An optimized peritonitis-induced ACLF model that reproduces the full spectrum of extrahepatic organ failures in mice

PMCID: PMC12180834

PMID: 40536682

DOI: 10.1097/HC9.0000000000000744

Journal: Hepatology communications

Publication Date: 2025-7

Authors: Flores-Costa R, Duran-Güell M, Romero-Grimaldo B, Contreras BJ, Salvatella A, et al.

Key Points

• First comprehensive murine model reproducing full spectrum of ACLF-associated extrahepatic organ failures
• Demonstrated significant increases in inflammatory markers (Il-6, Tnf) and organ-specific dysfunction markers
• Offers a refined experimental platform for investigating ACLF pathophysiology and potential treatment strategies

Summary

This preclinical study addresses a critical gap in experimental models for acute-on-chronic liver failure (ACLF) by developing a novel murine model that comprehensively reproduces the multisystemic organ failures characteristic of human ACLF. By combining chronic carbon tetrachloride (CCl4)-induced cirrhosis with cecal ligation and puncture (CLP) to simulate polymicrobial peritonitis, researchers created an experimental platform that faithfully mimics the systemic hyperinflammatory response and widespread organ dysfunction seen in patients.

The CCl4+CLP model demonstrated significant pathophysiological changes across multiple organ systems, including liver, kidney, respiratory, cerebral, circulatory, and coagulation domains. Key findings included increased inflammatory markers, organ-specific functional impairments, and widespread bacterial tissue colonization. Critically, this model provides researchers with an optimized experimental framework to explore ACLF mechanisms and potentially develop targeted therapeutic interventions.