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World J Gastroenterol. Apr 21, 2006; 12(15): 2320-2327
Published online Apr 21, 2006. doi: 10.3748/wjg.v12.i15.2320
Pathogenesis of primary biliary cirrhosis: A unifying model
Elias Kouroumalis, George Notas
Elias Kouroumalis, George Notas, Laboratory of Gastroenterology and Hepatology, University of Crete, Faculty of Medicine, Heraklion 71003, Greece
Correspondence to: Professor Elias Kouroumalis, Department of Gastroenterology, University Hospital of Heraklion, PO Box 1352, Heraklion 71100, Crete, Greece. kouroum@med.uoc.gr
Telephone: +30-2810-542085 Fax: +30-2810-542085
Received: November 18, 2005
Revised: December 2, 2005
Accepted: December 22, 2005
Published online: April 21, 2006

Primary biliary cirrhosis (PBC) is a disease of unknown etiology leading to progressive destruction of small intrahepatic bile ducts and eventually to liver cirrhosis and failure. It is characterised by female predominance and serum auto-antibodies to mitochondrial antigens targeting the E2 components of the 2-oxoacid dehydrogenase complex. Although they are associated with disease pathogenesis, no concrete evidence has been presented so far. Epidemiological data indicate that a geographical clustering of cases and possible environmental factors are implicated in pathogenesis. A number of genetic factors play a role in determining disease susceptibility or progression, although no definitive conclusion has been reached so far. A key factor to immune pathogenesis is considered to be the breakdown of immune tolerance, either through molecular mimicry or through the so called determinant density model. In this review, the available data regarding the pathogenesis of primary biliary cirrhosis are described and discussed. A new unifying hypothesis based on early endothelin overproduction in primary biliary cirrhosis (PBC) is presented and discussed.

Keywords: Primary biliary cirrhosis, Pathogenesis