Is Your Diagnosis Definitely PBC?

By 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 Cholangitis 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.

If you would like more information on PSC, please visit PSC Partners