UNEVEN HEPATIC COPPER DISTRIBUTION IN WILSONS-DISEASE

Background/Aims: Determination of hepatic copper concentration is impo rtant in the diagnosis of Wilson's disease, We studied copper distribu tion in the cirrhotic liver of a patient who died of Wilson's disease. Methods: A liver slice extending from the left to the right lobe was divided into 38 samples. Each sample was analyzed for copper content b y Induced Coupled Plasma Atomic Emission Spectroscopy. Results: The me an copper concentration in the liver was 1370 mu g/g dt, A striking va riability, up to 2-3-fold, in copper levels was observed between the s amples: the copper concentration ranged from 880 to 2100 mu g/g dt, wi th significant differences even between adjacent samples, Lobar differ ences were also observed, with a tendency of the right lobe to accumul ate more copper than the left lobe, Histochemical analyses confirmed t he uneven distribution of copper even at the acinar level, Copper was mainly stored in periportal hepatocytes (zone I) and at the periphery of the regenerating nodules, Moreover, we observed some nodules with t he majority of hepatocytes full of copper granules, adjacent to areas of parenchyma negative for copper stains. Conclusions: Our data show t hat: 1) copper is unevenly distributed in Wilson's disease in the cirr hotic stage; 2) a lobar pattern of copper distribution is evident in t his case, characterized by a higher copper concentration in the right lobe; 3) the observed lobar pattern is different from that described i n the newborn liver, characterized by a higher copper content in the l eft compartment of the liver; 4) copper content determined in a small liver sample cannot be considered as absolutely representative of the mean hepatic copper concentration. From a practical point of view, our data show that sampling variability deserves more consideration in th e diagnosis and in the monitoring of Wilson's disease. The use of hepa tic copper concentration in monitoring the efficacy of the copper-chel ating therapy may be unreliable, particularly in the cirrhotic stage, because of the patchy distribution of copper, as demonstrated in this study.