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Background/Aims: Determination of hepatic copper concentration is important in the diagnosis of Wilson's disease. We studied copper distribution 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 by Induced Coupled Plasma Atomic Emission Spectroscopy. Results: The mean copper concentration in the liver was 1370 μg/g dt. A striking variability, up to 2–3-fold, in copper levels was observed between the samples: the copper concentration ranged from 880 to 2100 μg/g dt, with significant differences even between adjacent samples. Lobar differences were also observed, with a tendency of the right lobe to accumulate more copper than the left lobe. Histochemical analyses confirmed the uneven distribution of copper even at the acinar level. Copper was mainly stored in periportal hepatocytes (zone 1) and at the periphery of the regenerating nodules. Moreover, we observed some nodules with the majority of hepatocytes full of copper granules, adjacent to areas of parenchyma negative for copper stains. Conclusions: Our data show that: 1) copper is unevenly distributed in Wilson's disease in the cirrhotic stage; 2) a lobar pattern of copper distribution is evident in this case, characterized by a higher copper concentration in the right lobe; 3) the observed lobal pattern is different from that described in the newborn liver, characterized by a higher copper content in the left 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 the diagnosis and in the monitoring of Wilson's disease. The use of hepatic copper concentration in monitoring the efficacy of the copper-chelating therapy may be unreliable, particularly in the cirrhotic stage, because of the patchy distribution of copper, as demonstrated in this study.

Background/Aims: Determination of hepatic iron concentration is crucial in the evaluation of iron-storage disease. Iron content in normally determined in a part of a needle liver biopsy and the value obtained is considered to be representative of the iron concentration in the whole liver. To evaluate the reliability of this procedure, we studied iron distribution in the liver of two beta-thalassemic patients. Since the transport of intracellular iron is mediated by phosphates, we also studied the hepatic phosphorus distribution. Methods: At autopsy, a liver slice extending from the left to the right lobe was divided into 51 and 49 samples, respectively. Each specimen was subdivided into two parts: oen of them was paraffin-embedded and utilized for the histochemical detection of iron: the second part was analyzed for iron and phosphorus content by induced coupled plasma atomic emission spectroscopy. Results: The histological picture of both livers was characterized by portal and periportal fibrosis associated with iron storage of different degree, without cirrhosis. The mean iron concentration of the liver was 20 631±4903 μg per g of dry tissue (μg/g dt) and 13 901±1976 μg/g dt, respectively. A striking variability in iron content between samples was also found: iron concentration ranged from 11 537 to 32 347 μ/g dt in the first case and from 6257 to 16 493 in the second case. We even observed regional differences in iron concentration, with a preferential peripheral accumulation in both cases and a tendency of the left compartment of the liver to accumulate more iron in the first case. Histochemical analyses confirmed the uneven iron distribution even at the acinar level, showing iron mainly being stored in hepatocytes and Kupffer cells of zone 1 of the acinus, with decreasing amounts of iron in zones 2 and 3. The mean hepatic phosphorus concentration was 6662± 1300 μ/g dt (range: 4348–9947) and 7502±986 μ/g dt (range: 5844–90 282), respectively. The regional distribution of phosphorus was similar to that observed for iron. A strict correlation between iron and phosphorus content was also observed. Conclusions: Our data show that: 1) iron and phosphorus are unevenly distributed in the beta-thalassemic liver, even in the non-cirrhotic stages; 2) a regional pattern of iron and phosphorus distribution is evident, characterized by higher concentrations at the periphery of the liver; 3) the observed uneven distribution of iron and phosphorus implies that their content determined in a small liver sample cannot be considered as absolutely representative of the mean hepatic iron concentration. Therefore, iron concentrations determined in a part of a needle liver biopsy should be interpreted with caution in monitoring the efficacy of the iron-chelating therapy in beta-thalassemic patients.