Although cirrhosis usually conjures images of alcohol abuse, cirrhosis can occur as an autoimmune disorder primarily affecting women.
Primary biliary cirrhosis (PBC) is an autoimmune liver disease that causes progressive inflammation, blockage and destruction of the bile ducts (cholestatic liver disease), and eventual cirrhosis. Normally, liver cells excrete bile through the bile ducts and feed it into the common bile duct leading to the intestine. Bile is a brown chemical produced by the liver that aids digestion.
In primary biliary cirrhosis, bile ducts become inflamed, and over time chronic inflammation causes scarring or fibrosis. Fibrosis eventually destroys the bile ducts and progresses to cirrhosis.
Symptoms and Signs
Chronic inflammation in PBC causes the bile to back up into the liver and into the bloodstream. Early on, there may be no symptoms (asymptomatic) although the liver enzyme alkaline phosphatase may be elevated. Early symptoms include itching of the skin (pruritis), right upper quadrant pain, increased skin pigmentation (hyperpigmentation), depression, obsessive-compulsive behavior, and fatigue.
Over time, granulomas may occur in the liver and regional lymph nodes. An increase in small bile ductules occurs as the liver compensates for the damaged bile ducts. The disease course varies with progression ranging from several months to more than 20 years. With newer more sensitive autoantibody tests for diagnosing PBC, it appears that some patients develop a mild or subclinical non-progressive disease.
Later symptoms include jaundice (yellowing of skin and eyes), cholesterol (yellow, waxy) deposits in the skin, especially near the eyes, enlarged spleen, edema (fluid retention), dry eyes and mouth and skin darkening. In the later stages, bone loss may occur and progress to osteoporosis. In the late stages of the disease, the liver is marked by cirrhosis, which is the end result of fibrosis or scarring.
Who Is Affected?
The typical patient diagnosed with PBC is a middle-aged woman. Women are 7-9 times more likely to be affected than men. However, men with PBC may have a more severe disease course and are more likely to develop hepatocellular carcinoma, a known potential consequence of cirrhosis.
PBC is usually diagnosed in people between 40 and 60 years. People with a family history of PBC or who have allergies or other autoimmune diseases, especially autoimmune thyroid disorders, scleroderma, ceratoconjunctivitis sicca, Raynaud phenomenon, esophageal motility disorder, scleodactyly and rheumatoid arthritis, are more likely to be affected.
The prevalence and incidence of PBC are similar in different regions of the world although recent reports suggest that PBC may be more prevalent in the United Kindom and Scandinavia. PBC is also more common in Northern Europeans and less common in individuals of African descent. Environmental agents suggested of triggering PBC in genetically predisposed individuals include cigarette smoke, urinary tract infections, and exogenous (from outside of the body) estrogens.
Diagnosis
Mitochondrial autoantibodies (AMA) are elevated early on in patients with primary biliary cirrhosis. Mitochondria are the energy sources found within cells. Individuals with signs of cholestatic disease, such as an elevated alkaline phosphatase or gamma glutamyl transpeptidase (gamma GT) level, with positive AMA results are suspected of having PBC. The liver enzymes asparate aminotransferase (AST) and alanine aminotransferase (ALT) and the sed rate may also be elevated; the cholesterol level and the immunoglobulin M (Ig) level are usually elevated; To confirm PBC, other causes of bile duct obstruction are looked for by using imaging tests and endoscopy.
In advanced disease, a liver biopsy is used to assess the degree of bile duct damage. Late in the disease, the serum bilirubin level rises, the platelet count falls, and the prothrombin level rises.
AMA against E2 are seen in about 90-95 percent of patients with PBC, and about 20-50 percent of patients also have antinuclear antibodies (ANA). AMA are seen in several diseases besides PBC, but the antimitochondrial antibodies against E2 are virtually diagnostic for PBC.
Stages of Primary Biliary Cirrhosis
PBC can be categorized into four stages depending on the changes seen in liver biopsy samples. Stage I is characterized by small bile duct lesions and inflammation. In stage II, there is a resulting proliferation or increase in small bile ductules. Stage III is characterized by fibrosis. Stage IV is characterized by cirrhosis. In general, without liver transplantation, the median survival duration from the time of diagnosis is 7.5 years for patients with symptoms and 16 years for patients without symptoms.
Treatment
Calcium and vitamin D are used to prevent bone loss, and Ursodiol (Actigall or Urso) is sometimes used to reduce itching and possibly prevent disease progression. Colchine is used to help inhibit liver fibrosis. Corticosteroids and other immunosuppressants are not usually used because of their contributions to bone loss. Liver transplants are used in patients who progress to cirrhosis.
Resources
Primary Biliary Cirrhosis, Jackson Siegelbaum Gastroenterology, www.gicare.com/pated/ecdlv34.htm.
Elaine Moore, Hepatitis, Causes, Treatment, and Resources, Jefferson, NC: McFarland Publishing, 2006.
Nikolaos Pyrsopoulos, Primary Biliary Cirrhosis, eMedicine from WebMD, Aug 7, 200, www.emedicine.com/med/topic 223.htm
