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Acute liver failure: Manifestations

The original term “fulminant hepatic failure,” defined 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,” remains applicable today(1). More modern definitions incorporate distinct disease phenotypes and quantify the interval between the onset of symptoms and the development of encephalopathy, which provides insight into the cause, complications and prognosis (1). Patients with subacute causes, despite having less marked coagulopathy and encephalopathy, have consistently worse outcomes (1).

See Figures 1 and 2:

Common Causes:

  • Viral infections (Hepatitis A, B, and E) – less common in the developed world due to vaccination
  • Drug-induced liver injury (Acetaminophen)– Most common cause in the United States
  • Other viral causes (CMV, EBV, HSV, Parvovirus)
  • Acute ischemic hepatocellular injury (hypoxic hepatitis)- critically ill patients with primary cardiac, circulatory, respiratory failure, or severe sepsis.
  • Illicit drug induced (MDMA, Cocaine)

Other Causes:

  • Neoplastic infiltration
  • Acute Budd–Chiari syndrome
  • Heat-stroke
  • Mushroom ingestion
  • Metabolic diseases such as Wilson’s disease

Often the cause of acute liver failure is not determined despite intensive investigation; these cases often follow a subacute presentation, and rates of survival are poor without transplantation (1).


  1. Bernal W, Wendon J. Acute Liver Failure. Crit Care Med. N Engl J Med 2013;369:2525-34 doi:10.1056/NEJMra1208937 PubMed Link