{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T05:47:43Z","timestamp":1782712063258,"version":"3.54.5"},"reference-count":89,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T00:00:00Z","timestamp":1782691200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100009331","name":"Beijing Municipal Administration of Hospitals Clinical Medicine Development of Special Funding Support","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100009331","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Cell. Infect. Microbiol."],"abstract":"<jats:p>HBeAg seroclearance represents a critical milestone in the treatment of HBeAg-positive chronic hepatitis B (CHB), which is closely associated with disease remission, functional cure, and reduced hepatocellular carcinoma risk. As HBeAg is a secreted viral protein associated with active HBV replication, infectivity, and host immune tolerance, its disappearance usually indicates a transition toward improved immune control rather than simple loss of a laboratory marker. This review comprehensively explores the immunological mechanisms underlying HBeAg seroclearance, thoroughly examines its impact on the natural course of CHB and systematically analyzes the regulatory roles of antiviral drug efficacy, host immune status, and viral genotypes in HBeAg clearance. Integrating updated guidelines and evidence-based research, we propose optimized strategies for managing HBeAg-negative CHB, including goal setting, treatment cessation criteria, and long-term monitoring protocols. Our findings emphasize that HBeAg clearance not only signifies virological suppression but also reflects the dynamic equilibrium of host immune responses, thereby providing both theoretical foundation and practical support for achieving functional cure and reducing HCC risk in CHB patients.<\/jats:p>","DOI":"10.3389\/fcimb.2026.1785154","type":"journal-article","created":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T05:38:56Z","timestamp":1782711536000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["The clinical significance and optimization strategies of HBeAg seroclearance in chronic hepatitis B treatment"],"prefix":"10.3389","volume":"16","author":[{"given":"Yaqin","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University","place":["Beijing, China"]},{"name":"HBV Infection, Clinical Cure and Immunology Joint Laboratory for Clinical Medicine, Capital Medical University","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanjiao","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinxin","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ziyu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiyu","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zixuan","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yao","family":"Xie","sequence":"additional","affiliation":[{"name":"Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University","place":["Beijing, China"]},{"name":"HBV Infection, Clinical Cure and Immunology Joint Laboratory for Clinical Medicine, Capital Medical University","place":["Beijing, China"]},{"name":"Department of Hepatology Division 2, Peking University Ditan Teaching Hospital","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minghui","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Hepatology Division 2, Beijing Ditan Hospital, Capital Medical University","place":["Beijing, China"]},{"name":"HBV Infection, Clinical Cure and Immunology Joint Laboratory for Clinical Medicine, Capital Medical University","place":["Beijing, China"]},{"name":"Department of Hepatology Division 2, Peking University Ditan Teaching Hospital","place":["Beijing, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,29]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.3390\/v14081691","article-title":"HBeAg-negative\/anti-HBe-positive chronic hepatitis B: A 40-year-old history","volume":"14","author":"Bonino","year":"2022","journal-title":"Viruses"},{"key":"B2","doi-asserted-by":"publisher","first-page":"1573","DOI":"10.1111\/apt.18278","article-title":"Eight-year efficacy and safety of tenofovir alafenamide for treatment of chronic hepatitis B virus infection: Final results from two randomised phase 3 trials","volume":"60","author":"Buti","year":"2024","journal-title":"Aliment Pharmacol. 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