Page 25 - Copper-associated hepatitis in the Labrador retriever diagnosis, treatment and genetics

General introduction
Figure 2 Histological appearance of copper-associated hepatitis in different dog breeds. Liver biopsies are stained with rubeanic acid and haematoxylin counterstain. A) Liver biopsy of a Bedlington terrier clearly showing centrolobular distribution of copper. B) Liver biopsy of a Bedlington terrier (female, 3 years old, hepatic copper concentration 11,500 μg/g dwl). A large number of copper granules are visible mainly in hepatocytes but also in Kupffer cells. The central vein is located in the middle of the picture. C) Liver biopsy of a Labrador retriever (female, 5 years old, hepatic copper concentration 2,360 μg/g dwl). Copper granules are present in hepatocytes and macrophages in the centrolobular area. The centrolobular region at the right area of the picture is characterized by loss of hepatocytes, mild fibrosis and moderate numbers of lymphocytes and plasma cells. D) Liver biopsy of a Dobermann (female, 6 years old, hepatic copper concentration of 1,700 μg/g dwl). The centrolobular area is characterized by mild fibrosis with multifocal accumulation of macrophages containing lipofuscin pigment and copper granules. This area shows moderate infiltration with lymphocytes. Hepatocytes in the centrolobular region contain moderate amounts of copper granules.
subclinical hepatitis was present and hepatic copper concentrations increased to 1,000 μg/g dwl over time. The etiological role of copper was demonstrated by the dramatic improvement of the prognosis upon treatment with D-penicillamine associated with a normalization of copper concentrations115. Mandigers et al. also demonstrated that the biliary excretion of intravenously injected 64Cu tends to be decreased in affected Dobermanns128. MHC class II antigen expression was detected in hepatocytes in cases with Dobermann hepatitis, but not in control tissue129, therefore Dobermann hepatitis was suggested to be an auto-immune disease. Induction of MHC class II antigen
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Chapter 1