Liver copper levels in intrahepatic cholestasis of childhood

Liver copper concentration was studied in four groups of age-matched patients and in 9 patients with Wilson's disease of comparable age. Neutron activation analysis of hepatic copper concentration revealed markedly elevated hepatic copper levels, comparable with those in Wilson's disease, in 13 of 15 patients (P less than 0.001) with intrahepatic cholestasis of childhood. In 1 patient, autopsy confirmed very high liver copper values, whereas other tissues, including brain and kidney, gave normal results. Total plasma copper values were elevated in 11 of 13 patients with intrahepatic cholestasis of childhood (P less than 0.001); 24-hr urinary copper excretion was normal in 7 of 12 patients and slightly elevated in 5 (P less than 0.001). Kayser-Fleischer rings were sought in 10 patients and were absent. Hepatic copper concentration was not accurately predicted by plasma copper or 24-hr urinary copper. However, increased urinary copper excretion was associated with hepatic copper concentration greater than 250 microgram per g. It is concluded that copper metabolism is abnormal in intrahepatic cholestastis of childhood and can be distinguished from Wilson's disease. If hepatic copper concentration is greater than 250 microgram per g, copper chelation therapy should be considered.