What is PBC

Primary Biliary Cirrhosis

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What is PBC

By Linie Moore

Many thanks to Doctors Melissa Palmer and Emil Miskovski for their help in writing this article

Primary Biliary Cirrhosis (PBC) is a chronic liver disease that slowly destroys the bile ducts within the liver (intrahepatic bile ducts). Liver inflammation over a period of years may cause scarring which leads to cirrhosis. PBC is NOT alcohol or drug related, and it is NOT contagious.

The name "Primary Biliary Cirrhosis" is somewhat deceiving since cirrhosis only occurs in the last stage of the disease (stage 4) after many years of inflammation. With early diagnosis and proper medications, most with PBC will never reach the cirrhosis stage of PBC.

PBC is also called "Chronic Nonsuppurative Destructive Cholangitis" and "Primary Autoimmune Cholangitis." However, these alternative terms are not widely accepted and therefore not in use.

Definition from New American Medical Dictionary:

Primary: First in order of development, most important, arising spontaneously.

Biliary: Relating to or affecting the bile duct system or bile.

Cirrhosis: An inflammatory disease of the liver associated with the replacement of liver cells by fibrous tissue. Passage of blood through the liver may eventually be obstructed by the cirrhosis.

The cause of PBC is still unknown, but it is not alcohol or drug induced. Current studies suggest it may involve autoimmunity, infection, or genetic predisposition, and does seem to appear more often in certain families. Women are affected 10 times more than men, and PBC is usually diagnosed in patients between the ages of 35 to 60 years.

Those with PBC usually look extremely healthy, and many are 10 to 30 pounds overweight. The slight bronze pigmentation of the skin is often present in the advanced stage of the disease, and makes the individual look tanned. The outward appearances doesn't tell the story of what is going on inside their bodies. Even on the transplant list stage, many with PBC look healthy. A person with PBC commonly hears comments such as "you look so healthy or you don't look sick."

Upon diagnosis, some doctors may suggest their patient start:

Start a reduced sodium diet and or low fat diet.

In severely damaged livers, proteins may be restricted.

Drink plenty of water and other fluids such as juice.

Calcium and Vitamin D. Calcium is the most common mineral in the body and is required for proper functioning of most organs. It is particularly needed in the normal development of the bones and teeth. Osteoporosis is a bone disease where calcium leaves the bones causing them to weaken, and is commonly associated with PBC.

Avoid or lower intake of alcohol.

Lower caffeine intake.

Avoid undue stress.

Exercise, if possible. Walking is the most common recommendation for exercise.

Stop smoking.

The above suggestions have been found to be very helpful in liver disease, but are common sense considered part of healthy living. PBC Menus and meal plans by Norma J. Thiel, RD, Clinical Nutrition Manager Mountainview Hospital.

The number of patients being diagnosed at the asymptomatic stage has risen dramatically over the past few years due to widespread laboratory screening. Typically, the blood lab pattern reveals an elevated alkaline phosphatase level with a normal bilirubin. Bilirubin does not increase until final disease stage. There are four disease stages of PBC.

Medical tests used to confirm PBC:

A liver biopsy helps confirms the diagnosis, but is not a requirement.

Ultrasound exam may be performed to visualize the bile ducts to exclude an obstruction.

Blood lab tests that show liver dysfunction:

Liver function tests

Antimitochondrial antibodies. Positive AMA is found in about 95% of PBC patients.

Serum cholesterol and lipoproteins may be increased.

Haptoglobin & ACE levels may be altered

Diagnostic tests

PBC advances slowly over a period of years. Most patients lead normal lives for years without symptoms, depending on how early diagnosis is made. There is no cure for PBC, but patients are showing good results in slowing the disease progress with URSO 250, Actigall and methotrexate. With the current medications, it is becoming more common for the PBC patient to live a long life without any complications from PBC, and in some cases actually lowering the disease stage from original diagnosis stage. See Ursodiol Treatment Dosage Chart.

PBC is considered an autoimmune disease. Some diagnosed with PBC, may also be diagnosed with one or more other autoimmune diseases. Click for diseases and conditions associated with PBC.

