• 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.

• 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.

• 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

• 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.

1. • Asterixis (video) https://www.youtube.com/watch?v=h5T8rWqLM-U
   • West Haven Criteria
   • https://www.mdcalc.com/hepatic-encephalopathy-grades-stages#use-cases
   • NU EM Blog: Hepatic Encephalopathy in the ED https://www.nuemblog.com/blog/hepatic-encephalopathy
   • Patient education: American Liver Foundation

   https://liverfoundation.org/wp-content/uploads/2019/11/Caring-for-a-Loved-One-With-Hepatic-Encephalopathy-HE-2013.pdf

   • AASLD: Practice guidelines for management of HE in context of acute liver failure

   https://www.aasld.org/publications/practice-guidelines

   
   

1. • Ong JP, Aggarwal A, Krieger D, et al. Correlation between ammonia levels and the severity of hepatic encephalopathy. Am J Med 2003; 114:188.
   
   
2. • Als-Nielsen B, Gluud OL, Gluud C. Non-absorbable disaccharides for hepatic encephalopathy: systematic review of randomized trials. BMJ 2004;328:1046.
   
   
3. • 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.
   
   
4. • 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.