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Acute-on-Chronic Liver Failure: An Eroded Cliff Hit by a Storm-A Narrative Review
Kinga Knop-Chodyła1,2, Beata Kasztelan-Szczerbinska2, Halina Cichoż-Lach2
1Doctoral School of the Medical University of Lublin, Medical University of Lublin, Witolda Chodźki 7, 20-093 Lublin, Poland.
International Journal of Molecular Sciences
|July 28, 2026
Summary
Acute-on-chronic liver failure (ACLF) involves severe inflammation and immune paralysis, driven by cellular metabolic shifts and gut-liver axis disruptions. Developing targeted therapies for ACLF is crucial due to the lack of effective treatments.
Area of Science:
- Hepatology
- Immunology
- Pathophysiology
Background:
- Acute-on-chronic liver failure (ACLF) is a severe syndrome with high mortality.
- It is characterized by multiorgan failure driven by systemic inflammation and immune paralysis.
- Current understanding involves complex interactions including the gut-liver and liver-spleen axes.
Purpose of the Study:
- To synthesize current mechanistic hypotheses on ACLF pathophysiology.
- To highlight the role of immune cell dysfunction and metabolic shifts.
- To identify challenges and potential therapeutic avenues for ACLF.
Main Methods:
- Review and synthesis of existing evidence on ACLF.
- Analysis of pathophysiological cascades including immune, metabolic, and axis disruptions.
- Discussion of current therapeutic limitations and future directions.
Main Results:
- ACLF involves a cytokine storm leading to immune paralysis via immune cell dysfunction and metabolic shifts.
- The gut-liver and liver-spleen axes play critical roles in amplifying disease severity.
- Endothelial dysfunction contributes to peripheral organ failure.
Conclusions:
- ACLF pathophysiology is complex and requires further ACLF-specific investigation.
- Liver transplantation is the only definitive treatment, but experimental immunomodulatory therapies show promise.
- Precision therapies targeting specific molecular pathways are needed to address the evolving phases of ACLF.
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