Elsevier

Journal of Critical Care

Volume 39, June 2017, Pages 25-30
Journal of Critical Care

Clinical Potpourri
Acute liver failure: An up-to-date approach,☆☆

https://doi.org/10.1016/j.jcrc.2017.01.003Get rights and content

Highlights

  • Outcomes of patients with acute liver failure have been improving, but morbidity and mortality are still of concern.

  • Earlier recognition and referral to the intensive care unit have been important to improve these patients' outcomes.

  • Intensive care management should take into consideration hepatic encephalopathy, cerebral edema and intracranial hypertension, hemodynamics, acute kidney injury, coagulopathy, and infection.

  • Selection of patients for liver transplantation has been based on prognostic scores (eg, Kings' College criteria) but limitations may apply.

Abstract

Acute liver failure is a rare but potentially devastating disease. Throughout the last few decades, acute liver failure outcomes have been improving in the context of the optimized overall management. This positive trend has been associated with the earlier recognition of this condition, the improvement of the intensive care unit management, and the developments in emergent liver transplantation. Accordingly, we aimed to review the current diagnostic and therapeutic approach to this syndrome, especially in the intensive care unit setting.

Introduction

Acute liver failure (ALF) is a rare condition characterized by new and rapidly evolving hepatic dysfunction associated with neurologic dysfunction and coagulopathy. It is more frequent in young individuals and its etiologies vary geographically, with impact on both clinical course and outcomes. Throughout the last decades, ALF outcomes have been improving in the context of the optimized overall management. However, its present morbidity and mortality remain high in patients fulfilling poor prognostic criteria and without emergent liver transplantation (LT).

Section snippets

Definition and epidemiology

Acute liver failure definition has evolved throughout the time and presently includes the following features: international normalized ratio (INR) at least 1.5, neurologic dysfunction with any degree of hepatic encephalopathy (HE), no preexisting cirrhosis, and disease course of 26 weeks or less [1]. Exceptions to this definition may be patients with acute presentations of Wilson disease, autoimmune hepatitis, or vertically transmitted hepatitis B if by the time of the new hepatic insult, they

Pathophysiology and clinical manifestations

In ALF, the liver insult results in extensive death of hepatocytes with activation of the innate immune system responses (Kupffer cells and circulating monocytes) causing a large production of inflammatory mediators. The “spill-over” of these inflammatory mediators into the circulation ultimately leads to the systemic disturbances and clinical manifestations of ALF [12]. An overwhelming systemic inflammatory response syndrome (SIRS) is associated with the several organ failures that may ensue.

General management

The initial management of acute liver injury (hepatitis) or ALF is supportive with the objective to optimize conditions for the liver to regenerate and prevent and treat as early as possible complications [17]. Although most patients with acute liver injury may be managed in a regular ward, patients with ALF should be referred to the ICU, ideally one in a center capable of providing emergent LT, as soon as possible as they may deteriorate quickly [1].

The initial diagnostic approach should be

Intensive care management

Acute liver failure may lead to several organ failures; therefore, ICU admission should be considered as early as possible, especially when HE is being difficult to control in a regular ward or coagulopathy is progressing. In this context, supporting organ failures follows the rules of general ICU patients but with some specificities, which deserve to be emphasized.

Liver transplantation

Liver transplantation is the only definitive treatment for patients with ALF. Overall survival after LT has been reported to be lower for patients with ALF in comparison to patients with cirrhosis until 1 year after transplant, but it tends to be similar from then on [68]. In fact, most deaths after LT for patients with ALF occur from infection during the first 3 postoperative months [4]. Nevertheless, survival after LT for ALF has been improving throughout the last decades, with 21-day

Conclusions

Acute liver failure diagnostic and therapeutic strategies have evolved throughout the time and that has been associated with improved outcomes. New advances in basic and clinical research may potentiate even more such outcomes. Despite this, these patients' early referral to an LT center, ICU timely treatment, and a comprehensive multidisciplinary strategy in risk stratification and selection for LT will continue to be fundamental steps for a successful approach.

References (77)

  • S.P. Pereira et al.

    Pharmacokinetics and efficacy of oral versus intravenous mixed-micellar phylloquinone (vitamin K1) in severe acute liver disease

    J Hepatol

    (2005)
  • J. Vaquero et al.

