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Here we review the role of HBsAg in HCC, the link between HBsAg and HCC recurrence post\u2010liver transplantation or resection, and the implications for therapy. HBV\u2010associated carcinogenesis is a multifactorial process. The observation that HBV\u2010related HCC can occur in the absence of cirrhosis is compatible with a direct oncogenic effect of the virus, which may occur via multiple mechanisms, including those mediated by both mutated and unmutated HBsAg. HCC recurrence in HBsAg\u2010positive patients post\u2010liver transplantation has been reported in 10%\u201015% of patients and is likely to be because of expansion of residual HCC tumour cell populations containing integrated HBV DNA, which expand and independently replicate HBV, leading to the recurrence of both HCC and HBV. The direct role of HBsAg in HCC recurrence post\u2010liver resection is less clear. Cirrhosis is the most important risk factor for HCC development, and precancerous cirrhotic liver remains after resection, with the potential to undergo malignant transformation regardless of the existence of HBV\u2010derived oncogenic drivers. The role of HBsAg in the development of HCC and its recurrence post\u2010surgical intervention has multiple implications for therapy and suggests a potential role for immunotherapy in the future management of HCC, in particular post\u2010liver transplantation. Use of hepatitis B immunoglobulins that target HBsAg directly, alongside immune\u2010oncology therapies, may be relevant in this setting.<\/jats:p>","DOI":"10.1111\/liv.15124","type":"journal-article","created":{"date-parts":[[2021,11,30]],"date-time":"2021-11-30T23:11:27Z","timestamp":1638313887000},"page":"288-298","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["State of the art treatment of hepatitis B virus hepatocellular carcinoma and the role of hepatitis B surface antigen post\u2010liver transplantation and resection"],"prefix":"10.1111","volume":"42","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4192-6155","authenticated-orcid":false,"given":"Peter","family":"Schemmer","sequence":"first","affiliation":[{"name":"General, Visceral and Transplant Surgery Department of Surgery Medical University of Graz Graz Austria"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8791-191X","authenticated-orcid":false,"given":"Patrizia","family":"Burra","sequence":"additional","affiliation":[{"name":"Department of Surgery, Oncology, and Gastroenterology Padua University Hospital Padua Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rey\u2010Heng","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Surgery National Taiwan University Hospital Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christian M.","family":"H\u00fcber","sequence":"additional","affiliation":[{"name":"Biotest AG Dreieich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmelo","family":"Loinaz","sequence":"additional","affiliation":[{"name":"Department of General and Digestive Surgery University Hospital 12 de Octubre Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keigo","family":"Machida","sequence":"additional","affiliation":[{"name":"Keck Hospital of University of Southern California Los Angeles California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arndt","family":"Vogel","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Hepatology and Endocrinology Medizinische Hochschule Hannover Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9481-3616","authenticated-orcid":false,"given":"Didier","family":"Samuel","sequence":"additional","affiliation":[{"name":"Centre Hepatobiliaire University Hospital Paul Brousse University Paris\u2010Saclay and Inserm\u2010Paris Saclay Research Unit 1193 Villejuif 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