Canine copper-associated hepatitis: A retrospective study of 17 clinical cases

Abstract

Background: Copper-associated hepatitis (CAH) is a well-documented chronic hepatic disease in dogs. In some breeds, the disease results from an inherited defect in copper metabolism. In others, it is unclear whether its acummulation is a primary or secondary condition. Reports of copper accumulation in dog breeds that are not genetically predisposed are increasing.Aim: To describe the epidemiology, clinical and laboratory findings, liver biopsy techniques, and treatment response in dogs with CAH.Methods: A retrospective study was performed, drawing upon medical records from CAH dogs at a Veterinary Referral Hospital in Paris, France. The diagnosis of CAH had been confirmed in these patients by positive rhodanine staining of hepatic tissue obtained through biopsy. Medical records were mined for the following data: age at presentation, sex, breed, chief presenting complaints, abdominal ultrasound (US) findings, and rhodanine staining pattern.Results: A total of 17 dogs were included in the study. Median age at presentation was 8-year old (4–11). No sex predisposition was found. Terriers (4/17) and German Shepherd Dogs (GSD, 3/17) were overrepresented. American Staffordshire Terriers and Beauceron had not previously appeared in case reports on CAH; two of each breed were identified in this study. Clinical signs of affected dogs were non-specific. An incidental identification of increased liverenzymes was observed in 5/17 dogs. A heterogeneous, mottled liver was frequently described (5/17) on abdominal US. Liver biopsies were performed by US-guided percutaneous approach in 10/17 dogs, laparoscopy and laparotomy in 6/17 and 1/17, respectively. The rhodanine staining pattern was centrilobular (zone 3) in 8/17 dogs and periportal (zone 1) in 3/17 dogs. The pattern was considered multifocal in 6/17 dogs.Conclusion: Increased liver enzymes may be the only clinical finding in dogs with copper-associated hepatitis, reflecting the silent progression of this disease. Centrilobular pattern of rhodanine staining was observed in the majority of cases suggesting the primary condition of the disease. Results of this study are consistent with the current literature, which reports that terriers and GSD are predisposed to CAH. This is the first description of CAH in Beauceron and American Staffordshire Terrier dogs.
 Keywords: American Staffordshire Terrier, Beauceron, Copper-associated hepatitis, Liver biopsy, Rhodanine.

Copper‐associated chronic hepatitis in Cavalier King Charles spaniels

“…29 Furthermore, significant copper staining is also observed within regenerative nodules, 29,47 similar to the dogs in this study. Furthermore, in different breeds of dog, other patterns of copper staining (including periportal ones) have been described, 22 with one study describing a multifocal pattern of HCA in LRs. 39 In addition, HCA and copper staining are either absent, 35,36 or mild and mostly centrilobular, 36 in dogs with extrahepatic cholestatic diseases, and in the present study, 40% of the CKCS had only mild increases in serum bilirubin concentration, suggesting that cholestasis was not a prominent feature in these dogs.…”

Low alanine aminotransferase activity gene variant in a Siberian Husky with copper-associated hepatopathy

“…Chronic hepatitis can be present in dogs with normal serum liver enzyme activities, despite being the most common biochemical abnormality in dogs with chronic hepatitis (4). In one study of dogs with CuCH, ALT activity was increased in all cases where it was measured; however, hepatic copper concentrations were not measured, precluding more direct comparisons (12). This case represents an additional challenge as serum ALT activity is frequently used as a surrogate marker for hepatocellular injury to guide therapy in dogs with CuCH (4).…”

Primary copper-associated chronic hepatitis without copper metabolism domain containing 1 mutation in a Dalmatian: a case report

“…The liver is an important organ for maintaining copper homeostasis, which stores copper and excretes excessive copper via the biliary system [1,2]. Excessive accumulation of copper in the hepatocytes can cause oxidative damage and inflammation, leading to copper-associated hepatitis [3][4][5][6]. Copper-associated hepatitis is diagnosed when significant copper accumulation is identified in the centrilobular areas (zone 3) on histological examination and copper concentrations over 1,000 ppm are confirmed in copper quantitation [7].…”

“…Copper-associated hepatitis can be classified into 2 broad categories, primary and secondary, depending on the underlying cause [4]. Primary copper-associated hepatitis is mainly related to genetic defects in copper metabolism and this type of disease has been reported in many breeds of dog, including Bedlington Terrier, Labrador Retriever, Doberman Pinscher, Dalmatian, West Highland White Terrier, and Skye Terrier [3][4][5]. In Bedlington Terrier, this disease was an inherited autosomal recessive disorder caused by a large deletion in exon 2 of the copper metabolism domain containing 1 (COMMD1) gene [1,6,8,9].…”

“…However, except for the Bedlington Terrier, the exact mechanisms of this disease are unknown in other breeds [3,10]. Recent reports of copper-associated hepatitis in dogs with no genetic predisposition, such as German Shepherds and Cocker Spaniels, suggest that environmental exposure to unknown factors may influence the pathogenesis of the disease [4].…”