{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T12:19:57Z","timestamp":1788265197536,"version":"build-2803163510"},"reference-count":47,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,9,5]],"date-time":"2025-09-05T00:00:00Z","timestamp":1757030400000},"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. Cell. Infect. Microbiol."],"abstract":"<jats:sec><jats:title>Background and aims<\/jats:title><jats:p>Hepatitis B surface antigen (HBsAg) clearance\u2014defined as an HBsAg level below the lower limit of detection\u2014is critical for the functional cure of chronic hepatitis B (CHB). This study evaluated the efficacy of short-term pegylated interferon alpha (Peg-IFN\u03b1) therapy in achieving HBsAg clearance in CHB patients with ultra-low HBsAg levels (&amp;lt;50 IU\/ml).<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A total of 378 CHB patients with HBsAg levels &amp;lt;50 IU\/ml were enrolled, including 206 nucleos(t)ide analogue (NUC)-treated patients and 172 inactive HBsAg carriers (IHCs). The NUC-treated cohort was divided into 83 patients receiving additional Peg-IFN\u03b1 treatment (NUC add-on Peg-IFN\u03b1 group) and 123 patients continuing NUC monotherapy (NUC group). The IHC cohort was divided into 86 patients receiving Peg-IFN\u03b1 treatment (Peg-IFN\u03b1 group) and 86 untreated patients (untreated group). The primary endpoint was the HBsAg clearance rate at week 24.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>At week 24, the HBsAg clearance rates in the NUC add-on Peg-IFN\u03b1 group and Peg-IFN\u03b1 group were 69.88% and 55.81%, respectively (p = 0.059), both significantly higher than the zero clearance rates in the NUC and untreated groups (p &amp;lt; 0.001). Patients with baseline HBsAg &amp;lt;10 IU\/ml achieved higher clearance rates [81.82% vs. 73.81% (p = 0.144)]. A decline of \u226595.8% in HBsAg levels from baseline to week 12 predicted HBsAg clearance at week 24 (AUC \u22650.9, sensitivity 0.765, specificity 0.961).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Short-term Peg-IFN\u03b1 therapy achieved high and comparable HBsAg clearance rates within 24 weeks in NUC-treated patients and IHCs with ultra-low HBsAg levels.<\/jats:p><\/jats:sec><jats:sec><jats:title>Clinical trial registration<\/jats:title><jats:p><jats:uri>https:\/\/www.medicalresearch.org.cn\/login<\/jats:uri>, identifier MR-50-24-011565.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fcimb.2025.1582997","type":"journal-article","created":{"date-parts":[[2025,9,5]],"date-time":"2025-09-05T05:41:20Z","timestamp":1757050880000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":4,"title":["Short-term pegylated interferon alpha in chronic HBV patients with ultra-low HBsAg: a retrospective study"],"prefix":"10.3389","volume":"15","author":[{"given":"Huimin","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongmei","family":"Gong","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaoxia","family":"Tan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yanyan","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lijian","family":"Ran","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qing","family":"Mao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guohong","family":"Deng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Jiang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Xia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,9,5]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"463","DOI":"10.1016\/j.cgh.2020.05.041","article-title":"Association between seroclearance of hepatitis B surface antigen and long-term clinical outcomes of patients with chronic hepatitis B virus infection: systematic review and meta-analysis","volume":"19","author":"Anderson","year":"2021","journal-title":"Clin. 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