Hepatic Encephalopathy

What is Encephalopathy?
Encephalopathy is a change in your mental condition almost always when cirrhosis is present, in
which toxins that normally circulate in the bloodstream are not cleared properly by the liver and
result in altered brain function. Encephalopathy can cause day night sleep reversal, poor
memory, mood changes, trouble with fine muscle movements, and trouble driving. Your doctor
may tell you to stop driving and may notify the DMV if needed.
Note: Worsening signs of encephalopathy include severe confusion, hand flapping,
disorientation, day night sleep disorders/reversal, poor handwriting, poor memory, mood
swings, drowsiness, and coma. Please seek immediate medical attention with your provider
or in your local Emergency Room if these symptoms occur.
What are the Tests for Encephalopathy?
The best test for encephalopathy is a mental and physical exam. Your doctor asks you about your
sleep habits and memory. There are many toxins involved, but the most commonly measured
blood test to evaluate encephalopathy is ammonia.
The best test for liver or hepatic encephalopathy is a thorough physical, mental and neurological
exam.

Blood tests for ammonia are rarely done:

The level of ammonia, which increases in some patients with encephalopathy is an

extrodinarily inaccurate test due to issues with strict requirements for best methods to
draw blood and also processing to the blood specimen.

Experts in the area of HE, do not test ammonia blood levels

The level of zinc, which is low in some patients with encephalopathy may need
replacement. Discuss this option with your provider.

What are the Treatments for Encephalopathy?

Recommendations for Your Diet:

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There is currently no restriction on eating meat. Due to potential risks, if there is a

fragile patient, your practitioner may ask you to decrease your red meat
consumption.

Eat 80 to 100 grams of protein a day. Sources of protein include soy beans, tofu,
beans, legumes, and fish. Diets too low in protein (40 60 grams/day) are dangerous
because they can decrease muscle mass.

What are the Treatments for Encephalopathy? (continued)

Medications
Rifaximin is the first line therapy for HE
Background
Rifaximin (Xifaxan) is an oral rifamycin based antibiotic structurally related to rifampin. Its
spectrum of anti-bacterial activity encompasses various gram-positive and gram-negative
aerobes and anaerobes. Rifaximin has virtually no systemic bioavailability (<3%) after
oral administration, and has been FDA approved for treatment of traveler's diarrhea since
2004. However, rifaximin (dosed 400 mg tid), was also extensively used off label to
reduce the risk for overt hepatic encephalopathy
In 2010, a modified regimen of rifaximin (dosed 550 mg bid) received FDA approval for
reducing the risk of overt hepatic encephalopathy.
Assessment
Adhering to the FDA approved dosing regimen of 550 mg bid has the following advantages:
1.
Rifaximin 550 mg 1 tab bid is FDA approved regimen
2.
Rifaximin 550 mg 1 tab bid takes up less nursing time to administer (1 tablet bid than 2
tablets tid)
Recommendation
Rifaximin 550 mg bid is a preferred regimen for reducing the risk of hepatic encephalopathy
or active treatment of HE.
PEG or Miralax is the co-first line therapy to maintain 1-2 BM per day in patients, do
not use if patient has diarrhea.
Cholac, Constilac, Constulose, Cephulac (Lactulose) is the former or old co-first line
therapy and is used less and less due to many side effects and noncompliance
Lactulose is a non-absorbable sugar that changes the acidity of the colon and decreases the
amount of ammonia as well as other toxins in the blood. This medication causes loose bowel
movements or diarrhea. Lactulose is works best if the patient has at least two to four bowel
movements each day. If the patient has more than four bowel movements, he or she can
decrease the lactulose dose by one-third. The patient should make dose adjustments at home.
If diarrhea continues, even after lactulose is stopped, an evaluation for yeast in the colon
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should take place as well as more frequent electrolyte testing. If you are having diarrhea, tell
your provider and ask that he/she prescribe Rifaximin alone or with one of the alternatives
below

