Primary Biliary Cirrhosis Linked to Toxin Exposure

By Michael Smith, MedPage Today Staff Writer
Reviewed by Zalman S. Agus, MD; Emeritus Professor at the University of Pennsylvania School of Medicine.
March 02, 2006


MedPage Today Action Points

* Explain to patients who ask that primary biliary cirrhosis is a chronic liver disease, whose precise etiology is not understood but may include both an inherited genetic predisposition and exposure to environmental toxins.
* Note that there is large geographical variation in prevalence of the disease, which might be explained by environmental factors. This study shows a link between liver transplants as a result of the disease and residence near contaminated waste sites.

Review
NEW YORK - Living near a toxic-waste site may be a significant risk factor for developing primary biliary cirrhosis, according to a study here that included liver-transplant patients.


Significant clusters of the disease, whose etiology is unknown, were found near Superfund toxic waste sites in New York, according to Aftab Ala, M.D. of the Mount Sinai School of Medicine, and colleagues, reported in the online edition of Hepatology.


Also, a majority of patients who needed liver transplants because of primary biliary cirrhosis lived near Superfund sites, Dr. Ala said.


Primary biliary cirrhosis, the chronic, cholestatic liver disease characterized by nonsuppurative intrahepatic portal tract inflammation and bile duct destruction, mainly affects middle-age women.


The prevalence of primary biliary cirrhosis has large geographic variations and differences in genetic susceptibility. Exposure to environmental toxins is thought to play a role in these variations, Dr. Ala and colleagues noted.


For this analysis, the researchers collected zip code data on 172 patients in New York city who needed orthotopic liver transplant between 1995 and 2003, either because of primary biliary cirrhosis or primary sclerosing cholangitis, the cholestatic liver disease that is not thought to be related to environmental toxins. Primary sclerosing cholangitis occurs mainly in men.


Ninety-nine patients with primary biliary cirrhosis were listed for transplant and 73 with primary sclerosing cholangitis during that time.


Patients' zip codes were compared with the zip codes of known Superfund sites. Of the 174 zip codes within New York City, 89 either included or bordered Superfund sites. The average zip code in the city is two square miles; many are much smaller.


Dr. Ala and colleagues compared the prevalence of liver transplants caused by primary biliary cirrhosis to transplants caused by primary sclerosing cholangitis They found that primary biliary cirrhosis transplants -- but not primary sclerosing cirrhosis transplants -- were significantly higher in zip codes containing or bordering Superfund sites.


Specifically, the authors said, the prevalence ratio of primary biliary cirrhosis-linked transplants in zip codes containing or bordering Superfund sites was 1.225, compared with 0.67 in regions distant from a Superfund site. The difference was statistically significant at p=0.025.


However, there was no significant difference between the two groups of zip codes for primary sclerosing cholangitis-linked transplants, they found.


The authors also analyzed the data at the borough level. Staten Island had the highest prevalence ratio, at 1.54, and also the highest density of Superfund sites - 3.15 per 1,200 square miles.


"This is the first epidemiological study to show a statistically significant clustering of primary biliary cirrhosis patients near known sources of environmental toxins and one of relatively few studies linking proximity to Superfund sites to a specific disease," Dr. Ala and colleagues said.


The study is valuable as the first to address the possible geographic clustering of primary biliary cirrhosis in the U.S., according to Jayant Talwalkar, M.D., and Konstantinos Lazaridis, M.D., both of the Mayo Clinic in Rochester, Minn.


The study "shows the gathering of primary biliary cirrhosis cases within or in proximity to known sites of environmental toxins," they wrote in an accompanying editorial.


But they noted that the method used in the study - linking cases to zip codes - is subject to an unavoidable bias. Patients might have lived in several places before they moved to near the Superfund site where they lived when they were listed for liver transplant.


The study also doesn't give data on the length of time patients lived at their address when they were listed for transplant, on any possible dose-response relationship between exposure and the risk of primary biliary cirrhosis, or on any relationship between exposure, duration, and severity of disease, the authors said.


Primary source: Hepatology
Source reference:
Ala A et al. Increased Prevalence of Primary Biliary Cirrhosis Near Superfund Toxic Waste Sites. Hepatology. 2006; DOI: 10.1002/hep.21076.
Additional source: Hepatology
Source reference:
Jayant Talwalkar and Konstantinos Lazaridis. Polluting the Pathogenesis of Primary Biliary Cirrhosis. Hepatology. 2006; DOI 10.1002/hep.21109.
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