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    Hepatic Encephalopathy – Diagnosis & Management

    Neurological

    Last Reviewed on Feb 17, 2022
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    By Julian Marsden,Aaron Chan

    Context

    • 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.

    OTHER INVESTIGATIONS

    • 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

    WESTHAVEN CLASSIFICATION

    • 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

    Management

    • 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?

    Justification

    • Benefit of lactulose in hepatic encephalopathy: MODERATE. Weak beneficial effect seen in several low-quality trials.
    Moderate
    • 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.
    Moderate

    Related Information

    OTHER RELEVANT 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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