Mechanisms and treatment approaches for ACLF

Author:

Piano Salvatore1ORCID,Mahmud Nadim2345ORCID,Caraceni Paolo67ORCID,Tonon Marta1ORCID,Mookerjee Rajeshwar Prosad89ORCID

Affiliation:

1. Unit of Internal Medicine and Hepatology, Department of Medicine – DIMED University and Hospital of Padova Padova Italy

2. Division of Gastroenterology and Hepatology University of Pennsylvania Perelman School of Medicine Philadelphia Pennsylvania USA

3. Leonard Davis Institute of Health Economics University of Pennsylvania Perelman School of Medicine Philadelphia Pennsylvania USA

4. Department of Biostatistics, Epidemiology, and Informatics University of Pennsylvania Philadelphia Pennsylvania USA

5. Gastroenterology Section Corporal Michael J. Crescenz VA Medical Center Philadelphia Pennsylvania USA

6. Department of Medical and Surgical Sciences Alma Mater Studiorum University of Bologna Bologna Italy

7. Unit of Semeiotics IRCCS Azienda Ospedaliero‐Universitaria di Bologna Bologna Italy

8. Institute for Liver and Digestive Health University College London London UK

9. Department of Hepatology and Gastroenterology Aarhus University Hospital Aarhus C Denmark

Abstract

AbstractAcute‐on‐chronic liver failure (ACLF) is a life‐threatening syndrome characterized by decompensation of cirrhosis, severe systemic inflammation and organ failures. ACLF is frequently triggered by intra‐ and/or extrahepatic insults, such as bacterial infections, alcohol‐related hepatitis or flares of hepatic viruses. The imbalance between systemic inflammation and immune tolerance causes organ failures through the following mechanisms: (i) direct damage of immune cells/mediators; (ii) worsening of circulatory dysfunction resulting in organ hypoperfusion and (iii) metabolic alterations with prioritization of energetic substrates for inflammation and peripheral organ ‘energetic crisis’. Currently, the management of ACLF includes the support of organ failures, the identification and treatment of precipitating factors and expedited assessment for liver transplantation (LT). Early LT should be considered in patients with ACLF grade 3, who are unlikely to recover with the available treatments and have a mortality rate > 70% at 28 days. However, the selection of transplant candidates and their prioritization on the LT waiting list need standardization. Future challenges in the ACLF field include a better understanding of pathophysiological mechanisms leading to inflammation and organ failures, the development of specific treatments for the disease and personalized treatment approaches. Herein, we reviewed the current knowledge and future perspectives on mechanisms and treatment of ACLF.

Publisher

Wiley

Subject

Hepatology

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