Encephalopathy and Liver Disease/Hepatitis
Encephalopathy is an altered or impaired mental status, typically leading to coma, that can occur in people with cirrhosis. It is often referred to as "brain fog". Encephalopathy is often associated with poor coordination, fetor hepaticus (foul-smelling breath), and asterixis (uncontrollable flapping of the hands). The exact cause of encephalopathy is not known, but is probably due to a combination of factors. Most researchers believe that it mainly has something to do with the ailing liver’s inability to clear toxins—primarily ammonia—from the body. In fact, elevated blood levels of ammonia are found in approximately 90 percent of people with encephalopathy. When ammonia and other poisons begin to accumulate in the brain, a variety of mental disturbances occur.
In mild cases – known as minimal hepatic encephalopathy, a person will develop subtle personality changes, such as irritability, a change in sleeping patterns, or short-term memory loss. A person may have a shortened attention span or appear to be apathetic toward life. Movements may appear poorly coordinated and clumsy. People suffering from encephalopathy will commonly lose their tempers over minor incidents or have mood swings for no apparent reason. Or a person may repeatedly enter a room, forgetting what he needed from the room in the first place. Or he may continually misplace common objects, such as reading glasses, only to find that they were on top of his head the whole time! These people may also have an increased incidence of automobile accidents, as their reaction time may be somewhat impaired.
In more severe cases, total confusion, associated with inappropriate behavior, will occur. A person may become outright violent or may be so confused that he cannot properly identify the current year, season, or even his own family members. Sometimes, a person will sleep all day and can only be partially aroused. This, obviously, is a more serious condition and requires hospitalization.
In most cases, encephalopathy is easily detected on a physical examination in a patient known to have cirrhosis. Whenever there is a question about the diagnosis, an imaging study, such as CT scan or MRI, of the brain should be performed in order to eliminate other potential causes - such as a brain tumor, blood clot, or meningitis (brain infection). The factors that can precipitate encephalopathy in the cirrhotic patient should be searched for and immediately addressed by the doctor. These factors as well as the treatment of encephalopathy will be discussed below.
Treatment of Encephalopathy
Treatment should begin with eliminating the factor that started the encephalopathy. Factors that can cause encephalopathy include the following:
• Excessive use of diuretics (water pills), known as overdiuresis.
• Use of pain medications, sleeping pills, or tranquilizers.
• Excess consumption of animal protein.
• Infection.
• Constipation.
• Bleeding in the digestive tract (for example, bleeding esophageal varices).
- Blood Transfusion
• Electrolyte imbalances (for example, low potassium level, a condition known as hypokalemia.)
- Dehydration ( for example fluid restriction, excessive diarrhea, overdiuresis)
• Kidney dysfunction.
- Portosystemic shunts (PSS)
• Excessive alcohol consumption.
• Liver cancer.
Treatment includes the discontinuation and avoidance of all sedatives, tranquilizers, and pain medications; discontinuation or reduction in the dosage of all diuretics; treatment of infection (particularly SBP); elimination of constipation; control of gastrointestinal bleeding; and reduction in amount, or total elimination of, animal protein from the diet. Some liver experts believe that strict vegetarian diets can help improve encephalopathy.
Further management involves oral administration of an antibiotic, most commonly neomycin (4-6 grams per day). Since bacteria that naturally live in the intestines produce ammonia, and since ammonia has been linked to encephalopathy, treatment with neomycin (which reduces bacteria) should improve encephalopathy. Neomycin should not be used in people who have renal (kidney) failure, as it can be toxic to the kidneys. Metronidazole (Flagyl) at a dose of 800 mg/day taken for a period of one week, may be used as an alternative to neomycin. People found to have Helicobacter pylori in their stomachs must be treated with antibiotics and a proton-pump inhibitor – such as Prevacid. Since this bacteria produces urease (an enzyme needed to produce ammonia), it may have a role in precipitating encephalopathy. Lactulose is a very sweet, synthetic sugar that acts as a powerful laxative. It acidifies the stool and thereby traps ammonia and drags it out of the body along with other fecal material. Therefore, lactulose can be quite useful in the management of encephalopathy. Kristolose (manufactured by Cumberland Pharmaceuticals), is a crystalline form of lactulose. It is not as sweet tasting and syrupy in texture as lactulose and is thus more palatable to some people than lactulose. The dose for either lactulose or kristolose ranges from 30-60 grams per day. The goal is for the patient to have 2-4 loose bowel movements per day. Once the initial bout of encephalopathy has been overcome, maintenance with lactulose should continue with a goal of 1-2 loose bowel movements per day.
Zinc levels should be checked and supplemented if found to be deficient, as zinc deficiency may be a contributing factor to encephalopathy. Thiamine deficiency should also be considered, and supplements should be routinely administered if the patient has a known history of alcoholic liver disease. Administration of branched-chain amino acids (leucine, isoleucine, and valine) may have some benefit; however, evidence supporting this is inconclusive. Two other drugs, flumazenil and bromocriptine, may be useful in the treatment of encephalopathy, although further study is needed to confirm this. Fortunately, if the precipitating factor is promptly corrected and if treatment with lactulose is expeditiously started, encephalopathy, in most cases, will be reversed—at least on a temporary basis. Liver dialysis should be considered if encephalopathy does not improve despite the use of conventional medical treatments. Liver dialysis is analogous to kidney dialysis. A catheter is inserted into a vein in the patient. Some blood is removed through the catheter and is passed through the liver dialysis unit. In liver dialysis, toxins such as ammonia - which may cause encephalopathy, are removed from the patient’s blood. Then, the newly cleaned blood is returned to the patient through the same catheter. It takes about 4-6 hours to clear the blood of potential toxins that may cause encephalopathy. The HemoTherapies Unit is currently the only FDA- approved liver dialysis device in the United States. Many other devices are in the process of being developed. In any case, people with encephalopathy should be evaluated for a liver transplant.
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All contents of this article are Copyright © Melissa Palmer, MD
Melissa Palmer, MD is the author of " Dr. Melissa Palmer's Guide of Hepatitis and Liver Disease". (Published 2004. Penguin Putnam).
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