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Medical Author:

John M. Vierling, MD, FACP

John M. Vierling, MD, FACP

John M. Vierling M.D. is Professor of Medicine and Surgery at the Baylor College of Medicine in Houston, Texas, where he also serves as Director of Baylor Liver Health and Chief of Hepatology. In addition, he is the Director of Advanced Liver Therapies, a center devoted to clinical research in hepatobiliary diseases at St. Luke's Episcopal Hospital. Dr. Vierling is board certified in internal medicine and gastroenterology and a Fellow of the American College of Physicians.

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Medical Editor:

Leslie J. Schoenfield, MD, PhD

Leslie J. Schoenfield, MD, PhD

Dr. Schoenfield served as associate professor of medicine and consultant in gastroenterology on the faculty of the Mayo Clinic for seven years. He became a professor of medicine in residence at UCLA from 1972 to 1999 (now emeritus). He was the director of gastroenterology at Cedars-Sinai Medical Center in Los Angeles for 25 years, where he received the chief resident's teaching award, the president's award, and the pioneer of medicine award.

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In this Article

• What is PBC?
• What is the scope of the problem?
• What is the cause of PBC?
• What are the symptoms and physical findings in PBC?
• What manifestations are specifically due to PBC itself?
• What are the manifestations of the complications of cirrhosis in PBC?
• What are the manifestations of diseases associated with PBC?
• What are risk factors for PBC?
• How is PBC diagnosed?
• What is the role of blood tests?
• What is the role of testing for antimitochondrial antibodies?
• What is the role of imaging tests?
• What is the role of liver biopsy?
• What are the criteria for a definitive diagnosis of PBC
• What is the course of natural progression in PBC?
• What are the sequential clinical phases of PBC?
• What is the role of mathematical models in predicting the outcome (prognosis) in PBC?
• What about pregnancy in PBC?
• Patient Comments: Primary Biliary Cirrhosis - Symptoms
• Patient Comments: Primary Biliary Cirrhosis - Diagnosis
• Find a local Gastroenterologist in your town
• Primary Biliary Cirrhosis Index

Jaundice

One of the principal signs of advanced PBC is jaundice, which is a yellow appearance of the whites of the eyes and skin. Jaundice is usually first noticeable as a yellowing of the whites of the eyes. The jaundice reflects increased levels of bilirubin in the blood. The bilirubin is a yellow waste product that is normally produced mostly in the liver, delivered in bile to the intestine, and passed out in the stools (bowel movements).

As cholestasis worsens as a result of destruction of the small bile ducts that carry bile from the liver, bilirubin levels rise in the blood resulting in jaundice. Subtle jaundice is detectable only in sunlight and not in artificial light. Still, the jaundice does not become visible until the bilirubin level in the blood (normally under about one mg%) gets up to about three mg%. The simultaneous onset of both jaundice and itching is less common than the onset of itching alone, but is more common than either jaundice preceding itching or jaundice without itching.

Hyperpigmentation

Cholestasis increases production of the dark pigment, melanin, which is found in the skin. The darkening of the skin is called hyperpigmentation. What is notable about the pigmentation is that it occurs in both sun-exposed and non-exposed areas of the body. Moreover, prolonged scratching because of severe itching in PBC may intensify the pigmentation, leading to darkened areas and a blotchy or mottled appearance of the skin.

Malignancy

Early reports indicated that women with PBC might have an increased risk of developing breast cancer. Subsequently, however, larger studies, did not confirm this possibility. Please see the section on liver cancer (hepatocellular cancer).

• Edema and ascites
• Bleeding from varices
• Hepatic encephalopathy
• Hypersplenism
• Hepatorenal syndrome
• Hepatopulmonary syndrome
• Liver Cancer (hepatocellular carcinoma)

Edema and ascites

As cirrhosis of the liver develops, signals are sent to the kidneys to retain salt and water. This excess fluid first accumulates in the tissue beneath the skin of the ankles and legs (due to the pressure of gravity). This accumulation of fluid is called edema or pitting edema. Pitting edema refers to the observation that pressing a fingertip against a swollen ankle or leg causes an indentation that persists for some time after release of the pressure. Actually, any type of sufficient pressure, such as from the elastic part of socks, can produce pitting edema. The swelling often is worse at the end of the day and may lessen overnight. As more salt and water are retained and liver function decreases, fluid may also accumulate in the abdomen. This accumulation of fluid (called ascites) causes swelling of the abdomen.

Bleeding from varices

In cirrhosis, the scar tissue (fibrosis) and the regenerating nodules of hepatocytes block (obstruct) blood flow in the portal vein in virtually all patients. The portal vein carries blood from the intestines, spleen, and other abdominal organs to the liver on the way back to the heart and lungs. The build-up of pressure caused by the blockage in the portal vein is called portal hypertension. When pressure in the portal vein becomes high enough, it causes blood to flow through alternative vessels (paths of lesser resistance.) Often, these vessels include veins in the lining of the lower part of the esophagus and the upper part of the stomach.

When these veins distend (dilate) because of the increased blood flow and pressure, they are referred to as esophageal or gastric varices, depending on where they are located. So, portal hypertension and varices develop in PBC after cirrhosis is established. Only a minority of patients with PBC develops portal hypertension and varices before cirrhosis occurs. The higher the portal pressure, the larger are the varices (distended veins).

Accordingly, patients with large varices are at risk for the varices to burst and bleed into the gut. It is recommended, therefore, that patients with PBC have an upper endoscopy done at the time of diagnosis and approximately every three years thereafter to detect and then, if necessary, treat the varices. An upper endoscopy is a direct look with a tubular instrument (an upper endoscope) into the esophagus and stomach.