Evidence for a relationship between concentrations of nucleos/tide analogue agents and treatment outcome in chronic hepatitis B infection: A systematic review

Evidence for a relationship between concentrations of nucleos/tide analogue agents and treatment outcome in chronic hepatitis B infection: A systematic review | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Systematic Review Evidence for a relationship between concentrations of nucleos/tide analogue agents and treatment outcome in chronic hepatitis B infection: A systematic review Gloria Sukali, Motswedi Anderson, Khadija Said Mohammed, Patti Biggs, and 9 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-8794288/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Introduction: Treatment of hepatitis B virus (HBV) primarily relies on nucleos(t)ide analogues to achieve viral suppression, with tenofovir or entecavir as first-line agents. Expanding treatment and improving its outcomes are crucial strategies to support advances towards targets for the elimination of viral hepatitis as a public health threat by 2030. However, therapeutic drug monitoring has not been systematically applied to optimize HBV therapy. Methods We conducted a systematic review (PROSPERO CRD420250599139) to identify studies that reported treatment outcomes of HBV in English from PubMed, Scopus and Web of Science. We collated the evidence for the relationship between drug concentrations and therapeutic outcomes in HBV. Our primary search included people living with HBV with or without Human Immunodeficiency Virus (HIV) coinfection, treated with tenofovir and/or entecavir linked to clinical or laboratory-based assessment of treatment outcome. Results We identified six studies reporting drug concentrations in people with HBV infection, of which five reported on HIV/HBV coinfection, and one on HBV monoinfection. Across all studies, tenofovir concentrations > 800 fmol/punch in dried blood spots were typically associated with viraemic suppression for both HIV and HBV. Evidence suggests that higher tenofovir concentrations (e.g. 1000–1500 fmol/punch) may be required for consistent suppression of HBV. However, evidence from HBV monoinfection was limited, and a therapeutic concentration for HBV could not be defined. Only one study reported entecavir concentrations in HBV and data are inconclusive. Discussion A therapeutic threshold cannot currently be defined for concentrations of tenofovir or entecavir in HBV. Larger cohort studies that focus on HBV monoinfection are needed to define therapeutic drug thresholds to optimize personalized care for people living with HBV and improve population health outcomes. therapeutic drug monitoring tenofovir entecavir HIV Hepatitis B virus HBV outcomes suppression Full Text Additional Declarations The authors declare potential competing interests as follows: PCM has received funding support from GSK for a graduate student in her group (2019-2023) and for the UK Health Informatics Collaborative for viral hepatitis and liver disease, and has received speaker fees from J&J for an educational event, outside the scope of this current work. Supplementary Files 260206ReviewSupplementaryMaterialGS.docx Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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","formattedTitle":"\u003cp\u003eEvidence for a relationship between concentrations of nucleos/tide analogue agents and treatment outcome in chronic hepatitis B infection: A systematic review\u003c/p\u003e","fulltext":[],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":false,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":true,"hideJournal":true,"highlight":"","institution":"The Francis Crick Institute","isAcceptedByJournal":false,"isAuthorSuppliedPdf":true,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":true,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"therapeutic drug monitoring, tenofovir, entecavir, HIV, Hepatitis B virus, HBV, outcomes, suppression","lastPublishedDoi":"10.21203/rs.3.rs-8794288/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-8794288/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003eIntroduction:\u003c/h2\u003e \u003cp\u003eTreatment of hepatitis B virus (HBV) primarily relies on nucleos(t)ide analogues to achieve viral suppression, with tenofovir or entecavir as first-line agents. Expanding treatment and improving its outcomes are crucial strategies to support advances towards targets for the elimination of viral hepatitis as a public health threat by 2030. However, therapeutic drug monitoring has not been systematically applied to optimize HBV therapy.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e \u003cp\u003e We conducted a systematic review (PROSPERO CRD420250599139) to identify studies that reported treatment outcomes of HBV in English from PubMed, Scopus and Web of Science. We collated the evidence for the relationship between drug concentrations and therapeutic outcomes in HBV. Our primary search included people living with HBV with or without Human Immunodeficiency Virus (HIV) coinfection, treated with tenofovir and/or entecavir linked to clinical or laboratory-based assessment of treatment outcome.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e \u003cp\u003eWe identified six studies reporting drug concentrations in people with HBV infection, of which five reported on HIV/HBV coinfection, and one on HBV monoinfection. Across all studies, tenofovir concentrations\u0026thinsp;\u0026gt;\u0026thinsp;800 fmol/punch in dried blood spots were typically associated with viraemic suppression for both HIV and HBV. Evidence suggests that higher tenofovir concentrations (e.g. 1000\u0026ndash;1500 fmol/punch) may be required for consistent suppression of HBV. However, evidence from HBV monoinfection was limited, and a therapeutic concentration for HBV could not be defined. Only one study reported entecavir concentrations in HBV and data are inconclusive.\u003c/p\u003e\u003ch2\u003eDiscussion\u003c/h2\u003e \u003cp\u003eA therapeutic threshold cannot currently be defined for concentrations of tenofovir or entecavir in HBV. Larger cohort studies that focus on HBV monoinfection are needed to define therapeutic drug thresholds to optimize personalized care for people living with HBV and improve population health outcomes.\u003c/p\u003e","manuscriptTitle":"Evidence for a relationship between concentrations of nucleos/tide analogue agents and treatment outcome in chronic hepatitis B infection: A systematic review","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2026-02-06 16:14:34","doi":"10.21203/rs.3.rs-8794288/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"91b3dc09-744e-472b-9fb7-fea216f4bd1c","owner":[],"postedDate":"February 6th, 2026","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2026-02-06T16:14:34+00:00","versionOfRecord":[],"versionCreatedAt":"2026-02-06 16:14:34","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-8794288","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-8794288","identity":"rs-8794288","version":["v1"]},"buildId":"XKTyCvWXoU3ODBz1xrDgd","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}