Acute-on-Chronic Liver Failure: A Distinct Clinical Condition

Since the publication of the first article proposing the hypothesis that acute-on-chronic liver failure (ACLF) was likely to be a distinct clinical condition, there are now over 400 fully published articles that provide clinical, biochemical, diagnostic, and pathophysiological characterization of the syndrome from all parts of the world. It is clear from reading these articles that there are distinct features that encompass ACLF.

Acute-on-chronic liver failure occurs in patients with chronic liver disease and is characterized by acute deterioration of the patient requiring hospitalization and is associated with (1) hepatic and extrahepatic organ dysfunction, (2) systemic inflammation, and (3) a high 28-day mortality rate. Acute-on-chronic liver failure occurs in approximately 30% of the hospitalized cirrhotic patients and affects younger individuals; in approximately 40% there is no previous history of hepatic decompensation—making this a very relevant and devastating complication of cirrhosis. At present, there are no specific treatments for ACLF apart from multiple organ support in the intensive care unit and there is no priority for liver transplantation despite the condition costing over $3 billion in the United States. Moreover, in Europe, there is no International Classification of Diseases (ICD) code for ACLF; therefore, the condition is difficult to develop new therapies for because reimbursement pathways are poorly defined.

To address these issues, many consortia have been developed in the United States, Europe, and Asia, which are actively studying this condition and generating a large amount of data. This issue of Seminars in Liver Disease aims to address this large growing body of literature by summarizing the current state of the art. Experts in their individual field have written each of the reviews and all are actively researching the condition.

We anticipate that this issue will serve as a source of relevant and up-to-date information about ACLF and stimulate further research in this field, where a lot needs to be done. The challenges are highlighted in each of the contributions, including better definitions of the epidemiology, costs, diagnostic and prognostic criteria, its pathophysiology, and treatment algorithms. We hope that regulators, research funding agencies, and financial controllers will take notice to help fund the management of ACLF patients and the development of appropriate therapies.