Histological demonstration of copper and copper-associated protein in chronic liver diseases

Liver copper concentrations in percutaneous biopsy specimens were measured by neutron activation analysis and compared with histological staining for copper by rubeanic acid and rhodanine, and with copper-associated protein stained by orcein. Liver copper concentrations were elevated in 31 of 35 biopsies from patients with primary biliary cirrhosis (PBC), and discrimination between normal and elevated liver copper was correct in 32 of the 35 biopsies by staining with rubeanic acid, and 31 of the 35 by staining with rhodanine. Orcein staining of copper-associated protein was positive in 33 of the 35 biopsies. All 17 biopsy specimens from patients with Wilson's disease had high liver copper concentrations, but only nine had positive staining for copper, and six were orcein positive. Similarly, histological stains gave little indication of the liver copper concentrations in tissue from 16 patients with chronic active hepatitis. Staining of liver sections can be useful in detecting elevation of liver copper in PBC, but not in Wilson's disease, where the absolute concentration must be measured. Excess copper appears to accumulate in the liver in different chemical forms in PBC and Wilson's disease.