Esophageal varices, ascites and edema, and encephalopathy are three complications of cirrhosis that can be managed medically. Physicians should screen for these in cirrhotic patients and institute appropriate therapy. This Viewpoint deals with management of esophageal varices. The next Viewpoint will focus on fluid overload (ascites and edema) and encephalopathy (the confusional state of liver disease)

Varices are large twisted blood vessels that develop in patients with cirrhosis. They are most commonly found in the esophagus (swallowing tube) but can also occur in the stomach. As excessive scar tissue is deposited in the liver, the resistance to blood flow increases with an accompanying increase in the pressure within the vein that feeds the liver (portal vein). As a result, small or previously insignificant blood vessels in the lining of the esophagus or the stomach become engorged and can ultimately burst and bleed.

Bleeding from varices is often massive. Patients often throw up blood, or pass blood from the rectum. The resultant low blood pressure can lead to decreased perfusion of vital organs resulting in complications such as loss of consciousness, heart attack and sometimes death. Because of a high mortality rate from an episode of variceal bleeding, it is recommended that physicians screen for the presence of esophageal varices in cirrhotic patients. An upper endoscopy (a procedure where a gastroeneterologist inserts a flexible tube with a camera into the stomach) is performed to visualize the number and size of the varices. If varices are present, patients are started on medication to decrease the pressure within the veins. Mutiple studies have shown that a decrease in the pressure of the veins reduces the risk of bleeding and saves lives. If these veins are absent, the procedure can be repeated in two years and medications started once the veins are noted.

This information was last reviewed 1/4/02.
Page Content Credits

Viewpoint is an editorial column that expresses the opinion of the specific Medical Director, who is solely responsible for its content.
Viewpoint does not represent the views or opinions of Veritas Medicine and does not reflect the opinions of other physicians and researchers If you have cirrhosis, or suspect that you have cirrhosis, of the liver due to HCV , hereditary hemochromatosis (or any other cause), you may have esophageal varices...75% of patients with cirrhosis of the liver, have these "varicose veins"of the esophagus. Knowing the warning signs of acute bleeding could save your life...

Confirmation of esophageal varices is made during an endoscopy (a tube with a light on the end of it put down your throat ( esophagus) and into your stomach) while the patient is sedated...the doctor can view the varices, their color, size, and predict their potential risk for a "first bleed" or acute bleeding episode based on the pressure in the veins, and other signs.

Warning signs include:

Nausea and vomiting blood (bright red blood or blood looking like "coffee grounds"
Pallor or pale appearance
Shock
Sudden drop in blood pressure
Black stool (usually means an upper GI bleed of some kind)

If you have these symptoms, GO TO AN EMERGENCY ROOM IMMEDIATELY!

Patients with known or suspected varices should:

Wear a medic alert bracelet which states on it "esophageal varices"
Know their blood type
Not strain at stool
Try to avoid violent coughing, vomiting, or sneezing
Avoid aspirin or NSAIDS
Avoid coarse or sharp foods
Take beta blockers if indicated prescribed by their doctors to keep their pulse slower than usual to reduce pressure in the varices

What can the patient with esophageal varices do to prevent a "first bleed"?

The patient needs to follow the suggestions above
Discuss medical options with his/her doctor such as:
medications to slow down the heart rate by 20 to 30%
Ligation (Banding) of varices
Chemical treatment of the varices to stop or prevent bleeding
Make sure that family members, friends, and physicians know that you have this condition

Web sites with further information, studies on esophageal varices, their treatment, etc. are plentiful
on the Internet

Encephalopathy (Hepatic or Portal-systemic)
Updated April 2000

WHAT IS HEPATIC or PORTAL-SYSTEMIC ENCEPHALOPATHY?
There are numerous types of Encephalopathy from a number of different
causes, but we will be focusing on Hepatic or Portal-systemic
Encephalopathy. Encephalopathy is a degenerative disease of the brain, and
refers to changes in the brain that can occur in some Hepatitis patients
with severe or advanced cirrhosis (it can occur in both acute and chronic
Hepatitis cases).

IT HELPS TO UNDERSTAND 4 FEATURES OF ENCEPHALOPATHY (as stated by Dr.
Gregory T. Everson, Director of Hepatology, University of Colorado Health
Sciences Center):
1 ~ Encephalopathy is usually brought on by some other problem, such as
gastrointestinal bleeding, infection or electrolyte imbalance);
2 ~ It's a completely reversible condition;
3 ~ Effective medical treatment exists and early therapy may prevent the
patient from lapsing into more advanced stages; and
4~ A successful liver transplant can completely reverse the condition.