    Infection and the progression of encephalopathy in acute liver failure

    Gastroenterology

    (2003)
  • N. Rolando et al.

    The systemic inflammatory response syndrome in acute liver failure

    Hepatology

    (2000)
  • H.J. Zimmerman et al.

    Acetaminophen (paracetamol) hepatotoxicity with regular intake of alcohol: analysis of instances of therapeutic misadventure

    Hepatology

    (1995)
  • M. Eefsen et al.

    Comparison of terlipressin and noradrenalin on cerebral perfusion, intracranial pressure and cerebral extracellular concentrations of lactate and pyruvate in patients with acute liver failure in need of inotropic support

    J Hepatol

    (2007)
  • S.R. Tujios et al.

    Risk factors and outcomes of acute kidney injury in patients with acute liver failure

    Clin Gastroenterol Hepatol

    (2015)
  • L.E. Schmidt et al.

    Serum phosphate is an early predictor of outcome in severe acetaminophen-induced hepatotoxicity

    Hepatology

    (2002)
  • R.F. Butterworth

    Pathogenesis of hepatic encephalopathy and brain edema in acute liver failure

    J Clin Exp Hepatol

    (2015)
  • R.J. Ede et al.

    Controlled hyperventilation in the prevention of cerebral oedema in fulminant hepatic failure

    J Hepatol

    (1986)
  • C.J. Karvellas et al.

    Current evidence for extracorporeal liver support systems in acute liver failure and acute-on-chronic liver failure

    Crit Care Clin

    (2016)
  • F.S. Larsen et al.

    High-volume plasma exchange in patients with acute liver failure: an open randomised controlled trial

    J Hepatol

    (2016)
  • C.L. Berg et al.

    Liver and intestine transplantation in the United States 1998-2007

    Am J Transplant

    (2009)
  • A. Pauwels et al.

    Emergency liver transplantation for acute liver failure. Evaluation of London and Clichy criteria

    J Hepatol

    (1993)
  • W. Bernal et al.

    Outcome after wait-listing for emergency liver transplantation in acute liver failure: a single centre experience

    J Hepatol

    (2009)
  • G. Germani et al.

    Liver transplantation for acute liver failure in Europe: outcomes over 20 years from the ELTR database

    J Hepatol

    (2012)
  • Lee W, Larson AM, Stravitz RT. AASLD position paper: the management of acute liver failure: update 2011. Available at:...
  • J.G. O'Grady et al.

    Acute liver failure: redefining the syndromes

    Lancet

    (1993)
  • G. Ostapowicz et al.

    Results of a prospective study of acute liver failure at 17 tertiary care centers in the United States

    Ann Intern Med

    (2002)
  • W. Bernal et al.

    Acute liver failure

    N Engl J Med

    (2013)
  • S.K. Acharya et al.

    Etiopathogenesis of acute hepatic failure: Eastern versus Western countries

    J Gastroenterol Hepatol

    (2002)
  • S.E. Gulmez et al.

    Liver transplant associated with paracetamol overdose: results from the seven-country SALT study

    Br J Clin Pharmacol

    (2015)
  • J. Hadem et al.

    Etiologies and outcomes of acute liver failure in Germany

    Clin Gastroenterol Hepatol

    (2012)
  • M. Areia et al.

    Fulminant hepatic failure: a Portuguese experience

    Eur J Gastroenterol Hepatol

    (2007)
  • R.J. Fontana et al.

    Two-year outcomes in initial survivors with acute liver failure: results from a prospective, multicentre study

    Liver Int

    (2015)
  • C.G. Antoniades et al.

    Source and characterization of hepatic macrophages in acetaminophen-induced acute liver failure in humans

    Hepatology

    (2012)
  • C.G. Antoniades et al.

    Secretory leukocyte protease inhibitor: a pivotal mediator of anti-inflammatory responses in acetaminophen induced acute liver failure

    Hepatology

    (2014)
  • C.G. Antoniades et al.

    Reduced monocyte HLA-DR expression: a novel biomarker of disease severity and outcome in acetaminophen-induced acute liver failure

    Hepatology

    (2006)
  • M.N. Yunos et al.

    Association between a chloride-liberal vs chloride-restrictive intravenous fluid administration strategy and kidney injury in critically ill adults

    JAMA

    (2012)
  • Cited by (0)

    Conflicts of interest: None.

    ☆☆

    Funding: None.

    View full text