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ACLF, which develops in patients with acute decompensation of cirrhosis, is characterized by single or multiple organ failure and high risk of short\u2010term (28\u2010day) mortality. Its poor outcome is closely associated with the severity of the systemic inflammatory response. In this review, we describe the key features of SI in patients with acutely decompensated cirrhosis and ACLF, including the presence of a high blood white cell count and increased levels of inflammatory mediators in systemic circulation. We also discuss the main triggers (i.e. pathogen\u2010 and damage\u2010associated molecular patterns), the cell effectors (i.e. neutrophils, monocytes and lymphocytes), the humoral mediators (acute phase proteins, cytokines, chemokines, growth factors and bioactive lipid mediators) and the factors that influence the systemic inflammatory response that drive organ failure and mortality in ACLF. The role of immunological exhaustion and\/or immunoparalysis in the context of exacerbated inflammatory responses that predispose ACLF patients to secondary infections and re\u2010escalation of end\u2010organ dysfunction and mortality are also reviewed. Finally, several new potential immunogenic therapeutic targets are debated.<\/jats:p>","DOI":"10.1111\/liv.15644","type":"journal-article","created":{"date-parts":[[2023,6,27]],"date-time":"2023-06-27T04:12:26Z","timestamp":1687839146000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":41,"title":["Mechanisms of immunity in acutely decompensated cirrhosis and acute\u2010on\u2010chronic liver failure"],"prefix":"10.1111","volume":"45","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2237-0881","authenticated-orcid":false,"given":"Cornelius","family":"Engelmann","sequence":"first","affiliation":[{"name":"Medical Department, Division of Hepatology and Gastroenterology, Campus Virchow\u2010Klinikum Charit\u00e9 \u2010 Universit\u00e4tsmedizin Berlin  Berlin Germany"},{"name":"Berlin Institute of Health  Berlin Germany"},{"name":"Institute for Liver and Digestive Health University College London  London 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