Encephalopathy is caused by toxic waste compounds such as ammonia, certain
fatty acids or other by-products of protein digestion which are not cleared
by the liver from the bloodstream. This can happen once liver cells have
been damaged; liver function deteriorates, and these toxins cannot be
cleared from the blood as they would be with a healthy liver.
Encephalopathy can range from very slight (decline in memory or reduced
mental abilities and confusion) to moderate (loss of memory, disorientation,
change in sleep habits, untidiness, muscle tremors or blackout spells) to
severe (leading to a form of chronic dementia or even coma). It is very
important that this condition be properly diagnosed by your physician. It's
a common mistake for Hepatitis patients to mistakenly self-diagnose
Encephalopathy when what the patient is experiencing are much less severe
but similar symptoms occurring as a result or by-product of Chronic
Hepatitis (such as the typical "brain fog" so many experience in varying
degrees).

WHO GETS HEPATIC ENCEPHALOPATHY?
A patient with Chronic Hepatitis and advanced Cirrhosis, may; over time
develop Encephalopathy. It can range from barely discernible to very
severe, so no two cases are the same. The precise cause is unknown, but
it's clear that it correlates with worsening liver function in some
patients. Renal failure and constipation are suspect in causing the
condition to worsen. External stresses such as infections, irregularities
of salts or electrolytes in the blood, some medications, excessive protein
intake and the protein load caused by gastrointestinal bleeding may also
worsen encephalopathy.

Large amounts of protein in the diet can lead to the buildup of protein
breakdown products in the blood which are normally eliminated through the
liver. When we break down protein, one of the substances we make from it is
called ammonia. This ammonia can circulate in the blood, and as it passes
through the liver, the ammonia is converted to another breakdown product,
urea. While urea is usually gotten rid of in the urine, ammonia builds up
in the blood if the damaged liver is not able to properly convert it. Our
bodies require protein to properly function, so restriction and diet should
be a decision made between you, your doctor, and (when available) a
nutritionist.

Gastrointestinal bleeding is when an individual bleeds into the stomach, and
the blood is broken down as it passes through the intestines. Partially
digested proteins in the blood are reabsorbed into the circulation, placing
an increased load on the liver.

TREATMENT
The treatment of Hepatic Encephalopathy involves, first, the removal of all
drugs that require detoxification in the liver and, second, the reduction of
the intake of protein (as it tends to irritate the symptoms). Restricting
the amount of protein in the diet will generally lower the levels of amino
acids and ammonia in the bloodstream and brain. At the same time, it is
imperative that a Hepatitis patient with cirrhosis take in enough protein to
avoid excessive muscle wasting and energy depletion, so it is imperative to
seek early medical attention and follow up with your health care specialist.
Some physicians advise their patients with this condition to carefully
monitor and limit the amount of protein they consume each day, and recommend
the majority of this protein come from vegetables, milk and easily digested
non-meat proteins.

Your doctor should be aware of your symptoms, and how much they have changed
in a specific period of time. He may follow your progress with Trailmaking
tests (a series of connect-the-numbered dots), clinical tests and lab work,
as well as your observations.

Doctors will often prescribe lactulose; a non-absorbable sugar to loosen
stools which may improve mental function. Some antibiotics, such as
Neomycin or Metronidazole are also used (in part, to lower amino acid
production) with some success. Certain amino acids can be used in
treatment, since they are considered less likely to cause mental impairment.
A dietary supplement rich in these amino acids is used at many liver
transplant centers. It is very important that you are taking the correct
amino acids for your body ... so you should be a partner with your doctor
and/or nutritionist when such decisions are made about your health care and
maintenance.

Friday June 29 5:01 PM ET

Cirrhosis-Blood Pressure Link Studied
By RANDOLPH E. SCHMID, Associated Press Writer

WASHINGTON (AP) - Researchers have discovered what they believe is the cause of blood pressure problems in patients suffering cirrhosis, potentially a first step in slowing the disease.

In people suffering advanced cirrhosis, blood vessels become dilated, lowering blood pressure and increasing blood flow to the liver and gut. Due to liver scarring, this increased blood flow meets with resistance, resulting in elevated pressure where the vessels meet the liver.

That can cause fluid to accumulate in the abdomen and dilated blood vessels to rupture - both life-threatening complications.

In tests on animals, the research team, led by Dr. George Kunos of the National Institute of Alcoholism and Alcohol Abuse, found that substances normally present in the body, called endocannabinoids, act on the blood vessel walls to cause dilation.

The researchers found elevated levels of the endocannabinoid anandamide associated with low blood pressure in two separate animal studies of cirrhosis. Using a chemical that blocks the action of anandamide, they raised blood pressure and reduced the so-called portal pressure where the blood enters the liver.

In addition to finding higher levels of anandamide in the cirrhosis cases, they also discovered that the blood vessels of the victims had increased receptors to react to that chemical.

The finding may suggest an approach for therapy to assist patients while they await a liver transplant, the researchers suggest in their paper. The findings are reported in the July issue of the journal Nature Medicine.

Kunos was out of the country and could not be reached to discuss the work.

