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WHAT IS PRIMARY BILIARY CIRRHOSIS (PBC)?

PBC is a chronic liver disease characterized by the slow destruction of the intrahepatic bile ducts. As discussed in earlier chapters, chronic connotes a duration of greater than six months. In fact, PBC may be accurately characterized as a lifelong illness. Like autoimmune hepatitis, which was discussed in Chapter 14 of my book, PBC is also believed to be an autoimmune disorder. An autoimmune disorder is a condition in which the immune system malfunctions and produces an immune response (an attack) against its own organs. In PBC, as with autoimmune hepatitis (AIH), the organ under attack is the liver. However, unlike AIH, in which the immune system attacks liver cells, in PBC the immune system attacks the cells lining the bile ducts within the liver. A consequence of the autoimmune attack is that the bile ducts become damaged. Once the bile ducts have become damaged, the bile acids within the ducts spill out.  Since bile acids are strong detergents, inflammation, damage, and scarring of liver tissue occur.

         As discussed in Chapter 1 of my book, bile ducts carry bile- a substance that aids in the digestion of fats and in the neutralization of poisons. When the bile ducts become inflamed and eventually destroyed, the surrounding liver tissue subsequently becomes damaged. This leads to scarring and cirrhosis. This explains the derivation of the name primary “biliary cirrhosis” This name can be a bit misleading since most people with PBC do not yet have cirrhosis at the time of initial diagnosis, and some may never even progress to cirrhosis in their lifetimes. Because this is a disease wherein the bile ducts become inflamed (a condition known as cholangitis) by a process that is not due to an infection, the alternative name, chronic nonsuppurative (not pus producing) cholangitis, has been suggested to be a more accurate description of this disease. However, this alternative name is not widely accepted and is therefore not in use.

THE TREATMENT OF PBC

Since PBC cannot be cured, treatment is aimed at slowing the progression of disease and at controlling its symptoms. Treatment of the symptoms associated with PBC will be discussed in Chapter 20. The following is a discussion of the treatment of the disease itself. People with PBC who do not have any symptoms, also have a decreased life expectancy, and progression to cirrhosis may occur prior to the development of any symptoms.  Therefore, people suffering from symptoms as well as people who are asymptomatic, both require treatment in an attempt to retard disease progression. People with PBC may be treated with a single medication, a combination of medications, or will need to undergo a liver transplantation.

Single Medications

A variety of medications have been evaluated for the treatment of people with PBC, some of which have been found to be beneficial. Unfortunately, the adverse side effects of these drugs outweigh the potential benefits that they provide. Examples include prednisone a steroid, which may accelerate   the rate of bone loss associated with PBC; cyclosporine, an antirejection drug, which may cause high blood pressure and kidney dysfunction; and chlorambucil, a chemotherapy drug, which may be toxic to bone marrow.

         Medications that have been studied but that have not been shown to provide significant benefits to people with PBC include D-penicillamine, a copper-binding drug; azathioprine, an antirejection, immunosuppressive drug; and malotolate, an anti-inflammatory drug.  The herb silymarin has also been tried on people with PBC, but did not appear to be of any benefit. (see chapter 21 of my book for more information on herbs).

         There are other medications that appear to benefit people with PBC, but are undergoing evaluation to confirm their effects. Examples of such medications include S-adenosylmethionine (SAMe), a type of amino acid; and tacrolimus, an antirejection, immunosuppressive drug. 

     Some investigators believe that PBC is caused by a type of virus, known as a retrovirus such as human immunodeficiency virus-1 (HIV-1).  This retrovirus is different than the HIV-2 - the retrovirus that causes acquired immunodeficiency syndrome (AIDS).  Based the assumption that PBC is caused by a retrovirus, pilot studies on people with PBC using antiretroviral therapy ñ either lamivudine, or Combivir (lamivudine 150mg, and zidovudine 300mg manufactured by GlaxoWellcome) are under way.  Preliminary results suggest that Combivir  may have some beneficial effects on people with PBC.   Further study is anticipated on this provocative concept.

