{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T15:54:59Z","timestamp":1793202899724,"version":"4.5.0"},"reference-count":48,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2021,5,17]],"date-time":"2021-05-17T00:00:00Z","timestamp":1621209600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/journals\/pages\/open_access\/funder_policies\/chorus\/standard_publication_model"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,12,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Long-term incidences and baseline determinants of functional cure (hepatitis B surface antigen [HBsAg] seroclearance) during entecavir (ETV) or tenofovir disoproxil fumarate (TDF) treatment are incompletely understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This is an international multicenter cohort study of treatment-naive patients with chronic hepatitis B who started ETV or TDF treatment without baseline cancer. Patients were observed for HBsAg seroclearance until death or loss to follow-up. We calculated the incidences and explored the baseline determinants of HBsAg seroclearance using competing risk regression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>The analysis included 4769 patients (median age, 50 years; 69.05% male), with a median follow-up of 5.16 years (26 614.47 person-years). HBsAg clearance occurred in 58 patients, yielding a 10-year cumulative incidence of 2.11% (95% confidence interval, 1.54%\u20132.88%) and an annual rate of 0.22% (.17%\u2013.28%). Baseline predictors included low-level viremia with hepatitis B virus DNA &amp;lt;2000 IU\/mL (adjusted subdistribution hazard ratio, 3.14 [95% confidence interval, 1.80\u20135.49]), elevated serum alanine aminotransferase &amp;gt;200 U\/L (3.68 [2.07\u20136.53]), serum bilirubin (1.11 per mg\/dL; [1.06\u20131.17 mg\/dL]), and fatty liver (1.84 [1.03\u20133.29]).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>HBsAg seroclearance rarely occurs in patients with chronic hepatitis B treated with ETV or TDF and is associated with low-level viremia, alanine aminotransferase flare, bilirubin level, and fatty liver.<\/jats:p>\n                    <jats:p>Functional cure of hepatitis B virus infection rarely occurred at an average annual rate of 0.22% during first-line oral antiviral treatment, with higher chances observed in patients with low-level viremia, high-level aminotransferase flare, elevation of serum bilirubin, and fatty liver.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/infdis\/jiab241","type":"journal-article","created":{"date-parts":[[2021,5,10]],"date-time":"2021-05-10T15:19:37Z","timestamp":1620659977000},"page":"1890-1899","source":"Crossref","is-referenced-by-count":95,"title":["Incidences and Determinants of Functional Cure During Entecavir or Tenofovir Disoproxil Fumarate for Chronic Hepatitis B"],"prefix":"10.1093","volume":"224","author":[{"given":"Yao-Chun","family":"Hsu","sequence":"first","affiliation":[{"name":"Center for Liver Diseases and School of Medicine, E-Da Hospital\/I-Shou University, Kaohsiung, Taiwan"},{"name":"Division of Gastroenterology, Fu-Jen Catholic University Hospital, New Taipei, Taiwan"},{"name":"Institute of Biomedical Informatics, National Yang-Ming University, New Taipei, Taiwan"},{"name":"Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming-Lun","family":"Yeh","sequence":"additional","affiliation":[{"name":"Hepatitis Center and Hepatobiliary Division, Department of Internal Medicine, Kaohsiung Medical University Hospital, Kaohsiung, Taiwan"},{"name":"School of Medicine and Hepatitis Research Center, College of Medicine, and Cohort Research Center, Kaohsiung Medical University, Kaohsiung, Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grace Lai-Hung","family":"Wong","sequence":"additional","affiliation":[{"name":"Department of Medicine and Therapeutics, Chinese University of Hong Kong, Hong Kong SAR, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chien-Hung","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung, 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