title: Copper-associated chronic hepatitis in Labrador Retrievers.
abstract: This study summarizes the clinical and pathologic findings in 15 Labrador Retrievers with copper-associated chronic hepatitis (CACH). Our hypothesis was that this form of hepatitis is caused by a defect in hepatic copper metabolism, which most likely originates from a genetic defect. Affected Labradors consisted of 11 female and 4 male Labrador Retrievers. Eight family members of 2 of these patients were examined prospectively, as were 6 unrelated healthy Labrador Retrievers. All dogs were registered at the breed club. The average age at clinical presentation was 7 years (range, 2.5-10.5 years). All dogs were presented for anorexia, which was associated with vomiting in 8 patients. The diagnosis of CACH was based on histologic examination of liver biopsy specimens in all dogs, including semiquantitation of copper. A disproportionate increase in alanine aminotransferase (ALT) activity relative to alkaline phosphatase (ALP) activity, as well as the centrolobular localization of copper and the association of copper accumulation with hepatic lesions, suggested a primary copper storage disease rather than primary cholestatic liver disease causing copper accumulation. Mean hepatic copper concentration measured in related Labradors was 1,317 microg/g dry weight liver (range, 402-2,576 microg/g). Mean hepatic copper concentration of unrelated normal Labradors was 233 microg/g dry weight liver (range, 120-304 microg/g). Our findings support the hypothesis that a hereditary form of hepatitis occurs in Labrador retrievers and is caused by a defect in hepatic copper metabolism.
authors.affiliation: Department of Clinical Sciences of Companion Animals, Faculty of Veterinary Medicine, Utrecht University, Netherlands. G.Hoffmann@vet.uu.nl
authors.forename: G
authors.initials: G
authors.lastname: Hoffmann
authors.forename: T S G A M
authors.initials: TS
authors.lastname: van den Ingh
authors.forename: P
authors.initials: P
authors.lastname: Bode
authors.forename: J
authors.initials: J
authors.lastname: Rothuizen
mesh_terms: D000410:Alanine Transaminase / Q000097:blood; D000469:Alkaline Phosphatase / Q000097:blood; D000818:Animals; D003300:Copper / Q000032:analysis / Q000378:metabolism*; D004283:Dog Diseases / Q000209:etiology* / Q000235:genetics; D004285:Dogs; D005260:Female; D020022:Genetic Predisposition to Disease; D006521:Hepatitis, Chronic / Q000188:drug therapy / Q000235:genetics / Q000662:veterinary*; D008099:Liver / Q000737:chemistry / Q000473:pathology; D008297:Male
chemical_list: D003300:Copper; D000410:Alanine Transaminase; D000469:Alkaline Phosphatase