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For further information, see CMDT Part 16-05: 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 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 infection or an alcohol binge and alcoholic 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)


  • Acetaminophen toxicity

  • Idiosyncratic drug reactions

  • 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


  • Most cases in the United States are caused by

    • Acetaminophen toxicity

    • Idiosyncratic drug reactions

    • Acute viral hepatitis, especially hepatitis B

    • Some cases are due to hepatitis A or unknown (non-ABCDE) viruses

  • 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; acute hepatitis A or B superimposed on chronic hepatitis C has a high risk of acute liver failure

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


Laboratory Tests

  • Severe hepatocellular damage (Table 16–3)

  • Coagulopathy

  • Elevated serum ammonia; correlates with development of encephalopathy and intracranial hypertension

  • In acetaminophen toxicity, serum aminotransferase elevations are often towering (> 5000 units/L)

  • Acetaminophen-protein adducts in serum and other biomarkers for early detection are under study

  • In acute liver failure due to microvesicular steatosis (eg, fatty liver disease of pregnancy), serum aminotransferase elevations may be modest (< 300 units/L)

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