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    Hepatic Encephalopathy – Diagnosis & Management


    Last Updated Feb 17, 2022
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    By Julian Marsden, Aaron Chan


    • Hepatic Encephalopathy (HE) defined as disturbances of brain function resulting from (1) advanced liver disease and/or (2) portosystemic shunting.
    • Patients with cirrhosis have 30-40% chance of experiencing HC at some time during their clinical course and it is associated with poor prognosis and high risk of recurrence.
    • We will focus on HE in the context of chronic liver disease which is the vast majority of cases.
      • Less common scenario is HE due to acute liver failure.

    Clinical Presenation

    • Tends to cause a more hypoactive delirium along a wide spectrum ranging from subtle alterations in level of consciousness to frank coma.
    • Hallmark sign on clinical examination is asterixis or “flapping tremor” although it is not specific to hepatic encephalopathy and may disappear in more severe forms of HE.

    Diagnostic Process

    • Should suspect HE in any patients with cirrhosis or possible liver disease who present with cognitive dysfunction.
    • It is a clinical diagnosis not always seen in isolation and clinicians should consider a broad, overlapping differential including subdural hematoma, hypoglycemia, hyponatremia, drug-induced, uremic encephalopathy, CNS infection and Wernicke’s encephalopathy.
    • Presence of precipitating factors that would support diagnosis of HE includes bacterial infections, GI bleed, constipation, renal failure, and electrolyte abnormalities.
    • Initial investigations should include fingerstick glucose, basic labwork including extended electrolytes and liver enzymes, CXR, urinalysis and blood cultures as indicated.
      • Diagnostic paracentesis should be performed in all patients with ascites.
      • Low threshold to perform non-contrast CT head.


    • Serum ammonia levels rarely change management and are not universally available
    • Isolated finding of elevated serum ammonia is not sufficient to diagnose and treat HE, especially if other causes of cognitive dysfunction have not been excluded
    • Serial ammonia levels may be more useful in testing efficacy of ammonia-lowering therapies


    • Severity grading criteria for HE
      • Grade I: Trivial lack of awareness
      • Grade II: Disorientation to time, asterixis, lethargy
      • Grade III: Gross disorientation, stupor
      • Grade IV: Coma


    • All patients with HE should be started on serum ammonia-lowering therapies:
      • Lactulose 25-30ml q1-2h until frequent BM, then down-titrate to target 2-3 daily bowel movements.
      • If Lactulose has proven ineffective within 48h, consulting services may add Rifaximin 550mg PO bid or PEG.
    • Initiate thiamine therapy with initial dosing regimen 100-200mg IV q8h.
      • Consider high-dose (500mg IV q8h) if concerned about Wernicke’s encephalopathy.
    • Correcting precipitating factors (i.e., antimicrobial therapy, correcting electrolyte abnormalities, treating GIB or AKI, thiamine replacement) will resolve symptoms of HE in 90% of patients.
    • (Grade I) Select patients may be managed as outpatient or but most require ward admission with frequent neurological assessments.
    • (Grade II) These patients will require hospital admission and have high likelihood to progressing to Grade III/IV HE.
    • (Grade III/IV) These patients will require airway management and urgent consultation with intensivist for high priority transfer to critical care center.

    Quality Of Evidence?


    • Benefit of lactulose in hepatic encephalopathy: MODERATE. Weak beneficial effect seen in several low-quality trials.
    • Rifaximin in hepatic encephalopathy: HIGH. Mortality benefit in treatment of overt HE in combination with lactulose and efficacy in secondary prevention with rifaximin alone in multiple RCTs.

    Related Information


    Related Information

    Reference List

      • Ong JP, Aggarwal A, Krieger D, et al. Correlation between ammonia levels and the severity of hepatic encephalopathy. Am J Med 2003; 114:188.

      • Als-Nielsen B, Gluud OL, Gluud C. Non-absorbable disaccharides for hepatic encephalopathy: systematic review of randomized trials. BMJ 2004;328:1046.

      • Kimer N, Krag A, Moller S, et al. Systematic review with meta-analysis: the effects of rifaximin in hepatic encephalopathy. Aliment Pharmacol Ther 2014;40:123.

      • Vilstrup H, Amodio P, Bajaj J, et al. Hepatic encephalopathy in chronic liver disease: 2014 Practice Guideline by the American Association of the Study of Liver Diseases and the European Association for the Study of the Liver. Hepatology 2014;60:715.


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