Gut-liver crosstalk in sepsis-induced liver injury
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REVIEW
Open Access
Gut-liver crosstalk in sepsis-induced liver injury Jian Sun1,2, Jingxiao Zhang1,2, Xiangfeng Wang3, Fuxi Ji1, Claudio Ronco2,4, Jiakun Tian1* and Yongjie Yin1*
Abstract Sepsis is characterized by a dysregulated immune response to infection leading to life-threatening organ dysfunction. Sepsis-induced liver injury is recognized as a powerful independent predictor of mortality in the intensive care unit. During systemic infections, the liver regulates immune defenses via bacterial clearance, production of acute-phase proteins (APPs) and cytokines, and metabolic adaptation to inflammation. Increased levels of inflammatory cytokines and impaired bacterial clearance and disrupted metabolic products can cause gut microbiota dysbiosis and disruption of the intestinal mucosal barrier. Changes in the gut microbiota play crucial roles in liver injury during sepsis. Bacterial translocation and resulting intestinal inflammation lead to a systemic inflammatory response and acute liver injury. The gut-liver crosstalk is a potential target for therapeutic interventions. This review analyzes the underlying mechanisms for the gut-liver crosstalk in sepsis-induced liver injury. Keywords: Sepsis, Liver injury, Gut-liver crosstalk, Inflammation, Metabolism, Microbiota dysbiosis
Introduction Sepsis is a life-threatening condition caused by dysregulated host response to infection [1]. Uncontrolled inflammation leads to loss of cellular and organ function, multiple organ dysfunction syndrome (MODS), and death [2]. Annually, more than 1.5 million patients suffer from sepsis in the USA, and the estimated global mortality rate is 25% [3, 4]. During systemic infections, the liver regulates immune defenses via bacterial clearance, production of acutephase proteins (APPs) and cytokines, and metabolic adaptation to inflammation. Liver injury has a critical effect on the severity and outcome of sepsis. The incidence of liver failure in sepsis is lower than the incidence of failure of other organs because of the high regenerative capacity of the liver and its ability to withstand assaults [5]. However, liver dysfunction and failure are associated with grave complications in sepsis. * Correspondence: [email protected]; [email protected] 1 Department of Emergency and Critical Care Medicine, Second Hospital of Jilin University, Changchun, Jilin Province, China Full list of author information is available at the end of the article
Mortality rates among sepsis patients with liver dysfunction or failure range from 54 to 68%, which is higher than the mortality rates of sepsis patients with lung dysfunction or failure (the organ most commonly affected in sepsis) [6–10]. Although the pathophysiology of sepsis-induced liver injury is complex, the inflammatory response plays a major role in this process. Furthermore, mitochondrial and endoplasmic reticulum (ER) dysfunctions during the acute phase response elicited by systemic inflammation lead to liver failure in sepsis [11]. In critically ill patients, the clinical manifestati
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