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Key Clinical Questions

  • image How is acute liver failure (ALF) defined and diagnosed, and how does it differ from acutely decompensated cirrhosis?

  • image Which causes of decompensated chronic liver failure can also be classified as “acute” failure with respect to transplant candidacy?

  • image How should clinicians acutely evaluate, triage, and manage ALF patients, including initial diagnostic and follow-up testing?

  • image What clinical and laboratory parameters should be frequently monitored?

  • image What complications of ALF lead to high mortality, and how are they managed?

  • image How is intracranial hypertension and cerebral edema managed medically?

  • image What prognostic measures best identify ALF patients who will require liver transplant in order to survive?

  • image What evidence-based interventions improve outcomes in patients with acute liver failure? Are they etiology specific?


Acute liver failure (ALF) is a rare clinical syndrome that is defined by coagulopathy, usually an international normalized ratio (INR) >1.5, and any degree of mental alteration (encephalopathy) that occurs over a span of less than 26 weeks in a patient without pre-existing liver disease. Based on the time to encephalopathy from the onset of jaundice, three types of ALF have been described: hyperacute (0-7 days), acute (8-21 days), and subacute (>21 days and <26 weeks).

Patients with subacute liver failure often pose a clinical challenge, as they may show signs suggesting chronic liver disease, such as ascites or prolonged encephalopathy. Also, patients with subacute liver failure (eg, drug induced) may follow a variable and unpredictable course, often leading to heightened anxiety for the patient, family, and medical providers.

As an exception to the definition of ALF, patients with Wilson disease, reactivation/superinfection of chronic hepatitis B, or autoimmune hepatitis may be considered to have ALF despite the presence of underlying chronic liver disease.


Approximately 2000 cases of ALF occur each year in the United States. ALF can affect people of all ages and is associated with high morbidity and mortality. Multiorgan failure (MOF) is the most common cause of death (>50% of cases), with infection and intracranial hypertension (ICH) responsible for most of the remaining deaths. With recent improvements in care, spontaneous recovery and overall survival now exceed 40% and 65%, respectively. Over the past 25 years in the United States, overall mortality from ALF has decreased from more than 80% to 33%.


Acute liver failure involves massive hepatocellular necrosis and liver dysfunction. A resulting cytokine storm leads to oxidative stress and a systemic inflammatory response syndrome. Anti-retroviral medications, Wilson disease, and acute fatty liver of pregnancy may uniquely cause severe mitochondrial dysfunction with resulting lactic acidosis. Ultimately, multiorgan dysfunction occurs.

Intracranial hypertension and cerebral edema may result from elevated ammonia levels that cause direct astrocyte toxicity and loss of cerebral blood flow autoregulation. Loss of cerebral autoregulation in ALF leads to ICH, and intracranial contents are rapidly damaged ...

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