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 mg/g dry weight liver (range, 402-2,576 mg/g). Mean hepatic copper concentration of unrelated normal Labradors was 233 mg/g dry weight liver (range, 120-304 mg/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.

Dependence between Cu concentration in the liver, kidneys and skeletal muscles of canine females

“…Copper toxicosis in some dog breeds arouses interest of many scientists due to its specific pathogenesis and numerous similarities to the storage diseases observed in human beings, such as Wilson's disease [2,5]. Up till now the hereditary copper toxicosis has been diagnosed, among others, in Bedlington terriers, Skye terriers, West highland white terriers, Dalmatians, Dobermanns and Retrievers [2,[5][6][7][8][9][10]. Genetic studies in the Bedlington terriers identified COMMD1 gene which plays an important role in copper metabolism.…”

Hepatic copper and iron accumulation and histologic findings in 104 feline liver biopsies

“…Unlike the Barton grading system, staining in the connective tissue in portal areas was not assessed. Previously published copper grading systems 7,21 graded the amount of copper staining on a scale of 0 (none) to 5 (abundant). This copper grading scheme was modified and simplified to match the iron grading system utilized.…”

A retrospective study of oral prednisolone treatment in canine chronic hepatitis

“…Dogs with histology-proven chronic hepatitis without any aetiology-specific changes, as described by the WSAVA liver standardization group, were included. Dogs with copper-associated chronic hepatitis, with a score !2 on a scale ranging from 0 to 5, were excluded 1 ( Van den Ingh et al 1988;Hoffmann et al 2006;Spee et al 2006), as were dogs with Leptospirosis, Leishmaniasis, and Herpesvirus infections, based on histopathology and serology in cases with clinical or clinicopathological signs suggestive of these infectious agents. Thirty-six dogs with chronic idiopathic hepatitis were included in the study.…”

“…Known aetiologies include viruses, toxins, and drugs (Watson 2004;Boomkens et al 2005;Rallis et al 2005;Decaro et al 2005;Newman et al 2007;Wagner et al 2007). Hepatic accumulation of copper is a major cause of chronic hepatitis in many breeds (Labrador retriever, Dalmatian, Dobermann, spaniel breeds, West Highland terriers, Bedlington terriers) and may account for about 35% of all cases of hepatitis in a referral hospital population (Van den Ingh et al 1988;Brewer et al 1992;Honeckman 2003;Mandigers et al 2005;Hoffmann et al 2006;Spee et al 2006;Poldervaart et al 2009;Smedley et al 2009). However, in the vast majority of dogs the aetiology of hepatitis is unknown and the disorder is referred to as idiopathic hepatitis.…”