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J Hepatol. 2015 Apr;62(1 Suppl):S131-43. doi: 10.1016/j.jhep.2014.11.045.

Acute-on-chronic liver failure: A new syndrome that will re-classify cirrhosis.

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Liver Unit, Hospital Clinic, University of Barcelona, IDIBAPS, Barcelona, Spain.
Inserm Unité 1149, Centre de Recherche sur l'inflammation (CRI) Paris, UMR S_1149, Université Paris Diderot, París, DHU UNITY, Service d'Hepatologie, Hôpital Beaujon, APHP, Clichy, France.
Liver Failure Group, Institute for Liver and Digestive Health, Royal Free Hospital, UCL, London, United Kingdom.
Liver Unit, Hospital Clinic, University of Barcelona, Insitut d'Investigacions Biomediques August Pi I Sunyer (IDIBAPS), Centro de Investigacion Biomedica en Red Enfermedades Hepaticas y Digestivas (CIBEReHD), Instituto Reina Sofia de Investigacion en Nefrologia (IRSIN), Spain. Electronic address:


Acute-on-chronic liver failure (ACLF) is a recently recognized syndrome characterized by acute decompensation (AD) of cirrhosis and organ/system failure(s) (organ failure: liver, kidney, brain, coagulation, circulation and/or respiration) and extremely poor survival (28-day mortality rate 30-40%). ACLF occurs in relatively young patients. It is especially frequent in alcoholic- and untreated hepatitis B associated-cirrhosis, in addition it is related to bacterial infections and active alcoholism, although in 40% of cases no precipitating event can be identified. It may develop at any time during the course of the disease in the patient (from compensated to long-standing cirrhosis). The development of ACLF occurs in the setting of a systemic inflammation, the severity of which correlates with the number of organ failures and mortality. Systemic inflammation may cause ACLF through complex mechanisms including an exaggerated inflammatory response and systemic oxidative stress to pathogen- or danger/damage-associated molecular patterns (immunopathology) and/or alteration of tissue homeostasis to inflammation caused either by the pathogen itself or through a dysfunction of tissue tolerance. A scoring system composed of three scores (CLIF-C OFs, CLIF-C AD, and CLIF-C ACLFs) specifically designed for patients with AD, with and without ACLF, allows a step-wise algorithm for a rational indication of therapy. The management of ACLF should be carried out in enhanced or intensive care units. Current therapeutic measures comprise the treatment for associated complications, organ failures support and liver transplantation.


Acute decompensation of cirrhosis; Acute-on-chronic liver failure; Artificial liver support systems; Danger/damage-associated molecular patterns (DAMPs); Organ failure; Pathogen-associated molecular patterns (PAMPs); Plasma exchange; Systemic inflammation

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