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Clinical and laboratory assessments were performed at baseline and at 12-week intervals (weeks 12, 24, 36, and 48). Serologic response (SR) was defined as hepatitis B surface antigen (HBsAg) loss (&lt;\u20090.05 IU\/mL), with or without HBsAg seroconversion (HBsAg\u2009&lt;\u20090.05 IU\/mL and HBsAb\u2009&gt;\u200910 mIU\/mL). Adverse events (AEs) were monitored at each assessment. Logistic regression and receiver operating characteristic curve analyses were used to identify predictors of HBsAg clearance.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The combination therapy of PEG-IFN \u03b1-2b and TMF resulted in significant reductions in HBsAg levels from baseline at weeks 24, 36, and 48. At these time points, the proportion of patients with undetectable HBV DNA increased progressively, with the proportion reaching 94.7% at week 48. In the SR group, the baseline HBsAg and HBeAg levels were significantly lower than those in the non-serological response (NSR) group, with greater reductions in HBsAg observed at weeks 12 and 24. Multivariate analysis revealed that baseline HBsAg levels and the degree of HBsAg decline at week 24 were independent predictors of HBsAg loss, with odds ratios of 4.609 and 3.237, respectively. The diagnostic performance of baseline HBsAg levels and their decline at week 24 demonstrated areas under the curves (AUCs) of 0.856 and 0.821, respectively, with a combined AUC of 0.908. The cumulative HBsAg clearance rates were 25% in treatment-na\u00efve patients and 26.7% in treatment-experienced patients. The most frequently reported AEs included fever, fatigue, rash, alopecia, elevated ALT and AST levels, neutropenia, and thrombocytopenia.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>PEG-IFN \u03b1-2b and TMF combination therapy effectively reduced HBsAg levels in CHB patients. Baseline HBsAg levels and the magnitude of their decline by week 24 served as robust predictors of serological response, exhibiting high diagnostic value.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12879-025-12296-1","type":"journal-article","created":{"date-parts":[[2025,12,19]],"date-time":"2025-12-19T06:27:51Z","timestamp":1766125671000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Efficacy and safety of PEG-IFN \u03b1-2b and tenofovir amibufenamide in combination therapy for chronic hepatitis B"],"prefix":"10.1186","volume":"26","author":[{"given":"Wen","family":"Zhao","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Longcan","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shihui","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wenjie","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yufeng","family":"Gao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zonghao","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaojun","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yi","family":"Luo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dongdong","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chuanmiao","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,12,19]]},"reference":[{"key":"12296_CR1","unstructured":"Global Hepatitis Report. 2024: Action for Access in Low- and Middle-Income Countries. 1st ed. 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