Sepsis-associated liver injury: Mechanisms and potential therapeutic targets

World J Gastroenterol. 2024 Nov 14;30(42):4518-4522. doi: 10.3748/wjg.v30.i42.4518.

Abstract

In this editorial, we examined a recent article in the World Journal of Gastroenterology that focused on sepsis-associated liver injury (SLI) and its treatment. SLI is a serious complication of sepsis, primarily caused by microcirculatory disturbances, the gut-liver axis, and inflammatory responses. Specific treatment recommendations for SLI are lacking. The gut-liver axis represents a potential therapeutic target, with metformin showing promise in modulating the gut microbiome and enhancing intestinal barrier function. Although immunomodulatory therapies are being explored, anti-tumor necrosis factor agents and interleukin-1 receptor antagonists have not demonstrated significant clinical benefits. Statins may reduce liver inflammation and prevent injury in sepsis, but their clinical application is limited. Reduced D-related human leucocyte antigen expression on monocytes and lymphocytes suggests immune suppression in patients, indicating that corticosteroids could reverse clinical deterioration in severe infections and address adrenal cortical insufficiency. Current large-scale studies on glucocorticoid therapy for sepsis have yielded mixed results, likely due to inadequate assessment of the immune status of the host. Future research should prioritize the development of personalized immunotherapy tailored to patients' immune profiles, focusing on identifying novel indicators of immune status and advancing immunomodulatory targets and therapeutics for septic patients.

Keywords: Adrenal cortical insufficiency; Glucocorticoid; Gut-liver axis; Immune dysregulation; Immunosuppression; Inflammation; Sepsis; Sepsis-associated liver injury.

Publication types

  • Editorial

MeSH terms

  • Gastrointestinal Microbiome* / drug effects
  • Gastrointestinal Microbiome* / immunology
  • Glucocorticoids / therapeutic use
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use
  • Liver / drug effects
  • Liver / immunology
  • Liver / metabolism
  • Liver / pathology
  • Liver Diseases / drug therapy
  • Liver Diseases / etiology
  • Liver Diseases / immunology
  • Metformin / therapeutic use
  • Microcirculation / drug effects
  • Sepsis* / complications
  • Sepsis* / drug therapy
  • Sepsis* / immunology

Substances

  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Metformin
  • Glucocorticoids