Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2017 Mar;66(3):541-553.
doi: 10.1136/gutjnl-2016-312670. Epub 2017 Jan 4.

Acute-on-chronic liver failure: an update

Ruben Hernaez  1 , Elsa Solà  2   3   4 , Richard Moreau  5   6   7   8   9 , Pere Ginès  2   3   4
Affiliations
Review

Acute-on-chronic liver failure: an update

Ruben Hernaez et al. Gut. 2017 Mar.

Abstract

Acute-on-chronic liver failure (ACLF) is a syndrome characterised by acute decompensation of chronic liver disease associated with organ failures and high short-term mortality. Alcohol and chronic viral hepatitis are the most common underlying liver diseases. Up to 40%-50% of the cases of ACLF have no identifiable trigger; in the remaining patients, sepsis, active alcoholism and relapse of chronic viral hepatitis are the most common reported precipitating factors. An excessive systemic inflammatory response seems to play a crucial role in the development of ACLF. Using a liver-adapted sequential organ assessment failure score, it is possible to triage and prognosticate the outcome of patients with ACLF. The course of ACLF is dynamic and changes over the course of hospital admission. Most of the patients will have a clear prognosis between day 3 and 7 of hospital admission and clinical decisions such as evaluation for liver transplant or discussion over goals of care could be tailored using clinical scores. Bioartificial liver support systems, granulocyte-colony stimulating factors or stem-cell transplant are in the horizon of medical care of this patient population; however, data are too premature to implement them as standard of care.

Keywords: LIVER CIRRHOSIS; LIVER FAILURE.

PubMed Disclaimer

Conflict of interest statement

Competing interests: PG declares that he has received research funding from Ferring Pharmaceuticals, Grifols S.A. and Sequana Medical. He has participated on Advisory Boards for Ferring Pharmaceuticals, Promethera and Novartis.

Figures

Figure 1
Figure 1
Inflammation caused by microbes. Top: Microbes (bacteria, viruses, fungi) induce inflammation via two classes of molecules: pathogen-associated molecular patterns (PAMPs) and virulence factors. Sensors of the innate immune system recognise the invading microbe via recognition of PAMPs, which are conserved molecular patterns (structural feature recognition). Sensors are known as pattern-recognition receptors. The second class of microbial inducers of inflammation includes a large number of virulence factors. Most of these factors are generally not recognised by dedicated receptors but can be sensed via the effects of their activity (functional feature recognition). For example, there are bacterial virulence factors which cause modifications and inactivation of host Rho GTPases and these alterations are sensed by the Pyrin inflammasome. Infection may be associated with tissue damage caused by the bacteria or by the immune response to bacteria. Tissue damage can induce inflammation which is committed to tissue repair (see text and reference32). Bottom: Proposed interventions. MELD, Model For End-Stage Liver Disease score.
Figure 2
Figure 2
Relationship between organ failure and mortality in acute-on-chronic liver failure (ACLF). Twenty-eight-day mortality rates of patients with decompensated cirrhosis with (red bars) and without (green bars) ACLF according to the diagnostic criteria proposed in the CANONIC study. Patients are divided into the following categories: patients with no organ failure (OF); patients with a single non-kidney organ failure without kidney dysfunction (KD; a serum creatinine level of 1.5–1.9 mg/dL) or brain dysfunction (BD; grade 1–2 hepatic encephalopathy); patients with a single kidney failure; patients with a single non-kidney organ failure with KD and/or BD; patients with two organ failures and patients with three or more organ failures. Adapted with permission from Arroyo et al.
Figure 3
Figure 3
Comparison of the area under the receiver operating curves (AUROCs) to predict 28-day (panel A) and 90-day (panel B) mortality of the chronic liver failure Consortium (CLIF-C) acute-on-chronic liver failure (ACLF) score compared with Model For End-Stage Liver Disease (MELD), Model For End-Stage Liver Disease sodium score (MELD-Na) and Child-Pugh-Turcotte scores (CPs). Adapted with permission from Jalan et al.
Figure 4
Figure 4
Proposed algorithm for the management of patients with acute-on-chronic liver failure (ACLF) or decompensated cirrhosis. A proposed management strategy for patients with ACLF based on mortality rate data from the CANONIC study. The first step is the assessment of ACLF grade at days 3–7 after initiation of medical management, including organ support. Liver transplantation should be assessed in all patients with ACLF because of high 90-day mortality rates (>20%). Liver transplantation should be performed as early as possible in patients with ACLF grade 2 and grade 3 as they are at considerable risk of short-term (28-day) mortality. In the case of contraindication of liver transplantation, the presence of four or more organ failures (OFs) or a Chronic Liver Failure Consortium (CLIF-C) ACLF score of >64 at days 3–7 after diagnosis could indicate the futility of care. ICU, intensive care unit. Adapted from Gustot et al and obtained from Arroyo et al with permission.
See this image and copyright information in PMC

Comment in

  • Acute-on-chronic liver failure-old concepts made clearer.
    de Mattos ÂZ, de Mattos AA. de Mattos ÂZ, et al. Transl Gastroenterol Hepatol. 2017 Dec 18;2:111. doi: 10.21037/tgh.2017.11.17. eCollection 2017. Transl Gastroenterol Hepatol. 2017. PMID: 29354768 Free PMC article. No abstract available.

