Hepatic copper accumulation in patients with primary biliary cirrhosis.

Liver biopsy specimens from 18 patients with primary biliary cirrhosis were examined histochemically and by energy-dispersive x-ray microanalysis. Using two indices, we classified hepatic copper accumulation into three stages based on the Cu x-ray intensity of cuproproteins that had accumulated in hepatocyte lysosomes and on the binding ratio of postulated copper transfer proteins between the cytosol and lysosomes. Eight patients were in stage 1 with an initial accumulation of lysosomal cuproproteins, mediated by transfer proteins not saturated with copper. Two patients were in stage 2, in which transfer proteins were saturated with copper. The first two stages gave negative results for histochemical copper. The remaining eight patients were in stage 3, in which copper accumulation detected by histochemical included transfer proteins saturated with copper and large amounts of lysosomal cuproproteins. Five patients (one each in stages 1 and 2, and three in stage 3) underwent a second liver biopsy after treatment with 600 mg of ursodeoxycholic acid daily for 14 to 39 months. Results of blood chemistry tests improved, but liver histologic findings and copper accumulation were unchanged in all five patients. It seems likely that ursodeoxycholic acid does not affect the copper accumulation in hepatocyte lysosomes that reflects the state of cholestasis in patients with primary biliary cirrhosis.