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In patients with cirrhosis or alcoholic hepatitis, sepsis is a major cause of death. As the metabolic center and a key immune tissue, liver is the guardian, modifier, and target of sepsis. Septic patients with liver dysfunction have the highest mortality rate compared with other organ dysfunctions. In addition to maintaining metabolic homeostasis, the liver produces and secretes hepatokines and acute phase proteins (APPs) essential in tissue protection, immunomodulation, and coagulation. Inflammatory liver diseases cause profound metabolic disorder and impairment of energy metabolism, liver regeneration, and production\/secretion of APPs and hepatokines. Herein, the author reviews the roles of (1) disorders in the metabolism of glucose, fatty acids, ketone bodies, and amino acids as well as the clearance of ammonia and lactate in the pathogenesis of inflammatory liver diseases and sepsis; (2) cytokines\/chemokines in inflammatory liver diseases and sepsis; (3) APPs and hepatokines in the protection against tissue injury and infections; and (4) major nuclear receptors\/signaling pathways underlying the metabolic disorders and tissue injuries as well as the major drug targets for inflammatory liver diseases and sepsis. Approaches that focus on the liver dysfunction and regeneration will not only treat inflammatory liver diseases but also prevent the development of severe infections and sepsis.<\/jats:p>","DOI":"10.1042\/cs20230522","type":"journal-article","created":{"date-parts":[[2024,4,4]],"date-time":"2024-04-04T06:02:36Z","timestamp":1712210556000},"page":"435-487","update-policy":"https:\/\/doi.org\/10.1042\/crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Inflammatory liver diseases and susceptibility to sepsis"],"prefix":"10.1042","volume":"138","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4389-7252","authenticated-orcid":false,"given":"Hong","family":"Lu","sequence":"first","affiliation":[{"name":"Department of Pharmacology, SUNY Upstate Medical University, Syracuse, NY 13210, U.S.A."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"288","published-online":{"date-parts":[[2024,4,4]]},"reference":[{"key":"2024040406022481000_B1","doi-asserted-by":"publisher","first-page":"55","DOI":"10.1038\/nrgastro.2016.168","article-title":"Liver - guardian, modifier and target of sepsis","volume":"14","author":"Strnad","year":"2017","journal-title":"Nat. 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