{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,10]],"date-time":"2026-11-10T17:07:08Z","timestamp":1794330428087,"version":"4.9.0"},"reference-count":29,"publisher":"BMJ","issue":"9","license":[{"start":{"date-parts":[[2025,9,21]],"date-time":"2025-09-21T00:00:00Z","timestamp":1758412800000},"content-version":"unspecified","delay-in-days":20,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Key R&D Program of China","award":["2023YFC2308100"],"award-info":[{"award-number":["2023YFC2308100"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2025,9,2]]},"published-print":{"date-parts":[[2025,9]]},"abstract":"<jats:sec>\n                  <jats:title>Introduction<\/jats:title>\n                  <jats:p>The functional cure of chronic hepatitis B (CHB) is an ideal goal of therapy, as it is associated with improved long-term outcomes. Patients with low levels of HBsAg have higher rates of functional cure by pegylated interferon \u03b1 (PEG-IFN\u03b1) therapy, and similar results have been observed in patients treated with PD-1 antibody. However, the combination therapy of PD-1 antibody and PEG-IFN\u03b1 for promoting functional cure has not been studied. This study protocol aims to evaluate the efficacy and safety of a novel combined strategy, PD-1 antibody combined with PEG-IFN\u03b1 therapy, in nucleos(t)ide analogues (NAs)-treated CHB patients.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Methods and analysis<\/jats:title>\n                  <jats:p>This is a prospective, multicentre, open-label, randomised controlled study. Virologically suppressed CHB patients by NAs therapy will be recruited and randomised into PEG-IFN\u03b1 group, PD-1 antibody group or PD-1 antibody combined PEG-IFN\u03b1 group. PD-1 antibody will be injected intravenously once per 3 weeks for 24 weeks, and PEG-IFN\u03b1 will be injected subcutaneously once a week for 48 weeks. The primary outcomes are the rate of HBsAg loss at 24 weeks. For safety analysis, adverse events in different groups will be compared.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Ethics and dissemination<\/jats:title>\n                  <jats:p>This study has been approved by the Ethics Committee of the Fifth Medical Center of the Chinese PLA General Hospital (KY-2023-12-86-3). All results of the study will be submitted to a peer-reviewed journal.<\/jats:p>\n               <\/jats:sec>\n               <jats:sec>\n                  <jats:title>Trial registration number<\/jats:title>\n                  <jats:p>\n                     <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"clintrialgov\" xlink:href=\"NCT06357806\">NCT06357806<\/jats:ext-link>.<\/jats:p>\n               <\/jats:sec>","DOI":"10.1136\/bmjopen-2025-105710","type":"journal-article","created":{"date-parts":[[2025,9,22]],"date-time":"2025-09-22T02:31:53Z","timestamp":1758508313000},"page":"e105710","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":4,"title":["Safety and efficacy of PD-1 antibody combined with pegylated interferon \u03b1 for functional cure in nucleos(t)ide analogues-suppressed chronic hepatitis B patients: protocol for a multicentre randomised controlled trial"],"prefix":"10.1136","volume":"15","clinical-trial-number":[{"clinical-trial-number":"nct06357806","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"Hongmin","family":"Wang","sequence":"first","affiliation":[{"name":"The First Affiliated Hospital of USTC, University of Science and Technology of China, Hefei, China"},{"name":"Senior Department of lnfectious Diseases, The Fifth Medical Center of Chinese PLA General Hospital, Beijing, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoying","family":"Li","sequence":"additional","affiliation":[{"name":"Shandong Public Health Clinical Center, Jinan, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junfeng","family":"Lu","sequence":"additional","affiliation":[{"name":"First Department of Liver Disease, Beijing You\u2019an Hospital, Capital Medical University, Beijing, 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