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  • Drugs, toxins, viral hepatitis, and hypoperfusion are the most common causes of acute liver failure (ALF).

  • Laboratory findings may confirm the cause and severity of presentation.

  • Consider acetaminophen toxicity in all patients, even without a history of toxic ingestion, particularly when serum aminotransferase levels are very high (>1000 units).

  • Depending on timing of ingestion, acetaminophen levels may not be elevated even in cases of overdose.

  • Rapid diagnostic and psychiatric evaluation is required at presentation.


Acute liver failure (ALF) is the rapid deterioration of liver function in a patient without preexisting liver disease. The most widely accepted definition of ALF includes evidence of coagulation abnormality (international normalized ratio [INR] ≥1.5), and encephalopathy in a patient without preexisting cirrhosis and with a hepatic illness manifested by hyperbilirubinemia of less than 26 weeks’ duration. ALF is a rare condition with an incidence of one to six cases per million per year in the developed world and affecting approximately 2000 people in the United States each year.

The US Acute Liver Failure Study Group (ALFSG) was formed in 1997 as a consortium of centers aimed at capturing nationwide data on ALF. Results of 1147 patients enrolled from 1998 to 2007 found that the most common causes of ALF were acetaminophen overdose (46%), indeterminate (14%), idiosyncratic drug reactions (11%), and viral hepatitis A or B (10%).

Currently in the United States, spontaneous survival is approximately 45% without liver transplantation. The outcome of ALF, however, varies by etiology with favorable prognoses being found with acetaminophen overdose, hepatitis A, and ischemia, and poor prognoses with other drug-induced ALF, hepatitis B, and indeterminate cases.

Larson  AM, Polson  J, Fontana  RJ  et al.; Acute Liver Failure Study Group. Acetaminophen-induced acute liver failure: results of a United States multicenter, prospective study. Hepatology. 2005;42:1364–1372.
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Lee  WM. Acute liver failure in the United States. Semin Liver Dis. 2003;23:217–226.
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Lee  WM, Squires  RH  Jr, Nyberg  SL  et al.. Acute liver failure: summary of a workshop. Hepatology. 2008;47:1401–1415.
[PubMed: 18318440]  
Ostapowicz  G, Fontana  RJ, Schi⊘dt  FV  et al.. Results of a prospective study of acute liver failure at 17 tertiary care centers in the United States. Ann Intern Med. 2002;137:947–954.
[PubMed: 12484709]  


ALF is a multisystem disorder, comprised of the acute onset of jaundice in a previously healthy person and the rapid onset of altered mental status accompanied by laboratory evidence of coagulopathy and acute hepatic injury.

A. Signs and Symptoms

Jaundice is a common physical examination finding on initial presentation, often prompting medical attention by the patient, but when minimal and the patient presents with altered mental status, the diagnosis ...

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