{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T18:31:44Z","timestamp":1788546704370,"version":"build-2803163510"},"reference-count":42,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2022,9,20]],"date-time":"2022-09-20T00:00:00Z","timestamp":1663632000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100003399","name":"Science and Technology Commission of Shanghai Municipality","doi-asserted-by":"publisher","award":["18411966500"],"award-info":[{"award-number":["18411966500"]}],"id":[{"id":"10.13039\/501100003399","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100003399","name":"Science and Technology Commission of Shanghai Municipality","doi-asserted-by":"publisher","award":["21S11905600"],"award-info":[{"award-number":["21S11905600"]}],"id":[{"id":"10.13039\/501100003399","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Aliment Pharmacol Ther"],"published-print":{"date-parts":[[2022,11]]},"abstract":"<jats:title>Summary<\/jats:title><jats:sec><jats:title>Background &amp; Aims<\/jats:title><jats:p>The strategies of adding on or switching to peginterferon (PEG\u2010IFN) improved the serological response rates in patients with chronic hepatitis B (CHB) who had previously experienced treatment with nucleos(t)ide analogues. However, robust data on which combination strategy is more effective remain lacking.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In this multicentre, parallel, open\u2010label, randomised, controlled trial, patients with HBeAg\u2010positive CHB who were treated with entecavir \u22652\u2009years, and had hepatitis B surface antigen (HBsAg) &lt;3000\u2009IU\/ml, HBeAg &lt;200S\/CO and HBV DNA &lt;50\u2009IU\/ml were randomly assigned in a 1:1:1 ratio to add on PEG\u2010IFN, switch to PEG\u2010IFN or continue entecavir monotherapy for 48\u2009weeks. The primary endpoint was HBeAg seroconversion at week 48.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A total of 153 patients were randomised into three treatment arms (50 in add\u2010on, 52 in switch\u2010to and 51 in monotherapy). Compared with continuous entecavir monotherapy, both add\u2010on and switch\u2010to strategies achieved higher rates of HBeAg seroconversion (18.0% vs. 2.0%, <jats:italic>p<\/jats:italic>\u00a0=\u00a00.007; 19.2% vs. 2.0%, <jats:italic>p<\/jats:italic>\u00a0=\u00a00.005, respectively), HBeAg loss (24.0% vs. 5.9%, <jats:italic>p<\/jats:italic>\u00a0=\u00a00.010; 23.1% vs. 5.9%, <jats:italic>p<\/jats:italic>\u00a0=\u00a00.013, respectively), HBsAg\u2009&lt;\u2009100\u2009IU\/ml (30.0% vs. 0%, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001; 34.6% vs. 0%, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001, respectively), and higher HBsAg reduction (\u22120.90 vs. \u22120.06 log<jats:sub>10<\/jats:sub>IU\/ml, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001; \u22120.92 vs. \u22120.06 log<jats:sub>10<\/jats:sub>IU\/ml, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001, respectively) at week 48. The efficacy was comparable between add\u2010on and switch\u2010to arms (<jats:italic>p\u2009&gt;<\/jats:italic>\u00a00.05). Adverse events were mainly related to PEG\u2010IFN but generally tolerable.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>In patients with CHB who achieved virological response with long\u2010term entecavir, both adding on and switching to PEG\u2010IFN are alternative strategies resulting in higher rates of HBeAg seroconversion and HBsAg reduction than continuous entecavir.<\/jats:p><\/jats:sec><jats:sec><jats:title>Clinical trials registration<\/jats:title><jats:p>Chinese Clinical Trial Registry (<jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.chictr.org.cn\">www.chictr.org.cn<\/jats:ext-link>, identifier: ChiCTR\u2010IPR\u201017012055).<\/jats:p><\/jats:sec>","DOI":"10.1111\/apt.17222","type":"journal-article","created":{"date-parts":[[2022,9,21]],"date-time":"2022-09-21T06:23:47Z","timestamp":1663741427000},"page":"1394-1407","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["The efficacy and safety of adding on or switching to peginterferon \u03b1\u20102b in HBeAg\u2010positive chronic hepatitis B patients with long\u2010term entecavir treatment: a multicentre randomised controlled trial"],"prefix":"10.1111","volume":"56","author":[{"given":"Qiankun","family":"Hu","sequence":"first","affiliation":[{"name":"Department of Liver Diseases, Shanghai Public Health Clinical Center Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xun","family":"Qi","sequence":"additional","affiliation":[{"name":"Department of Liver Diseases, Shanghai Public Health Clinical Center Fudan 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