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Hepatic Encephalopathy (HE)                 SX  |  DX  |  RX                                                                                  

Hepatic encephalopathy is a complex neuropsychiatric disorder that complicates acute and chronic liver failure.   HE is a potentially reversible metabolic disorder of the brain in the milieu of hepatic failure.  Patients with chronic liver disease develop a more indolent encephalopathy, called portosystemic encephalopathy (PSE).

SX of encephalopathy:
may begin with mild confusion, irrational behavior, euphoria, or psychosis. It is usually associated with a widely fluctuating but progressive deterioration of the mental state. Stupor & coma may develop rapidly within several days of onset of symptoms.

DX of hepatic encephalopathy:
The diagnosis of hepatic encephalopathy is clinical and depends on documentation of the presence of mental status changes, fetor hepaticus (feculent-fruity odor of the breath), and asterixis (flapping motion of the hands caused by intermittent loss of extensor tone) in a patient with parenchymal liver disease with abnormal liver enzymes & elevated ammonia levels.

Stages of overt hepatic encephalopathy:

  1. Patients exhibit inappropriate behavior, altered sleep pattern, loss of affect, depression, or euphoria. There is usually asterixis and difficulty with writing and other fine motor skills.
  2. Patients are moderately obtunded, confused, and disoriented. There is accompanying fetor hepaticus and asterixis.
  3. Patients are stuporous with marked confusion. They are barely responsive to painful stimuli. If it can be elicited, asterixis should be present. There is usually hyperreflexia, clonus, rigidity of limbs, extensor response, grasping, and sucking responses.
  4. Patients are in deep coma, usually with no response to stimuli. Muscle tone may be totally absent, limbs flaccid, and reflexes depressed.

   

Laboratory abnormalities in hepatic encephalopathy:
Blood tests may show abnormal liver chemistry tests, increased blood ammonia level, respiratory alkalosis with central hyperventilation is usually present. The arterial ammonia level does not correlate linearly with the depth of the coma. However, serial measurements are helpful in following the course of the hepatic encephalopathy in individual patients. The spinal fluid glutamine is a more sensitive test than arterial ammonia and correlates closely with the depth of the coma.

The EEG shows characteristic slowing or flattening of the waves with 3 : 1 high-voltage waves. Focal abnormalities should not be present.

The visual evoked potential recording is a useful tool in the diagnosis of hepatic encephalopathy. It has been demonstrated that latency of the N3 component of the flash visual evoked response (VER) is useful for the diagnosis of preclinical PSE and the assessment of patients with clinically overt PSE. VER may replace the tedious psychometric testing of patients suspected to have preclinical PSE.

Pathogenesis of hepatic encephalopathy (HE):
It is unknown, perhaps multifactorial but associated with changes in "neurotoxic" substances as ammonia and short-chain fatty acid metabolism, , increased activity of the g-aminobutyric acid transmitter system, and the presence of benzodiazepine-like substances in the brain, and  "false neurotransmitters" as octopamine.  Other causes of coma, such as hypoglycemia, hypoperfusion, anoxia, electrolyte disturbances, and brain edema, may contribute to its pathogenesis.

Precipitating Factors:
In patients with compensated cirrhosis, encephalopathy may be precipitated by gastrointestinal bleeding, infection, hypokalemia, azotemia, excessive dietary protein, central nervous system depressants, (particularly opioids), constipation, and worsening liver disease.

   

Treatment of hepatic encephalopathy

The main points in the treatment of hepatic encephalopathy are

  1. Diet: Low protein (<40 gm/day) or amino acids diet (Hepatamine or Hepaticaid may be used as protein source or supplement), adequate calories (1800-2400/day) in the form of glucose or carbohydrates.
  2. Removal of any sedative drugs.
  3. Bowel cleansing:  a synthetic disaccharide lactulose 1-3 tbsp tid in a dose that produces two to three soft stools per day,  Lactitol (a new synthetic disaccharide) also is effective - not available yet in US.
    cleansing enemas    ,  cathartics as magnesium citrate, or evacuation by giving a balanced electrolyte solution (e.g., GoLYTELY or Colyte).
  4. Neomycin PO 2-6 gm/day or as a 1% enema if the patient has ileus.
    Metronidazole     PO 250 mg 2-4x/day, it may be preferred because of its lack of nephro- and ototoxicity.
    Vancomycin     has been shown to be effective in the management of resistant hepatic encephalopathy
    Neomycin & metronidazole combination may be even more efficacious in some instances.
    Neomycin & lactulose combination has been used when either agent was unsatisfactory.
  5. Benzodiazepine receptor antagonists such as flumazenil (Romazicon) - recent data indicate a dramatic rapid response.
  6. Zinc sulfate or acetate 600 mg/day  PO may be useful in some patients.
  7. Liver transplantation

Ref:
ACP Library on Disk 2- (c) 1997 - American College of Physicianss
Manual of Gastroenterology 1994 - Gregory Eastwoord & Canan Avunduk
Current Therapy in Adult Medicine 4th Ed, 1997 - Jerome Kassierer & Harry Greene II

         04102001

Hepatic encephalopathy (Review)
Souheil Abou-Assi, MD; Z. Reno Vlahcevic, MD*
VOL 109 / NO 2 / FEBRUARY 2001 / POSTGRADUATE MEDICINE

Bleeding esophageal varices (Review)
How to treat this dreaded complication of portal hypertension
Ahmed M. Hegab, MD; Velimir A. Luketic, MD
VOL 109 / NO 2 / FEBRUARY 2001 / POSTGRADUATE MEDICINE

Minimizing ascites
Complication of cirrhosis signals clinical deterioration
Nelson Garcia Jr, MD; Arun J. Sanyal, MBBS, MD
VOL 109 / NO 2 / FEBRUARY 2001 / POSTGRADUATE MEDICINE

Long-term management of cirrhosis
Appropriate supportive care is both critical and difficult
Adil Habib, MD; Wendy M. Bond, RN; Douglas M. Heuman, MD
VOL 109 / NO 3 / MARCH 2001 / POSTGRADUATE MEDICINE