$Unique_ID{BRK03607} $Pretitle{} $Title{Cirrhosis, Primary Biliary} $Subject{Cirrhosis, Primary Biliary Hanot's Cirrhosis PBC Wilson's Disease Extrahepatic Bile Duct Obstruction Obstructive Biliary Cirrhosis Alcoholic Cirrhosis} $Volume{} $Log{} Copyright (C) 1989, 1990, 1991 National Organization for Rare Disorders, Inc. 602: Cirrhosis, Primary Biliary ** IMPORTANT ** It is possible that the main title of the article (Primary Biliary Cirrhosis) is not the name you expected. Please check the SYNONYM listing to find the alternate names and disorder subdivisions covered by this article. Synonyms Hanot's Cirrhosis PBC Information on the following diseases can be found in the Related Disorders section of this report: Wilson's Disease Extrahepatic Bile Duct Obstruction Obstructive Biliary Cirrhosis Alcoholic Cirrhosis General Discussion ** REMINDER ** The information contained in the Rare Disease Database is provided for educational purposes only. It should not be used for diagnostic or treatment purposes. If you wish to obtain more information about this disorder, please contact your personal physician and/or the agencies listed in the "Resources" section of this report. Primary Biliary Cirrhosis is a chronic progressive liver disorder thought to be related to abnormalities in the immune system. Obstruction of the small bile ducts is accompanied by yellow discoloration of the skin (jaundice). Excessive amounts of copper accumulate in the liver, and fibrous or granular hardening (induration) of the soft liver tissue develops. This disorder occurs mainly in women during the fourth to the seventh decade of life, and is marked by four progressive stages. Symptoms Primary Biliary Cirrhosis is characterized initially by blockage, then deterioration and loss of the small bile ducts inside the liver. This results in the abnormal retention (cholestasis) of bile acids, bilirubin, copper, and other substances that are normally excreted into bile. These substances cause further damage to liver cells. Itching often results from the abnormal passage of these substances into the blood, skin and other soft tissues of the body. Excessive amounts of fat soluble substances (lipids) and cholesterol are found circulating in the blood. Yellow nodules or plaques form on the skin and possibly in internal organs. The bile acid concentration in the intestines is inadequate for complete digestion and absorption of fats (triglycerides) in the diet. Additionally, normal absorption of Vitamins A, D, E, and K as well as calcium may be diminished, and iron deficiency anemia may develop. Loss of bone density (osteoporosis) and bone softening (osteomalacia) occurs in approximately twenty-five percent of patients. Primary Biliary Cirrhosis is divided into four symptomatic stages. In stage I, the liver is enlarged and destructive lesions affect the large bile ducts. Unexplained itching is common and is often worse at night. Increased amounts of melanin pigmentation appear in the skin, and patches of skin may be shed (excoriation). Fatigue and unexplained weight loss are also common. In stage II, lesions are more widespread but less specific. Normal bile ducts may be lost and increased numbers of poorly formed bile ducts with irregularly shaped interior spaces (lumens) are seen on biopsy tests. Fibrous cells infiltrate and spread within the liver. Stoppage of bile is limited to portal areas. Stage III is characterized by more progressive lesions in the liver, with fibrous infiltration becoming very widespread. Nodule formation may now become apparent. Intestinal malabsorption of nutrients may occur in some patients, resulting in nocturnal diarrhea, frothy, bulky stools, or weight loss even though the patient has a voracious appetite and increased caloric intake. Yellow plaques (xanthomas) appear on the skin in approximately ten percent of patients. These may be found on the palms of the hands, soles of the feet, elbows, knees, in tendons of wrists and/or ankles, and on the buttocks. Bone pain is common, as are spontaneous collapse of spinal bone segments and hairline fractures of the ribs, usually due to loss of bone density (osteoporosis). Stage IV represents the end stage of lesion formation, with widespread hardening of soft liver tissue (cirrhosis) and regenerative nodules. Yellowish discoloration (jaundice) of the skin becomes pronounced due to the presence of excess bilirubin. It is difficult to distinguish stage IV from other types of cirrhosis. Causes The exact cause of Primary Biliary Cirrhosis is not known. Some scientists believe an autoimmune abnormality may be the cause. Autoimmune disorders are caused when the body's natural defenses (antibodies or lymphocytes) against invading organisms suddenly begin to attack healthy tissue. Affected Population Primary Biliary Cirrhosis affects females in approximately ninety percent of cases. Symptoms usually appear in the fourth to seventh decade of life. Related Disorders Symptoms of the following disorders can be similar to those of