Published online Nov 14, 2015. doi: 10.3748/wjg.v21.i42.12125
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.
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.