Copper and hepatic function.

When hepatic excretion of copper into bile is impaired, the amount of copper in the liver increases. This happens in extrahepatic cholestasis, primary biliary cirrhosis and in two inherited diseases of copper disease. By six months of age the homozygously affected Bedlington terrier has already begun to accumulate copper in its liver. The trend continues, peaking at the age of five to eight years, when hepatic copper may exceed 10 000 microgram/g dry weight (normal 90--400 microgram/g in livers from mongrels). Despite these concentrations, which are several times higher than those found in any human disease, there is remarkable little evidence of hepatic inflammation or fibrosis in younger Bedlington terriers. The copper is condensed in lysosomes and is identified by X-ray emission spectroscopy. Hepatic cirrhosis eventually develops and death is often associated with ascites and jaundice. Despite characteristic histological differences between the livers in Wilson's disease and in the Bedlington disease, there is a striking general resemblance between the two conditions.