{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T21:50:44Z","timestamp":1791496244319,"version":"4.3.4"},"reference-count":25,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"1","license":[{"start":{"date-parts":[[2022,2,14]],"date-time":"2022-02-14T00:00:00Z","timestamp":1644796800000},"content-version":"unspecified","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2022,7]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Background and Aims<\/jats:title>\n            <jats:p>HBV can integrate in the host genome of the hepatocyte and recent findings suggest that integrated HBV contributes to the persistent production of viral proteins. Here, we quantified the levels of integrated HBV in patients with chronic hepatitis B (CHB) and analyzed the relation between HBV integration, virological activity (plasma HBV DNA and HBsAg levels), and clinical outcomes.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Approach and Results<\/jats:title>\n            <jats:p>We developed and validated a multistep Arthrobacter luteus (Alu)\u2010PCR that specifically amplifies integrated HBV and RT\u2010Alu\u2010PCR detecting mRNA transcripts derived from integrated HBV. Pretreatment liver biopsy samples and baseline characteristics of 124 patients with CHB either treated for 48 weeks with pegylated interferon plus adefovir or tenofovir or receiving no treatment were available for analysis. Integrated HBV sequences containing open reading frame S and X (but not C) and S and X mRNA transcripts derived from integrated HBV could be detected and quantified in liver biopsies. Integrated HBV levels correlated with HBV DNA, HBsAg, alanine aminotransferase plasma levels, and the liver histology activity index but not to levels of intrahepatic covalently closed circular DNA (cccDNA), plasma pregenomic RNA, or hepatitis B core\u2010related antigen. Multivariable logistic regression analysis showed that lower baseline HBV integration levels were independently associated with HBsAg loss (functional cure) within 5 years follow\u2010up.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>Integrated HBV levels are strongly correlated with surrogate markers for virological activity but not to cccDNA levels and are predictive for HBsAg loss. Our data suggest that integrated HBV is closely related to HBV replication and may therefore be an important tool in the evaluation and development of treatment modalities aiming to cure CHB.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1002\/hep.32352","type":"journal-article","created":{"date-parts":[[2022,1,24]],"date-time":"2022-01-24T19:49:46Z","timestamp":1643053786000},"page":"196-206","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":27,"title":["Quantified integrated hepatitis B virus is related to viral activity in patients with chronic hepatitis B"],"prefix":"10.1097","volume":"76","author":[{"given":"Robin","family":"Erken","sequence":"first","affiliation":[{"name":"Department of Experimental Immunology,Amsterdam UMC, location AMC,Amsterdam Infection & Immunity Institute,University of Amsterdam,Amsterdam,the Netherlands"},{"name":"Department of Gastroenterology and Hepatology,Amsterdam Gastroenterology Endocrinology Metabolism,Amsterdam UMC, location AMC,Amsterdam,the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vladimir","family":"Loukachov","sequence":"additional","affiliation":[{"name":"Department of Experimental Immunology,Amsterdam UMC, location AMC,Amsterdam Infection & Immunity Institute,University of Amsterdam,Amsterdam,the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karel","family":"van Dort","sequence":"additional","affiliation":[{"name":"Department of Experimental Immunology,Amsterdam UMC, location AMC,Amsterdam Infection & Immunity Institute,University of Amsterdam,Amsterdam,the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anne","family":"van den Hurk","sequence":"additional","affiliation":[{"name":"Department of Experimental Immunology,Amsterdam UMC, location AMC,Amsterdam Infection & Immunity Institute,University of Amsterdam,Amsterdam,the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. Bart","family":"Takkenberg","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology,Amsterdam Gastroenterology Endocrinology Metabolism,Amsterdam UMC, location AMC,Amsterdam,the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anniki","family":"de Niet","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology,Amsterdam Gastroenterology Endocrinology Metabolism,Amsterdam UMC, location AMC,Amsterdam,the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louis","family":"Jansen","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology,Amsterdam Gastroenterology Endocrinology Metabolism,Amsterdam UMC, location AMC,Amsterdam,the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophie","family":"Willemse","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology,Amsterdam Gastroenterology Endocrinology Metabolism,Amsterdam UMC, location AMC,Amsterdam,the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henk","family":"Reesink","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology,Leiden University Medical Center,Leiden,the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Neeltje","family":"Kootstra","sequence":"additional","affiliation":[{"name":"Department of Experimental Immunology,Amsterdam UMC, location AMC,Amsterdam Infection & Immunity Institute,University of Amsterdam,Amsterdam,the Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2022,2,14]]},"reference":[{"issue":"6","key":"hep32352-bib-0001-20250824","doi-asserted-by":"crossref","first-page":"383","DOI":"10.1016\/S2468-1253(18)30056-6","article-title":"Global prevalence, treatment, and prevention of hepatitis B 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ARB\u20101740 has inhibitory effect on hepatitis delta virus in a new dually\u2010infected humanized mouse model","volume":"5","year":"2019","journal-title":"ACS Infect Dis"},{"issue":"8","key":"hep32352-bib-0009-20250824","doi-asserted-by":"crossref","first-page":"576","DOI":"10.1016\/S2468-1253(17)30083-3","article-title":"Peg\u2010interferon plus nucleotide analogue treatment versus no treatment in patients with chronic hepatitis B with a low viral load: a randomised controlled, open\u2010label trial","volume":"2","year":"2017","journal-title":"Lancet Gastroenterol Hepatol"},{"issue":"7","key":"hep32352-bib-0010-20250824","doi-asserted-by":"crossref","first-page":"895","DOI":"10.3851\/IMP2580","article-title":"Baseline hepatitis B surface antigen (HBsAg) as predictor of sustained HBsAg loss in chronic hepatitis B patients treated with pegylated interferon\u2010alpha2a and adefovir","volume":"18","year":"2013","journal-title":"Antivir 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