Similar articles

  • Update on acute-on-chronic liver failure.
    Solé C, Solà E. Solé C, et al. Gastroenterol Hepatol. 2018 Jan;41(1):43-53. doi: 10.1016/j.gastrohep.2017.05.012. Epub 2017 Jun 24. Gastroenterol Hepatol. 2018. PMID: 28655410 Review. English, Spanish.
  • Acute-on-chronic liver failure in cirrhosis.
    Arroyo V, Moreau R, Kamath PS, Jalan R, Ginès P, Nevens F, Fernández J, To U, García-Tsao G, Schnabl B. Arroyo V, et al. Nat Rev Dis Primers. 2016 Jun 9;2:16041. doi: 10.1038/nrdp.2016.41. Nat Rev Dis Primers. 2016. PMID: 27277335 Review.
  • Acute-on-chronic liver failure: A new syndrome that will re-classify cirrhosis.
    Arroyo V, Moreau R, Jalan R, Ginès P; EASL-CLIF Consortium CANONIC Study. Arroyo V, et al. J Hepatol. 2015 Apr;62(1 Suppl):S131-43. doi: 10.1016/j.jhep.2014.11.045. J Hepatol. 2015. PMID: 25920082 Review.
  • PREDICT identifies precipitating events associated with the clinical course of acutely decompensated cirrhosis.
    Trebicka J, Fernandez J, Papp M, Caraceni P, Laleman W, Gambino C, Giovo I, Uschner FE, Jansen C, Jimenez C, Mookerjee R, Gustot T, Albillos A, Bañares R, Jarcuska P, Steib C, Reiberger T, Acevedo J, Gatti P, Shawcross DL, Zeuzem S, Zipprich A, Piano S, Berg T, Bruns T, Danielsen KV, Coenraad M, Merli M, Stauber R, Zoller H, Ramos JP, Solé C, Soriano G, de Gottardi A, Gronbaek H, Saliba F, Trautwein C, Kani HT, Francque S, Ryder S, Nahon P, Romero-Gomez M, Van Vlierberghe H, Francoz C, Manns M, Garcia-Lopez E, Tufoni M, Amoros A, Pavesi M, Sanchez C, Praktiknjo M, Curto A, Pitarch C, Putignano A, Moreno E, Bernal W, Aguilar F, Clària J, Ponzo P, Vitalis Z, Zaccherini G, Balogh B, Gerbes A, Vargas V, Alessandria C, Bernardi M, Ginès P, Moreau R, Angeli P, Jalan R, Arroyo V; PREDICT STUDY group of the EASL-CLIF CONSORTIUM. Trebicka J, et al. J Hepatol. 2021 May;74(5):1097-1108. doi: 10.1016/j.jhep.2020.11.019. Epub 2020 Nov 20. J Hepatol. 2021. PMID: 33227350
  • Acute-on-chronic liver failure: a new clinical entity.
    Moreau R, Arroyo V. Moreau R, et al. Clin Gastroenterol Hepatol. 2015 May;13(5):836-41. doi: 10.1016/j.cgh.2014.02.027. Epub 2014 Feb 28. Clin Gastroenterol Hepatol. 2015. PMID: 24583872
See all similar articles

Cited by

See all "Cited by" articles

References

    1. Schuppan D, Afdhal NH. Liver cirrhosis. Lancet 2008;371:838–51. 10.1016/S0140-6736(08)60383-9 - DOI - PMC - PubMed
    1. Ginés P, Quintero E, Arroyo V, et al. . Compensated cirrhosis: natural history and prognostic factors. Hepatology 1987;7:122–8. 10.1002/hep.1840070124 - DOI - PubMed
    1. Kjaergard LL, Liu J, ls-Nielsen B, et al. . Artificial and bioartificial support systems for acute and acute-on-chronic liver failure: a systematic review. JAMA 2003;289:217–22. 10.1001/jama.289.2.217 - DOI - PubMed
    1. Sarin SK, Kumar A, Almeida JA, et al. . Acute-on-chronic liver failure: consensus recommendations of the Asian Pacific Association for the study of the liver (APASL). Hepatol Int 2009;3:269–82. 10.1007/s12072-008-9106-x - DOI - PMC - PubMed
    1. Sarin SK, Kedarisetty CK, Abbas Z, et al. . Acute-on-chronic liver failure: consensus recommendations of the Asian Pacific Association for the Study of the Liver (APASL) 2014. Hepatol Int 2014;8:453–71. 10.1007/s12072-014-9580-2 - DOI - PubMed

Publication types

MeSH terms