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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) affects approximately 2000 people in the United States each year. 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.

The U.S. 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 occurs in 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 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.   [PubMed: 16317692]
Lee WM. Acute liver failure in the United States. Semin Liver Dis. 2003;23:217–226.   [PubMed: 14624381]
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, Schiødt 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]

The constellation of clinical findings in ALF includes jaundice in a previously healthy person, often preceded by malaise or nausea, and the rapid onset of altered mental status and coma accompanied by laboratory evidence of coagulopathy and acute hepatic injury.

Symptoms and Signs

History-taking should include a review of all possible exposures to viral infection, drugs, and toxic ingestions, as well as risk factors for underlying chronic liver disease. If the patient shows evidence of severe encephalopathy, a history should be obtained from family members.

Jaundice and right upper quadrant tenderness may or may not be present. An enlarged liver may be seen early in viral hepatitis, malignant infiltration, congestive heart failure, or acute Budd-Chiari syndrome. Alternatively, there may be decreased hepatic dullness to percussion, indicating diminished hepatic mass. The most ...

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