parts":[[2025,1,8]],"date-time":"2025-01-08T06:26:38Z","timestamp":1736317598000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Predictors of HBsAg seroclearance in HBeAg-negative chronic hepatitis B patients treated with nucleotide analogs plus polyethylene glycol interferon"],"prefix":"10.3389","volume":"11","author":[{"given":"Yan","family":"Peng","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingzhe","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ting","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenmin","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shutao","family":"Lin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wa","family":"Zhong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaohui","family":"Min","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,1,8]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","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":"ref2","doi-asserted-by":"publisher","first-page":"463","DOI":"10.1016\/j.cgh.2020.05.041","article-title":"Association between Seroclearance of hepatitis B surface antigen and long-term clinical outcomes of patients with chronic hepatitis B virus infection: systematic review and Meta-analysis","volume":"19","author":"Anderson","year":"2021","journal-title":"Clin Gastroenterol Hepatol"},{"key":"ref3","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":"ref4","doi-asserted-by":"publisher","first-page":"370","DOI":"10.1016\/j.jhep.2017.03.021","article-title":"EASL 2017 clinical practice guidelines on the Management of Hepatitis B Virus Infection","volume":"67","year":"2017","journal-title":"J Hepatol"},{"key":"ref5","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1002\/cpt.3287","article-title":"Optimal treatment based on interferon no longer makes clinical cure of chronic hepatitis B far away: an evidence-based review on emerging clinical data","volume":"116","author":"Li","year":"2024","journal-title":"Clin Pharmacol Ther"},{"key":"ref6","doi-asserted-by":"publisher","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":"ref7","doi-asserted-by":"publisher","first-page":"1039","DOI":"10.1016\/S0140-6736(22)01468-4","article-title":"Hepatitis B","volume":"401","author":"Jeng","year":"2023","journal-title":"Lancet"},{"key":"ref8","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":"ref9","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1111\/jvh.13150","article-title":"Effects of Pegylated interferon-alpha based therapies on functional cure and the risk of hepatocellular carcinoma development in patients with chronic hepatitis B","volume":"26","author":"Ren","year":"2019","journal-title":"J Viral Hepat"},{"key":"ref10","doi-asserted-by":"publisher","first-page":"52","DOI":"10.1007\/s12072-022-10415-7","article-title":"The effectiveness of combination therapy with interferon and nucleoside analogs in pediatric patients with chronic hepatitis B: a systematic review and Meta-analysis","volume":"17","author":"Li","year":"2023","journal-title":"Hepatol Int"},{"key":"ref11","doi-asserted-by":"publisher","first-page":"4521","DOI":"10.1021\/acs.biomac.1c00775","article-title":"Molecular insights into site-specific interferon-\u03b12a bioconjugates originated from PEG, LPG, and PEtOx","volume":"22","author":"Hauptstein","year":"2021","journal-title":"Biomacromolecules"},{"key":"ref12","doi-asserted-by":"publisher","first-page":"e00442","DOI":"10.1128\/JVI.00442-20","article-title":"Interferon alpha induces multiple cellular proteins that coordinately suppress Hepadnaviral covalently closed circular DNA transcription","volume":"94","author":"Cheng","year":"2020","journal-title":"J Virol"},{"key":"ref13","doi-asserted-by":"publisher","first-page":"1221","DOI":"10.1126\/science.1243462","article-title":"Specific and non-hepatotoxic degradation of nuclear hepatitis B virus Cccdna","volume":"343","author":"Lucifora","year":"2014","journal-title":"Science"},{"key":"ref14","doi-asserted-by":"publisher","first-page":"e49568","DOI":"10.15252\/embr.201949568","article-title":"Interferon-induced degradation of the persistent hepatitis B virus Cccdna form depends on Isg20","volume":"22","author":"Stadler","year":"2021","journal-title":"EMBO Rep"},{"key":"ref15","doi-asserted-by":"publisher","first-page":"686","DOI":"10.1093\/infdis\/jiaa399","article-title":"Interferon-induced macrophage-derived exosomes mediate antiviral activity against hepatitis B virus through Mir-574-5p","volume":"223","author":"Wu","year":"2021","journal-title":"J Infect Dis"},{"key":"ref16","doi-asserted-by":"publisher","first-page":"e01578","DOI":"10.1128\/JVI.01578-18","article-title":"Exosomes exploit the virus entry machinery and pathway to transmit alpha interferon-induced antiviral activity","volume":"92","author":"Yao","year":"2018","journal-title":"J Virol"},{"key":"ref17","doi-asserted-by":"publisher","first-page":"733364","DOI":"10.3389\/fimmu.2021.733364","article-title":"Interferon and hepatitis B: current and future perspectives","volume":"12","author":"Ye","year":"2021","journal-title":"Front Immunol"},{"key":"ref18","doi-asserted-by":"publisher","first-page":"12","DOI":"10.1111\/jvh.12755","article-title":"Peginterferon is preferable to Entecavir for prevention of Unfavourable events in patients with HBeAg-positive chronic hepatitis B: a five-year observational cohort study","volume":"24","author":"Li","year":"2017","journal-title":"J Viral Hepat"},{"key":"ref19","doi-asserted-by":"publisher","first-page":"966","DOI":"10.1093\/infdis\/jiv547","article-title":"Peginterferon is superior to Nucleos(T)ide analogues for prevention of hepatocellular carcinoma in chronic hepatitis