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Acute-on-chronic liver failure in cirrhosis

Nature Reviews Disease Primers volume 2, Article number: 16041 (2016) | Download Citation


The definition of acute-on-chronic liver failure (ACLF) remains contested. In Europe and North America, the term is generally applied according to the European Association for the Study of the Liver-Chronic Liver Failure (EASL-CLIF) Consortium guidelines, which defines this condition as a syndrome that develops in patients with cirrhosis and is characterized by acute decompensation, organ failure and high short-term mortality. One-third of patients who are hospitalized for acute decompensation present with ACLF at admission or develop the syndrome during hospitalization. ACLF frequently occurs in a closed temporal relationship to a precipitating event, such as bacterial infection or acute alcoholic, drug-induced or viral hepatitis. However, no precipitating event can be identified in approximately 40% of patients. The mechanisms of ACLF involve systemic inflammation due to infections, acute liver damage and, in cases without precipitating events, probably intestinal translocation of bacteria or bacterial products. ACLF is graded into three stages (ACLF grades 1–3) on the basis of the number of organ failures, with higher grades associated with increased mortality. Liver and renal failures are the most common organ failures, followed by coagulation, brain, circulatory and respiratory failure. The 28-day mortality rate associated with ACLF is 30%. Depending on the grade, ACLF can be reversed using standard therapy in only 16–51% of patients, leaving a considerable proportion of patients with ACLF that remains steady or progresses. Liver transplantation in selected patients with ACLF grade 2 and ACLF grade 3 increases the 6-month survival from 10% to 80%.

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The European Association for the Study of the Liver-Chronic Liver Failure (EASL-CLIF) Consortium is endorsed by the European Association for the Study of the Liver and supported by an unrestricted grant from Grifols. The authors thank D. J. Kim for the supply of the published Korean data and the Data Management Centre of the EASL-CLIF Consortium for providing the unpublished European data used in Figure 2.

Author information


  1. European Foundation for the Study of Chronic Liver Failure (EF-CLIF), Travessera de Gracia 11, 08021 Barcelona, Spain.

    • Vicente Arroyo
    • , Richard Moreau
    • , Rajiv Jalan
    • , Pere Ginès
    • , Frederik Nevens
    •  & Javier Fernández
  2. Grifols Chair for the Study of Cirrhosis, Barcelona, Spain.

    • Vicente Arroyo
  3. European Association for the Study of the Liver-Chronic Liver Failure (EASL-CLIF) Consortium, Barcelona, Spain.

    • Vicente Arroyo
    • , Richard Moreau
    • , Rajiv Jalan
    • , Pere Ginès
    • , Frederik Nevens
    •  & Javier Fernández
  4. Inserm, U 1149, Centre de Recherche sur l'Inflammation (CRI), Paris, France.

    • Richard Moreau
  5. Université Paris Diderot, Faculté de Médecine, Paris, France.

    • Richard Moreau
  6. Département Hospitalo-Universitaire (DHU) UNITY, Service d'Hépatologie, Hôpital Beaujon, AP-HP, Clichy, France.

    • Richard Moreau
  7. Laboratoire d'Excellence (Labex) Inflamex, ComUE Sorbonne Paris Cité, Paris, France.

    • Richard Moreau
  8. Division of Gastroenterology, Hepatology and Internal Medicine, Mayo Clinic College of Medicine, Rochester, Minnesota, USA.

    • Patrick S. Kamath
  9. Institute of Hepatology, UCL Medical School, London, UK.

    • Rajiv Jalan
  10. Royal Free Hospital, UCL Medical School, London, UK.

    • Rajiv Jalan
  11. Liver Unit, Hospital Clinic, University of Barcelona, Barcelona, Spain.

    • Pere Ginès
    •  & Javier Fernández
  12. Department of Hepatology, University Hospitals KU Leuven, Leuven, Belgium.

    • Frederik Nevens
  13. Yale Digestive Diseases, Temple Medical Center, New Haven, Connecticut, USA.

    • Uyen To
    •  & Guadalupe García-Tsao
  14. Veterans Administration, Yale-New Haven Hospital, New Haven, Connecticut, USA.

    • Uyen To
    •  & Guadalupe García-Tsao
  15. Department of Medicine, University of California San Diego, La Jolla, San Diego, California, USA.

    • Bernd Schnabl
  16. Department of Medicine, VA San Diego Health Care System, San Diego, California, USA.

    • Bernd Schnabl


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Introduction (V.A.); Epidemiology (P.S.K.); Mechanisms/pathophysiology (R.M. and B.S.); Diagnosis, screening and prevention (P.G., V.A. and J.F.); Management (R.J., G.G.-T., U.T. and J.F.); Quality of life (P.S.K.); Outlook (F.N. and V.A.); Overview of Primer (V.A.). V.A. and R.M. contributed equally to this work.

Competing interests

V.A. has received research funding from Grifols and has served on the scientific advisory board for Takeda. P.G. has received research funding from Grifols, served on the scientific advisory board for Ferring and Squana Medical and received research funding from Sequana Medical. R.J. has received research funding from Vital Therapies, has served on the scientific advisory board for Conatus Pharma and Takeda, has ongoing research collaborations with Gambro and Grifiols and is the principal investigator of an industry sponsored study (Sequana Medical). F.N. has served on the scientific advisory board of Center Fract, Croix Rouge Belgium, Intercept, Gore, Bristol-Myers Squibb, AbbVie, Novartis, MSD, Janssen-Cilag, Promethera Biosciences and Gilead, and has received grants from Roche, Astellas, Ferring, Novartis, Janssen-Cilag and AbbVie. All other authors declare no competing interests.

Corresponding author

Correspondence to Vicente Arroyo.

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