Dr. Bruce Bacon of the St. Louis University School of Medicine, who was not involved in the study, said the finding is ``a significant observation and an important one.''

But he cautioned, ``whether that will lead to therapeutic intervention (in people) is yet to be determined.''

Management of Bleeding in the Cirrhotic Patient

Important advances have been made in the management of variceal (enlarged veins or arteries) bleeding. Despite these advances, bleeding in the patient with cirrhosis (liver scarring) remains one of the most demanding clinical challenges that a gastroenterologist or gastrointestinal surgeon may face.

This article from the Journal of Gastroenterology and Hepatology addresses the management of bleeding in the patient with cirrhosis.

The aim of management is to identify the source of bleeding, control active bleeding, and prevent re-bleeding. This requires a multidisciplinary team, and the optimal management algorithm depends on the clinical circumstance of the patient and the local availability of endoscopic, radiological, and surgical expertise.

Injection sclerotherapy is effective in stopping acute variceal bleeding, but has the drawback of a high incidence of complications.

Endoscopic variceal ligation is just as effective, and is associated with fewer complications.

To prevent re-bleeding, beta-blockers are recommended for all patients with large varices (including those which have never bled).

Injection sclerotherapy or band ligation, conducted at weekly intervals after the initial control of bleeding, is equally effective at obliterating varices and decreasing the risk of further hemorrhage. Band ligation results in fewer complications.

Other newer treatment options for variceal bleeding, such as somatostatin analogs, transjugular intrahepatic portosystemic shunt and liver transplantation, offer more optimal approaches to control bleeding and prevent re-bleeding, but may be prohibitively expensive.

Even for the most affluent communities, affordability, cost-effectiveness, and resource rationing are important considerations in management of patients with cirrhosis complicated by gastrointestinal bleeding.

05/19/03

Source

S Chung. Journal of Gastroenterology and Hepatology 17(4): 355-360. April 2002.

Available from Blackwell Science. 54 University Street, Carlton South 3053, Victoria, Australia. +61393470300. Fax +61393475001. E-mail: Rob.Turner@blacksci-asia.com.au. Website: www.blackwell-science.com.

Salty Issues

Author: Contributing Editor Heidi Gennaro, RD
Author Date: 10/10/2001

Reducing Salt for Edema, Advanced Cirrhosis or Ascites

You have just returned from your doctor visit with a frown and a prescription note in your hand that reads, "make an appointment with the dietitian regarding a low sodium diet", or maybe a "2 gram sodium, fluid restricted diet" or even worse a "no-salt diet."

Oh My! You have visions of dull-tasting food and constant deprivation. Maybe you're a "pour salt on everything" type, or maybe you like "just a little" salt on certain foods. In either case, you're worried that this will be a tough road to take.

Why Do I Have to Watch My Sodium Intake?

If you have edema, advanced cirrhosis or ascites you need to know the answer to this question...

Limiting sodium intake to around 2000 milligrams (2 Grams)per day is important to any person who has a disease that affects their heart. Why? Sodium retains water in your body. Think about a sponge...and how much water it can hold. Sodium acts the same way in your body. It holds on to the water you have in your system.

If you have pulmonary hypertension, part of the challenge in managing your disease is to minimize the "fluid load" on your heart. Taking your "doctor prescribed" medications, which often include a diuretic, and limiting the amount of sodium in your diet, will help to decrease the amount of fluid in the body. Therefore, the stress on your heart will be lessened.

Limiting salt at the table or in cooking is your first step to controlling the amount of fluid you retain in your body. And looking carefully for the amount of sodium in pre-packaged and commercial foods is your second step. If you haven't already, begin learning the art of 'label reading'. You would be surprised at how much sodium may be in some of your favorite commercial foods!

Be cautious about using products containing "salt, soda, sodium, monosodium glutamate, bisodium phosphate, baking powder, baking soda, or any other ingredients that contain the word sodium".The bottom line is how much TOTAL SODIUM per serving the product contains. Ask yourself: will this work in a 2000 milligram sodium food plan?

Also be careful of certain medicines that may contain substantial amounts of sodium such as certain cough medicines, stomach antacids, and laxatives, for example. It is also a good idea to contact your city water municipality to find out the sodium content in your drinking water, or having your well water tested for sodium by a qualified laboratory.

Low Sodium Dining: Some Practical Tips

Tips to consume less salt and sodium:

Shop around and choose grocery stores that offer more choices of lower-sodium foods. Or ask your local grocer or supermarket to offer more low-sodium foods.

When selecting canned foods, select those prepared with reduced or no sodium.

Remember that fresh fish, poultry, and meat are lower in sodium than most canned and processed ones.

Remember that many frozen dinners, packaged mixes, canned soups, and salad dressings contain a considerable amount of sodium.

