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This study aimed to determine the drug susceptibility and surface antigenicity of the patient\u2010derived mutants.<\/jats:p><\/jats:sec><jats:sec><jats:title>Patients and Methods<\/jats:title><jats:p>Full\u2010length HBV genomes isolated from four entecavir\u2010resistant CHB patients were cloned and sequenced. Around 10 clones of full\u2010length HBV obtained from each patient were analysed and registered in the NCBI GenBank. Representative clones were further characterized by in vitro drug susceptibility and surface antigenicity assays.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The rtL180M\u00a0+\u00a0rtM204V mutations were common among all the clones analysed. Additionally, the ETV resistance mutations rtT184A\/L, rtS202G and rtM250V were found among three patients. Most of the ETV\u2010resistant mutants had amino acid alterations within the known epitopes recognized by T\u2010 and B\u2010cells in the HBV surface and core antigens. The in vitro drug susceptibility assay showed that all tested clones were resistant to ETV treatment. However, they were all susceptible to ADV and TDF. More importantly, the rtI169T mutation in the RT domain, led to the sF161L mutation in the overlapping S gene, which decreased in surface antigenicity.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The ETV resistance mutations can affect the antigenicity of the HBsAg proteins due to changes in the overlapping sequence of this surface antigen. Thus, the apparent decline or disappearance of HBsAg needs to be interpreted cautiously in patients with previous or current antiviral resistance mutations.<\/jats:p><\/jats:sec>","DOI":"10.1111\/liv.14446","type":"journal-article","created":{"date-parts":[[2020,3,26]],"date-time":"2020-03-26T03:05:52Z","timestamp":1585191952000},"page":"1564-1577","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Entecavir\u2010resistant hepatitis B virus decreases surface antigenicity: A full genome and functional characterization"],"prefix":"10.1111","volume":"40","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0500-2227","authenticated-orcid":false,"given":"Soree","family":"Park","sequence":"first","affiliation":[{"name":"Department of Pharmacology Center for Cancer Research and Diagnostic Medicine IBST Konkuk University School of Medicine Seoul 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