{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,26]],"date-time":"2026-06-26T16:41:55Z","timestamp":1782492115022,"version":"3.54.5"},"reference-count":26,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2025,5,19]],"date-time":"2025-05-19T00:00:00Z","timestamp":1747612800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2022YFC2303600"],"award-info":[{"award-number":["2022YFC2303600"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2022YFC2304800"],"award-info":[{"award-number":["2022YFC2304800"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82170610"],"award-info":[{"award-number":["82170610"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100021171","name":"Basic and Applied Basic Research Foundation of Guangdong Province","doi-asserted-by":"publisher","award":["2023A1515011211"],"award-info":[{"award-number":["2023A1515011211"]}],"id":[{"id":"10.13039\/501100021171","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":[[2025,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>The role of alanine aminotransferase (ALT) dynamics during nucleos(t)ide analogue (NA) therapy in chronic hepatitis B (CHB) is unclear. We aimed to evaluate the correlation between ALT dynamics and liver\u2010related events (LRE), and explore the optimal threshold of ALT during NA treatment.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We enrolled 18,129 NA\u2010treated patients, comprising 3104 patients from the Search\u2010B study (NCT02167503) and 15,025 patients from a real\u2010world cohort in Hong Kong. Latent\u2010class mixed model (LCMM) was adopted to identify trajectory patterns of ALT during treatment. ALT value at the 95<jats:sup>th<\/jats:sup> percentile of the trajectory group with the lowest LRE risk was obtained as the optimal threshold.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>During a median follow\u2010up of 53.3\u2009months, 1164 patients developed LRE with a 7\u2010year cumulative incidence of 9.9%. In the Search\u2010B cohort, LCMM recognised 3 trajectory groups with progressively increasing ALT levels, which were positively associated with LRE risk. Subsequently, the optimal thresholds for ALT were obtained as 23\u2009U\/L for men and 16\u2009U\/L for women. The 7\u2010year cumulative incidence of LRE was 5.5% for ALT\u2009\u2264\u200923 or 16\u2009U\/L, significantly lower than that for ALT\u2009&gt;\u200923 or 16\u2009U\/L but \u2264\u200940\u2009U\/L (10.8%; aHR\u2009=\u20092.0, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001), and ALT &gt;\u200940\u2009U\/L (15.1%; aHR\u2009=\u20093.4, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001). Similarly, in the Hong Kong cohort, ALT &gt;\u200923 or 16\u2009U\/L but &lt;\u200940\u2009U\/L and ALT &gt;\u200940\u2009U\/L also increased the LRE risk, with aHRs of 2.0 (<jats:italic>p\u2009=<\/jats:italic>\u20090.003) and 6.1 (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001), respectively.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>On\u2010treatment ALT levels were significantly correlated with the prognosis of CHB. ALT \u2264\u200923\u2009U\/L for men and \u2264\u200916\u2009U\/L for women were identified as the optimal thresholds during NA treatment, suggesting that CHB patients should strive for a lower ALT level beyond the traditional normal range.<\/jats:p><\/jats:sec>","DOI":"10.1111\/apt.70195","type":"journal-article","created":{"date-parts":[[2025,5,19]],"date-time":"2025-05-19T05:40:42Z","timestamp":1747633242000},"page":"419-429","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Long\u2010Term Dynamic Changes of Alanine Aminotransferase Levels Are Associated With Liver\u2010Related Events in Nucleos(t)ide Analogue\u2010Treated Chronic Hepatitis B Patients in China"],"prefix":"10.1111","volume":"62","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5922-483X","authenticated-orcid":false,"given":"Rong","family":"Fan","sequence":"first","affiliation":[{"name":"Department of Infectious Diseases Nanfang Hospital, Southern Medical University; State Key Laboratory of Organ Failure Research; Key Laboratory of Infectious Diseases Research in South China, Ministry of Education; Guangdong Provincial Key Laboratory for Prevention and Control of Major Liver Diseases  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ning","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases Nanfang Hospital, Southern Medical University; State Key Laboratory of Organ Failure Research; Key Laboratory of Infectious Diseases Research in South China, Ministry of Education; Guangdong Provincial Key Laboratory for Prevention and Control of Major Liver Diseases  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5749-1598","authenticated-orcid":false,"given":"Jimmy Che\u2010To","family":"Lai","sequence":"additional","affiliation":[{"name":"Medical Data Analytics Centre