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Genetics, environment affect risk for primary biliary cirrhosis.

SAN FRANCISCO -- Two separate studies have produced strong evidence supporting both genetic and environmental risk factors for primary biliary cirrhosis. The findings were presented at the annual meeting of the American Association for the Study of Liver Diseases.

Little is known about the cause of this autoimmune cholestatic liver disease that affects an estimated 100,000 people in the United States. Primary biliary cirrhosis typically strikes women in the prime of their lives, attacking small ducts of the liver and ultimately requiring a liver transplant.

Symptoms include intractable itching, fatigue, and sometimes jaundice, although today many patients are diagnosed while asymptomatic based on abnormal liver function tests.

Detailed telephone surveys of 1,032 patients (93% women) and 1,041 closely matched controls (92% women) in all but two U.S. states found that the risk for primary biliary cirrhosis increased with a family history of the disease or of other autoimmune diseases. Other risk factors were smoking, a history of urinary tract infection (UTI), and high income, plus a slight increase in risk with the use of nail polish, Dr. Carlo Selmi reported.

The average age at diagnosis of primary biliary cirrhosis was 58 years in Dr. Selmi's study; the control subjects also averaged 58 years.

Six percent of patients with primary biliary cirrhosis had another family member with the disease--usually a mother or sister. One-third of patients had another autoimmune disease, reported Dr. Selmi of the University of California, Davis, and his associates.

A family history of primary biliary cirrhosis increased a person's risk for the disease 11-fold. The risk doubled with a family history of lupus and increased sixfold with a family history of Sjogren's disease.

Previous UTIs were associated with a 50% increase in risk for primary biliary cirrhosis. The risk increased by 60% with a history of smoking more than 10 cigarettes per day. Use of nail polish increased the risk only slightly, but the difference was significant, he said.

Patients with primary biliary cirrhosis had significantly higher family incomes, compared with controls, a risk factor that's hard to explain, said Dr. M. Eric Gershwin, a coinvestigator in the study and chief of rheumatology, allergy, and clinical immunology at the university.

One "hygiene hypothesis" posits that wealthier people may be "too clean," disrupting the autoimmune system, he said at a press briefing.

Noting the higher rate of UTIs in patients with primary biliary cirrhosis, he hypothesized that certain bacteria resembling the pathogens of UTIs may predispose someone to primary biliary cirrhosis if the body attacks the lookalike bacteria by mistake.

A separate British study comparing 2,576 patients with primary biliary cirrhosis to 2,438 controls produced results that were "extraordinarily similar" to those of the U.S. study, Dr. Oliver James said in a separate presentation.

The cirrhosis group included 318 consecutive patients seen in one region and 2,258 members of the Primary Biliary Cirrhosis Foundation support group living in the United Kingdom.

A family history of primary biliary cirrhosis doubled the risk for disease in the regional patient group and quadrupled risk in the Foundation group, compared with controls. Previous obstetrical pruritus doubled the risk in both patient groups compared with controls, said Dr. James of the University of Newcastle Upon Tyne.

Other factors that increased risk for the disease in both patient groups, compared with controls, included smoking, use of hair dye, recurrent UTIs, thyroid disease, and rheumatoid arthritis. Additional factors increased risk in at least one of the patient groups; these factors were celiac disease, history of shingles, or prior tonsillectomy or appendectomy.

History of pregnancy slightly but significantly reduced risk in women and also in men whose partners became pregnant.


San Francisco Bureau
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Title Annotation:Gastroenterology
Author:Boschert, Sherry
Publication:Internal Medicine News
Geographic Code:1U9CA
Date:Apr 15, 2006
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