{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T01:05:15Z","timestamp":1790730315466,"version":"4.1.0"},"reference-count":33,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2024,7,5]],"date-time":"2024-07-05T00:00:00Z","timestamp":1720137600000},"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. Pharmacol."],"abstract":"<jats:p><jats:bold>Introduction:<\/jats:bold> Chronic hepatitis B (CHB) is a worldwide infectious disease caused by hepatitis B virus (HBV). Optimizing antiviral treatment strategies could improve the functional cure (FC) rate of patients with CHB. This study aims to systematically review the FC rate of the <jats:italic>de novo<\/jats:italic> combination of nucleos(t)ide analogs (NAs) and pegylated interferon \u03b1 (PEG-IFN\u03b1) versus that of PEG-IFN\u03b1 monotherapy for CHB.<\/jats:p><jats:p><jats:bold>Methods:<\/jats:bold> Databases were searched until 31 December 2023. Selected studies included randomized controlled trials on the <jats:italic>de novo<\/jats:italic> combination of NAs and PEG-IFN\u03b1 versus PEG-IFN\u03b1 monotherapy for 48\u00a0weeks in patients with CHB to achieve FC, which was defined as hepatitis B surface antigen (HBsAg) loss and\/or HBsAg seroconversion. Meta-analysis was conducted in accordance with the efficacy at the end of treatment and different time points during follow-up.<\/jats:p><jats:p><jats:bold>Results:<\/jats:bold> A total of 10 studies, encompassing 2,339 patients in total, were included. Subgroup analysis was conducted in accordance with whether first-line NAs were used. It found no statistically significant difference between HBsAg loss and HBsAg seroconversion at the end of treatment. Serum HBV DNA &amp;lt;500 copies\/mL significantly differed between the two groups at the end of treatment and did not significantly differ during follow-up. Meanwhile, HBsAg loss and HBsAg seroconversion showed statistically significant differences at 24\u00a0weeks of follow-up. By contrast, no statistically significant difference was found in HBsAg loss at 48\u00a0weeks of follow-up.<\/jats:p><jats:p><jats:bold>Discussion:<\/jats:bold> Without distinguishing the eligible preponderant population, the efficacy of the <jats:italic>de novo<\/jats:italic> combination of NAs and PEG-IFN\u03b1 in treating patients with CHB was not superior to that of PEG-IFN\u03b1 monotherapy.<\/jats:p><jats:p><jats:bold>Systematic Review Registration:<\/jats:bold> PROSPERO, identifier CRD42022325239.<\/jats:p>","DOI":"10.3389\/fphar.2024.1403805","type":"journal-article","created":{"date-parts":[[2024,7,5]],"date-time":"2024-07-05T05:14:46Z","timestamp":1720156486000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":9,"title":["Systematic review and meta-analysis: de novo combination of nucleos(t)ide analogs and pegylated interferon alpha versus pegylated interferon alpha monotherapy for the functional cure of chronic hepatitis B"],"prefix":"10.3389","volume":"15","author":[{"given":"Na","family":"Wei","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bin","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongfu","family":"Cai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Na","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Yang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maobai","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2024,7,5]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"3487","DOI":"10.1007\/s10620-018-5251-9","article-title":"Hepatitis B Surface Antigen Loss with tenofovir disoproxil fumarate plus peginterferon alfa-2a: week 120 analysis","volume":"63","author":"Ahn","year":"2018","journal-title":"Dig. 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