{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,14]],"date-time":"2025-12-14T11:54:27Z","timestamp":1765713267027,"version":"3.48.0"},"reference-count":26,"publisher":"BMJ","issue":"10","license":[{"start":{"date-parts":[[2021,10,25]],"date-time":"2021-10-25T00:00:00Z","timestamp":1635120000000},"content-version":"unspecified","delay-in-days":24,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"name":"Sun Yat-Sen University Clinical Research 5010 Program","award":["2020007"],"award-info":[{"award-number":["2020007"]}]},{"name":"Third Affiliated Hospital of Sun Yat-Sen University, Clinical Research Program","award":["QHJH201903"],"award-info":[{"award-number":["QHJH201903"]}]}],"content-domain":{"domain":["bmj.com"],"crossmark-restriction":true},"short-container-title":["BMJ Open"],"accepted":{"date-parts":[[2021,9,27]]},"published-print":{"date-parts":[[2021,10]]},"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>Combination antiviral therapy of nucleos(t)ide analogue (NA) and pegylated interferon alpha (peg-IFN alpha) decrease hepatitis B virus (HBV) surface antigen (HBsAg) levels to achieve functional cure and improve long-term prognosis in chronic hepatitis B patients. However, for hepatitis B-related liver fibrosis, studies on combination of these two medicines are limited. This study was designed to compare the efficacy between peg-IFN alpha combined with tenofovir (TDF) and TDF monotherapy for the clearance of HBsAg in NA-experienced patients with HBV-related liver fibrosis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and analysis<\/jats:title>\n                    <jats:p>This study was designed to be a prospective, multicentre, open, randomised controlled study. A total of 272 patients with HBV-related liver fibrosis will be randomised into the combination therapy group or the monotherapy group at a 1:1 ratio. Participants in the combination group will receive subcutaneous injections of peg-IFN alpha 180\u2009\u00b5g per week for 48 weeks combined with oral TDF 300\u2009mg daily. Participants in the monotherapy group will receive 300\u2009mg oral TDF daily alone. All participants will undergo long-term treatment with TDF and will be followed up at the outpatient department for 144 weeks after randomisation. Clinical symptoms, laboratory tests and examination indicators will be collected at each follow-up time point, and adverse events will be recorded. The primary endpoint is serological clearance rate of HBsAg at 48 weeks.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Ethics and dissemination<\/jats:title>\n                    <jats:p>The ethics committee of the Third Affiliated Hospital at Sun Yat-sen University approved this study (Approval Number: (2020)02-183-01). The results of the study will be presented at relevant meetings and published in an appropriate journal after the completion of the trial and the analysis of the data.<\/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\" specific-use=\"clinicaltrial pre-results\" xlink:href=\"NCT04640129\">NCT04640129<\/jats:ext-link>\n                      .\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1136\/bmjopen-2021-049104","type":"journal-article","created":{"date-parts":[[2021,10,25]],"date-time":"2021-10-25T14:45:14Z","timestamp":1635173114000},"page":"e049104","update-policy":"https:\/\/doi.org\/10.1136\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":0,"title":["Prospective, multicentre, randomised controlled trial comparing the seroclearance of HBsAg between combination therapy of peg-interferon alpha and tenofovir with tenofovir monotherapy in nucleos(t)ide analogue-experienced patients with HBV-related liver fibrosis: a study protocol"],"prefix":"10.1136","volume":"11","clinical-trial-number":[{"clinical-trial-number":"nct04640129","registry":"10.18810\/clinical-trials-gov","type":"preResults"},{"clinical-trial-number":"nct04640129","registry":"10.18810\/clinical-trials-gov"},{"clinical-trial-number":"nct04640129","registry":"10.18810\/clinical-trials-gov"}],"author":[{"given":"Shu","family":"Zhu","sequence":"first","affiliation":[{"name":"Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lina","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yongyu","family":"Mei","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhihua","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Infectious Disease, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Luping","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Traditional Chinese Medicine, Guangzhou Eighth People\"s Hospital, Guangzhou Medical University, Guangzhou, Guangdong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Yuan","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, The Third People\"s Hospital Of Shenzhen, Second Hospital Affiliated to Southern University of Science and Technology, Shenzhen, Guangdong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jianguo","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xuejun","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6184-5750","authenticated-orcid":false,"given":"Liang","family":"Peng","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, Guangdong, 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