Primary Biliary Cirrhosis. Comparisons may be useful for a differential diagnosis: Wilson's Disease is a rare genetic disorder of copper metabolism characterized by excess storage of copper in the body tissues, particularly in the liver, brain and corneas of the eyes. It leads eventually to liver disease, brain dysfunction, and a characteristic rusty-brown colored ring around the cornea of each eye known as a Kayser-Fleischer ring. (For more information on this disorder, choose "Wilson" as your search term in the Rare Disease Database). Extrahepatic Bile Duct Obstruction originates outside the liver but may produce symptoms similar to those of Primary Biliary Cirrhosis. Obstructive Biliary Cirrhosis is characterized by fibroid or granular hardening of the soft liver tissue due to bile duct obstruction rather than deterioration inside the liver typical of Primary Biliary Cirrhosis. Alcoholic Cirrhosis is characterized by gradual hardening of the soft tissue of the liver (cirrhosis) that frequently develops in chronic alcoholism. The early stage is marked by liver enlargement due to fatty infiltration with mild fibrosis. In late stages, normal liver lobes are replaced with small nodules, separated by a framework of fine fibrous tissue strands (hobnail liver). Therapies: Standard Treatment of Primary Biliary Cirrhosis is often directed at symptoms. The drug cholestyramine relieves itching in almost all patients. Colestipol hydrochloride may also be effective against itching. Large-volume plasmapheresis may relieve itching in patients who do not respond to drug treatment. This procedure is a method for removing unwanted substances (toxins, metabolic substances and plasma parts) from the blood. Blood is removed from the patient and blood cells are separated from plasma. The patient's plasma is then replaced with other human plasma and the blood is retransfused into the patient. Malabsorption of fat-soluble vitamins may be treated with vitamin K 1, A, D, and calcium supplementation. Iron deficiency anemia responds to oral iron supplements. Additional folic acid is recommended for patients taking cholestyramine because this drug can cause a folic acid deficiency. Folic acid and cholestyramine should be taken several hours apart since they may react and prevent folic acid absorption when taken together. Loss of fat in the stools (steatorrhea) may be treated by a low-fat diet supplemented with medium-chain triglycerides to maintain high caloric intake. Therapies: Investigational Experimental treatment of Primary Biliary Cirrhosis may involve liver transplantation. More research is necessary before this procedure can be recommended for all but the most severe cases of this disorder. Trials of several drugs including colchicine, prednisolone, D-penicillamine, azathioprine, cyclosporin A and chlorambucil are being conducted. However, long-term safety and effectiveness of these drugs has not been determined. The FDA has approved for testing the orphan drug Actigall (Ursodeoxycholic Acid) for treatment of Primary Biliary Cirrhosis. The drug is manufactured by the Ciba-Geigy Corp., 556 Morris Ave., Summit, NJ, 07901. The orphan drug Urosofalk (Ursodeoxycholic Acid) is being tested by the FDA as a treatment of Primary Biliary Cirrhosis. The drug is manufactured by Interfolk U.S., Inc., 25 Margaret St., Plattsburgh, NY, 12901. This disease entry is based upon medical information available through July 1991. Since NORD's resources are limited, it is not possible to keep every entry in the Rare Disease Database completely current and accurate. Please check with the agencies listed in the Resources section for the most current information about this disorder. Resources For more information on Primary Biliary Cirrhosis, please contact: National Organization for Rare Disorders (NORD) P.O. Box 8923 New Fairfield, CT 06812-1783 (203) 746-6518 Primary Billary Cirrhosis Patient Support Network Box 177 Tamworth, Ontario KOK 3GO Canada (613) 379-2534 American Liver Foundation 1425 Pompton Ave. Cedar Grove, N.J. 07009 (201) 857-2626 (800) 223-0179 The United Liver Foundation 11646 West Pico Blvd. Los Angeles, CA 90064 (213) 445-4204 or 445-4200 Children's Liver Foundation 14245 Ventura Blvd. Sherman Oaks, CA 91423 (818) 906-3021 National Digestive Diseases Information Clearinghouse Box NDDIC Bethesda, MD 20892 (301) 468-6344 References INTERNAL MEDICINE, 2nd Ed.: Jay H. Stein, ed.-in-chief; Little, Brown and Co., 1987. Pp. 225-226. TRANSPLANTATION OF LIVER, HEART, AND LUNGS FOR PRIMARY BILIARY CIRRHOSIS AND PRIMARY PULMONARY HYPERTENSION: J. Wallwork, et al.; Lancet (July 25, 1987, issue 2(8552)). Pp. 182-185. CLINICAL AND STATISTICAL ANALYSES OF NEW AND EVOLVING THERAPIES FOR PRIMARY BILIARY CIRRHOSIS: R.H. Wiesner, et al.; Hepatology (May-June 1988, issue 8(3)). Pp. 668-676. TREATMENT OF PRURITIS IN PRIMARY BILIARY CIRRHOSIS WITH RIFAMPIN. RESULTS OF A DOUBLE-BLIND, CROSSOVER, RANDOMIZED TRIAL: C.N. Ghent, et al.; Gastroenterology (February 1988, issue 94(2)). Pp. 488-493.