{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,24]],"date-time":"2026-10-24T11:03:22Z","timestamp":1792839802894,"version":"4.5.0"},"reference-count":36,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2024,12,3]],"date-time":"2024-12-03T00:00:00Z","timestamp":1733184000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100015383","name":"Stichting voor Lever- en Maag-Darm Onderzoek","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100015383","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Aliment Pharmacol Ther"],"published-print":{"date-parts":[[2025,2]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Severe flares (ALT\u2009\u2265\u200910\u00d7ULN) are a well\u2010recognised adverse outcome after nucleos(t)ide analogue (NA) cessation and may lead to liver failure. Thus, identification of patients at risk for these flares is of major importance.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>Data were used from two prospective studies on NA cessation conducted in the Netherlands and Canada. Patients were eligible based on EASL criteria. HBcrAg and anti\u2010HBc levels were measured at end of treatment (EOT) and week 6 (FUW6). Logistic regression was used to study the association with severe flares.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Seventy\u2010eight patients were analysed with a mean age of 49\u2009years, 16 (21%) Caucasian and a majority (65%) were treated with Tenofovir. Overall, 22 patients (28%) developed a severe flare, and 29 (37%) patients were retreated. At EOT, higher HBcrAg levels (aOR: 1.97, <jats:italic>p<\/jats:italic>\u2009=\u20090.05; \u2265\u20094log: 47% severe flare vs. &lt;\u20093log: 19%, <jats:italic>p<\/jats:italic>\u2009=\u20090.036), lower anti\u2010HBc (aOR: 0.29, <jats:italic>p<\/jats:italic>\u2009=\u20090.036; &lt;\u20092log: 50% vs. \u2265\u20093log: 11%, <jats:italic>p<\/jats:italic>\u2009=\u20090.029) and higher HBcrAg\/anti\u2010HBc\u2010ratio (aOR: 3.17, <jats:italic>p<\/jats:italic>\u2009=\u20090.015; \u2265\u20092: 58% vs. &lt;\u20091.5: 14%, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001) were associated with an increased risk of severe flares, adjusted for HBsAg. At FUW6, higher HBcrAg (aOR: 2.91, <jats:italic>p<\/jats:italic>\u2009=\u20090.035; \u2265\u20095log: 83%, &lt;\u20093log: 4%, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001), lower anti\u2010HBc (aOR: 0.46, <jats:italic>p<\/jats:italic>\u2009=\u20090.29; &lt;\u20092log: 50% vs. \u2265\u20093log: 0%, <jats:italic>p<\/jats:italic>\u2009=\u20090.003) and higher HBcrAg\/anti\u2010HBc\u2010ratio (aOR: 2.19, <jats:italic>p<\/jats:italic>\u2009=\u20090.048; \u2265\u20091.75: 52% vs. &lt;\u20091.75: 8%, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001) were associated with an increased risk of severe flares, adjusted for HBV DNA and ALT.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Higher HBcrAg, lower anti\u2010HBc and higher HBcrAg\/anti\u2010HBc ratio at EOT and during the first weeks of post\u2010treatment follow\u2010up are associated with an increased risk of hepatic flares after NA withdrawal and could therefore potentially be used to select patients eligible for therapy cessation and to identify patients requiring retreatment.<\/jats:p><jats:p><jats:bold>Trial Registration:<\/jats:bold> This study was a post hoc and follow\u2010up study of two previously registered clinical trials (NCT01911156 &amp; NTR7001). No new patients were prospectively included<\/jats:p><\/jats:sec>","DOI":"10.1111\/apt.18416","type":"journal-article","created":{"date-parts":[[2024,12,3]],"date-time":"2024-12-03T10:01:44Z","timestamp":1733220104000},"page":"570-578","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Early <scp>HBcrAg<\/scp> and Anti\u2010<scp>HBc<\/scp> Levels Identify Patients at High Risk for Severe Flares After Nucleos(t)ide Analogue Cessation\u2014A Pooled Analysis of Two Clinical Trials"],"prefix":"10.1111","volume":"61","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2746-1643","authenticated-orcid":false,"given":"Edo J.","family":"Dongelmans","sequence":"first","affiliation":[{"name":"Department of Gastroenterology and Hepatology Erasmus University Medical Centre  Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jordan J.","family":"Feld","sequence":"additional","affiliation":[{"name":"Toronto Centre for Liver Disease, Toronto General Hospital University Health Network  Toronto ON Canada"},{"name":"The Toronto Viral Hepatitis Care Network (VIRCAN)  Toronto ON Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e9","family":"Boonstra","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Erasmus University Medical Centre  Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7687-4036","authenticated-orcid":false,"given":"Sylvia M.","family":"Brakenhoff","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Erasmus University Medical Centre  Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David","family":"Wong","sequence":"additional","affiliation":[{"name":"Toronto Centre for Liver Disease, Toronto General Hospital University Health Network  Toronto ON Canada"},{"name":"The Toronto Viral Hepatitis Care Network (VIRCAN)  Toronto ON Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colina","family":"Yim","sequence":"additional","affiliation":[{"name":"Toronto Centre for Liver Disease, Toronto General Hospital University Health Network  Toronto ON Canada"},{"name":"The Toronto Viral Hepatitis Care Network (VIRCAN)  Toronto ON Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mark","family":"Claassen","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine Rijnstate Hospital  Arnhem The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pieter","family":"Honkoop","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Albert Schweitzer Hospital  Dordrecht The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bettina E.","family":"Hansen","sequence":"additional","affiliation":[{"name":"Toronto Centre for Liver Disease, Toronto General Hospital University Health Network  Toronto ON Canada"},{"name":"The Toronto Viral Hepatitis Care Network (VIRCAN)  Toronto ON Canada"},{"name":"Department of Epidemiology and Biostatistics Erasmus University Medical Centre  Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert A.","family":"de Man","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Erasmus University Medical Centre  Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0501-8800","authenticated-orcid":false,"given":"Scott","family":"Fung","sequence":"additional","affiliation":[{"name":"Toronto Centre for Liver Disease, Toronto General Hospital University Health Network  Toronto ON Canada"},{"name":"The Toronto Viral Hepatitis Care Network (VIRCAN)  Toronto ON Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thomas","family":"Berg","sequence":"additional","affiliation":[{"name":"Division of Hepatology, Department of Medicine II Leipzig University Medical Center  Leipzig Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2679-0672","authenticated-orcid":false,"given":"Florian","family":"van B\u00f6mmel","sequence":"additional","affiliation":[{"name":"Division of Hepatology, Department of Medicine II Leipzig University Medical Center  Leipzig Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harry L. 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