ABSTRACT
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.
Subject(s)
Copper/analysis , Hepatocytes/ultrastructure , Hepatolenticular Degeneration/pathology , Inclusion Bodies/ultrastructure , Iron/analysis , Adenosine Triphosphatases/genetics , Adolescent , Cation Transport Proteins/genetics , Ceruloplasmin/analysis , Copper/metabolism , Copper-Transporting ATPases , Electron Probe Microanalysis , Hemochromatosis Protein , Hepatocytes/chemistry , Hepatolenticular Degeneration/metabolism , Histocompatibility Antigens Class I/genetics , Histocytochemistry , Humans , Immunohistochemistry , Iron/metabolism , Lipofuscin/chemistry , Lipofuscin/metabolism , Male , Membrane Proteins/genetics , Microscopy, Electron, Transmission , MutationABSTRACT
BACKGROUND: To examine the relationship between hepatitis C virus (HCV) infection and diabetes mellitus (DM) in Japanese populations, a retrospective study was done in 866 patients with chronic viral disease. METHODS: The present study included 707 HCV-infected and 159 hepatitis B virus (HBV)-infected patients. The prevalences of HBV- and HCV-related cirrhosis were 32% and 33%, respectively. A case-control study was also conducted to determine the seroprevalence of HCV infection in a cohort of 459 diabetics. RESULTS: The prevalence of DM was higher in HCV-infected patients (20.9%; P < 0.02) than in HBV-infected subjects (11.9%). In the cirrhotic patients, DM was observed in 30.8% of the subjects with HCV compared with 11.8% of those with HBV ( P < 0.01). Multivariate analysis revealed that the major independent variables associated with type II DM were male sex (odds ratio, 1.54; p = 0.020) and cirrhosis (odds ratio, 1.97; P = 0.0007). The relative odds of the development of DM were calculated to be 3.2 times higher in HCV-infected cirrhotic patients than in HBV-infected ones. In the case-control study of the diabetic cohort, 10.5% of patients were infected with HCV compared with 1.1% with HBV ( P < 0.0001). The results indicate that HCV infection is closely associated with DM, compared with HBV infection. Cirrhosis was an independent risk factor for DM. CONCLUSIONS: 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.
