{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,10]],"date-time":"2026-04-10T21:42:16Z","timestamp":1775857336578,"version":"3.50.1"},"reference-count":35,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,8,22]],"date-time":"2025-08-22T00:00:00Z","timestamp":1755820800000},"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. Med."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Low-level viremia (LLV) is associated with the progression of liver fibrosis and a high risk of hepatocellular carcinoma in patients with chronic hepatitis B (CHB). The present study aimed to compare the efficacy between nucleos(t)ide analogs (NAs) therapy and combination therapy of NAs and pegylated interferon-\u03b1 (pegIFN-\u03b1) in entecavir (ETV)-treated CHB patients with LLV.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This was a retrospective cohort study. ETV-treated CHB patients with LLV were included and divided into the NA group and the NA+IFN group. The NA group comprised patients switching to tenofovir alafenamide fumarate, whereas the NA+IFN group comprised those adding on pegIFN-\u03b1 additionally. We compared changes in HBV markers and complete virological response (CVR) between the two groups.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>A total of 127 patients were enrolled, including 51 in NA+IFN group and 76 in NA group. In the NA+IFN group, the decline in HBsAg level from baseline (\u25b3 HBsAg) was significantly greater (\u22120.17 log<jats:sub>10<\/jats:sub>IU\/mL vs. \u22120.06 log<jats:sub>10<\/jats:sub>IU\/mL, <jats:italic>P<\/jats:italic> = 0.011) at week 24, and HBsAg clearance rate and \u25b3 HBsAg were significantly higher (8.9% vs. 0%, <jats:italic>P<\/jats:italic> = 0.017; \u22120.27 log<jats:sub>10<\/jats:sub>IU\/mL vs. \u22120.11 log<jats:sub>10<\/jats:sub>IU\/mL, <jats:italic>P<\/jats:italic> = 0.023) at week 48. The 48-week CVR rate in the NA+IFN group was 66.7% (34\/51), which was comparable to 68.4% (52\/76) in the NA group (<jats:italic>P<\/jats:italic> = 0.836).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>In ETV-treated patients with LLV, receiving NAs plus pegIFN-\u03b1 tends to increase the effect of HBsAg clearance.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fmed.2025.1642961","type":"journal-article","created":{"date-parts":[[2025,8,22]],"date-time":"2025-08-22T05:27:38Z","timestamp":1755840458000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":3,"title":["Adding pegylated interferon-\u03b1 to nucleos(t)ide analogs improves HBsAg clearance in chronic hepatitis B with low-level viremia"],"prefix":"10.3389","volume":"12","author":[{"given":"Lilin","family":"Wang","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Junfeng","family":"Lu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dan","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shan","family":"Ren","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xinyue","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhongjie","family":"Hu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sujun","family":"Zheng","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2025,8,22]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"545","DOI":"10.1016\/S2468-1253(19)30119-0","article-title":"A 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