Most patients remain without symptoms for many years, and some may never notice any symptoms. The initial symptoms vary among PBC patients, and the varying symptoms can sometimes make it difficult for doctors to actually diagnose PBC. The varying symptoms may be do to the individual, autoimmune nature or other diseases associated with PBC.

Symptoms may be present in any combination and include any of the following:

Fatigue may be the first symptom the patient notices, causing him or her to visit their doctor. The fatigue associated with PBC appears to be totally different from any other sort of fatigue. In early stages, many patients have commented they could sleep for hours. While some in the later stages say sleeping becomes more difficult. At this time, there is little research into the cause and treatment of the liver disease fatigue. It is usually not due to depression, and some researchers believe it is an abnormality of the axis between the pituitary and the adrenal glands. Support and understanding from family members, friends and the doctor is very important, making it somewhat bearable. Intense and unrelenting itching of the skin.

Gradual darkening (hyperpigmentation) or changes in skin texture, and various skin rashes.

Small yellow or white bumps (xanthomas) under the skin, or around the eyes.

Dry Eye Syndrome.

Dry mouth, sometimes referred to as cotton mouth.

Thyroid problems.

Arthritic aches and pains in bones, muscles and joints are common. In some, the pains can be severe and debilitating. Some even report severe pain just touching leg, feet and hip bones, but this is NOT common.

Over the years, as the PBC progresses, other symptoms may appear. These symptoms may include any of the following:

Osteoporosis or other metabolic bone disease.

Enlarged abdomen from fluid accumulation.

Easy bruising or bleeding.

Jaundice (yellowing of the skin and eyes).

Increased bilirubin.

Internal bleeding in upper stomach and esophagus, that may be caused by varcies.

Hepatic encephalopathy causing personality changes: dulling of mental functions, neglect of personal appearance, forgetfulness and trouble concentrating, changes in sleeping habits, confusion, breath odor and muscle stiffness. Encephalopathy occurs in final stage of PBC.

Hypersplenism, enlarged spleen.

Fever, nausea and vomiting.

Reflux and stomach ulcers.

Weight increase or decrease.

Swelling of the hands, legs and ankles. See edema and ascites.

Sexual problems (impotence in men, absence of periods in women, lack of desire.)

Trembling hands.

Difficulty in sleeping and changes in sleeping habits. Some PBC patients have noted that itching intensifies when they lay down to sleep, and those who have liver pain say it is more severe in a sleeping position.

Hepatorenal syndrome, progressive deterioration of kidney function leading to kidney failure in a person with liver failure.

Hepatopulmonary syndrome, associated with difficulty with breathing.

Liver cancer (hepatocellular carcinoma).

Abdominal pain or pressure in the liver area. (Yes it's real)

As the PBC progresses, some patients require vitamin A, vitamin D, vitamin E and vitamin K replacement therapy to add back fat-soluble vitamins which are lost in fatty stools. A calcium supplement may be prescribed to help prevent osteomalacia and osteoporosis.

When ursodiol treatments, such as URSO 250 & URSO Forte, Actigall and methotrexate, no longer control the disease, the patient should be evaluated for a liver transplant. The end stage of PBC is liver failure. Many signs indicate liver failure: increased bilirubin, jaundice, fluid accumulation or ascites, malnutrition, gastrointestinal bleeding, intractable itching, bone fractures and hepatic coma. Transplant is recommended before most of these symptoms occur. Recent studies suggest that about 30% of those diagnosed with PBC will require a transplant. The transplant outcome for PBC patients is excellent.

As with any other chronic illness, support and understanding is very important in helping the PBC patient cope with day to day living.

Is Your Diagnosis Definitely PBC?
Melissa Palmer, M.D.

Three other liver diseases resemble and thus, may be confused with PBC. They are: autoimmune cholangitis, PBC with "autoimmune features", also known as the "overlap disease" and primary sclerosing cholangitis (PSC). As treatment and prognosis may differ in these diseases, it is most important to distinguish between them and PBC and to make sure that your diagnosis is correct.

