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It is well known that severe systemic inflammation is an important event in chronic hepatitis B (CHB)-ACLF, which eventually leads to liver injury. However, the initial CHB-ACLF events are unclear; moreover, the effect of these events on host immunity as well as that of immune imbalance on CHB-ACLF progression are unknown. Here, we investigate the initial events of ACLF progression, discuss possible mechanisms underlying ACLF progression, and provide a new model for ACLF prediction and treatment. We review the characteristics of ACLF, and consider its plausible immune predictors and alternative treatment strategies.<\/jats:p>","DOI":"10.3389\/fmicb.2020.583423","type":"journal-article","created":{"date-parts":[[2020,12,7]],"date-time":"2020-12-07T04:22:11Z","timestamp":1607314931000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":24,"title":["Acute-on-Chronic Liver Failure From Chronic-Hepatitis-B, Who Is the Behind Scenes"],"prefix":"10.3389","volume":"11","author":[{"given":"Qian","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mengji","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuanwang","family":"Qiu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hongzhou","family":"Lu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2020,12,7]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"783","DOI":"10.1016\/j.cell.2006.02.015","article-title":"Pathogen recognition and innate immunity.","volume":"124","author":"Akira","year":"2006","journal-title":"Cell"},{"key":"B2","doi-asserted-by":"publisher","first-page":"283","DOI":"10.7555\/JBR.31.20160060","article-title":"Acute-on-chronic liver failure: recent update.","volume":"31","author":"Alam","year":"2017","journal-title":"J. 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