THE SIGNIFICANCE OF VARIATIONS IN THE DISTRIBUTION OF COPPER IN LIVER-DISEASE

  • 1 January 1980
    • journal article
    • research article
    • Vol. 99  (3) , 715-729
Abstract
Biopsy and autopsy liver specimens from patients with Wilson''s disease in various stages, chronic cholestatic conditions (including primary biliary cirrhosis, extrahepatic biliary obstruction, sclerosing cholangitis and biliary atresia), chronic active hepatitis and Indian childhood cirrhosis, as well as normal neonates, were examined by histochemical techniques for Cu, and Cu-associated protein. The intracellular localization of Cu and the lobular distribution of the metal and its associated protein differed in these conditions. Periportal hepatocytes containing granules (lysosomes) that were reactive for Cu and for Cu-associated protein were characteristic of cholestasis and neonatal liver. In cholestasis extralysosomal Cu was often present in the hepato-cellular cytoplasm. In Wilson''s disease, despite very high concentrations of Cu in the early stages, the metal was diffuse in the cytoplasm and the histochemical reactions for granular Cu and its associated protein were usually negative. A failure to stain for Cu does not exclude the diagnosis of Wilson''s disease. In the late stages of Wilson''s disease staining varied in different nodules. In Indian childhood cirrhosis Cu was present throughout the parenchyma, with periportal predominance. Differences in the distribution of Cu and the cellular changes associated with its deposition suggest different pathogenetic mechanisms and possibly different intracellular targets are susceptible to the toxic effects of the metal. For diagnosis, staining for Cu and for Cu-associated protein may assist in the differentiation of primary biliary cirrhosis from chronic active hepatitis.