{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,26]],"date-time":"2026-10-26T21:00:33Z","timestamp":1793048433357,"version":"4.5.0"},"reference-count":25,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,12,9]],"date-time":"2025-12-09T00:00:00Z","timestamp":1765238400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,12,9]],"date-time":"2025-12-09T00:00:00Z","timestamp":1765238400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"The National Key Research and Development Program of China","award":["2023YFC2308600"],"award-info":[{"award-number":["2023YFC2308600"]}]},{"name":"The National Key Research and Development Program of China","award":["2021YFC2600200"],"award-info":[{"award-number":["2021YFC2600200"]}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82202502"],"award-info":[{"award-number":["82202502"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Chinese National Thirteenth-Five Years Project in Science and Technology","award":["2017ZX10202201"],"award-info":[{"award-number":["2017ZX10202201"]}]}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Hepatol Int"],"published-print":{"date-parts":[[2026,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and aim<\/jats:title>\n                    <jats:p>Functional cure is considered the advanced treatment goal for patients with chronic hepatitis B (CHB). We aimed to evaluate hepatitis B surface antigen (HBsAg) loss rates after combination treatment of entecavir (ETV) and peginterferon alfa-2b (Peg-IFN) with or without granulocyte\u2013macrophage colony-stimulating factor (GM-CSF).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>In this randomized controlled trial, virally suppressed patients undergoing nucleos(t)ide analogs with HBsAg\u2009&lt;\u20093000\u00a0IU\/mL were randomized 1:1:1 to receive either ETV for 96\u00a0weeks (E group), or 48\u00a0weeks of Peg-IFN\u2009+\u2009ETV, followed by 48-week Peg-IFN alone (EP group), or 48\u00a0weeks of Peg-IFN\u2009+\u2009ETV\u2009+\u2009GM-CSF, followed by 48-week Peg-IFN alone (EPG group). The primary outcome is HBsAg loss at week 96.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Among 249 patients (81 in E group, 83 in EP group and 85 in EPG group), EP group (30.12%, 25.30%) and EPG group (22.35%, 20.00%) achieved significantly higher HBsAg loss and HBsAg seroconversion rates than E group (0.00%, 0.00%;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u2009.0001,\n                      <jats:italic>p<\/jats:italic>\n                      \u2009&lt;\u2009.0001) at week 96. At week 120, HBsAg loss was maintained in 22 of 25 patients (88.00%) in EP group and 15 of 19 (78.95%) in EPG group. During the 24-week off-treatment follow-up, late HBsAg loss occurred in one EP and three EPG patients. Multivariate analysis showed that age, baseline HBsAg level, and 24-week HBsAg decline correlated with HBsAg loss and HBsAg seroconversion at week 96. 24-week HBV RNA decline correlated with HBsAg loss. The HBsAg dynamics during therapy could predict HBsAg loss with an area under the curve of 0.944. More patients in EP group and EPG group experienced adverse events than E group.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>In virally suppressed patients with HBsAg level\u2009&lt;\u20093000\u00a0IU\/mL, ETV plus Peg-IFN significantly increased HBsAg loss and HBsAg seroconversion, whereas adding GM-CSF conferred no\u00a0additional efficacy\u00a0benefit. Age, early on-treatment HBsAg level and 24-week HBV RNA decline correlated with HBsAg loss.<\/jats:p>\n                    <jats:p>This trial is registered at ClinicalTrials.gov, NCT02327416.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1007\/s12072-025-10977-2","type":"journal-article","created":{"date-parts":[[2025,12,9]],"date-time":"2025-12-09T18:30:12Z","timestamp":1765305012000},"page":"31-45","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Efficacy and safety of entecavir, peginterferon alfa-2b and GM-CSF combination therapy: the anchor randomized controlled trial"],"prefix":"10.1007","volume":"20","author":[{"given":"Di","family":"Wu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Da","family":"Huang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shifang","family":"Peng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongping","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fengchun","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoyun","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lei","family":"Fu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lanman","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaji","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qi","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyue","family":"Chen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yali","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoguang","family":"Dou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ke","family":"Ma","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong","family":"Xi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peng","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruoyi","family":"He","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuchen","family":"Tian","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Yin","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiming","family":"Yan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meifang","family":"Han","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2027-9593","authenticated-orcid":false,"given":"Qin","family":"Ning","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,12,9]]},"reference":[{"key":"10977_CR1","doi-asserted-by":"publisher","first-page":"1146","DOI":"10.1111\/jvh.13126","volume":"26","author":"Q Ning","year":"2019","unstructured":"Ning Q, Wu D, Wang GQ, et al. 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