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  • May be fulminant or subfulminant; both forms carry a poor prognosis.

  • Acetaminophen and idiosyncratic drug reactions are the most common causes.


Acute liver failure may be fulminant or subfulminant. Fulminant hepatic failure is characterized by the development of hepatic encephalopathy within 8 weeks after the onset of acute liver injury. Coagulopathy (INR 1.5 or higher) is invariably present. Subfulminant hepatic failure occurs when these findings appear between 8 weeks and 6 months after the onset of acute liver injury and carries an equally poor prognosis. Acute-on-chronic liver failure refers to acute deterioration in liver function (often caused by infection) and associated failure of other organs in a person with preexisting chronic liver disease.

An estimated 1600 cases of acute liver failure occur each year in the United States. Toxicity caused by acetaminophen (a direct hepatotoxin) is the most common cause, accounting for at least 45% of cases. Suicide attempts account for 44% of cases of acetaminophen-induced hepatic failure, and unintentional overdoses (“therapeutic misadventures”), which are often a result of a decrease in the threshold toxic dose because of chronic alcohol use or fasting and have been reported after weight loss surgery, account for at least 48%. Other causes include idiosyncratic (in some cases, immune-mediated) drug reactions (the second most common cause, with antibiotics, antituberculosis drugs, and antiepileptics implicated most commonly), viral hepatitis, poisonous mushrooms (Amanita phalloides), shock, heat stroke, Budd-Chiari syndrome, malignancy (most commonly lymphomas), Wilson disease, Reye syndrome, fatty liver of pregnancy and other disorders of fatty acid oxidation, autoimmune hepatitis, parvovirus B19 infection, and rarely grand mal seizures. The cause is indeterminate in approximately 5.5% of cases. The risk of acute liver failure is increased in patients with diabetes mellitus, and outcome is worsened by obesity. Herbal and dietary supplements are thought to be contributory to acute liver failure in a substantial portion of cases, regardless of cause, and may be associated with lower rates of transplant-free survival. Acute-on-chronic liver failure is often precipitated by a bacterial infection or an alcohol binge and alcohol-associated hepatitis.

Viral hepatitis now accounts for only 12% of all cases of acute liver failure. The decline of viral hepatitis as the principal cause of acute liver failure is due to universal vaccination of infants and children against hepatitis B and the availability of the hepatitis A vaccine. Acute liver failure may occur after reactivation of hepatitis B in carriers who receive immunosuppressive therapy. In endemic areas, hepatitis E is an important cause of acute liver failure, particularly in pregnant women. Hepatitis C is a rare cause of acute liver failure in the United States, but acute hepatitis A or B superimposed on chronic hepatitis C may cause acute liver failure.


Gastrointestinal symptoms, systemic inflammatory response, and kidney dysfunction are common. Clinically significant bleeding is uncommon and reflects severe systemic ...

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