Journal
NATURE REVIEWS GASTROENTEROLOGY & HEPATOLOGY
Volume 14, Issue 1, Pages 55-66Publisher
NATURE PORTFOLIO
DOI: 10.1038/nrgastro.2016.168
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Funding
- Interdisciplinary Center for Clinical Research (IZKF) within the faculty of Medicine at the RWTH Aachen University
- Deutsche Forschungsgemeinschaft (DFG) [SFB/TRR57, DFG TR 285/10-1, SPP 1782]
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Sepsis and septic shock are characterized by life-threatening organ dysfunction caused by a dysregulated host response to infection. The liver has a central role during sepsis, and is essential to the regulation of immune defence during systemic infections by mechanisms such as bacterial clearance, acute-phase protein or cytokine production and metabolic adaptation to inflammation. However, the liver is also a target for sepsis-related injury, including hypoxic hepatitis due to ischaemia and shock, cholestasis due to altered bile metabolism, hepatocellular injury due to drug toxicity or overwhelming inflammation, as well as distinct pathologies such as secondary sclerosing cholangitis in critically ill patients. Hence, hepatic dysfunction substantially impairs the prognosis of sepsis and serves as a powerful independent predictor of mortality in the intensive care unit. Sepsis is particularly problematic in patients with liver cirrhosis (who experience increased bacterial translocation from the gut and impaired microbial defence) as it can trigger acute-on-chronic liver failure a syndrome with high short-term mortality. Here, we review the importance of the liver as a guardian, modifier and target of sepsis, the factors that contribute to sepsis in patients with liver cirrhosis and new therapeutic strategies.
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