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  • • Acute hepatic injury causes sudden loss in hepatocytes due to toxins, ischemia, or inflammatory reaction to liver

    • Fulminant hepatic failure defined as onset of encephalopathy within 8 weeks (9-24 weeks for subfulminant) after onset of acute hepatocellular injury

    • Etiologies include:

    • -Hepatitis viruses

      -Cytomegalovirus (CMV)

      -Epstein-Barr virus (EBV)



      -Toxins (acetaminophen, isoniazid most common)


      -Fatty liver of pregnancy

      -Reye syndrome

      -Wilson disease


      -Hereditary metabolic disorders


  • • 2000 cases of fulminant or subfulminant hepatic failure annually in United States with 80% mortality

Symptoms and Signs

  • • Jaundice

    • Right upper quadrant pain

    • Bleeding

    • Encephalopathy

    • Hypotension

    • Sepsis

    • Renal failure

    • Uncal herniation

    • Corneal rings

Laboratory Findings

  • • Hyperbilirubinemia

    • Elevated transaminases

    • Prolonged prothrombin time (PT)

    • Elevated creatinine

Imaging Findings

  • • Head CT can show cerebral edema

  • • History of chronic liver disorder

    • Family history of liver failure (eg, Wilson disease)

    • Exposure to toxins or drugs

    • Rapidity of encephalopathy onset

  • • History and physical exam

    • Serum antibodies for hepatitis viruses, CMV, and EBV

    • Ceruloplasmin level (Wilson disease)

    • Head CT if grade IV encephalopathy present (coma)

    • Temperature

When to Admit

  • • Any patient with acute hepatic injury, ICU for fulminant cases

When to Refer

  • • Transplantation center whenever encephalopathy develops


  • • Liver transplantation

    • Ventriculostomy for grade IV encephalopathy


  • • Fulminant or subfulminant failure unresponsive to medical management


  • • Medical comorbidities precluding transplantation, active malignancy


  • • N-acetylcysteine

    • Minimizing hypoglycemia

    • Broad-spectrum antibiotics for any fever (avoid aminoglycosides)

    • Fresh frozen plasma for planned invasive interventions

    • Mannitol for elevated intracranial pressure

    • Vasopressor support for hypotension

    • Mechanical ventilation for grade IV encephalopathy

Treatment Monitoring

  • • Frequent neurologic exams and head CT scans when indicated

    • Liver function tests

    • PT


  • • Primary nonfunction

    • Rejection

    • Biliary leak or stricture

    • hemorrhage

    • Hepatic artery thrombosis


  • • 60-70% 5-year survival following liver transplant

    • All patients recover from acute illness in absence of encephalopathy

    • Greater than 50% recovery for patients with grade III encephalopathy

    • Overall survival correlated with grade of encephalopathy

    • Rapid onset associated with more favorable prognosis

    • Associated sepsis, acidosis, age < 2 or > 40 years, renal failure, PT > 50 all associated with worse prognosis


Schiodt FV, Lee WM. Fulminant liver disease. ...

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