Observations on copper associated protein in childhood liver disease.
Hepatic copper concentrations were compared with staining grades of copper associated protein (CAP) and histochemical copper in liver sections from 44 patients (one fetus, one pre-term infant, four term infants, eight normal children, 16 children with various liver diseases, and 14 patients with intrahepatic cholestasis of childhood (IHCC)). A similar comparative study of hepatic copper concentration with CAP and histochemical copper was performed in 21 patients with Wilson's disease. CAP occurred in the fetus, pre-term infant, and term infants without liver disease. This suggests that CAP is a normal constituent of the hepatocyte and is not a consequence of liver disease or biliary obstruction. CAP was not seen when hepatic copper concentration was normal; it was absent in eight children with no evidence of liver disease, eight children with non-cirrhotic liver disease, and seven of eight children with cirrhosis. When hepatic copper concentration exceeded 4.0 mumol/g dry liver weight grade 2 or grade 3 staining for CAP and histochemical copper was found in the fetus, pre-term infant, infants, and IHCC. CAP was found in IHCC only in the presence of raised hepatic copper levels, supporting evidence of a relationship between copper and CAP. In 17 of 21 patients with Wilson's disease hepatic copper concentrations exceeded 4 mumol/g. Positive staining for CAP was seen in seven of these patients being usually grade 1. CAP is a normal associated protein, present when hepatic copper concentrations are increased in normal liver cells. It is usually absent in hepatocytes from Wilson's disease despite similar hepatic copper levels. CAP may represent material which protects the hepatocyte from the toxic effects of copper.
D000293:Adolescent; D000328:Adult; D002352:Carrier Proteins / Q000032:analysis*; D002648:Child; D002675:Child, Preschool; D002780:Cholestasis, Intrahepatic / Q000378:metabolism; D003300:Copper / Q000032:analysis*; D005260:Female; D005333:Fetus / Q000032:analysis; D006527:Hepatolenticular Degeneration / Q000378:metabolism; D006651:Histocytochemistry; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007232:Infant, Newborn, Diseases / Q000378:metabolism; D008099:Liver / Q000032:analysis; D008107:Liver Diseases / Q000378:metabolism*
D002352:Carrier Proteins; C023548:copper-binding protein; D003300:Copper