{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T00:41:54Z","timestamp":1792024914122,"version":"4.4.0"},"reference-count":23,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2024,7,29]],"date-time":"2024-07-29T00:00:00Z","timestamp":1722211200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2024,10]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background and Aims<\/jats:title><jats:p>Molecular processes driving immune\u2010active chronic hepatitis B (CHB) with and without hepatitis B e antigen (HBeAg) remain incompletely understood. This study aimed to investigate expression profiles of serum and intrahepatic HBV markers and replicative activity of HBV in CHB patients with or without HBeAg.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This study recruited 111 untreated immune\u2010active CHB (60 HBeAg\u2010positive and 51 HBeAg\u2010negative) patients and quantified intrahepatic covalently closed circular DNA (cccDNA), pre\u2010genomic RNA (pgRNA), total HBV DNA (tDNA), and replicative intermediates as well as serum HBV markers (HBV DNA, hepatitis B surface antigen, hepatitis B core\u2010related antigen). Correlations between HBV markers and clinico\u2010virological factors influencing expression levels of HBV markers were analysed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Levels of all serum markers and intrahepatic cccDNA\/tDNA as well as cccDNA transcriptional activity and virion productivity were significantly reduced in HBeAg\u2010negative patients compared to those in HBeAg\u2010positive patients. Additionally, correlations between intrahepatic cccDNA\/pgRNA and serum markers were impaired in HBeAg\u2010negative individuals. Aminotransferase levels were positively correlated with cccDNA transcriptional activity in HBeAg\u2010positive patients, but not in HBeAg\u2010negative patients. Notably, among HBeAg\u2010positive patients, there was a progressive decline in pgRNA level, transcriptional activity, and serum HBV markers as liver fibrosis advanced, which was not observed in HBeAg\u2010negative patients.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>HBeAg loss is correlated with diminished intrahepatic HBV reservoirs and cccDNA transcription, leading to decreased serum HBV marker levels. Circulating HBV markers are not reliable indicators of intrahepatic HBV replicative activity for HBeAg\u2010negative patients. Our findings reveal distinct disease phenotypes between immune\u2010active CHB with and without HBeAg, highlighting the need to establish optimal surrogate biomarkers that can accurately mirror intrahepatic viral activity to aid in decision\u2010making for antiviral therapy for immune\u2010active CHB.<\/jats:p><\/jats:sec>","DOI":"10.1111\/liv.16032","type":"journal-article","created":{"date-parts":[[2024,7,29]],"date-time":"2024-07-29T10:29:27Z","timestamp":1722248967000},"page":"2753-2762","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Differential <scp>HBV<\/scp> replicative markers and covalently closed circular <scp>DNA<\/scp> transcription in immune\u2010active chronic hepatitis B with and without <scp>HBeAg<\/scp>"],"prefix":"10.1111","volume":"44","author":[{"given":"Hye Seon","family":"Kim","sequence":"first","affiliation":[{"name":"The Catholic University Liver Research Center, Collage of Medicine The Catholic University of Korea  Seoul Republic of Korea"},{"name":"Department of Biomedicine &amp; Health Sciences, Graduate School The Catholic University of Korea  Seoul Republic of Korea"},{"name":"Cancer Research Institute, College of Medicine The Catholic University of Korea  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jin Seoub","family":"Kim","sequence":"additional","affiliation":[{"name":"The Catholic University Liver Research Center, Collage of Medicine The Catholic University of Korea  Seoul Republic of Korea"},{"name":"Department of Biomedicine &amp; Health Sciences, Graduate School The Catholic University of Korea  Seoul Republic of Korea"},{"name":"Cancer Research Institute, College of Medicine The Catholic University of Korea  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji Min","family":"Kim","sequence":"additional","affiliation":[{"name":"The Catholic University Liver Research Center, Collage of Medicine The Catholic University of Korea  Seoul Republic of Korea"},{"name":"Department of Biomedicine &amp; Health Sciences, Graduate School The Catholic University of Korea  Seoul Republic of Korea"},{"name":"Cancer Research Institute, College of Medicine The Catholic University of Korea  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji Won","family":"Han","sequence":"additional","affiliation":[{"name":"The Catholic University Liver Research Center, Collage of Medicine The Catholic University of Korea  Seoul Republic of Korea"},{"name":"Department of Internal Medicine, College of Medicine The Catholic University of Korea  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Soon Kyu","family":"Lee","sequence":"additional","affiliation":[{"name":"The Catholic University Liver Research Center, Collage of Medicine The Catholic University of Korea  Seoul Republic of Korea"},{"name":"Department of Internal Medicine, College of Medicine The Catholic University of Korea  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Heechul","family":"Nam","sequence":"additional","affiliation":[{"name":"The Catholic University Liver Research Center, Collage of Medicine The Catholic University of Korea  Seoul Republic of Korea"},{"name":"Department of Internal Medicine, College of Medicine The Catholic University of Korea  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5780-9607","authenticated-orcid":false,"given":"Pil Soo","family":"Sung","sequence":"additional","affiliation":[{"name":"The Catholic University Liver Research Center, Collage of Medicine The Catholic University of Korea  Seoul Republic of Korea"},{"name":"Department of Internal Medicine, College of Medicine The Catholic University of Korea  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jung Hyun","family":"Kwon","sequence":"additional","affiliation":[{"name":"The Catholic University Liver Research Center, Collage of Medicine The Catholic University of Korea  Seoul Republic of Korea"},{"name":"Department of Internal Medicine, College of Medicine The Catholic University of Korea  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Si Hyun","family":"Bae","sequence":"additional","affiliation":[{"name":"The Catholic University Liver Research Center, Collage of Medicine The Catholic University of Korea  Seoul Republic of Korea"},{"name":"Department of Internal Medicine, College of Medicine The Catholic University of Korea  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jong Young","family":"Choi","sequence":"additional","affiliation":[{"name":"The Catholic University Liver Research Center, Collage of Medicine The Catholic 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