Skip to Main Content

We have a new app!

Take the Access library with you wherever you go—easy access to books, videos, images, podcasts, personalized features, and more.

Download the Access App here: iOS and Android


Fulminant hepatic failure (FHF), now referred to as acute liver failure (ALF), is a rare but life-threatening condition that relies on early recognition and treatment to achieve optimal outcomes. The term “fulminant hepatic failure” was initially coined in 1970 by Charles Trey and Charles Davison, who defined FHF as “a severe liver injury, potentially reversible in nature and with onset of hepatic encephalopathy within 8 weeks of the first symptoms in the absence of pre-existing liver disease.” This definition was refined in 1993 by John O’Grady and colleagues, who subdivided the disease based on the time that it takes to progress from jaundice to encephalopathy. Their time frames were hyperacute, which progressed in ≤7 days; acute, which progressed in ≤4 weeks; and subacute, which progressed in ≤12 weeks. Currently, the most widely used definition is a variation of the original Trey and Davison model and recognizes ALF as evidence of an abnormality in coagulation (practically, an international normalized ratio [INR] >1.5) with any amount of encephalopathy in a patient without cirrhosis and an illness of <26 weeks in duration. The term FHF is still occasionally used to refer to a subtype of ALF where encephalopathy develops within 8 weeks in a patient with no prior liver disease.

Criteria for Acute Liver Failure

  • Abnormal coagulation

  • Encephalopathy

  • Less than 26 weeks in duration

  • No prior history of cirrhosis


The etiology of ALF varies throughout the world (Table 12-1). In the United States, the most common cause is acetaminophen overdose, followed by unknown causes and “other causes,” which include acute ischemic hepatocellular injury, malignancy, Budd-Chiari, and Wilson disease. Viral hepatitis is relatively uncommon in the United States, only accounting for approximately 10% of cases. Similar numbers are seen in the United Kingdom, although they have an even higher incidence of acetaminophen (paracetamol) toxicity. On the other hand, in other countries such as Japan, India, Bangladesh, and France the most common cause of ALF is viral hepatitis (hepatitis A, hepatitis B, and hepatitis E). Among viral hepatitis, hepatitis A and B are the most common causes globally, especially in endemic nations. Other major causes of ALF apart from those mentioned earlier include nonacetaminophen drug toxicity, which includes both illicit (3,4-methylenedioxy-N-methylamphetamine [ecstasy], cocaine, mushroom ingestion) and prescription (isoniazid, pyrazinamide and phenytoin) drugs (Table 12-2). It is important to obtain a thorough history from any patient (or family if the patient is unable) specifically asking about both prescription and over-the-counter drugs, as supplements such as kava kava, Herbalife, ma huang, and Hydroxycut have also been associated with hepatotoxicity.

TABLE 12-1Etiology of Acute Liver Failure in Selected Countries1

Pop-up div Successfully Displayed

This div only appears when the trigger link is hovered over. Otherwise it is hidden from view.