Primary Biliary Cirrhosis Treatment (PBC) (cont.)

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What treatments are used for the symptoms of PBC?

Itching

Cholestyramine: Cholestyramine (Questran) is a drug taken orally that is not absorbed in the gut. The drug attaches (binds) to substances in the gut, including those that came from the bile, and then removes them from the body into the bowel movements. Presumably, cholestyramine is helpful because it binds both bile acids and unidentified substances that cause itching after they are absorbed from the gut into the blood stream. Cholestyramine is the most effective therapy for most patients with cholestatic itching. For optimal effects, cholestyramine should be taken with meals when bile flow into the gut is highest. A somewhat larger dose with breakfast is recommended for patients with gallbladders since the bile stored overnight in the gallbladder is released at this time.

It is important to note that cholestyramine can also bind to medications. Therefore, it is important that other medicines be taken one hour before or two hours after cholestyramine. The usual dosage is 8 grams with breakfast, 4 grams with lunch, and 4 grams with dinner. Cholestyramine does not dissolve well in liquids and often feels gritty as it is swallowed. Mixing it in carbonated beverages, however, can reduce this problem. The principal side effect of cholestyramine is constipation. The constipation occurs because the drug binds the bile acids that otherwise would make more water available in the colon to soften the stool. Another bile acid-binding medication that can be tried to relieve itching is colestipol (Colestid).

Rifampin: An antibiotic, rifampin (Rifidin) was initially found to improve itching due to cholestasis actually by chance. Then, a study of patients with PBC that included a cross-over between rifampin and an inactive compound (placebo) showed that rifampin did reduce itching at a dose of 150 mg taken two or three times per day. This drug may take up to one month to be effective, but should not take longer. Therefore, if the drug is not effective after one month, it should be discontinued. Not all patients with PBC benefit from this drug.

The way in which rifampin works is poorly understood. It can induce biochemical pathways in hepatocytes that theoretically may alter the bile acid environment within these cells. The side effects of rifampin include elevation of bilirubin, dark urine, hepatitis (more rarely), reduced numbers of blood platelets (small elements that help stop bleeding from a cut surface), and kidney damage.

Opiod antagonists: The fact that some patients who receive opiate narcotics (such as morphine) develop itching led to the hypothesis that itching in cholestasis may be caused by the body's natural opiates, called endorphins. To test this hypothesis, patients with PBC who had itching were treated with the oral drug nalmephene, an antagonist (acts against or blocks the action) of opiates. Itching improved over a 9-month period. Some patients treated with the opiate antagonist, however, developed very unpleasant symptoms of opiate withdrawal when their natural endorphins were inhibited. Therefore, this drug is not appropriate for long-term use in PBC. A controlled study comparing an intravenous opiate antagonist called naloxone (Narcan) with inactive intravenous fluids showed that the naloxone improved itching in PBC patients. Because it must be given intravenously, naloxone also is inappropriate for long-term use.

Recently, the oral opiate antagonist, naltrexone (Revia), was tested in a small, randomized, controlled trial in PBC patients with itching. It improved itching in 50% of patients and did not cause opiate withdrawal symptoms. Naltrexone also improved symptoms of fatigue and depression, possibly by restoring the ability to sleep at night when itching is most severe. However, future studies are needed to assess its safety, how long it can be given, and whether patients will eventually become unresponsive (refractory) to its effects.

Charcoal hemoperfusion: In uncontrolled studies, patients with PBC who had severe itching underwent a procedure called plasmapheresis. (Uncontrolled studies are studies in which the treatment is not compared with other treatments or placebos.) In this procedure, the blood is removed from the body, and the fluid phase (called plasma) of the blood is separated from the blood cells and platelets. The plasma is then percolated through a column containing activated charcoal. Finally, the plasma is remixed with the blood cells and returned intravenously to the patient. The idea is that the charcoal would remove some compound or compounds (as yet unknown) from the plasma that caused the itching. Anecdotally, many patients had relief of itching for periods ranging from days to months. However, no controlled trials (compared with other treatments or placebos) were performed. Hence, this procedure is still considered experimental and is not often used.

Medically Reviewed by a Doctor on 4/30/2014