We searched Medline with the terms “acute liver failure” and “fulminant hepatic failure” between 1997 and 2009. We also reviewed reference lists of publications we identified and selected those most relevant to practice. We have not attempted to give a comprehensive review of all features of acute liver failure, but have focused on areas in which there have been substantial advances in understanding of the disorder and in which there have been major new developments in treatment.
SeminarAcute liver failure
Introduction
Acute liver failure is the clinical manifestation of sudden and severe hepatic injury and arises from many causes. After abrupt loss of hepatic metabolic and immunological function, it leads to hepatic encephalopathy, coagulopathy, and, in many cases, progressive multiorgan failure (panel 1). Although uncommon, this critical illness occurs mostly in young adults and is associated with high mortality and resource cost. In many countries it is the most frequent indication for emergency liver transplantation.
In the past 10 years, there have been major changes in the understanding of the cause and pathogenesis of the disease, and an evidence base for treatment has evolved. In this Seminar, we summarise these changes, present approaches to management, and suggest future developments.
Section snippets
Definitions
The term fulminant hepatic failure was first used11 in 1970 to describe a potentially reversible disorder that was the result of severe liver injury, with an onset of encephalopathy within 8 weeks of symptom appearance and in the absence of pre-existing liver disease. The key elements of this definition remain relevant, although classifications have changed to recognise that prognosis and complications vary in relation to the rate of evolution of illness.
The terminology developed by O'Grady and
Incidence
Acute liver failure is rare. Reports from the developed world suggest an overall incidence of between one and six cases per million people every year.16, 17, 18 Data for other regions are sparse, although rates are probably high in locations where infective hepatitis is common and medical therapies that interrupt progression of hepatic injury and development of extrahepatic organ dysfunction are not readily available.
Viral infections
The main causal agents for the hepatic injury that triggers the onset of liver failure show wide geographical variation, and depend on the prevalent hepatotropic virus infections and patterns of drug use (table 2).13, 27, 28 In the developing world, viral causes predominate, with infection by hepatitis A, B, and E viruses accounting for most cases. By contrast, acute viral infection is an uncommon cause in the USA and much of western Europe, where drug-induced liver injury predominates.
Principles of care
Acute liver failure leads to a unique combination of often rapidly progressive, severe multiorgan failure with unpredictable complications, and necessitates urgent decision making about use of the only effective treatment for those with advanced disease: emergency liver transplantation. However, the general principles of care are straightforward. Standard intensive care is delivered with additional specific measures aimed at identification and removal or amelioration of the insult that caused
Future directions
A range of extracorporeal supportive devices has been advocated to replace liver function in patients with acute liver failure, either to stabilise the patient before transplantation, or to improve native liver regeneration. Despite many uncontrolled case series and individual randomised trials,151, 152, 153 conclusive evidence of benefit to patients has not been reported. There are no published data to support the use of either biological or non-biological systems as sole treatment when
Search strategy and selection criteria
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Gastroenterology
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Clinical importance of adrenal insufficiency in acute hepatic dysfunction
Hepatology
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Early evidence of bone marrow dysfunction in children with indeterminate fulminant hepatic failure who ultimately develop aplastic anemia
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Fulminant hepatic failure: outcome after listing for highly urgent liver transplantation—12 years experience in the nordic countries
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Prognostic implications of lactate, bilirubin, and etiology in German patients with acute liver failure
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Infection with a novel human DNA virus (TTV) has no pathogenic significance in patients with liver diseases
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How has legislation restricting paracetamol pack size affected patterns of deprivation related inequalities in self-harm in Scotland?
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Paracetamol: are therapeutic doses entirely safe?
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Influence of acetaminophen at therapeutic doses on surrogate markers of severity of acute viral hepatitis
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Clin Gastroenterol Hepatol
The systemic inflammatory response syndrome is predictive of renal dysfunction in patients with non-paracetamol-induced acute liver failure
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Energy expenditure in acetaminophen-induced fulminant hepatic failure
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The importance of immune dysfunction in determining outcome in acute liver failure
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Therapeutic hypothermia for acute liver failure
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Elevated troponin I levels in acute liver failure: is myocardial injury an integral part of acute liver failure?
Hepatology
The role of etiology in the hyperamylasemia of acute liver failure
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The management of fulminant hepatic failure
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Acute liver failure: redefining the syndromes
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Etiology and prognosis of fulminant hepatitis in adults
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Fulminant and subfulminant liver failure: definitions and causes
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Fulminant hepatic failure: pediatric aspects
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Population-based surveillance for acute liver failure
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Acute liver failure in Spain: analysis of 267 cases
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Predictors of fatal outcome in fulminant hepatic failure
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Fulminant hepatic failure in an African setting: etiology, clinical course, and predictors of mortality
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