{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T05:03:04Z","timestamp":1789448584454,"version":"build-2803163510"},"reference-count":20,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T00:00:00Z","timestamp":1789430400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Med."],"abstract":"<jats:p>Long-term administration of nucleos(t)ide analogues (NAs) has substantially mitigated the risk of post-transplant hepatitis B virus (HBV) recurrence. However, the safety and feasibility of NA withdrawal in liver transplant (LT) recipients, even following prolonged virological suppression and sustained hepatitis B surface antigen (HBsAg) loss, remain poorly defined. We present the case of an 84-year-old male with a &amp;gt;40-year history of chronic HBV infection, who progressed to HBV-related cirrhosis and hepatocellular carcinoma, culminating in a deceased-donor liver transplantation (DDLT) in 2004. Post-transplant HBV prophylaxis consisted of HBIG combined with nucleos(t)ide analogue therapy, followed by long-term entecavir maintenance alongside tacrolimus-based immunosuppression. The patient achieved sustained HBsAg seroclearance and maintained undetectable HBV DNA levels for 17 years. Consequently, ETV was discontinued in June 2021. In October 2022, an asymptomatic elevation of hepatic transaminases was noted, though HBV-specific virological assessments were omitted. By March 2023, further evaluation of persistent transaminase elevation confirmed robust HBV reactivation: HBV DNA surged to 5.10 \u00d7 10\u2078 IU\/mL, accompanied by HBeAg positivity and a quantitative HBsAg level of 98,008 IU\/mL (Abbott Architect assay). Salvage therapy comprising ETV and tenofovir alafenamide (TAF) was promptly initiated, yielding rapid virological suppression and biochemical normalization. HBV DNA fell below the lower limit of detection (&amp;lt;20 IU\/mL) within 9 months of retreatment (December 2023) and has remained fully suppressed through April 2026. This case emphasizes that fulminant HBV reactivation may transpire following NA cessation in LT recipients, irrespective of protracted virological suppression and stable HBsAg seroclearance. This trajectory reinforces the paradigm that HBsAg loss in the context of chronic immunosuppression reflects functional viral control rather than complete viral eradication. In concordance with major hepatology guidelines, indefinite NA prophylaxis should remain the cornerstone of management for LT recipients with HBV-related disease, precluding routine drug withdrawal.<\/jats:p>","DOI":"10.3389\/fmed.2026.1954979","type":"journal-article","created":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T04:28:02Z","timestamp":1789446482000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Case Report: Unexpected HBV reactivation upon nucleos(t)ide analogue discontinuation despite 17 years of sustained HBsAg loss post-liver transplantation"],"prefix":"10.3389","volume":"13","author":[{"given":"Shuchang","family":"Shang","sequence":"first","affiliation":[{"name":"Department of Infectious Diseases, Hebei Medical University Third Hospital","place":["Shijiazhuang, Hebei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuexia","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Hebei Medical University Third Hospital","place":["Shijiazhuang, Hebei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Caiyan","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Infectious Diseases, Hebei Medical University Third Hospital","place":["Shijiazhuang, Hebei, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,9,15]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"1036","DOI":"10.1002\/hep.29191","article-title":"Long-term outcomes of entecavir monotherapy for chronic hepatitis B after liver transplantation: results up to 8 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