State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, the Chinese University of Hong Kong  Hong Kong SAR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vicki Wing\u2010Ki","family":"Hui","sequence":"additional","affiliation":[{"name":"Medical Data Analytics Centre State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, the Chinese University of Hong Kong  Hong Kong SAR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0928-3134","authenticated-orcid":false,"given":"Jie","family":"Peng","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases Nanfang Hospital, Southern Medical University; State Key Laboratory of Organ Failure Research; Key Laboratory of Infectious Diseases Research in South China, Ministry of Education; Guangdong Provincial Key Laboratory for Prevention and Control of Major Liver Diseases  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongpeng","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases Nanfang Hospital, Southern Medical University; State Key Laboratory of Organ Failure Research; Key Laboratory of Infectious Diseases Research in South China, Ministry of Education; Guangdong Provincial Key Laboratory for Prevention and Control of Major Liver Diseases  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1142-3589","authenticated-orcid":false,"given":"Zhihong","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases Nanfang Hospital, Southern Medical University; State Key Laboratory of Organ Failure Research; Key Laboratory of Infectious Diseases Research in South China, Ministry of Education; Guangdong Provincial Key Laboratory for Prevention and Control of Major Liver Diseases  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xieer","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases Nanfang Hospital, Southern Medical University; State Key Laboratory of Organ Failure Research; Key Laboratory of Infectious Diseases Research in South China, Ministry of Education; Guangdong Provincial Key Laboratory for Prevention and Control of Major Liver Diseases  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7790-1611","authenticated-orcid":false,"given":"Henry Lik\u2010Yuen","family":"Chan","sequence":"additional","affiliation":[{"name":"Medical Data Analytics Centre State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, the Chinese University of Hong Kong  Hong Kong SAR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junhua","family":"Yin","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases Nanfang Hospital, Southern Medical University; State Key Laboratory of Organ Failure Research; Key Laboratory of Infectious Diseases Research in South China, Ministry of Education; Guangdong Provincial Key Laboratory for Prevention and Control of Major Liver Diseases  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2215-9410","authenticated-orcid":false,"given":"Vincent Wai\u2010Sun","family":"Wong","sequence":"additional","affiliation":[{"name":"Medical Data Analytics Centre State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, the Chinese University of Hong Kong  Hong Kong SAR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunxiu","family":"Zhong","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases Nanfang Hospital, Southern Medical University; State Key Laboratory of Organ Failure Research; Key Laboratory of Infectious Diseases Research in South China, Ministry of Education; Guangdong Provincial Key Laboratory for Prevention and Control of Major Liver Diseases  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grace Lai\u2010Hung","family":"Wong","sequence":"additional","affiliation":[{"name":"Medical Data Analytics Centre State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, the Chinese University of Hong Kong  Hong Kong SAR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5320-227X","authenticated-orcid":false,"given":"Jian","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases Nanfang Hospital, Southern Medical University; State Key Laboratory of Organ Failure Research; Key Laboratory of Infectious Diseases Research in South China, Ministry of Education; Guangdong Provincial Key Laboratory for Prevention and Control of Major Liver Diseases  Guangzhou China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1819-2464","authenticated-orcid":false,"given":"Terry Cheuk\u2010Fung","family":"Yip","sequence":"additional","affiliation":[{"name":"Medical Data Analytics Centre State Key Laboratory of Digestive Disease, Li Ka Shing Institute of Health Sciences, the Chinese University of Hong Kong  Hong Kong SAR China"}],"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 Nanfang Hospital, Southern Medical University; State Key Laboratory of Organ Failure Research; Key Laboratory of Infectious Diseases Research in South China, Ministry of Education; 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