Remember that condiments such as soy and many other sauces, pickles, and olives are high in sodium. Ketchup and mustard, when eaten in large amounts, can also contribute significant amounts of sodium to the diet. Choose lower sodium varieties.

Choose fresh fruits and vegetables as a lower sodium alternative to salted snack foods.

Throw away your saltshaker! If you salt foods in cooking or at the table, add small amounts. Salt added to food in cooking or at the table accounts for 1/3 of all the sodium we eat. Yes, you can do it!

Ignore your "salt tooth"...Of course you can learn to prefer low-sodium food... just by eating it. Within 2 months, your tastes should adjust, and you won't miss the salt. Try it!!

Experiment with salt-free seasonings. Try lemon juice, pepper, onion, parsley, oregano on some of those foods that you usually salt. Learn to use spices and herbs, rather than salt, to enhance the flavor of food.

Consult with your doctor before trying a salt substitute. Many brands contain potassium instead of sodium and may interact with some of your medications.

Make food from scratch!! This way you can control the amount of salt that goes into it.

Choose fresh fruits and veggies. When planning meals, consider that fresh and most plain frozen vegetables are low in sodium. Be radical: go for five servings a day!

Invest in a low-sodium cookbook. There are a whole new variety of foods and recipes waiting to be tested! Don't want to BUY a cookbook---then check one out at your local library.

Request less salt in your meals when eating out or traveling.If you dine out often, ask the staff person if the nutritional information is available on the dish or take-out fare that you are considering. If not, choose wisely and then ask that they not ADD any additional salt.

Read the Nutrition Facts Label to determine the amount of sodium in the foods you purchase. The sodium content of processed foods -- such as cereals, breads, soups, and salad dressings -- often varies widely. Get smart with common label terms:

'Sodium free' - less than 5mg of sodium per serving
'Very low sodium' - 35mg or less per serving
'Low sodium' - 140mg or less per serving

Small esophageal varices in cirrhotic patients

SourceURL:http://www.gastrohep.com/news/news.asp?id=1868

Endoscopy surveillance should be planned taking into account cause and
degree of liver dysfunction, find researchers in the latest issue of the
Journal of Hepatology.

In this study, researchers from Italy prospectively evaluated 206
cirrhotics during a mean follow up of 37 months. Of these patients, 113
were without varices and 93 with small EV.

Patients with previous gastrointestinal bleeding or receiving any treatment
for portal hypertension were excluded.

Endoscopy was performed every 12 months.

The research team found that the incidence of EV was 5% at 1 year and 28%
at 3 years.

In addition, the rate of EV progression was 12% at 1 year and 31% at 3 years.

The team identified post-alcoholic origin of cirrhosis, Child-Pugh's class
B or C, and the finding of red wale marks at first examination, as
predictors for the variceal progression.

The 2-years risk of bleeding from EV was higher in patients with small
varices upon enrolment than in those without varices, 12% versus 2%,
respectively.

Predictor for bleeding was the presence of red wale marks at first endoscopy.

In addition, predictor for bleeding was the presence of red wale marks at
first endoscopy.

Dr Manuela Merli's team concluded, "In patients with no or small EV,
endoscopy surveillance should be planned taking into account cause and
degree of liver dysfunction".

In a related editorial in the same publication, Dr Roberto de Franchis
discusses the evaluation and follow-up of patients with cirrhosis and
esophageal varices.

Dr de Franchis considers the results of several studies concerning the
timing of follow-up endoscopies.

Concluding that, "It appears reasonable to maintain the recommended
interval of 1 to 2 years, adopting a shorter interval for patients with
alcoholic cirrhosis".

J Hepatology 2003; 38(3): 266-72
24 February 2003

Cirrhosis and Bleeding: The Need for Very Early Management

Retrospective studies suggest that the prognosis of patients with cirrhosis and variceal hemorrhage has improved in more recent decades.

In a prospective cohort study in which the choice of prophylactic therapy was left to each practitioner, French researchers followed cirrhotic patients with medium/large varices to determine factors predictive of bleeding and death.

Three hundred fourteen patients with grades 2 or 3 esophageal varices (Child A and B/C: 218 and 96) were enrolled at multiple medical centers.

One hundred seventy-three patients had no previous history of variceal bleeding. Only 245 patients (100% of patients with prior variceal hemorrhage, 61% of patients without prior hemorrhage) were receiving some form of prophylactic therapy. The median follow-up was 18 months.

There were 76 bleeding events and 14 related deaths (18%); nine of these deaths occurred within 24 h of bleeding onset (two at home, two during hospital transfer, and five in hospital, a mean of 2.5 h after onset; six involved Child C patients).

Twenty-five deaths were not due to bleeding but were closely related to cirrhosis. In a Cox model, the presence of tense ascites) and a prior history of hemorrhage were independent predictors of variceal hemorrhage.

