Taken together, the findings indicate that cirrhosis appears to be a more important predictor of glucose intolerance than HCV infection, and the combination of both factors increases the risk of DM in our populations.

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A 17-year-old male patient appeared with the biochemical liver damage associated with hypoceruloplasminemia and mild iron overload. Genetic analysis identified a compound heterozygosity of ATP7B responsible for the primary copper toxicosis of Wilson disease without mutations in HFE. A liver specimen consisted of cirrhotic nodules of large-sized hepatocytes with fatty change and those of fat-free small-sized hepatocytes. Histochemically, iron was distributed diffusely in the small-sized hepatocytes, while copper grains appeared in a few of the hepatocytes near the fibrous bands. X-ray microanalysis on the liver tissue fixed with a 0.1% osmium tetroxide solution and embedded in epoxy resin disclosed (1) complex formation of copper with sulfur, and iron with phosphorus in the hepatocyte lipofuscin particles, (2) intraparticle localization of the cuprothionein in the less dense matrix and ferric proteins in the dense matrix, and (3) high affinity of the cuprothionein to lead staining. Considering the fact that ceruloplasmin is the major ferroxidase essential for iron efflux, iron deposits in the hypoceruloplasminemic patients with Wilson disease are not a complication, but a natural event. This study disclosed for the first time the diagnostic ultrastructures of Wilson disease, which might represent different detoxification processes to the reactive metals of copper and iron.

Ceruloplasmin is a major ferroxidase in sera, and people with hypoceruloplasminemia might have iron load complications. We used histochemical and X-ray microanalysis techniques on pretreatment liver specimens from five patients with WilsonÕs disease. Serum levels of ceruloplasmin and ferritin were determined before chelation therapy. All the patients showed hypoceruloplasminemia ranging from 15 to 160 mg/L. Histochemical copper was positively stained in four of the five patients. Copper deposits were clearly observed in the hepatocyte lysosomes of one patient. High serum ferritin levels ranging from 188 to 400 ng/mL were found. Histochemical iron was positive in the livers of two patients. Iron-specific X-rays were positive in the hepatocyte lysosomes of all the patients. These findings suggest that compound load of copper and iron is a fundamental finding in the liver of WilsonÕs disease with hypoceruloplasminemia. Copper cytotoxicity is a primary target for chelation therapy, and iron load, if hepatotoxic, should be treated by phlebotomy.

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