Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Gastroenterol. Nov 14, 2015; 21(42): 12125-12140
Published online Nov 14, 2015. doi: 10.3748/wjg.v21.i42.12125
Acute-on-chronic liver failure: Pathogenesis, prognostic factors and management
Sara Blasco-Algora, José Masegosa-Ataz, María Luisa Gutiérrez-García, Sonia Alonso-López, Conrado M Fernández-Rodríguez
Sara Blasco-Algora, José Masegosa-Ataz, María Luisa Gutiérrez-García, Sonia Alonso-López, Conrado M Fernández-Rodríguez, Service of Gastroenterology, Hospital Universitario Fundación, 28922 Alcorcón, Madrid, Spain
Author contributions: Blasco-Algora S, Masegosa-Ataz J, Gutiérrez-García ML, Alonso-López S and Fernández-Rodríguez CM contributed to the study idea, study design, literature search, manuscript writing and final revision of the article.
Conflict-of-interest statement: The authors declared that they do not have anything to disclose regarding funding or conflict of interest with respect to this manuscript.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See:
Correspondence to: Conrado M Fernandez-Rodriguez, MD, Service of Gastroenterology, Hospital Universitario Fundación, Alcorcón, Av Budapest-1, 28922 Alcorcón, Madrid, Spain.
Telephone: +34-91-6219513 Fax: +34-91-6219975
Received: June 28, 2015
Peer-review started: July 1, 2015
First decision: July 20, 2015
Revised: August 17, 2015
Accepted: September 30, 2015
Article in press: September 30, 2015
Published online: November 14, 2015

Acute-on-chronic liver failure (ACLF) is increasingly recognized as a complex syndrome that is reversible in many cases. It is characterized by an acute deterioration of liver function in the background of a pre-existing chronic liver disease often associated with a high short-term mortality rate. Organ failure (OF) is always associated, and plays a key role in determining the course, and the outcome of the disease. The definition of ACLF remains controversial due to its overall ambiguity, with several disparate criteria among various associations dedicated to the study of liver diseases. Although the precise pathogenesis needs to be clarified, it appears that an altered host response to injury might be a contributing factor caused by immune dysfunction, ultimately leading to a pro-inflammatory status, and eventually to OF. The PIRO concept (Predisposition, Insult, Response and Organ Failure) has been proposed to better approach the underlying mechanisms. It is accepted that ACLF is a different and specific form of liver failure, where a precipitating event is always involved, even though it cannot always be ascertained. According to several studies, infections and active alcoholism often trigger ACLF. Viral hepatitis, gastrointestinal haemorrhage, or drug induced liver injury, which can also provoke the syndrome. This review mainly focuses on the physiopathology and prognostic aspects. We believe these features are essential to further understanding and providing the rationale for improveddisease management strategies.

Keywords: Acute on-chronic liver failure, Immune dysfunction, Systemic inflammatory response, Hepatic encephalopathy, Hepatorenal syndrome, Acute decompensation of cirrhosis, Liver failure, Organ failure, Severity score, Chronic liver failure-sequential organ failure assessment

Core tip: Acute on-chronic liver failure is a newly recognized syndrome characterized by acute deterioration of a compensated or decompensated chronic liver disease, leading to organ failure, and a mortality rate ≥ 15% at 28-d. Pathogenesis involves an exaggerated systemic inflammatory response in the setting of immune dysregulation and oxidative stress. Alcohol is a frequent precipitating factor seen most commonly in the West, and untreated hepatitis B virus infection is more prevalently seen in the East. However, it must be noted, that specific precipitant factors cannot be established in up to the 40% of cases. Recent prospective work has generated data on definition, prevalence, precipitating factors and scoring systems. Treatment of precipitant factors, complications, organ failure support, and liver transplantation are the current therapeutic options.