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Hepatitis B virus (HBV) infection is the major cause of ALF worldwide, however, the underlying mechanism by which HBV infection leads to ALF has not been fully disclosed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>D-GalN-induced hepatocyte injury model and LPS\/D-GalN-induced ALF mice model were used to investigate the effects of HBV X protein (HBx) in vitro and in vivo, respectively. Cell viability and the levels of Glutathione (GSH), malondialdehyde (MDA) and iron were measured using commercial kits. The expression of ferroptosis-related molecules were detected by qRT-PCR and western blotting. Epigenetic modification and protein interaction were detected by chromatin immunoprecipitation (ChIP) assay and co-immunoprecipitation (co-IP), respectively. Mouse liver function was assessed by measuring aspartate aminotransferase (AST) and alanine aminotransferase (ALT). The histological changes in liver tissues were monitored by hematoxylin and eosin (H&amp;E) staining, and SLC7A11 immunoreactivity was assessed by immunohistochemistry (IHC) analysis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>D-GalN triggered ferroptosis in primary hepatocytes. HBx potentiated D-GalN-induced hepatotoxicity and ferroptosis in vitro, and it suppressed SLC7A11 expression through H3K27me3 modification by EZH2. In addition, EZH2 inhibition or SLC7A11 overexpression attenuated the effects of HBx on D-GalN-induced ferroptosis in primary hepatocytes. The ferroptosis inhibitor ferrostatin-1 (Fer-1) protected against ALF and ferroptosis in vivo. By contrast, HBx exacerbates LPS\/D-GalN-induced ALF and ferroptosis in HBx transgenic (HBx-Tg) mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>HBx facilitates ferroptosis in ALF via EZH2\/H3K27me3-mediated SLC7A11 suppression.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12929-021-00762-2","type":"journal-article","created":{"date-parts":[[2021,10,7]],"date-time":"2021-10-07T04:40:39Z","timestamp":1633581639000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":130,"title":["HBx facilitates ferroptosis in acute liver failure via EZH2 mediated SLC7A11 suppression"],"prefix":"10.1186","volume":"28","author":[{"given":"Guo-Zhen","family":"Liu","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xu-Wen","family":"Xu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shu-Hui","family":"Tao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ming-Jian","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9957-2716","authenticated-orcid":false,"given":"Zhou-Hua","family":"Hou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2021,10,6]]},"reference":[{"issue":"10201","key":"762_CR1","doi-asserted-by":"publisher","first-page":"869","DOI":"10.1016\/S0140-6736(19)31894-X","volume":"394","author":"RT Stravitz","year":"2019","unstructured":"Stravitz RT, Lee WM. 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