In patients without a prior history of bleeding, bleeding risk was higher with more prolonged prothrombin time and lower when patients were receiving propranolol.

The authors conclude, “Despite the advent of effective drugs and endoscopic therapy for variceal bleeding, about a quarter of deaths occur very early after bleeding onset, confirming the need for rapid specific management.”

10/22/03

Reference
D Nidegger and others. Cirrhosis and bleeding: the need for very early management. Journal of Hepatology 39(4): 509-514. October 2003.

American Journal of Medicine February 15, 2003

Do Ammonia Levels Correlate with Hepatic Encephalopathy?

Hepatic encephalopathy in patients with chronic liver dysfunction is believed to be caused by a failure of the liver to clear toxic products from the stomach. The exact toxins that cause hepatic encephalopathy have not been established, but ammonia may be involved.

Many physicians determine ammonia levels to diagnose hepatic encephalopathy and as a guide to treatment. However, studies have shown that the correlation between serum ammonia levels and severity of hepatic encephalopathy is inconsistent.

A recent study suggested that the partial pressure of ammonia may correlate more closely with the severity of hepatic encephalopathy than the total plasma ammonia level.

Ong and associates evaluated the correlation between plasma ammonia levels and the severity of hepatic encephalopathy. They also determined the best of the four types of ammonia measurements for this correlation by comparing arterial total ammonia, venous total ammonia, arterial partial pressure of ammonia, and venous partial pressure of ammonia.

Consecutive patients who were admitted to a tertiary care center with the diagnosis of cirrhosis between September 1998 and December 1999 were enrolled in the study. The diagnosis of cirrhosis was established by biopsy or by signs of portal hypertension such as gastroesophageal varices, previous variceal bleeding, or ascites. Researchers collected clinical and laboratory data at the time of admission. The mental status of the patients was assessed using the West Haven Criteria for grading of mental status. A diagnosis of hepatic encephalopathy was established when the patients' mental status was altered and other causes of mental status changes had been excluded. After diagnosis, fasting arterial and venous blood samples were obtained, and total ammonia and partial pressure of ammonia were determined.

The 121 patients who were enrolled in the study had the following West Haven Criteria grades: 30 patients (25 percent) had grade zero encephalopathy; 27 patients (22 percent) had grade 1; 23 patients (19 percent) had grade 2; 28 patients (23 percent) had grade 3; and 13 patients (11 percent) had grade 4. All four measurements of ammonia increased with the severity of hepatic encephalopathy. The arterial total ammonia level had the highest correlation, but it was not statistically significant. Other variables that had a correlation to the severity of hepatic encephalopathy included International Normalized Ratio (INR) values, serum creatinine levels, bilirubin levels, and lactulose use. A multivariable ordered logistic regression analysis revealed that only serum ammonia levels and INR values were independently associated with the severity of hepatic encephalopathy.

The authors conclude that venous total ammonia levels do correlate with severity of hepatic encephalopathy and should be adequate in evaluating patients with this condition. Total arterial ammonia levels and partial pressure of ammonia levels had similar correlation but did not prove to be better markers than venous total ammonia levels.

KARL E. MILLER, M.D.

Ong JP, et al. Correlation between ammonia levels and the severity of hepatic encephalopathy. Am J Med February 15, 2003;114:188-93.

http://www.aafp.org/afp/20031001/tips/8.html

Hepatogastroenterology. 2004 Mar-Apr;51(56):541-6.

Antibiotic prophylaxis after variceal hemorrhage reduces incidence of early
rebleeding.

Pohl J, Pollmann K, Sauer P, Ring A, Stremmel W, Schlenker T.

Department of Internal Medicine IV, Ruprechts-Karls-University, Heidelberg,
Germany. juergen_pohl@med.uni-heidelberg.de

BACKGROUND/AIMS: This study aims to evaluate the role of new onset infection
in the initiation of early rebleeding after variceal hemorrhage in patients
with liver cirrhosis and the effect of prophylactic antibiotic treatment.
METHODOLOGY: Two hundred and twenty-one consecutive admissions for variceal
bleeding with no signs of infection at the time of admission were evaluated
retrospectively. RESULTS: Systemic antibiotic prophylaxis was administered
in 126 cases and significantly reduced the overall incidence of new onset
infections (19.8% vs. 34.71%; p<0.01) and of early rebleeding (17.5% vs.
32.6%; p<0.01). Multivariate analysis showed strong correlation of
rebleeding with new onset infection (p<0.001) and lack of prophylactic
antibiotic treatment (p<0.05). Child-Pugh C cirrhosis, ventilatory
assistance, and balloon tamponade were independent predictors of new onset
infection (p<0.001, respectively). In the subgroup of patients with at least
one predictor prophylactic treatment nearly halved the incidence of
infections and rebleedings while in patients without predictors it had no
significant effect. CONCLUSIONS: For the first time our data indicate a role
for new onset infections in initiating early rebleedings. Immediate
prophylactic antibiotic treatment for patients at high risk of infection
might be effective in lowering both, the risk of acquiring infections and
early rebleeding.

