{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,7]],"date-time":"2026-07-07T10:46:38Z","timestamp":1783421198793,"version":"3.54.6"},"reference-count":43,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2025,1,28]],"date-time":"2025-01-28T00:00:00Z","timestamp":1738022400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100020950","name":"National Science and Technology Council","doi-asserted-by":"publisher","award":["110\u20102314\u2010B\u2010214 \u2010006 \u2010MY3"],"award-info":[{"award-number":["110\u20102314\u2010B\u2010214 \u2010006 \u2010MY3"]}],"id":[{"id":"10.13039\/501100020950","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004738","name":"E-Da Hospital","doi-asserted-by":"publisher","award":["EDPJ110058"],"award-info":[{"award-number":["EDPJ110058"]}],"id":[{"id":"10.13039\/501100004738","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004738","name":"E-Da Hospital","doi-asserted-by":"publisher","award":["EDPJ111056"],"award-info":[{"award-number":["EDPJ111056"]}],"id":[{"id":"10.13039\/501100004738","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":[[2025,4]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Alanine aminotransferase (ALT) frequently elevates in chronic hepatitis B patients stopping nucleos(t)ide analogs (NAs).<\/jats:p><\/jats:sec><jats:sec><jats:title>Aims<\/jats:title><jats:p>To clarify the association between ALT elevation and HBsAg seroclearance after NA withdrawal.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This multicenter cohort study reviewed consecutive patients discontinuing NA between 2004\/04\/01 and 2022\/05\/24. Treatment initiation and discontinuation generally followed the Asian\u2010Pacific guidelines. Eligible patients had negative HBeAg and undetectable HBV DNA before treatment cessation, without malignancy, organ transplant or autoimmune disorders. We used competing risk analysis to estimate HBsAg seroclearance incidence and a time\u2010dependent model to investigate post\u2010cessation ALT elevation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Among 841 patients (74.7% male; median age, 53.2\u2009years; median treatment duration, 34.7\u2009months), 38 patients cleared HBsAg over a median follow\u2010up of 3.7\u2009years, with a 10\u2010year cumulative incidence of 12.4%. The median peak ALT level was significantly lower in patients achieving HBsAg seroclearance versus not (93 vs. 127\u2009U\/L; <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001). Hepatitis flare after NA cessation (&gt;\u20095 times upper limit) was inversely associated with HBsAg seroclearance in the univariable analysis (sub\u2010distribution hazard ratio [SHR], 0.31; 95% confidence interval [CI], 0.13\u20130.73; <jats:italic>p<\/jats:italic>\u2009=\u20090.007), and the association was not significant (adjusted SHR, 0.42; 95% CI, 0.09\u20132.01; <jats:italic>p<\/jats:italic>\u2009=\u20090.28) in the multivariable analysis adjusted for pretreatment HBV DNA. Consistent results were observed in the sensitivity analyses with different ALT cutoffs and subgroup analysis adjusted for HBsAg levels at treatment cessation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>ALT elevation after NA cessation is not associated with HBsAg seroclearance following NA withdrawal, suggesting cytolytic pathways are not essential for a functional cure.<\/jats:p><\/jats:sec>","DOI":"10.1111\/apt.18515","type":"journal-article","created":{"date-parts":[[2025,1,28]],"date-time":"2025-01-28T07:23:52Z","timestamp":1738049032000},"page":"1208-1217","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Association Between Elevation of Serum Alanine Aminotransferase and <scp>HBsAg<\/scp> Seroclearance After Nucleos(t)ide Analog Withdrawal"],"prefix":"10.1111","volume":"61","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8759-5259","authenticated-orcid":false,"given":"Ying\u2010Nan","family":"Tsai","sequence":"first","affiliation":[{"name":"Division of Gastroenterology and Hepatology, E\u2010Da Cancer Hospital I\u2010Shou University  Kaohsiung Taiwan"},{"name":"School of Medicine, College of Medicine I\u2010Shou University  Kaohsiung Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia\u2010Ling","family":"Wu","sequence":"additional","affiliation":[{"name":"Department of Public Health, College of Medicine National Cheng Kung University  Tainan Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4507-2414","authenticated-orcid":false,"given":"Cheng\u2010Hao","family":"Tseng","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology, E\u2010Da Cancer Hospital I\u2010Shou University  Kaohsiung 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