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The immunopathogenesis is related to induction of inflammatory cells and cytokines by the rise in HBV DNA. There are multiple causes of flares, and they carry the risk of progression to hepatic decompensation and acute-on-chronic liver failure (ACLF) with associated mortality, potentially requiring liver transplantation. Initial assessment should exclude other causes of liver dysfunction and determine severity and prognosis. General prognostic models of ACLF are useful but the COSSH-ACLF II score is specific to HBV. Early initiation of nucleos(t)ide analogues is crucial, even in severe HBV flares; it can reduce mortality by 73.6%. Once jaundice and coagulopathy occur, salvage by antivirals is challenging, and liver transplantation should be considered. However, many patients may not be suitable candidates for transplant or donor livers may not be available, as is common in Asia. Recently, there has been increasing evidence of the benefits of adjunctive therapies such as corticosteroids and plasma exchange, but there are associated risks and these approaches should be considered rescue therapies in severe HBV flares or ACLF. Liver transplant is the ultimate intervention when these other strategies fail. In summary, HBV flares are clinically serious events that can lead to hepatic decompensation, ACLF, and the need for a donor liver; however, strategies for rescue should be considered before liver transplantation.<\/jats:p>","DOI":"10.3350\/cmh.2026.0177","type":"journal-article","created":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T08:06:11Z","timestamp":1773821171000},"page":"1117-1134","update-policy":"https:\/\/doi.org\/10.3350\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Severe hepatitis B flare and liver failure: current assessment and management"],"prefix":"10.3350","volume":"32","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-0994-4932","authenticated-orcid":true,"given":"Seng Gee","family":"Lim","sequence":"first","affiliation":[{"name":"Division of Gastroenterology and Hepatology, Department of Medicine, National University Health System, Singapore"},{"name":"Department of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Buti","sequence":"additional","affiliation":[{"name":"Liver Unit, Hospital General Universitari Valle Hebron, Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jordan J.","family":"Feld","sequence":"additional","affiliation":[{"name":"Toronto Center for Liver Disease, Toronto General Hospital, University of Toronto, Toronto, ON, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Fung","sequence":"additional","affiliation":[{"name":"Department of Medicine, Queen Mary Hospital, The University of Hong Kong, Hong Kong SAR"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam J.","family":"Gehring","sequence":"additional","affiliation":[{"name":"Toronto Center for Liver Disease, Toronto General Hospital, University of Toronto, Toronto, ON, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K. 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