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With the advancement in technology, various components of the viral cycle can now be measured in the blood to assess viral activity. In this review article, we summarize the relevant data of how antiviral therapies impact viral biomarkers, and discuss their potential implications. Viral nucleic acids including hepatitis B virus (HBV) double-stranded deoxy-ribonucleic acid (DNA) and to a lesser extent, pre-genomic RNA, are readily suppressed by nucleos(t)ide analogues (NUCs). The primary role of these markers include risk prediction for hepatocellular carcinoma (HCC) and risk stratification for partial cure, defined as off-therapy virological control, or functional cure, defined as hepatitis B surface antigen (HBsAg) seroclearance plus undetectable serum HBV DNA for \u22656 months. Viral translational products including hepatitis e antigen, quantitative HBsAg and hepatitis B core-related antigen can be reduced by NUCs and pegylated interferon a. They are important in defining disease phase, delineating treatment endpoints, and predicting clinical outcomes including HCC risk and partial\/ functional cure. As the primary outcome of phase III trials in chronic hepatitis B is set as HBsAg seroclearance, appropriate viral biomarkers can potentially inform the efficacy of novel compounds. Early viral biomarker response can help with prioritization of subjects into clinical trials. However, standardization and validation studies would be crucial before viral biomarkers can be broadly implemented in clinical use.<\/jats:p>","DOI":"10.3350\/cmh.2022.0448","type":"journal-article","created":{"date-parts":[[2023,1,19]],"date-time":"2023-01-19T02:08:11Z","timestamp":1674094091000},"page":"263-276","update-policy":"https:\/\/doi.org\/10.3350\/crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["The role of different viral biomarkers on the management of chronic hepatitis B"],"prefix":"10.3350","volume":"29","author":[{"given":"Lung-Yi","family":"Mak","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rex Wan-Hin","family":"Hui","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Fung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wai Kay","family":"Seto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7985-7725","authenticated-orcid":true,"given":"Man-Fung","family":"Yuen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1902","reference":[{"key":"ref1","first-page":"383","volume-title":"Global prevalence, treatment, and prevention of hepatitis B virus infection in 2016: a modelling study","year":"2018"},{"key":"ref2","volume-title":"","year":"2017"},{"key":"ref3","first-page":"S29","volume-title":"The incidence of chronic HBV by age at the global and regional level, 2022","author":"Razavi-Shearer"},{"key":"ref4","doi-asserted-by":"publisher","DOI":"10.1053\/j.gastro.2013.12.024"},{"key":"ref5","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1730940100"},{"key":"ref6","doi-asserted-by":"publisher","DOI":"10.1038\/s41564-020-0678-0"},{"key":"ref7","first-page":"E4244","volume-title":"Involvement of the host DNA-repair enzyme TDP2 in formation of the covalently closed circular DNA persistence reservoir of hepatitis B viruses","author":"K\u00f6niger","year":"2014"},{"key":"ref8","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2015.02.031"},{"key":"ref9","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(86)90602-1"},{"key":"ref10","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2018.08.012"},{"key":"ref11","doi-asserted-by":"publisher","DOI":"10.3390\/v9040075"},{"key":"ref12","doi-asserted-by":"publisher","DOI":"10.3350\/cmh.2020.0115"},{"key":"ref13","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2013-306648"},{"key":"ref14","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2017.07.012"},{"key":"ref15","doi-asserted-by":"publisher","DOI":"10.1002\/hep.21187"},{"key":"ref16","doi-asserted-by":"publisher","DOI":"10.1126\/science.1243462"},{"key":"ref17","doi-asserted-by":"publisher","DOI":"10.1172\/jci58847"},{"key":"ref18","doi-asserted-by":"publisher","DOI":"10.1002\/hep.31030"},{"key":"ref19","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2020-321299"},{"key":"ref20","doi-asserted-by":"publisher","DOI":"10.1002\/hep.22930"},{"key":"ref21","doi-asserted-by":"publisher","DOI":"10.1136\/gutjnl-2014-308989"},{"key":"ref22","doi-asserted-by":"publisher","DOI":"10.1002\/hep.20353"},{"key":"ref23","doi-asserted-by":"publisher","DOI":"10.1002\/jmv.21863"},{"key":"ref24","doi-asserted-by":"publisher","DOI":"10.1097\/meg.0b013e32834ba13a"},{"key":"ref25","doi-asserted-by":"publisher","DOI":"10.1128\/jcm.00760-17"},{"key":"ref26","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2017.03.021"},{"key":"ref27","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2016.05.029"},{"key":"ref28","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2016.09.028"},{"key":"ref29","doi-asserted-by":"publisher","DOI":"10.7150\/ijms.71737"},{"key":"ref30","doi-asserted-by":"publisher","DOI":"10.1111\/jvh.12908"},{"key":"ref31","first-page":"349","volume-title":"Serum hepatitis B virus RNA levels as an early predictor of hepatitis B envelope antigen seroconversion during treatment with polymerase inhibitors. 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