PMID: 15086198 [PubMed - indexed for MEDLINE]

Normal protein diet for episodic hepatic encephalopathy

Restricting the protein content of diets fed to cirrhotic patients during episodes of encephalopathy has no beneficial effect, suggests a study in the latest issue of the Journal of Hepatology.

Protein-restricted diets are often prescribed for cirrhotic patients with hepatic encephalopathy. Yet protein restriction may lead to a worsening of nutritional status, without leading to any improvement of hepatic encephalopathy.

Juan Córdoba and fellow researchers from Barcelona, Spain, have therefore conducted a study to assess the effects of the amount of protein in the diet on the evolution of episodic hepatic encephalopathy.

They studied 30 cirrhotic patients admitted to hospital due to an episode of encephalopathy. The patients were randomized to receive either a low-protein diet with progressive increments or a normal diet for 14 days, in addition to standard measures to treat hepatic encephalopathy.

Protein synthesis and breakdown were then studied at day 2 and day 13 with the glycine-N¹⁵ infusion method.

Using this technique the researchers found there was no significant difference in the outcome of hepatic encephalopathy between the two treatment groups.

Although protein breakdown was greater in those patients receiving the low-protein diet, both groups showed similar levels of protein synthesis, regardless of whether they were fed a low or a normal protein diet.

The researchers conclude that diets with a normal content of protein, which are metabolically more adequate, can be safely administered to cirrhotic patients with episodic hepatic encephalopathy.

They add that restriction of the content of protein of the diet does not appear to have any beneficial effect for cirrhotic patients during an episode of encephalopathy.

J Hepatol 2004; 41 (1): 38 - 43
14 July 2004

First Principles of Gastroenterology
GI Textbook
Hepatic Encephalopathy

Hepatic encephalopathy (HE) is a complex, potentially reversible neuropsychiatric condition that occurs as a consequence of acute or chronic liver disease.
It is characterized by changes of personality, consciousness, behavior and neuromuscular function (see below).

Early features include reversal of sleep pattern, apathy, hypersomnia, irritability and personal neglect. In later stages, delirium and coma may occur.

Neurologic signs may include hyperreflexia, rigidity, myoclonus and asterixis. Asterixis is not specific to hepatic encephalopathy and may be present in other causes of metabolic encephalopathy. Seizures and lateralizing signs are uncommon and are more commonly seen in acute than chronic liver failure.

Clinically, a number of encephalopathic patterns can be observed: acute, acute recurrent, chronic recurrent and chronic permanent encephalopathy (the last often forms part of the spectrum of acquired hepatocerebral degeneration).

Grading of hepatic encephalopathy:

Grade: 1
Level of consciousness: Lack of awareness, Personality change, Day/night reversal
Intellectual function: Short attention
Neurological findings: Incoordination, Mild asterixis
EEG: Slowing (5-6 cps) Triphasic

Grade: 2
Level of consciousness: Lethargic, Inappropriate behavior
Intellectual function: Disoriented
Neurological findings: Asterixis, Abnormal reflexes
EEG: Slowing Triphasic

Grade: 3
Level of consciousness: Asleep, Rousable
Intellectual function: Loss of meaningful communication
Neurological findings: Asterixis, Abnormal reflex
EEG: Slowing Triphasic

Grade: 4
Level of consciousness: Unrousable
Intellectual function: Absent
Neurological findings: Decerebrate
EEG: Very slow (2-3 cps), delta

There is no specific biochemical test for hepatic encephalopathy.

Blood tests should help to rule out other causes of encephalopathy and detect precipitating factors such as hypoglycemia or electrolyte imbalance.
An elevated serum ammonia level is characteristic but not essential, and correlates poorly with the level of encephalopathy.

The cerebrospinal fluid is usually normal or may show increased protein with increased GABA levels.
Lumbar puncture and CT scan may be necessary to rule out other concomitant CNS pathology.

The EEG shows slow, triphasic wave activity found mainly over frontal areas, but this pattern is not specific.

Factors of importance in the pathogenesis of encephalopathy are the shunting of blood around the hepatocytes into the systemic circulation and the presence of hepatocellular dysfunction.
Encephalopathy probably results from one or more toxic products of gut origin that are usually metabolized by the liver entering this systemic circulation and reaching the brain.
Abnormalities of ammonia metabolism are most frequently implicated in the pathophysiology.

The normal gut flora produce a urease that enzymatically cleaves NH3 from protein in the lumen.
Nonionized ammonia is then absorbed into the portal circulation.
It reaches the systemic circulation because of shunts and the inability of the liver to metabolize the ammonia.

