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Review
. 2022 Jul 30;28(1):84.
doi: 10.1186/s10020-022-00510-8.

The liver in sepsis: molecular mechanism of liver failure and their potential for clinical translation

Dustin Beyer  1 , Jessica Hoff  1   2 , Oliver Sommerfeld  1   2 , Alexander Zipprich  3 , Nikolaus Gaßler  4 , Adrian T Press  5   6   7
Affiliations
Review

The liver in sepsis: molecular mechanism of liver failure and their potential for clinical translation

Dustin Beyer et al. Mol Med. .

Abstract

Liver failure is a life-threatening complication of infections restricting the host's response to infection. The pivotal role of the liver in metabolic, synthetic, and immunological pathways enforces limits the host's ability to control the immune response appropriately, making it vulnerable to ineffective pathogen resistance and tissue damage. Deregulated networks of liver diseases are gradually uncovered by high-throughput, single-cell resolved OMICS technologies visualizing an astonishing diversity of cell types and regulatory interaction driving tolerogenic signaling in health and inflammation in disease. Therefore, this review elucidates the effects of the dysregulated host response on the liver, consequences for the immune response, and possible avenues for personalized therapeutics.

Keywords: Cholestasis; Inflammation; Intensive care; Liver failure; Molecular medicine; Personalized medicine; Sepsis.

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Conflict of interest statement

The authors declare that they have no competing interests.

Figures

Fig. 1
Fig. 1
The liver in sepsis. Key changes in the liver tissue during systemic infection that ultimately result in a dysbalanced host response and liver failure. (LSEC - Liver sinusoidal endothelial cell; KC - Kupffer cell; HS - Hepatic stellate cell)
Fig. 2
Fig. 2
Main cell death mechanisms. The liver harbors parenchymal cells and different immune cell populations that contribute to immune reaction till their death through a regulated cell death mechanism. Hepatocytes are classical apoptotic cells since their death due to toxic metabolites occurs naturally and should not trigger inflammation. Recently, oxidative-regulated cell death Ferroptosis had been highlighted in various liver injuries, including sepsis driving reactive oxygen formation and inflammation. Necroptosis and pyroptosis are carried out by multiple cells after, e.g., TNF-α stimulation and drive inflammation during liver infection. NETosis dying neutrophils leave a vast number of extracellular debris and nucleotide nets to trap and destroy microorganisms even after their death. Finally, mechanically or chemical destruction of cells is apparent due to liver hypoxia or directly due to pathogen spread and toxic immune response
See this image and copyright information in PMC

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