Hepatic Failure, Acute

• • 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)

    -Varicella

    -Herpesvirus

    -Toxins (acetaminophen, isoniazid most common)

    -Ischemia

    -Fatty liver of pregnancy

    -Reye syndrome

    -Wilson disease

    -Lymphoma

    -Hereditary metabolic disorders

Epidemiology

• • 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

Surgery

• • Liver transplantation

  • Ventriculostomy for grade IV encephalopathy

Indications

• • Fulminant or subfulminant failure unresponsive to medical management

Contraindications

• • Medical comorbidities precluding transplantation, active malignancy

Medications

• • 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

Complications

• • Primary nonfunction

  • Rejection

  • Biliary leak or stricture

  • hemorrhage

  • Hepatic artery thrombosis

Prognosis

• • 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

References