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We evaluated hepatitis B surface antigen (HBsAg) kinetics after NAs discontinuation and during retreatment due to off\u2010treatment clinical relapse among non\u2010cirrhotic HBeAg\u2010positive CHB patients. Four groups were studied: 129 HBeAg\u2010positive patients from a prospective cohort who stopped NAs therapy after achieving sustained response (Group A), 39 patients who received retreatment after off\u2010treatment clinical relapse in the discontinuation group (Group B), 214 patients who maintained treatment after achieving sustained response (Group C) and 291 patients who firstly initiated antiviral treatment (Group D). During a 5\u2010year follow\u2010up, the cumulative incidence of HBsAg loss was significantly higher in Group A than Group C (22.3% vs. 1.6%, <jats:italic>p<\/jats:italic>\u00a0&lt;\u00a0.001). The quantitative HBsAg (qHBsAg) level at enrolment and NAs discontinuation were independently associated with HBsAg loss. Additionally, patients in Group B showed significantly greater HBsAg loss than those in the Groups C and D, with 5\u2010year cumulative incidences of 9.0%, 1.6% (<jats:italic>p<\/jats:italic>\u00a0=\u00a0.040) and 0.6% (<jats:italic>p<\/jats:italic>\u00a0&lt;\u00a0.001), respectively. Moreover, patients in the Group B exhibited better virologic response (100% vs. 98.8%, <jats:italic>p<\/jats:italic>\u00a0&lt;\u00a0.001) and HBeAg seroconversion (92.6% vs. 69.8%, <jats:italic>p<\/jats:italic>\u00a0&lt;\u00a0.001) than those in Group D at year 5. Propensity score\u2010matched analysis also showed the similar trend of HBsAg decline. NAs discontinuation with or without subsequent retreatment resulted in a more profound reduction of HBsAg in non\u2010cirrhotic HBeAg\u2010positive patients, suggesting that discontinuation may be a potential cure strategy for those with sustained virological suppression.<\/jats:p>","DOI":"10.1111\/jvh.13526","type":"journal-article","created":{"date-parts":[[2021,4,26]],"date-time":"2021-04-26T13:41:30Z","timestamp":1619444490000},"page":"1121-1129","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Hepatitis B surface antigen kinetics after discontinuation of and retreatment with oral antivirals in non\u2010cirrhotic HBeAg\u2010positive chronic hepatitis B"],"prefix":"10.1111","volume":"28","author":[{"given":"Hongjie","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Infectious Diseases Nanfang Hospital Southern Medical University State Key Laboratory of Organ Failure Research Guangdong Provincial Key Laboratory of Viral Hepatitis Research Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xia","family":"Ding","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases Nanfang Hospital Southern Medical University State Key Laboratory of Organ Failure Research Guangdong Provincial Key Laboratory of Viral Hepatitis Research Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guichan","family":"Liao","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases Nanfang Hospital Southern Medical University State Key Laboratory of Organ Failure Research Guangdong Provincial Key Laboratory of Viral Hepatitis Research Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Muye","family":"Xia","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases Nanfang Hospital Southern Medical University State Key Laboratory of Organ Failure Research Guangdong Provincial Key Laboratory of Viral Hepatitis Research Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zuning","family":"Ren","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases Nanfang Hospital Southern Medical University State Key Laboratory of Organ Failure Research Guangdong Provincial Key Laboratory of Viral Hepatitis Research Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rong","family":"Fan","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases Nanfang Hospital Southern Medical University State Key Laboratory of Organ Failure Research Guangdong Provincial Key Laboratory of Viral Hepatitis Research Guangzhou China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jie","family":"Peng","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases Nanfang Hospital Southern Medical University State Key Laboratory of Organ Failure Research Guangdong Provincial Key Laboratory of Viral Hepatitis Research Guangzhou 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