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Sepsis and the Liver.

Eleni V Geladari1, Anastasia-Amalia C Kalergi1, Apostolos A Evangelopoulos2

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Summary

Sepsis-associated liver injury (SALI) involves distinct inflammatory and immunosuppressive phases impacting patient outcomes. Research aims to develop personalized therapies targeting inflammation, metabolism, and the gut-liver axis for improved SALI management.

Keywords:
biomarkersgut–liver axisinflammatory cascademitochondrial dysfunctionsepsis-associated liver injury (SALI)

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Area of Science:

  • Hepatology
  • Immunology
  • Critical Care Medicine

Background:

  • Sepsis-associated liver injury (SALI) is a critical complication of sepsis, characterized by distinct hyper-inflammatory and immunosuppressive phases.
  • These phases dictate patient phenotypes and influence therapeutic strategies.

Purpose of the Study:

  • To characterize the distinct inflammatory and immunosuppressive phases of SALI.
  • To establish a foundation for developing immunomodulation strategies tailored to individual immune responses in sepsis.

Main Methods:

  • Review of existing literature on the pathogenesis of SALI.
  • Analysis of cellular pathways, metabolic disturbances, and the gut-liver axis in sepsis.
  • Evaluation of current and investigational diagnostic and therapeutic approaches.

Main Results:

  • The inflammatory phase involves NF-κB and NLRP3 inflammasome activation, leading to a cytokine storm, hepatocyte damage, and increased mortality risk.
  • The immunosuppressive phase is marked by impaired infection control, metabolic dysfunction (e.g., impaired fatty acid oxidation), and mitochondrial dysfunction.
  • The gut-liver axis is central to SALI pathogenesis, with dysbiosis and increased intestinal permeability exacerbating liver injury; novel biomarkers show diagnostic promise.

Conclusions:

  • Future research should prioritize developing representative models and validating biomarkers for SALI.
  • Clinical trials are needed to enable personalized therapies targeting inflammation, metabolism, and the gut-liver axis.
  • Improving outcomes in SALI requires a multi-faceted approach addressing its complex pathophysiology.