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We previously demonstrated that pre\u2010S expression in some GGHs is resistant to current hepatitis B virus (HBV) antiviral therapies. This study aimed to investigate whether integrated HBV DNA (iDNA) is the primary HBV DNA species responsible for sustained pre\u2010S expression in GGH after effective antiviral therapy. We characterized 10 sets of micro\u2010dissected, formalin\u2010fixed\u2010paraffin\u2010embedded, and frozen GGH, HCC, and adjacent hepatitis B surface antigen\u2010negative stained tissues for iDNA, pre\u2010S deletions, and the quantity of covalently closed circular DNA. Eight patients had detectable pre\u2010S deletions, and nine had detectable iDNA. Interestingly, eight patients had integrations within the <jats:italic>TERT<\/jats:italic> and <jats:italic>CCNE1<\/jats:italic> genes, which are known recurrent integration sites associated with HCC. Furthermore, we observed a recurrent integration in the <jats:italic>ABCC13<\/jats:italic> gene. Additionally, we identified variations in the type and quantity of pre\u2010S deletions within individual sets of tissues by junction\u2010specific PacBio long\u2010read sequencing. The data from long\u2010read sequencing indicate that some pre\u2010S deletions were acquired following the integration events. Our findings demonstrate that iDNA exists in GGH and can be responsible for sustained pre\u2010S expression in GGH after effective antiviral therapy.<\/jats:p>","DOI":"10.1002\/jmv.29348","type":"journal-article","created":{"date-parts":[[2024,1,5]],"date-time":"2024-01-05T11:54:24Z","timestamp":1704455664000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Characterization of integrated hepatitis B virus DNA harboring pre\u2010S mutations in hepatocellular carcinoma patients with ground glass hepatocytes"],"prefix":"10.1002","volume":"96","author":[{"given":"Yih\u2010Ping","family":"Su","sequence":"first","affiliation":[{"name":"Department of Microbiology and Immunology Drexel University College of Medicine Philadelphia Pennsylvania USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Selena Y.","family":"Lin","sequence":"additional","affiliation":[{"name":"Department of Research and Development JBS Science, Inc.  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