Elsevier

JHEP Reports

Volume 3, Issue 1, February 2021, 100176
JHEP Reports

Review
Acute-on-chronic liver failure: Definitions, pathophysiology and principles of treatment

https://doi.org/10.1016/j.jhepr.2020.100176Get rights and content
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Summary

The term acute-on-chronic liver failure (ACLF) defines an abrupt and life-threatening worsening of clinical conditions in patients with cirrhosis or chronic liver disease. In recent years, different definitions and diagnostic criteria for the syndrome have been proposed by the major international scientific societies. The main controversies relate to the type of acute insult (specifically hepatic or also extrahepatic), the stage of underlying liver disease (cirrhosis or chronic hepatitis) and the concomitant extrahepatic organ failure(s) that should be considered in the definition of ACLF. Therefore, different severity criteria and prognostic scores have been proposed and validated. Current evidence shows that the pathophysiology of ACLF is closely associated with an intense systemic inflammation sustained by circulating pathogen-associated molecular patterns and damage-associated molecular patterns. The development of organ failures may be a result of a combination of tissue hypoperfusion, direct immune-mediated damage and mitochondrial dysfunction. Management of ACLF is currently based on the supportive treatment of organ failures, mainly in an intensive care setting. For selected patients, liver transplantation is an effective treatment that offers a good long-term prognosis. Future studies on potential mechanistic treatments that improve patient survival are eagerly awaited.

Keywords

Acute decompensation
Multiorgan failure
Inflammatory response
Bacterial infections
Bacterial translocation
Sterile inflammation
Immunopathology
Metabolism

Abbreviations

AARC
APASL ACLF Research Consortium
ACLF
acute-on-chronic liver failure
AKI
acute kidney injury
APASL
Asian Pacific Association for the Study of the Liver
CLIF
Chronic Liver Failure-Consortium
COSSH
Chinese Group on the Study of Severe Hepatitis
DAMPs
damage-associated molecular patterns
EASL
European Association for the Study of the Liver - Chronic Liver
ER
endoplasmic reticulum
HMGB1
high mobility group box 1
ICU
intensive care unit
INR
international normalised ratio
MELD
model for end-stage liver disease
NACSELD
North American Consortium for the Study of End-stage Liver Disease
NO
nitric oxide
OF
organ failure
PAMPs
pathogen-associated molecular patterns
PRR
pattern-recognition receptors
TLR
Toll-like receptor
UNOS
United Network for Organ Sharing

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