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Nucleotide analogues (NTs) monotherapy may have a more significant effect on reducing hepatitis B surface antigen (HBsAg) than nucleoside analogues (NSs) due to their immunomodulatory function. However, this superiority remains unknown when combined with PEGylated interferon \u03b1 (PegIFN\u03b1). Therefore, this study aimed to explore whether NTs have more significant antiviral effects than NSs in combination therapy with PegIFN\u03b1. Methods. Chronic hepatitis B (CHB) patients treated with PegIFN\u03b1 plus nucleos(t)ide analogues (NAs) were retrospectively recruited. Efficacy and the predictors of hepatitis B surface antigen (HBsAg) reduction &gt;1 log10 IU\/mL after 48 weeks were analyzed. Results. A total of 95 patients were included and divided into the PegIFN\u03b1\u2009+\u2009NTs group and the PegIFN\u03b1\u2009+\u2009NSs group. Propensity score matching (PSM) was performed. The PegIFN\u03b1\u2009+\u2009NTs group had a greater reduction of HBsAg (\u22123.52 vs. \u22122.33 log10 IU\/mL, <jats:inline-formula>\n                     <a:math xmlns:a=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M1\">\n                        <a:mi>P<\/a:mi>\n                        <a:mo>=<\/a:mo>\n                        <a:mn>0.032<\/a:mn>\n                     <\/a:math>\n                  <\/jats:inline-formula>) and a higher proportion of patients with HBsAg reduction &gt;1 log10 IU\/mL (100.0% vs. 72.2%, <jats:inline-formula>\n                     <c:math xmlns:c=\"http:\/\/www.w3.org\/1998\/Math\/MathML\" id=\"M2\">\n                        <c:mi>P<\/c:mi>\n                        <c:mo>=<\/c:mo>\n                        <c:mn>0.003<\/c:mn>\n                     <\/c:math>\n                  <\/jats:inline-formula>) even after PSM. However, HBsAg and hepatitis B e-antigen (HBeAg) loss rates, HBeAg seroconversion rates, degree of HBeAg and hepatitis B virus (HBV) DNA decline, HBV DNA undetectable rates, and alanine aminotransferase (ALT) normalization rates showed no significant differences. Subgroup analyses showed the difference in the reduction of HBsAg was particularly evident in HBeAg-positive and the \u201cadd-on\u201d subgroups. PegIFN\u03b1 plus NTs (OR\u2009=\u200936.667, 95% CI\u2009=\u20093.837\u2013350.384) was an independent predictor for HBsAg reduction &gt;1 log10 IU\/mL after 48 weeks. Conclusion. This study suggests that PegIFN\u03b1 plus NTs may lead to more HBsAg reduction, especially in HBeAg-positive and \u201cadd-on\u201d patients.<\/jats:p>","DOI":"10.1155\/2022\/4325352","type":"journal-article","created":{"date-parts":[[2022,12,7]],"date-time":"2022-12-07T13:20:09Z","timestamp":1670419209000},"page":"1-14","source":"Crossref","is-referenced-by-count":3,"title":["Reduction of Hepatitis B Surface Antigen May Be More Significant in PEGylated Interferon-Alpha Therapy Combined with Nucleotide Analogues than Combined with Nucleoside Analogues in Chronic Hepatitis B Patients: A Propensity Score Matching Study"],"prefix":"10.1155","volume":"2022","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5115-2037","authenticated-orcid":true,"given":"Yiran","family":"Xie","sequence":"first","affiliation":[{"name":"Department of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, Shanghai Institute of Infectious Diseases and Biosecurity, 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China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4465-292X","authenticated-orcid":true,"given":"Feifei","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, Shanghai Institute of Infectious Diseases and Biosecurity, National Medical Center for Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5534-8299","authenticated-orcid":true,"given":"Richeng","family":"Mao","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, Shanghai Institute of Infectious Diseases and Biosecurity, National Medical Center for Infectious Diseases, Huashan Hospital, Fudan University, Shanghai, 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