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Causes of primary biliary cirrhosis


Large study pinpoints genetic and environmental factors

A case-control study of more than 2000 people has identified a number of factors that may induce primary biliary cirrhosis (PBC) in genetically susceptible individuals. These include a history of urinary tract infections, hormone replacement therapy, tobacco use, and nail polish use. The study is published in the November 2005 issue of Hepatology, the official journal of the American Association for the Study of Liver Diseases (AASLD). Published by John Wiley & Sons, Inc., Hepatology is available online via Wiley InterScience at

PBC is a rare autoimmune disease which leads to liver failure. The cause of the disease is unknown. It is more prominent in women, and researchers have found instances of familial clustering, as well as association with urinary tract infections, tobacco smoking, and estrogen use, though some of the existing studies have offered conflicting evidence.

To better understand the origins of the disease, researchers, led by M. Eric Gershwin, M.D. of the University of California at Davis School of Medicine, conducted a case-control study including 1032 PBC patients and 1041 controls. The patients were recruited from 23 medical centers throughout the United States. The controls were generated from random telephone dialing and were matched to cases by sex, age, race and geographical location. All participants completed an extensive telephone questionnaire covering demographics, lifestyle, personal and familial medical history, and reproductive and occupational history. Researchers then analyzed and compared the data.

After multivariable statistical analyses, they found a number of factors significantly associated with PBC. These include a family history of PBC or Sjogren’s syndrome, individual history of urinary tract infection, history of smoking, use of nail polish, and history of hormone replacement therapy. By contrast, never having been pregnant was significantly associated with protection from developing the disease.

As the largest study to date on risk factors and comorbidities associated with PBC, the results support some of the previously proposed risk factors for PBC, but not others, such as the increased prevalence of breast cancer in female PBC patients. "We further identified new putative risk factors (the use of cosmetic products) and autoimmune conditions (SLE) associated with PBC," the authors report.

The study may have been limited by differing socioeconomic status between cases and controls since reported annual household income was significantly higher in patients with PBC. Also misclassifications may have occurred in the course of self-reporting. "Despite these limitations," say the authors, "we believe that our findings represent the soundest evidence of associations yet reported for PBC."

They conclude: "the results indicate that environmental factors, possibly including infectious agents through urinary tract infections of chemicals contained in cigarette smoke, may induce PBC in genetically susceptible individuals. Exogenous estrogens may also contribute to explain the female predominance of the disease."

The authors suggest future efforts should concentrate on interactions of genetic and environmental factors in relation to PBC. They propose a worldwide gene database for PBC patients and family members as well as animal studies with the identified agents. "Only these combined efforts will provide the solution to the enigma of PBC etiology," they say.

* This study was made possible by funding from the National Institutes of Health and with the help of the PBCers Organization (, a non-profit support group.

David Greenberg | EurekAlert!
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