Hepatic Encephalopathy

1. See Also
   1. Cirrhosis
2. Risk Factors: Precipitating Events
   1. Gastrointestinal Bleeding
      1. Blood loss of 100 ml absorbed as 14-20 g Protein
   2. Azotemia
   3. Constipation
   4. High protein dietary intake
   5. Hypokalemic acidosis
   6. CNS depressants (e.g. Benzodiazepines)
   7. Hypoxia
   8. Hypercarbia
   9. Sepsis
3. Pathophysiology
   1. Severe liver disease resulting in liver failure
   2. Inability to detoxify CNS toxins
      1. Ammonia
      2. Mercaptans
      3. Fatty Acids
      4. Gamma-aminobutyric acid (GABA)
4. Symptoms and Signs
   1. Mild Disease (insidious onset)
      1. Day-night reversal
      2. Somnolence
      3. Confusion
      4. Personality change
      5. Asterixis (Flapping Tremor)
   2. Severe Disease
      1. Stupor
      2. Coma
      3. Dementia
      4. Extrapyramidal signs
      5. Fetor hepaticus (Odor of breath from mercaptans)
5. Labs: Markers correlated with Hepatic Encephalopathy
   1. International Normalized Ratio (INR)
   2. Venous total ammonia
      1. Ong (2003) Am J Med 114:188-93
6. Evaluation: West Haven Criteria Grading System
   1. Grade 1
      1. Trivial lack of awareness
      2. Euphoria or anxiety
      3. Shortened attention span
      4. Impaired performance of addition or subtraction
   2. Grade 2
      1. Lethargy or apathy
      2. Minimal disorientation for time or place
      3. Subtle personality change
      4. Inappropriate behavior
   3. Grade 3
      1. Somnolence to semi-stupor
      2. Responsive to verbal stimuli
      3. Confusion
      4. Gross disorientation
   4. Grade 4
      1. Coma (unresponsive to verbal or noxious stimuli)
   5. References
      1. Ferenci (2002) Hepatology 335(3): 716-21
7. Diagnosis
   1. Electroencephalogram (EEG)
8. Management
   1. Initial Measures
      1. Avoid precipitating factors listed above
      2. Reduce blood ammonia
         1. Lactulose (key management)
            1. Dose: 30-45 ml syrup PO titrated to qid or
            2. Retention enema 300 ml until >1 stool/day
         2. Decrease protein intake
            1. Limit to 20-30 g/day
            2. Protein restriction may not be needed
               1. Cordoba (2004) J Hepatol 41:38-43
   2. Refractory cases
      1. Nasogastric lavage
      2. Neomycin 4-12 grams orally divided q6-8 hours
      3. Consider unproven or experimental methods
         1. IV branched chain amino acids
         2. Bromocriptine (may improve extrapyramidal symptoms)
         3. Flumazenil (may improve mental status)
         4. Lactilol (alternative to Lactulose)
9. References
   1. Abou-Assi (2001) Postgrad Med 109(2):52-65
   2. Biel (2001) Am J Gastroenterol 96:1968-76