Probiotics
Dose is 4 capsules per day of VSL# 3; total 450 billion CFU/day
Probiotics could emerge as a treatment plan to manage hepatic encephalopathy (HE)
therapy after a new study[1] announced at the International Liver Congress 2013 found
they significantly reduced development of the notoriously difficult-to-treat disease.
The study analysed the efficacy of probiotics in preventing the development of HE in 160
cirrhotic patients over a period of approximately nine months and found significant
improvements in reducing patients arterial ammonia levels after three months of
treatment with probiotics.
Ammonia, produced by gut bacteria, is thought to be one of the main mediators of
cerebral dysfunction in HE. Probiotics work by enriching the gut flora with a non-urease
producing microorganisms, which decrease ammonia production.[2] Probiotics are live
microorganisms (mostly bacteria) that produce a health benefit on the host when
administered in adequate amounts.[3]
Twice as many patients taking a placebo developed overt HE (the studys primary
endpoint) compared to patients taking probiotics in the form of a capsule.
EASLs Treasurer, Prof. Mauro Bernardi welcomed the findings and said they would
provide a positive impact for cirrhotic patients at risk of developing HE for whom the
prognosis is typically very poor.
Prof. Bernardi said: Hepatic encephalopathy is an insidious disease thats caused by an
accumulation of toxins in the blood that are normally removed by the liver. Treatment
normally involves the use of antibiotics or laxatives to suppress the production of toxic
substances in the intestine but there is still a great deal of room for improvement so it will
be exciting to see the results of further studies to determine if clinicians have a new form
of treatment on the cards.
Hepatic encephalopathy is a spectrum of neuropsychiatric abnormalities including
personality changes, intellectual impairment and reduced levels of consciousness in
patients with liver failure, after exclusion of other known brain disease.
[1] M.K Lunia, AN OPEN LABEL RANDOMISED CONTROLLED TRIAL OF PROBIOTICS
FOR PRIMARY PROPHYLAXIS OF HEPATIC ENCEPHALOPATHY IN PATIENTS
WITH CIRRHOSIS. Presented at the International Liver CongressTM 2013.
[2] A. Agrawal, Secondary Prophylaxis of Hepatic Encephalopathy in Cirrhosis, An Open-Label,
Randomized Controlled Trial of Lactulose, Probiotics, and No Therapy. Available
http://www.medscape.com/viewarticle/767674_3 [Accessed 9/4/13].
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[3] World Health Organization and Food and Agriculture Organizationof the United
Nations. Health and Nutritional Properties of Probiotics in Food including Powder
Milk with Live Lactic Acid Bacteria.
Avahttp://www.who.int/foodsafety/publications/fs_management/en/probiotics.pdf
[Accessed 9/4/13].
Reference EASL Website: 2014

Flagyl (Metronidazole)
Metronidazole is an oral antibiotic that changes the colonic and intestinal bacteria and may
have a favorable effect on patients with chronic encephalopathy. Side effects include an
"antabuse" reaction (do not drink alcohol or use medications that contain alcohol with this
medication) and nervous system reactions including confusion, loss of taste or metal taste
and nerve tingling.
Zinc
A deficiency of zinc worsens the amount of encephalopathy a patient may be having with
liver failure or cirrhosis. Zinc supplements are available through pharmacies or health food
stores. Patients with zinc deficiencies should take between 50 to 200 mg per day.
Ucephan (Sodium Benzoate and Sodium Phenylacetate)
An alternative therapy for encephalopathy is sodium benzoate powder and sodium
phenylacetate tablets or powder. Sodium benzoate and sodium phenylacetate absorb
ammonia in the intestinal tract and enable excretion in bowel movements. They also increase
the activity of the urea cycle, which binds ammonia in the liver, allowing increase removal of
ammonia from the blood in the liver. The usual dose of sodium benzoate is 2 to 5 gm by
mouth each day and sodium phenylacetate is dosed at 2 grams to 10 grams per day
L-carnitine
L-carnitine improved hepatic encephalopathy symptoms in several small studies of patients with
cirrhosis. Whether the medication works by improving blood ammonia levels or whether it
works centrally perhaps by decreasing brain ammonia uptake remains unclear.
.
Neo-Fradin, Neo-Rx (Neomycin) SHOULD NEVER BE USED
Neomycin is an antibiotic that changes the chemistry and bacteria in the intestine and
decreases the amount of ammonia and other toxins released into the blood. This medication
is usually given at a dose of 500 mg four times a day. If this medication is prescribed for
more than six months, hearing tests should be performed since there may be a risk of hearing
loss. Hearing tests are critical if a patient is using Lasix (Furosemide) along with Neomycin.

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