Role of Intestinal Barrier Disruption to Acute-on-Chronic Liver Failure

Julian Pohl; Dimitrios Aretakis; Frank Tacke; Cornelius Engelmann; Michael Sigal

doi:10.1055/a-2516-2361

Seminars in Liver Disease, Table of Contents

Semin Liver Dis 2025; 45(01): 052-065
DOI: 10.1055/a-2516-2361

Review Article

Role of Intestinal Barrier Disruption to Acute-on-Chronic Liver Failure

Julian Pohl

¹Department of Hepatology and Gastroenterology, Campus Virchow-Klinikum and Campus Charité Mitte, Charité—Universitätsmedizin Berlin, Berlin, Germany

,

Dimitrios Aretakis

¹Department of Hepatology and Gastroenterology, Campus Virchow-Klinikum and Campus Charité Mitte, Charité—Universitätsmedizin Berlin, Berlin, Germany

,

Frank Tacke

¹Department of Hepatology and Gastroenterology, Campus Virchow-Klinikum and Campus Charité Mitte, Charité—Universitätsmedizin Berlin, Berlin, Germany

,

Cornelius Engelmann

¹Department of Hepatology and Gastroenterology, Campus Virchow-Klinikum and Campus Charité Mitte, Charité—Universitätsmedizin Berlin, Berlin, Germany

²Berlin Institute of Health at Charité - Universitätsmedizin Berlin, Berlin, Germany

³Institute for Liver and Digestive Health, University College London, London, United Kingdom

,

Michael Sigal

¹Department of Hepatology and Gastroenterology, Campus Virchow-Klinikum and Campus Charité Mitte, Charité—Universitätsmedizin Berlin, Berlin, Germany

⁴Berlin Institute for Medical Systems Biology (BIMSB), Max Delbrück Center for Molecular Medicine in the Helmholtz Association, Berlin, Germany

› Author Affiliations

Abstract

Acute-on-chronic liver failure (ACLF) is a severe condition in patients with decompensated liver cirrhosis, marked by high short-term mortality. Recent experimental and clinical evidence has linked intestinal dysfunction to both the initiation of ACLF as well as disease outcome. This review discusses the significant role of the gut–liver axis in ACLF pathogenesis, highlighting recent advances. Gut mucosal barrier disruption, gut dysbiosis, and bacterial translocation emerge as key factors contributing to systemic inflammation in ACLF. Different approaches of therapeutically targeting the gut–liver axis via farnesoid X receptor agonists, nonselective beta receptor blockers, antibiotics, and probiotics are discussed as potential strategies mitigating ACLF progression. The importance of understanding the distinct pathophysiology of ACLF compared with other stages of liver cirrhosis is highlighted. In conclusion, research findings suggest that disruption of intestinal integrity may be an integral component of ACLF pathogenesis, paving the way for novel diagnostic and therapeutic approaches to manage this syndrome more effectively.

Keywords

liver cirrhosis - acute-on-chronic liver failure - gut - bacterial translocation - systemic inflammation

Full Text

References

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