UMass Chan Medical School Faculty Publications

UMMS Affiliation

Department of Medicine, Division of Gastroenterology; UMass Metabolic Network

Publication Date


Document Type

Article Postprint


Digestive System Diseases | Gastroenterology | Hepatology | Palliative Care | Surgical Procedures, Operative | Therapeutics


Acute on chronic liver failure (ACLF) is a culmination of chronic liver disease and extra-hepatic organ failures, which is associated with a high short-term mortality and immense healthcare expenditure. There are varying definitions for organ failures and ACLF in Europe, North America and Asia. These differing definitions need to be reconciled to enhance progress in the field. The pathogenesis of ACLF is multi-factorial and related to interactions between the immuno-inflammatory system, microbiota and the precipitating factors. Individual organ failures related to the kidney, brain, lungs and circulation have cumulative adverse effects on mortality and are often complicated or precipitated by infections. Strategies to prevent and rapidly treat these organ failures are paramount in improving survival. With the aging population and paucity of organs for liver transplant, the prognosis of ACLF patients is poor, highlighting the need for novel therapeutic strategies. The role of liver transplant in ACLF is evolving and needs further investigation across large consortia. A role for early palliative care and management of frailty as approaches to alleviate disease burden and improve patient-reported outcomes is being increasingly recognized.

CONCLUSION: ACLF is a clinically relevant syndrome that is epidemic worldwide and which requires a dedicated multi-national approach focused on prognostication and management. Investigations are underway worldwide to get ACLF ready for prime time. Compensated cirrhosis with > 90% 1-year survival can transition into the decompensated stage with the onset of jaundice, ascites, variceal bleeding and hepatic encephalopathy (HE) (1)Acute on chronic liver failure (ACLF) is associated with rapid deterioration of liver function leading to liver failure, multiple extra-hepatic organ failures and high short-term mortality (2). Even if patients survive the acute insult, they may never return to their pre-episode functional state (3). The term "acute decompensation" has been used to characterize ascites, gastrointestinal bleeding, hepatic encephalopathy or infections without organ failure(4). There are several gaps in knowledge surrounding ACLF, which will be highlighted in this review. The prevalence of ACLF is difficult to assess due to varying regional definitions (5). ACLF, once thought to occur only in decompensated cirrhosis, has been recognized even in chronic liver disease without cirrhosis (5). ACLF occurs in approximately 10-30% of hospitalized cirrhotic patients (6-8). Because of its acuity, patients are frequently admitted into the intensive care unit (ICU), and every effort is made to stabilize these patients for liver transplantation (LT). This drives healthcare costs(9). Despite this intensive management, ACLF is associated with substantial morbidity and mortality. Because curative LT is only available to < 10% of cirrhotic patients each year and ACLF patients are often delisted, the morbidity and mortality rates remain high, especially with an increasing number of organ failures (10).


cirrhosis, definitions, infections, liver transplant, palliative

Rights and Permissions

© 2018 by the American Association for the Study of Liver Diseases. The version of the article available for download is the authors' accepted manuscript as prepared for publication in: Hepatology. Accepted manuscript posted after 12 months as allowed by the publisher's self-archiving policy at:

DOI of Published Version



Hepatology. 2018 Apr 24. doi: 10.1002/hep.30056. [Epub ahead of print] Link to article on publisher's site

Related Resources

Link to Article in PubMed

Journal/Book/Conference Title

Hepatology (Baltimore, Md.)

PubMed ID