Other hypotheses relate to the findings of increased levels of short-chain fatty acids and increased levels of aromatic amino acids associated with the decreased levels of branched-chain amino acids.

As well, the principal neuro-inhibitory neurotransmitter g-aminobutyric acid (GABA) is increased in encephalopathy.
Other concepts include other false neurotransmitters, including an endogenous modulator of GABA receptors, suggesting involvement of the GABA-diazepam receptor complex in the pathogenesis of HE.

It is likely that hepatic encephalopathy results from the complicated interplay of many factors, not just one.

Hepatic encephalopathy may arise spontaneously but more commonly will develop as a result of some precipitating factor in the course of acute or chronic liver disease.
See Table below.

TABLE - Common precipitants of hepatic encephalopathy:

Increased nitrogen load:
- Gastrointestinal bleeding
- Excess dietary protein
- Azotemia
- Constipation
Electrolyte imbalance:
- Hyponatremia
- Hypokalemia
- Metabolic alkalosis/acidosis
- Hypoxia
- Hypovolemia
Drugs:
- Narcotics, tranquilizers, sedatives
Miscellaneous:
- Infection
- Surgery
- Superimposed acute liver disease
- Progressive liver disease
- Transjugular intrahepatic portal-systemic shunt (TIPS)

The most important aspect of management is prompt recognition and treatment of these precipitating factors.

Exogenous factors include increased dietary protein, administration of certain drugs (such as sedatives), gastrointestinal bleeding, azotemia, electrolyte imbalance from diuretic therapy, hypoxia and infection.
Also important is the necessity to provide meticulous care of the confused and often comatose patient.

Otherwise, the goal of therapy is to lower the level of toxic substances by reducing or excluding protein from the diet and by cleaning nitrogenous materials from the gut.
To this end, constipation is avoided by the use of laxatives and, in more urgent cases, cleansing of the gut with enemas or colonic lavage.

A commonly used laxative is "lactulose", a synthetic disaccharide that is degraded by intestinal bacteria to produce acidification and an osmotic diarrhea. The acidification of colonic contents reduces ammonia absorption in part by trapping nitrogenous compounds in the lumen.
The dosage of lactulose should be titrated to the patient to achieve two to four loose stools per day. The average daily dosages are 45-90 g.
Too much diarrhea can result in fluid and electrolyte depletion and can worsen HE and cause renal failure.
Its chronic use can reduce the frequency of episodes of encephalopathy.

Alternatively, antibiotics such as metronidazole may be used; these inhibit urea splitting and deaminating bacteria, reducing the production of ammonia and other potential toxins.
The previously commonly used antibiotic neomycin is no longer recommended as it has the potential for ototoxic and nephrotoxic side effects.

Other experimental therapeutic approaches exist, particularly when the encephalopathy becomes refractory.

On the basis of increased aromatic amino acids and decreased branched-chain amino acids found in encephalopathy (and the resulting effect on neurotransmitter synthesis), branched-chain amino acids given orally or intravenously have a potentially therapeutic role in improving encephalopathy.
Some of the new benzodiazepine-receptor antagonists may be of value. These drugs, which BLOCK the benzodiazepine/ GABA-receptor complex, may lead to a decrease in inhibitory GABA-mediated transmission in the brain and lessen the encephalopathy.
Based on the possible relationship of a defect in dopaminergic neurotransmission and encephalopathy, both L-dopa and bromocriptine have been tried, with controversial results.

Orthotopic liver transplantation should entirely reverse the hepatic encephalopathy. Thus, this should be considered in all patients with hepatic encephalopathy whose liver disease makes them suitable for liver transplantation.

http://gastroresource.com/GITextbook/en/chapter14/14-13.htm

Editorial in the March issue of
Am J Gastroenterol

Screening for Varices in Patients With Cirrhosis:
Where Do We Stand?

