Different pathomorphologic patterns in exogenic infantile copper intoxication of the liver

Pathomorphology of the liver has been reviewed in 12 German infants with chronic exogenic copper intoxication. In 8 cases severe liver damage with diffuse accumulation of Mallory bodies and liver cell necrosis mimicking florid Indian childhood cirrhosis (ICC) was found. Seven of these children died because of liver failure. One child received liver transplantation at the age of 9 months. In contrast, 4 children with a stable clinical course had a complete micronodular cirrhosis in liver biopsy. The characteristic morphological features of ICC, especially ballooning of liver cells and accumulation of Mallory bodies, were only slightly expressed or even lacking. There was no correlation between the copper content of the liver and the severity of liver damage. The copper concentration varied between 541 micrograms/g dry weight (norm < 50 micrograms/g) and 2.154 micrograms/g dry weight in fatal cases. In surviving infants even higher concentrations of up to 698 micrograms/g fresh weight (norm < 5 micrograms/g), were found. The amount of free cytosolic copper varied between 900-4,900 ng/mg protein (13-70 times of normal). In conclusion, a spectrum of pathomorphological alterations exists in exogenic infantile copper disease which correlates with the clinical outcome in contrast to the copper content of the liver. Copper intoxication of the liver should be of diagnostic concern in any case of unclear micronodular cirrhosis in early infancy.