B","volume":"213","author":"Liang","year":"2016","journal-title":"J Infect Dis"},{"key":"ref20","doi-asserted-by":"publisher","first-page":"1085","DOI":"10.1080\/14712598.2018.1518423","article-title":"Interferon-based treatment is superior to Nucleos(T)ide analog in reducing Hbv-related hepatocellular carcinoma for chronic hepatitis B patients at high risk","volume":"18","author":"Ren","year":"2018","journal-title":"Expert Opin Biol Ther"},{"key":"ref21","doi-asserted-by":"publisher","first-page":"545","DOI":"10.1016\/S2468-1253(19)30119-0","article-title":"A global scientific strategy to cure hepatitis B","volume":"4","author":"Revill","year":"2019","journal-title":"Lancet Gastroenterol Hepatol"},{"key":"ref22","doi-asserted-by":"publisher","first-page":"1214","DOI":"10.14309\/ajg.0000000000002125","article-title":"Randomized trial of Tenofovir with or without Peginterferon alfa followed by Protocolized treatment withdrawal in adults with chronic hepatitis B","volume":"118","author":"Terrault","year":"2023","journal-title":"Am J Gastroenterol"},{"key":"ref23","doi-asserted-by":"publisher","first-page":"1456","DOI":"10.3390\/ijms22031456","article-title":"Combination of Entecavir or Tenofovir with Pegylated interferon-alpha for long-term reduction in hepatitis B surface antigen levels: simultaneous, sequential, or add-on combination therapy","volume":"22","author":"Yoshida","year":"2021","journal-title":"Int J Mol Sci"},{"key":"ref24","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":"ref25","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":"ref26","doi-asserted-by":"publisher","first-page":"1","DOI":"10.14218\/JCTH.2017.00073","article-title":"Consensus on Pegylated interferon alpha in treatment of chronic hepatitis B","volume":"6","author":"Zhang","year":"2018","journal-title":"J Clin Transl Hepatol"},{"key":"ref27","doi-asserted-by":"publisher","first-page":"1076","DOI":"10.4254\/wjh.v12.i11.1076","article-title":"Hepatitis B surface antigen and hepatitis B Core-related antigen kinetics after adding Pegylated-interferon to Nucleos(T)ids analogues in hepatitis B E antigen-negative patients","volume":"12","author":"Broquetas","year":"2020","journal-title":"World J Hepatol"},{"key":"ref28","doi-asserted-by":"publisher","first-page":"1559","DOI":"10.1007\/s11739-020-02622-7","article-title":"Effect of Pegylated interferon alfa-2a in HBeAg-negative chronic hepatitis B during and 48 weeks after off-treatment follow-up: the limitation of pre-treatment Hbsag load for the Seroclearance of Hbsag","volume":"16","author":"Mimura","year":"2021","journal-title":"Intern Emerg Med"},{"key":"ref29","doi-asserted-by":"publisher","first-page":"1545","DOI":"10.1080\/22221751.2021.1952851","article-title":"Restoration of a functional antiviral immune response to chronic Hbv infection by reducing viral antigen load: if not sufficient, is it necessary?","volume":"10","author":"Yang","year":"2021","journal-title":"Emerg Microbes Infect"},{"key":"ref30","doi-asserted-by":"publisher","first-page":"1835","DOI":"10.1038\/s41598-020-58870-2","article-title":"Circulating serum Hbsag level is a biomarker for Hbv-specific T and B cell responses in chronic hepatitis B patients","volume":"10","author":"Kim","year":"2020","journal-title":"Sci Rep"},{"key":"ref31","doi-asserted-by":"publisher","first-page":"1151","DOI":"10.1002\/hep.22744","article-title":"Early serum Hbsag drop: a strong predictor of sustained virological response to Pegylated interferon alfa-2a in HBeAg-negative patients","volume":"49","author":"Moucari","year":"2009","journal-title":"Hepatology"},{"key":"ref32","doi-asserted-by":"publisher","first-page":"1165","DOI":"10.3851\/IMP1466","article-title":"A randomized controlled trial of Pegylated interferon-Alpha2a plus Adefovir Dipivoxil for hepatitis B E antigen-negative chronic hepatitis B","volume":"14","author":"Piccolo","year":"2009","journal-title":"Antivir Ther"},{"key":"ref33","doi-asserted-by":"publisher","first-page":"2002","DOI":"10.1053\/j.gastro.2009.08.061","article-title":"Factors that predict response of patients with hepatitis B E antigen-positive chronic hepatitis B to Peginterferon-alfa","volume":"137","author":"Buster","year":"2009","journal-title":"Gastroenterology"},{"key":"ref34","doi-asserted-by":"publisher","first-page":"427","DOI":"10.1080\/17474124.2021.1866985","article-title":"Hepatitis B infection: Progress in identifying patients Most likely to respond to Peginterferon alfa","volume":"15","author":"Yeh","year":"2021","journal-title":"Expert Rev Gastroenterol Hepatol"},{"key":"ref35","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 <\/= 1500 Iu\/ml: an observational study","volume":"26","author":"Wu","year":"2020","journal-title":"World J Gastroenterol"},{"key":"ref36","doi-asserted-by":"publisher","first-page":"406","DOI":"10.1016\/S2468-1253(19)30344-9","article-title":"Serum alanine aminotransferase flares in chronic hepatitis B infection: the good and the bad","volume":"5","author":"Ghany","year":"2020","journal-title":"Lancet Gastroenterol Hepatol"}],"container-title":["Frontiers in Medicine"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2024.1510230\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,1,8]],"date-time":"2025-01-08T06:26:41Z","timestamp":1736317601000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fmed.2024.1510230\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,1,8]]},"references-count":36,"alternative-id":["10.3389\/fmed.2024.1510230"],"URL":"https:\/\/doi.org\/10.3389\/fmed.2024.1510230","relation":{},"ISSN":["2296-858X"],"issn-type":[{"value":"2296-858X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,1,8]]},"article-number":"1510230"}}