{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T16:03:17Z","timestamp":1785168197637,"version":"3.55.0"},"reference-count":25,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2022,9,14]],"date-time":"2022-09-14T00:00:00Z","timestamp":1663113600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009663","name":"University Health Network","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100009663","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Journal of Viral Hepatitis"],"published-print":{"date-parts":[[2022,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>When patients with chronic hepatitis B (CHB) stop nucleos(t)ide analogue (NA) therapy before achieving HBsAg loss, flares often ensue which are challenging to predict early. We determined the incidence, severity, outcome and predictors of flares after NA withdrawal. Forty\u2010five patients enrolled in an RCT were included; 107 patients from an external, prospective cohort were used for validation. Retreatment criteria were pre\u2010defined. Pre\u2010 and post\u2010treatment predictors of alanine aminotransferase (ALT) flare (&gt;5\u00d7 ULN) were evaluated by Cox proportional\u2010hazards regression. Seventy\u2010two weeks after NA withdrawal, 23\/45 (51%) patients had developed &gt;5\u00d7 ULN and 14 (31%) &gt;20\u00d7 ULN. Median time to develop ALT &gt;5\u00d7 ULN was 12\u2009weeks after NA withdrawal. Independent predictors of ALT &gt;5\u00d7 ULN were male sex (HR [95% CI] 3.2 [1.2\u20138.9]; <jats:italic>p<\/jats:italic>\u00a0=\u00a00.03) and serum HBV DNA (1.2 [1.0\u20131.8]; <jats:italic>p<\/jats:italic>\u00a0=\u00a00.03) at Week 6 off\u2010therapy. Specifically, week 6 HBV DNA &gt;10,000\u2009IU\/ml predicted ALT &gt;5\u00d7 ULN (3.4 [1.4\u20138.4]; <jats:italic>p<\/jats:italic>\u00a0=\u00a00.01), which was externally validated. In conclusion, this study on post\u2010treatment flares revealed a high cumulative incidence in CHB. Week 6 HBV DNA &gt;10,000\u2009IU\/ml independently predicted flares. The proposed threshold enables prediction of imminent flares in patients who may benefit from closer monitoring and earlier retreatment.<\/jats:p>","DOI":"10.1111\/jvh.13742","type":"journal-article","created":{"date-parts":[[2022,9,1]],"date-time":"2022-09-01T17:53:47Z","timestamp":1662054827000},"page":"986-993","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Early virologic relapse predicts alanine aminotransferase flares after nucleos(t)ide analogue withdrawal in patients with chronic hepatitis B"],"prefix":"10.1111","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3585-2778","authenticated-orcid":false,"given":"Kin Seng","family":"Liem","sequence":"first","affiliation":[{"name":"Toronto Centre for Liver Disease University Health Network  Toronto Ontario Canada"},{"name":"Department of Gastroenterology and Hepatology Erasmus University Medical Center Rotterdam  Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9105-954X","authenticated-orcid":false,"given":"Heng","family":"Chi","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Erasmus University Medical Center Rotterdam  Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott","family":"Fung","sequence":"additional","affiliation":[{"name":"Toronto Centre for Liver Disease University Health Network  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David K.","family":"Wong","sequence":"additional","affiliation":[{"name":"Toronto Centre for Liver Disease University Health Network  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Colina","family":"Yim","sequence":"additional","affiliation":[{"name":"Toronto Centre for Liver Disease University Health Network  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seham","family":"Noureldin","sequence":"additional","affiliation":[{"name":"Toronto Centre for Liver Disease University Health Network  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiayun","family":"Chen","sequence":"additional","affiliation":[{"name":"Toronto Centre for Liver Disease University Health Network  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert A.","family":"de Man","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology and Hepatology Erasmus University Medical Center Rotterdam  Rotterdam The Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arif","family":"Sarowar","sequence":"additional","affiliation":[{"name":"Toronto Centre for Liver Disease University Health Network  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jordan J.","family":"Feld","sequence":"additional","affiliation":[{"name":"Toronto Centre for Liver Disease University Health Network  Toronto Ontario Canada"},{"name":"McLaughlin\u2010Rotman Centre for Global Health  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bettina E.","family":"Hansen","sequence":"additional","affiliation":[{"name":"Toronto Centre for Liver Disease University Health Network  Toronto Ontario Canada"},{"name":"Department of Gastroenterology and Hepatology Erasmus University Medical Center Rotterdam  Rotterdam The Netherlands"},{"name":"Institute of Health Policy, Management and Evaluation University of Toronto  Toronto Ontario Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8230-8583","authenticated-orcid":false,"given":"Jinlin","family":"Hou","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Nanfang Hospital Southern Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Peng","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Guangdong Provincial Key Laboratory of Viral Hepatitis Research, Nanfang Hospital Southern Medical University  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harry L. 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