{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T20:00:30Z","timestamp":1792008030291,"version":"4.4.0"},"reference-count":33,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","license":[{"start":{"date-parts":[[2021,6,18]],"date-time":"2021-06-18T00:00:00Z","timestamp":1623974400000},"content-version":"vor","delay-in-days":17,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2021,6,1]],"date-time":"2021-06-01T00:00:00Z","timestamp":1622505600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["lww.com","ovid.com"],"crossmark-restriction":true},"short-container-title":["Hepatology"],"published-print":{"date-parts":[[2021,6]]},"abstract":"<jats:sec>\n            <jats:title>Background and Aims<\/jats:title>\n            <jats:p>HBsAg seroclearance is considered a realistic goal in patients with chronic hepatitis B (CHB), known as \u201cfunctional cure.\u201d However, it remains elusive whether nucleos(t)ide analogue (NUC)\u2010induced HBsAg seroclearance, compared with spontaneous HBsAg seroclearance, differs in its association with favorable long\u2010term clinical outcomes.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Approach and Results<\/jats:title>\n            <jats:p>A total of 1,972 CHB patients with confirmed HBsAg seroclearance at least two consecutive times, 6\u00a0months apart, were retrospectively analyzed. Risks of HCC development and composite clinical events, including HCC, liver\u2010related death, and liver transplantation, were compared between spontaneous and NUC\u2010induced HBsAg seroclearance. Of 1,972 patients, mean patient age was 53.7\u00a0years, and 64.4% were men. Cirrhosis was present in 297 (15.1%) patients. HBsAg seroclearance was achieved spontaneously in 1,624 (82.4%) patients and by NUC treatment in 348 (17.6%). HCC developed in 49 patients, with an annual incidence of 0.38 of 100\u00a0person\u2010years (PY) during a median follow\u2010up of 5.6\u00a0years. With 336 propensity\u2010score\u2013matched pairs, risks of HCC (<jats:italic toggle=\"yes\">P<\/jats:italic>\u00a0=\u00a00.52) and clinical events (<jats:italic toggle=\"yes\">P<\/jats:italic>\u00a0=\u00a00.14) were not significantly different between NUC\u2010induced and spontaneous HBsAg seroclearance. By multivariable analysis, NUC\u2010induced HBsAg seroclearance, compared with spontaneous HBsAg seroclearance, was not associated with the significantly higher risk of HCC (adjusted HR [AHR], 1.49; <jats:italic toggle=\"yes\">P<\/jats:italic>\u00a0=\u00a00.26) and clinical events (AHR, 1.78; <jats:italic toggle=\"yes\">P<\/jats:italic>\u00a0=\u00a00.06).<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p>Risks of HCC and clinical events were not significantly different between spontaneous and NUC\u2010induced HBsAg seroclearance. Nonetheless, annual risk of HCC exceeds the recommended cutoff for HCC surveillance even after HBsAg seroclearance, suggesting that continued HCC surveillance is required.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1002\/hep.31610","type":"journal-article","created":{"date-parts":[[2020,11,1]],"date-time":"2020-11-01T13:27:05Z","timestamp":1604237225000},"page":"2155-2166","update-policy":"https:\/\/doi.org\/10.1097\/lww.0000000000001000","source":"Crossref","is-referenced-by-count":38,"title":["Comparison of Long\u2010Term Clinical Outcomes Between Spontaneous and Therapy\u2010Induced HBsAg Seroclearance"],"prefix":"10.1097","volume":"73","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7470-5850","authenticated-orcid":false,"given":"Jonggi","family":"Choi","sequence":"first","affiliation":[{"name":"Department of Gastroenterology, Liver Center,Asan Medical Center,University of Ulsan College of Medicine,Seoul,Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sun","family":"Yoo","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Liver Center,Asan Medical Center,University of Ulsan College of Medicine,Seoul,Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1544-577X","authenticated-orcid":false,"given":"Young\u2010Suk","family":"Lim","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Liver Center,Asan Medical Center,University of Ulsan College of Medicine,Seoul,Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","published-online":{"date-parts":[[2021,6,18]]},"reference":[{"key":"hep31610-bib-0001-20250824","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1002\/hep.28156","article-title":"AASLD guidelines for treatment of chronic hepatitis 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