INTRODUCTION
Biliary cirrhosis is a condition that slowly damages the bile ducts in the liver. In time, the flow of bile is restricted and bile builds up in the liver. This damages liver cells which in some cases leads to cirrhosis. Biliary cirrhosis is a rare form of liver cirrhosis, caused by disease or defects of the bile ducts. Symptoms usually include cholestasis (accumulation of bile in the liver). There are two types of biliary cirrhosis:
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Environmental Factors
Molecular mimicry is the most widely proposed mechanism for the initiation of autoimmunity in primary biliary cirrhosis. Several candidates have been suggested as causative agents, including bacteria, viruses, and chemicals in the environment. Bacteria, in particular Escherichia coli, have attracted the most attention because of the reported elevated incidence of urinary tract infections in patients with primary biliary cirrhosis and the highly conserved nature of the mitochondrial autoantigens.
AUTOIMMUNE RESPONSES
a. Antimitochondrial-antibody response
The targets of the antimitochondrial antibodies are members of the family of the 2-oxo-acid dehydrogenase complexes, including the E2 subunits of the pyruvate dehydrogenase complex, the branchedchain 2-oxo-acid dehydrogenase complex, the ketoglutaric acid dehydrogenase complex, and the dihydrolipoamide dehydrogenase–binding protein. There is substantial homology among these four autoantigens, and all participate in oxidative phosphorylation and share lipoic acid moieties (Fig. 2).
Most commonly, antibodies react against the pyruvate dehydrogenase E2 complex (PDC-E2); antibodies from some patients react with PDC-E2 alone, whereas antibodies from most patients also show reactivity against the branched-chain 2-oxo-acid dehydrogenase E2 complex, the ketoglutaric acid dehydrogenase E2 complex, or both.
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PRIMARY BILIARY CIRRHOSIS (PBC)
This is a slowly progressive disease of the liver and biliary system, with destruction of the small interlobular bile ducts, cholestasis, fibrosis and eventually cirrhosis. Cirrhosis is a late feature.
EPIDEMIOLOGY
g The prevalence has been estimated as 12.9 per 100,000 population in the UK with up to 90% being women.
g It is commoner amongst those of northern European descent and less common amongst those of African origin.
g Diagnosis is usually between about 45 and 55 years old.
g The prevalence appears to be rising since 1980. This may be in part due to increased survival but also better awareness of the disease leading to more frequent diagnosis. Nevertheless, there does seem to be evidence of a true increase in incidence
AETIOLOGY
Epidemiologic and genetic factors
Primary biliary cirrhosis is most prevalent in northern Europe. The prevalence differs considerably in different geographic areas, ranging from 40 to 400 per million. Primary biliary cirrhosis is considerably more common in first-degree relatives of patients than in unrelated persons. The available data indicate that 1 to 6 percent of all patients have at least one affected family member, with mother– daughter and sister–sister combinations occurring most often. The concordance rate of primary biliary cirrhosis in monozygotic twins is 63 percent.
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