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  • Symptoms may include nausea, vomiting, itching, fever.

  • Signs may include encephalopathy, ascites, scleral icterus/jaundice.

  • Though there are no strict diagnostic criteria, consider acute liver failure if all of these are present:

    • Hepatic failure within 8 weeks of onset of hepatic disease

    • Elevated serum AST, ALT, and/or bilirubin

    • Coagulopathy (PT >15, INR >1.5) does not correct with vitamin K

    • No prior history of chronic liver disease

    • Encephalopathy (confirmatory, not required)


  • Likelihood of various etiologies depends on age and geography

  • Causes can be classified into the following categories:

    • Infectious

    • Metabolic

    • Autoimmune

    • Toxin or drug mediated

    • Indeterminate

    • Other


  • Physical exam: look for jaundice, encephalopathy, Kayser-Fleischer rings.

  • History: ask about timing of symptom onset, family history, medications or recreational drugs, and fever.

  • Serum labs: coagulation factors, complete metabolic panel, amylase, lipase, complete blood count, acetaminophen level, ammonia, lactate

  • Secondary testing once diagnosis of acute liver failure is confirmed:

    • If cytopenia is present in two cell lines perform hemophagocytic lymphohistiocytosis (HLH) testing with ferritin, triglyceride, and fibrinogen.

    • If older than 5 years perform Wilson's disease testing with serum ceruloplasmin.

    • Viral hepatitis serology, viral PCR (herpes simplex virus [HSV], Epstein-Barr virus [EBV], cytomegalovirus [CMV], adenovirus, parvovirus, enterovirus)

    • Perform tests for specific genetic etiologies based on age of patient and newborn screening results.

  • Liver biopsy may be indicated if etiology remains unknown.


  • Acute liver failure may lead to rapid systemic decompensation, so PICU admission is often appropriate.

  • Frequently monitor for hyponatremia, hypoglycemia, hypokalemia, and hypophosphatemia.

  • Manage fluids to avoid fluid overload. Consider continuous renal replacement therapy early in the treatment course.

  • Routine monitoring of coagulation factors:

    • Give vitamin K one time to assess response in coagulopathy.

    • Empiric correction of coagulopathy with plasma infusion is not indicated, unless done prior to an invasive procedure.

  • Respiratory support: respiratory failure requiring mechanical ventilation is common due to fluid overload, pulmonary edema or hemorrhage, encephalopathy, or sepsis.

  • Frequently reassess the clinical exam, including assessment of encephalopathy staging. See Table 66-1.

  • Neurologic care in early stages of hepatic encephalopathy (grades 0–II):

    • Head of bed elevated 30 degrees

    • Oxygen saturation >96%

    • Temperature control to maintain normothermia

    • Maintain adequate blood pressures to ensure good cerebral perfusion pressure (CPP)

    • Target serum sodium 145 to 150 mEq/L and serum osmolarity 300 to 320 mOsm/L with hypertonic saline

    • Baseline EEG

    • Obtain baseline head imaging to evaluate for cerebral edema (MR ventricle with diffusion weighted imaging [DWI]).

  • Neurologic care when worsening clinical exam and/or hepatic encephalopathy grades III and IV:

    • Invasive intracranial pressure (ICP) monitoring can be considered, but there is risk of bleeding and lack of evidence it improves survival.

      • Mannitol and/or hypertonic saline may be used for acutely elevated ICP

      • CPP goal range 40 to 60 mmHg depending on age

    • Target PaCO2 35 to 40 mmHg using mechanical ventilation.

    • Active cooling to keep temperature <37.5°

  • Monitor ...

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