         At present, the most effective drug treatment for PBC appears to be with one of the following three medications-ursodeoxycholic acid, methotrexate, and colchicine. The following is a discussion of ursodeoxycholic acid. Please refer to my book for discussion of other potential treatments.

Ursodeoxycholic Acid

Ursodeoxycholic acid (also known as UDCA or ursodiol) is the drug most commonly used to treat PBC. In fact, it is the only drug that is FDA approved for the treatment of PBC. Ursodeoxycholic acid was initially found to be beneficial for people with PBC in the early 1980s and became FDA approved in 1998. It is manufactured by Axcan Pharma(Mont Saint Hillaine, Quebec, Canada) under the brand name URSO. URSO is taken with food in oral pill form at a dosage of 13 to 15 milligrams per kilograms of body weight each day administered in four divided doses. Each pill is 250 milligrams.  In November 2004 a new form of URSO will be available - known as URSO Forte. Each pill of URSO Forte will be 500 mg. Thus, this pill will allow for the ease of taking only one pill twice a day as the typical dosage. Actigall is another brand name for ursodeoxycholic acid.  Actigall is marketed by Novartis (Summit, NJ) in tablets of 300mg.  This drug is not FDA approved for the treatment of PBC, therefore its use is considered “off label”.  Generic ursodeoxycholic acid is also available ñ known as ursodiol.  Since ursodiol costs about 10 percent less than the brand name products (URSO and Actigall), many insurance companies prefer its use for the treatment of PBC.

         Ursodeoxycholic acid (UDCA) is a naturally occurring bile acid, but unlike many other bile acids in the body, it is not toxic to the liver. It is found in humans in small quantities, but is found in large quantities in bears. UDCA was initially used to dissolve gallstones, a treatment that is no longer common. The exact mechanism by which ursodeoxycholic acid works in people with PBC is not known. However, it has been established that increasing the amount of UDCA in the body will generally decrease the amount of liver-toxic bile acids in the body. This, in turn, should diminish or prevent destruction of bile duct cells. In fact, in some studies, people treated with ursodeoxycholic acid have been shown to have decreased   bile duct destruction.  However, other studies have shown that UDCA does not prevent bile duct destruction.  Instead, UDCA appears only to protect against the consequences of bile duct destruction.  This finding explains that while UDCA can delay, it does not prevent, the progression of disease to cirrhosis in people with PBC.

         UDCA provides significant benefits to people with PBC. Levels of liver function tests, IgM, AMA, and cholesterol typically show notable improvement. People find that UDCA, on occasion, relieves some of the symptoms associated with PBC, such as fatigue and itching. Most importantly, ursodeoxycholic acid has been found to slow the progression of PBC, and to delay the occurrence of cirrhosis. Thus, people with PBC who are treated with UDCA have been found to live longer, have less liver-related complications, and need liver transplants less often when compared with those who are not treated with UDCA. UDCA may also have the additional benefit of decreasing the recurrence of colon polyps, however, this finding needs to be confirmed by further studies.

         Side effects of UDCA are minimal. Most studies have indicated that less than 3 percent of people develop adverse side effects from UDCA. When side effects are experienced, they include diarrhea, decreased white blood cell count, elevated glucose levels, elevated creatinine levels, peptic ulcers, and skin rashes. Overall, UDCA is a well-tolerated, safe, and effective medicine for the treatment of people with PBC.

The beneficial effects of ursodeoxycholic acid are experienced by approximately 80 percent of people with PBC who use this medication. These effects are most likely to occur the sooner a person is treated-for example, when the person is treated during the first or second stage of the disease. Higher doses than are currently used may work even better, but further study is needed. People who have PBC who do not respond to UDCA should consider combination therapy involving UDCA with another medication, or they should consider trying a different medication. People whose bilirubin levels continue to worsen despite treatment with UDCA or any other medication should be evaluated for liver transplantation.

Melissa Palmer, MD is the author of " Dr. Melissa Palmer's Guide of Hepatitis and Liver Disease". (Published 2004. Penguin Putnam).

The office of Melissa Palmer, M.D. is located at:

1097 Old Country Road Suite 104

Plainview, N.Y 11803

To arrange an appointment with Dr. Palmer, call

(516) 939-2626

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