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This study aimed to investigate the effects of NAs on HBsAg reduction and association with serum IFN\u2010\u03bb3 levels in chronic hepatitis B (CHB) patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>A total of 91 patients [51 treated with nucleoside analog entecavir hydrate (ETV) and 40 treated with nucleotide analog adefovir dipivoxil (ADV) or tenofovir disoproxil fumarate (TDF)] with clinically evident CHB (chronic hepatitis, 57; liver cirrhosis, 34) were enrolled in this study. Serum IFN\u2010\u03bb3 levels among patients receiving ETV and ADV\/TDF were measured before the initiation of therapy and 1, 3, and 5\u00a0years post\u2010therapy.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The change (mean\u00a0\u00b1\u00a0standard deviation) in serum HBsAg levels from baseline to year five was \u22120.38\u00a0\u00b1\u00a00.46 and \u22120.84\u00a0\u00b1\u00a00.64 log<jats:sub>10<\/jats:sub> IU\/ml in ETV and ADV\/TDF groups, respectively (<jats:italic>p<\/jats:italic>\u00a0=\u00a00.0004). Higher serum IFN\u2010\u03bb3 levels were observed in ADV\/TDF group compared with ETV group during treatment (<jats:italic>p<\/jats:italic>\u00a0&lt;\u00a00.001). Serum IFN\u2010\u03bb3 levels showed negative correlation with HBsAg reduction in ADV\/TDF group (<jats:italic>r<\/jats:italic> = \u22120.386, <jats:italic>p<\/jats:italic> = 0.038) at week 48. Nucleotide analogs (ADV\/TDF) treatment has associated factors with \u22120.3 log HBsAg decline at 1\u00a0year, \u22120.5 log HBsAg decline at 3\u00a0years, and \u22120.8 log HBsAg decline at 5\u00a0years after NAs treatment on multivariate analysis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Nucleotide analog (ADV\/TDF) treatment reduced HBsAg levels greater compared with nucleoside analog (ETV) in parallel with IFN\u2010\u03bb3 induction.<\/jats:p><\/jats:sec>","DOI":"10.1111\/hepr.13768","type":"journal-article","created":{"date-parts":[[2022,3,30]],"date-time":"2022-03-30T05:29:42Z","timestamp":1648618182000},"page":"586-596","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Effects of nucleos(t)ide analogs on hepatitis B surface antigen reduction with interferon\u2010lambda 3 induction in chronic hepatitis B 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