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ACLF is frequently triggered by intra\u2010 and\/or extrahepatic insults, such as bacterial infections, alcohol\u2010related hepatitis or flares of hepatic viruses. The imbalance between systemic inflammation and immune tolerance causes organ failures through the following mechanisms: (i) direct damage of immune cells\/mediators; (ii) worsening of circulatory dysfunction resulting in organ hypoperfusion and (iii) metabolic alterations with prioritization of energetic substrates for inflammation and peripheral organ \u2018energetic crisis\u2019. Currently, the management of ACLF includes the support of organ failures, the identification and treatment of precipitating factors and expedited assessment for liver transplantation (LT). Early LT should be considered in patients with ACLF grade 3, who are unlikely to recover with the available treatments and have a mortality rate\u2009&gt;\u200970% at 28\u2009days. However, the selection of transplant candidates and their prioritization on the LT waiting list need standardization. Future challenges in the ACLF field include a better understanding of pathophysiological mechanisms leading to inflammation and organ failures, the development of specific treatments for the disease and personalized treatment approaches. Herein, we reviewed the current knowledge and future perspectives on mechanisms and treatment of ACLF.<\/jats:p>","DOI":"10.1111\/liv.15733","type":"journal-article","created":{"date-parts":[[2023,9,16]],"date-time":"2023-09-16T05:05:32Z","timestamp":1694840732000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":37,"title":["Mechanisms and treatment approaches for\n                    <scp>ACLF<\/scp>"],"prefix":"10.1111","volume":"45","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9356-5830","authenticated-orcid":false,"given":"Salvatore","family":"Piano","sequence":"first","affiliation":[{"name":"Unit of Internal Medicine and Hepatology, Department of Medicine \u2013 DIMED University and Hospital of Padova  Padova Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1889-3954","authenticated-orcid":false,"given":"Nadim","family":"Mahmud","sequence":"additional","affiliation":[{"name":"Division of Gastroenterology and Hepatology University of Pennsylvania Perelman School of Medicine  Philadelphia Pennsylvania USA"},{"name":"Leonard Davis Institute of Health Economics University of Pennsylvania Perelman School of Medicine  Philadelphia Pennsylvania USA"},{"name":"Department of Biostatistics, Epidemiology, and Informatics University of Pennsylvania  Philadelphia Pennsylvania USA"},{"name":"Gastroenterology Section Corporal Michael J. 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