Abstract
Non-Wilsonian hepatic copper toxicosis of infancy and childhood includes pathologically indistinguishable liver disorders in which there is increasing evidence for a genetic predisposition to a raised copper intake. North Ronaldsay sheep, a possible animal model ofthe human disease, likewise display a susceptibility to environmental copper with a similar pathology in respect to liver copper accumulation associated with a florid pericellular fibrosis. The aim of this retrospective study was to establish the morphological basis of copper-induced fibrogenesis in North Ronaldsay sheep in order to increase understanding of the childhood disorder. Livers from 13 mainland-bred North Ronaldsay sheep and 3 island-bred sheep were categorized for liver copper content and patho-morphology, particularly with regard to hepatic stellate cell transformation as indicated by α-smooth muscle actin (ASMA) and collagen production. It was found that all 13 mainland-bred sheep contained excess liver copper and exhibited pathological changes characterized by pericellular fibrosis. EM identified large numbers of collagen-producing hepatic stellate cells. Immunocytochemistry confirmed the prescence of ASMA in transformed hepatic stellate cells conforming to the patterns of fibrosis. Copper-induced dysregulation of hepatic stellate cells from a vitamin A storing phenotype to one of collagen synthesis plays an important role in the pathogenesis of RCT and by analogy may also operate in non-Wilsonian childhood copper toxicosis.
Published Version
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