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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. Clin Liver Dis. 2003;7:331.  [PubMed: 12879987]

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