Acute-on-chronic liver failure: A distinct clinical syndrome

There are different operating definitions for acute-on-chronic liver failure (ACLF) in different geographic regions. Consortia in Western countries have developed definitions that apply to patients with cirrhosis, while consortia in Asia have developed definitions that apply to patients with chronic liver diseases with or without cirrhosis. Investigators of the Chinese and Western Consortia believe that ACLF can be precipitated by acute insults that are intrahepatic (e.g. alcoholic hepatitis) or extrahepatic (e.g. bacterial infection, gastrointestinal haemorrhage), and that extrahepatic organ system failures can be used to define ACLF. In contrast, the Asia Pacific consortium believe that ACLF is only defined by an acute onset of liver failure in response to an acute hepatic insult. Of note, although ACLF has received different operating definitions, every definition recognises that ACLF is a distinct clinical entity. This article provides an updated overview of the distinctive features of ACLF according to the definitions used to characterise it. In addition, we discuss future directions for research aimed at identifying the hallmarks of ACLF.