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Here, we conducted a prospective study to analyze the effect of <jats:italic>STAT4<\/jats:italic> genetic polymorphism on the response of pegylated interferon\u2010\u03b1\u20102a (PegIFN\u2010\u03b1\u20102a) in HBeAg\u2010positive patients. A prospective, multicenter, open\u2010label, parallel\u00a0cohort study was performed. One hundred and fifty\u00a0treatment\u2010na\u00efve and 156 nucleos(t)ide analog\u00a0(NA)\u2010experienced HBeAg\u2010positive CHB patients were enrolled, respectively. All patients received PegIFN\u2010\u03b1\u20102a treatment for 48 weeks and 24\u2010week follow\u2010up post PegIFN\u2010\u03b1\u20102a treatment. Before treatment, <jats:italic>STAT4<\/jats:italic> genetic polymorphism was determined by PCR and DNA sequencing. Serological markers, serum HBV DNA levels, and adverse events were collected at each visit. We observed a larger reduction of HBV DNA load and a significantly higher HBeAg seroconversion rate in the\u00a0GT\/TT\u00a0group than in the\u00a0GG group at week 72 (<jats:italic>p<\/jats:italic>\u2009=\u20090.002 and <jats:italic>p<\/jats:italic>\u2009=\u20090.023) in treatment\u2010na\u00efve patients. In NA\u2010experienced patients, the HBeAg seroconversion rate in the\u00a0GT\/TT group was higher than that in the\u00a0GG group at week 72 (<jats:italic>p<\/jats:italic>\u2009=\u20090.005). <jats:italic>STAT4<\/jats:italic> rs7574865 gene polymorphism was the strongest independent predictor of\u00a0HBeAg seroconversion in both paralleled cohorts. Also, patients in the\u00a0GT\/TT group had a higher hepatitis B surface antigen\u00a0loss rate than in the\u00a0GG group in the study. There was no significant difference in adverse events between GG and GT\/TT groups. This prospective cohort study confirmed that <jats:italic>STAT4<\/jats:italic> rs7574865 gene polymorphism is associated with HBeAg seroconversion and HBsAg loss irrespective of na\u00efve and NA\u2010experienced HBeAg\u2010positive CHB patients treated with PegIFN\u2010\u03b1\u20102a.<\/jats:p>","DOI":"10.1002\/jmv.27880","type":"journal-article","created":{"date-parts":[[2022,5,25]],"date-time":"2022-05-25T03:54:56Z","timestamp":1653450896000},"page":"4449-4458","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["<i>STAT4<\/i> genetic polymorphism significantly affected HBeAg seroconversion in HBeAg\u2010positive chronic hepatitis B patients receiving Peginterferon\u2010\u03b1 therapy: A prospective cohort study in China"],"prefix":"10.1002","volume":"94","author":[{"given":"Xun","family":"Qi","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, National Medical Center for Infectious Diseases,\u00a0Huashan Hospital Fudan University  Shanghai China"},{"name":"Department of Hepatology, Shanghai Public Health Clinical Center Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fahong","family":"Li","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,\u00a0Huashan Hospital Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yao","family":"Zhang","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,\u00a0Huashan Hospital Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haoxiang","family":"Zhu","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,\u00a0Huashan Hospital Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"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,\u00a0Huashan Hospital Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinyan","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Hepatology, Shanghai Public Health Clinical Center Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xuhua","family":"Jiang","sequence":"additional","affiliation":[{"name":"Department of Hepatology, Shanghai Public Health Clinical Center Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liang","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Hepatology, Shanghai Public Health Clinical Center Fudan University  Shanghai China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuxian","family":"Huang","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Shanghai Key Laboratory of Infectious Diseases and Biosafety Emergency Response, Shanghai Institute of Infectious 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