Naga Chalasani, M.D.a and Thomas F. Imperiale,
M.D.b

Variceal bleeding is perhaps the most dreaded
complication in patients with cirrhosis. During
the past 10-15 yr, there has been great interest
in primary prevention of variceal bleeding.
Numerous studies have demonstrated the efficacy of
pharmacotherapy for primary prevention of variceal
bleeding in patients with high-risk varices.
Additionally, recent data suggest that variceal
banding is effective in preventing variceal
bleeding in these patients. However, to apply
these primary preventive measures, one must first
identify cirrhotic patients with high-risk
varices. In 1997, guidelines from the American
College of Gastroenterology (ACG) recommended
screening endoscopy for patients with established
cirrhosis who were candidates for medical therapy
. In 1998, the American Association for the Study
of Liver Disease (AASLD) also recommended that
patients with cirrhosis undergo screening
endoscopy for varices . The AASLD recommended, in
particular, that endoscopic screening should be
routine for patients with Child class B and C
cirrhosis, but limited to those Child A patients
with clinical evidence of portal hypertension
(thrombocytopenia or large portal vein/collaterals
on abdominal imaging) .
How often is screening for gastroesophageal
varices performed among patients with cirrhosis?
To what extent is primary and secondary
prophylaxis against esophageal variceal bleeding
implemented in clinical practice in the United
States? It has been our experience that, despite
these guidelines, screening for high-risk varices
has not become the standard of care in clinical
practice. The report by Arguedas et al. in this
issue of the Journal begins to provide answers to
these important questions, as they report on 125
patients with advanced cirrhosis who were referred
for liver transplantation. Just 46% (52 of 113) of
these patients had been screened for varices
despite having had the diagnosis of cirrhosis for
a median duration of 3 yr . Fifteen of 52 screened
patients received primary prophylaxis
with -adrenergic antagonists (presumably for the
presence of large varices), and just three (5.8%)
experienced variceal bleeding during a median
follow-up interval of 20 months. In contrast, of
the 61 patients who were not screened, 22 (36%)
bled from varices during a median follow-up of 15
months following the diagnosis of cirrhosis. The
investigators concluded that screening for varices
is underused and that such underuse may contribute
to morbidity and mortality among cirrhotics.
<snip>
we note that their results are consistent with
the results of a survey of gastroenterologists
practicing in the Northwestern United States,
which revealed a screening rate of 39%
Assuming that these findings are representative of
current practice across the country, what are the
possible explanations for underuse of variceal
screening? First, the ACG and AASLD guidelines,
published in July 1997 and September 1998,
respectively, may not have had adequate
"dissemination" time to affect the clinical
practice of gastroenterologists. The study by
Arguedas et al. involved patients referred for
liver transplantation to the University of Alabama
at Birmingham between September 1998 and May 1999.
Second, for endoscopy to be useful as a screening
test, an effective treatment must exist for
primary prophylaxis against variceal bleeding.
Pharmacological therapy with
nonselective -blockers is the current standard of
care. Although -blockers have been shown to reduce
the risk of first variceal bleeding by 40-50%,
there are several practical limitations with their
widespread use, including unpredictable effects on
the hepatic venous pressure gradient, frequent
side effects and contraindications, less than
satisfactory patient compliance, lifelong need for
therapy, and the risk of rebound bleeding upon
abrupt discontinuation. Thus, it is possible that
such limitations of -blockers create the
perception that effective therapy is largely
"unavailable," and lower enthusiasm for endoscopic
screening. A third possible explanation is that an
alternative strategy of empiric pharmacological
therapy for all cirrhotic subjects (regardless of
their variceal status) is being employed. Several
of our colleagues have argued against the
necessity of knowing variceal size and suggested
instead that all cirrhotics should be placed
on -blockers. However, there is no current
evidence that this strategy is practiced in the
United States as supported by the current study.
Fourth, and possibly the most important
explanation is the issue of reimbursement for
screening endoscopy. It is not known how third
party payers reimburse endoscopy performed to
screen for varices. Our limited survey of local
community-based gastroenterologists suggests that
the third party payers regularly provide
reimbursement for a screening endoscopy.
Recent developments in the area of primary
prophylaxis of variceal bleeding deserve mention.
Recent data suggest that ultrathin endoscopes
(transnasal or peroral) could be used for
screening varices in unsedated cirrhotics . This
technology presents the possibility of endoscopic
screening for varices in the office setting,
enhancing the feasibility and probably reducing
costs. Furthermore, several investigators have
shown that readily available clinical variables
predict the presence of large esophageal varices .
Our group has shown that a "clinical decision aid"
comprising two variables (splenomegaly and
thrombocytopenia) stratifies the risk for large
esophageal varices and may be cost-effective . On
the treatment end, recent data suggest that
prophylactic ligation reduces the risks of
variceal bleeding and mortality as compared to "no
treatment" and reduces the risk for first variceal
bleed as compared to -blockers Preliminary
studies suggest that newer agents such as
carvedilol (a nonselective -blocker with intrinsic
anti-1-adrenergic activity) and losartan
(angiotensin-II receptor antagonist) reduce portal
pressure to a greater extent than the -blockers .
These developments are likely to improve the
feasibility of detecting large esophageal varices
and of instituting measures for primary
prophylaxis.
The findings by Arguedas et al. need to be
confirmed and extended to explore the reasons for
nonadherence to published guidelines, and more
research needs to be done to establish the
cost-effectiveness of endoscopic variceal
screening. Furthermore, it is important to provide
continued exposure to the guidelines through
educational efforts. It is possible that ongoing
research, such as the multicenter study of timolol
to prevent the development of varices and the
evaluation of variceal ligation for primary
prevention, may result in modification of these
guidelines. Meanwhile, it is essential that all of
us who care for patients with cirrhosis adhere to
the published guidelines for primary prophylaxis
of variceal bleeding, beginning with endoscopic
screening for their detection.