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Understanding fatigue in chronic liver disease

Liver disease is often associated with "sickness behaviors," such as malaise, listlessness, anorexia, difficulty concentrating, and fatigue. In cholestatic liver diseases (where bile production is impaired) such as primary biliary cirrhosis, fatigue occurs in up to 86 percent of patients. Previous studies have suggested that these symptoms originate from changes to the central nervous system (CNS), but little is understood about how these changes occur or the pathways involved.

In a study led by Steven M. Kerfoot of the Immunology Research Group at the University of Calgary in Canada and published in the January 2006 issue of Hepatology, researchers speculated that cholestatic liver damage may be associated with an immune response affecting the central nervous system, specifically the brain, which could represent a novel and potentially important pathway.

Hepatology, the official journal of the American Association for the Study of Liver Diseases (AASLD), published by John Wiley & Sons, Inc. is available online via Wiley InterScience at http://www.interscience.wiley.com/journal/hepatology.

The study involved creating cholestasis in mice by tying off the bile duct. Cerebral endothelial cells (cells lining the blood vessels of the brain) were then isolated and examined to see if they were activated, as activated endothelium tends to interact with activated immune cells. In addition, researchers analyzed TNF-alpha (a messenger protein involved in inflammation) production by monocytes, a type of white blood cell, to determine if a peripheral immune response was present.

The results showed an increase in TNF-alpha production by monocytes and activated endothelial cells in the cholestatic mice versus the control mice. The authors suggest that cholestasis is also associated with a broad activation of other immune cells within the central nervous system that produce TNF-alpha. "Given the significant behavioral effects of TNF-alpha within th
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Contact: David Greenberg
dgreenbe@wiley.com
201-748-6484
John Wiley & Sons, Inc.
5-Jan-2006


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