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Sepsis-associated liver injury: Mechanisms and potential therapeutic targets
Jia-Wen Chen1, Chen-Yi Liu1, Shu Li1
1Department of Infectious Diseases, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, Zhejiang Province, China.
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.
Insights
Sepsis-associated liver injury (SLI) lacks specific treatments. Targeting the gut-liver axis and understanding immune status are key for developing personalized immunotherapies for sepsis patients.
Area of Science:
- Gastroenterology
- Immunology
- Critical Care Medicine
Background:
- Sepsis-associated liver injury (SLI) is a severe complication of sepsis, driven by microcirculatory dysfunction, the gut-liver axis, and inflammation.
- Current therapeutic strategies for SLI are limited, highlighting the need for novel treatment approaches.
Discussion:
- The gut-liver axis presents a promising therapeutic target, with metformin showing potential in modulating the gut microbiome and improving intestinal barrier function.
- Immunomodulatory therapies, including anti-tumor necrosis factor agents and interleukin-1 receptor antagonists, have shown limited clinical efficacy.
- Statins may offer hepatoprotective effects by reducing liver inflammation, but their use in sepsis is not well-established.
- Corticosteroids might reverse clinical decline in severe infections by addressing immune suppression and adrenal insufficiency, though large-scale studies show mixed results.
Key Insights:
- Personalized immunotherapy based on individual immune profiles is crucial for effective sepsis treatment.
- Identifying novel biomarkers of immune status is essential for tailoring therapeutic interventions.
- The gut-liver axis and immune modulation represent critical areas for future research in SLI.
Outlook:
- Future research should focus on developing personalized immunotherapies for sepsis, considering host immune status.
- Advancing immunomodulatory targets and therapeutics is vital for improving outcomes in septic patients.
- Further investigation into the role of the gut-liver axis and host immune responses is warranted.
