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For further information, see CMDT Part 18-05: Acute Liver Failure

KEY FEATURES

Essentials of Diagnosis

  • May be fulminant or subfulminant and both carry an equally poor prognosis

  • Acetaminophen and idiosyncratic drug reactions are the most common causes

General Considerations

  • Acute liver failure may occur after reactivation of hepatitis B in carriers who receive immunosuppressive therapy

  • In fulminant liver failure, encephalopathy and coagulopathy (international normalized ratio [INR] ≥ 1.5) develop within 8 weeks after the onset of acute liver injury

  • Subfulminant liver failure occurs when encephalopathy and coagulopathy appear between 8 weeks and 6 months after the onset of acute liver injury

  • Acute-on-chronic liver failure

    • Refers to acute deterioration in liver function and associated failure of other organs in a person with preexisting chronic liver disease

    • Often precipitated by bacterial infection or an alcohol binge and alcohol-associated hepatitis

  • Acetaminophen toxicity accounts for 45% of cases; idiosyncratic drug reactions are second most common

  • Among cases caused by acetaminophen

    • 44% are due to suicide attempts

    • 48% are due to unintentional overdose (the threshold for liver failure is lowered by chronic alcohol use or fasting and have been reported after weight loss surgery)

  • The risk of acute liver failure is increased in patients with diabetes mellitus, and outcome is worsened by obesity

  • Viral hepatitis accounts for only 12% of all cases of acute liver failure, due in part to universal vaccination of infants and children against hepatitis B and the availability of the hepatitis A vaccine

  • 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

Etiology

  • Acetaminophen toxicity

  • Idiosyncratic drug reactions (eg, antibiotics, antituberculosis drugs, antiepileptics, and a marked increase in cases due to herbal and dietary supplements since 1995)

  • Mushroom poisoning (Amatoxins)

  • Viruses (hepatitis A, B, C, D, E, CMV, EBV, HSV, parvovirus B19, influenza virus, yellow fever virus, Middle East respiratory syndrome virus, Ebola virus, SARS coronavirus)

  • Shock

  • Heat stroke

  • Budd-Chiari syndrome

  • Malignancy (especially lymphomas)

  • Wilson disease

  • Reye syndrome

  • Fatty liver of pregnancy and other disorders of fatty acid oxidation

  • Autoimmune hepatitis

  • Grand mal seizures (rarely)

  • Cause is indeterminate in approximately 5.5% of cases

Demographics

  • An estimated 1600 cases of acute liver failure occur each year in the United States

  • In endemic areas, hepatitis E is an important cause of acute liver failure, particularly in pregnant women

CLINICAL FINDINGS

Symptoms and Signs

  • Gastrointestinal symptoms (nausea, vomiting, anorexia)

  • Jaundice may be absent or minimal early

  • Systemic inflammatory response

  • Acute kidney injury

  • Clinically significant bleeding is uncommon and reflects severe systemic inflammation rather than coagulopathy

  • Severity of extrahepatic organ dysfunction (as assessed by the Sequential Organ Failure Assessment [SOFA]) correlates ...

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