Autoimmune Cholangitis

Autoimmune cholangitis is characterized by liver enzyme abnormalities suggestive of cholestasis and biopsy results resembling those of people with PBC. However, the autoantibody AMA is not present in the blood of people with autoimmune cholangitis. Instead, other autoantibodies, namely ANA and SMA, are found in the blood. Accordingly, this disease is often referred to as "AMA-negative PBC". Some studies demonstrate that people with autoimmune cholangitis benefit from treatment with prednisone, either alone or in combination with azathioprine. Other studies have found a greater benefit from the use of ursodeoxycholic acid on this group of people. In fact, there was no difference in the response to UDCA therapy in people with autoimmune cholangitis when compared to people with PBC who are AMA positive. Thus, is usually more prudent to treat people with autoimmune cholangitis with UDCA, especially in light of the fact that prednisone therapy worsens osteoporosis in people with PBC.

Whether autoimmune cholangitis is a totally separate entity from PBC or simply PBC without the manifestation of a positive AMA on blood tests remains a subject of ongoing debate and research.

Primary Biliary Cirrhosis and Autoimmune Hepatitis (AIH) -the "Overlap Syndrome"

PBC overlaps with autoimmune hepatitis (AIH) approximately 8- 12 percent of the time. These people have the clinical features of AIH, such as very elevated transaminases and the autoantibodies of AIH ñ antinuclear antibody (ANA) and/or smooth muscle antibody (SMA). However, they also have the presence of antimitochondrial antibody (AMA) in their blood, which is diagnostic of PBC. It has been suggested by some experts that those people who test positive for AMA should not be considered to have AIH. This is because there is such a strong association of AMA with PBC. In fact, it has been demonstrated that features of AIH in people with PBC may be transient. Furthermore, response to UDCA appears to be similar in people with PBC with and without features of AIH.

It is important to always test people with the AIH/PBC overlap syndrome for the autoantibody- liver kidney microsomal antibody (anti-LKM). If anti-LKM is positive, the diagnosis of AIH is more likely. There is also a small group of people who are found to have AMA in their blood and who genuinely have AIH. These individuals have very elevated transaminase levels with minimal elevation of alkaline phosphatase levels. AMA titers typically are low - less than 1:160 in most cases. These people typically respond well to conventional treatment for AIH.

Primary Sclerosing Cholangitis

Primary sclerosing cholangitis (PSC) like PBC is a chronic cholestatic liver disease that results in damage to the intrahepatic bile ducts. Unlike PBC, PSC also results in damage to the extrahepatic bile ducts. Also unlike PBC, most people with PSC are male, and approximately two-thirds of people with PSC have an inflammatory disease of the colon (the large intestine) known as ulcerative colitis. Symptoms of PBC and PSC may overlap, as fatigue and itching are common to people with either disease.

There is a drastic difference in the way that the two diseases are diagnosed. Unlike the presence of AMA as a diagnostic marker in people with PBC, there are no diagnostic autoantibodies that occur in people with PSC. Instead, PSC requires a special procedure called an endoscopic retrograde cholangiopancreatography (ERCP) to be done in order for the disease to be accurately diagnosed. In an ERCP, a lighted tube (a special endoscope) is inserted into the patient's mouth and then is snaked through the stomach and into the small intestine. There is a tiny opening in the small intestine called the ampulla of vater that leads to the extrahepatic bile ducts. A thin wire is inserted into this opening and then into the extrahepatic bile ducts. This wire allows access into the extrahepatic bile ducts so that contrast dye needed to visualize the bile ducts on an x-ray can be injected. An x-ray can then be taken of the extrahepatic bile ducts to determine if they have suffered damage, thus making a diagnosis of PSC.

Complications from PBC and PSC are somewhat different. Extrahepatic bile duct blockages, due to bile duct damage and bile duct stones, occur in PSC but not in PBC, as only the intrahepatic bile ducts are damaged in PBC.

Medical treatment of people with PSC has been somewhat disappointing. Drugs that have been used with success in treating PBC patients have not shown an ability to slow the progression of PSC or to prevent its complications. Nor have these drugs exhibited much success at prolonging the survival of people with PSC. Liver transplantation is the best option for people with advanced PSC. For these people, results have been good with approximately 80 percent of transplant recipients surviving at least five years.

Finally, I would like to make everyone aware of a new non-profit foundation "The Findling Foundation" dedicated to increasing the awareness of PSC, as well as raising funding for research that will lead to improved diagnostic testing, treatment, and ultimately a cure for PSC. Please visit them as www.psccure.org or call (973) 535-5629 for more information.