Pertinent Breeds

Hepatitis associated with copper storage disease in dogs can be acute, subacute, or chronic, although it is often characterized as chronic hepatitis. The breeds affected with copper storage disease are listed in Table 62-7 along with evidence of heritability. Some of these same breeds are affected by a separate idiopathic chronic hepatitis not associated with copper storage disease (Table 62-8) and there are geographical variations in the relative proportions of each of these diseases (Tables 62-7 and 62-8). Consequently, liver biopsies and copper determinations are very important for effective diagnosis and treatment of hepatitis in these breeds. Bedlington Terriers are the original, and best understood, example of canine copper storage disease, but other breeds have been more recently reported. Copper storage disease has only been reported in a small number of cats (Table 62-7).

Table 62-7 Breed Relationships in Copper Storage Disease in Dogs and Cats

Table 62-8 Breed Associations in Canine Idiopathic Chronic Hepatitis

Disease Association

Copper storage disease in dogs affects the liver and not other organs, unlike Wilson’s disease in humans, which affects other parts of the body such as the eyes and basal ganglia. In one feline case report, copper was found in the epithelium of the proximal convoluted tubules and collecting ducts of the kidney, and alveolar epithelium and macrophages in the lung.²

Evidence of Heritability

Heritability of copper storage disease has been reported extensively in the Bedlington Terrier and to a lesser extent in the Labrador Retriever and West Highland White Terrier breeds (see Table 62-7). Evidence in other breeds is restricted to isolated case reports (see Table 62-7).

Definitive Diagnosis

In the normal liver, copper is excreted in the bile. Consequently, it can build up in the periportal area (zone 1) secondary to cholestasis. It is important to differentiate this “secondary” copper retention from “primary” copper storage disease where the degree of pathology is directly related to the amount of copper found in the centroacinar area (zone 3). Any breed of dog will show evidence of copper-associated hepatotoxicity if there is a large excess of copper in the diet. What is accepted as a “normal” hepatic copper concentration has increased over the last 30 to 40 years. Increasing reports of copper storage disease in dogs may represent an interaction between genetic susceptibility and dietary copper content. Diagnosis can only be definitively obtained with liver biopsy. Ideally, a large sample (at least 1 g of tissue) should be submitted for copper determination, and histopathology should be performed with a copper stain (rubeanic acid or rhodanine) to show copper distribution in the liver and its association with pathology. If measurement of copper content is not possible, a semiquantitative estimate of copper content can be made with histologic scoring as described by Hoffman and others.³ A genetic screening test is now available for copper storage disease in Bedlington Terriers, but there are inconsistent results in some cases, as detailed in Table 62-7.

Therapy

Copper storage disease can be successfully managed with diet and chelating agents (see Chapter 43), particularly if diagnosed early, or, better still, it can be prevented in susceptible individuals by feeding a low-copper diet from weaning. Chapters 32, 43, and 61 describe the details of therapy.

Pertinent Breeds

Chronic hepatitis is the most common liver disease recognized in dogs, with a reported prevalence of 12% in older dogs in the United Kingdom.⁴ The current prevalence in the United States is unknown. In those cases not associated with copper storage disease, the cause remains unknown. It can occur in any breed or crossbreed, but there are reports of increased prevalence in certain breeds as outlined in Table 62-8. These increased prevalences provide opportunities for research in to the cause(s) of this disease, and the causes are likely to be different in different breeds. Table 62-9 outlines the potential reasons for increased breed associations in canine chronic hepatitis, and Table 62-8 details any evidence or suggestions of causes reported in breeds in the literature.

Table 62-9 Potential Reasons for Genetic Susceptibility to Chronic Hepatitis in Dogs

Lobular dissecting hepatitis is a histologically distinct form of chronic hepatitis reported predominantly in young dogs, particularly Standard Poodles, Rottweilers, and Mastinos.^5,6 This has led to the suggestion of a breed-related disease in Standard Poodles. However, the original authors suggested an infectious rather than inherited etiology⁶ and the occurrence in litters could be because of environmental rather than inherited factors. Of course, both could interact (an inherited predisposition to an environmental trigger) but the absence of any prevalence data^1,7,8 argues more strongly for an environmental cause. Lobular dissecting hepatitis has been reported anecdotally by breeders with increased prevalence in Finnish Spitz dogs in the United Kingdom (personal communication) but no studies have yet confirmed this.

Evidence of Heritability

Most of the published breed prevalence data come from a study performed in Sweden in 1991⁷ that reviewed 299 cases of histopathologically confirmed chronic hepatitis between 1984 and 1989 and compared them with a control population of Swedish Kennel Club registrations. This study found Labrador Retrievers, American Cocker Spaniels, English Cocker Spaniels, West Highland White Terriers, Scottish Terriers, and Dobermans at increased risk of disease. A recent study in the United Kingdom⁸ that reviewed 4,551 cases of histologically confirmed chronic hepatitis in dogs between 2001 and 2008 compared with a control population of dogs registered by a UK microchip company (175,442 dogs in 2001 and 311,085 dogs in 2008) found overrepresentation of Labrador Retrievers, American and English Cocker Spaniels, Dalmatians, and Dobermans. In addition, English Springer Spaniels, Cairn Terriers, Great Danes, and Samoyeds were significantly overrepresented with idiopathic chronic hepatitis in the UK compared with the control population. A clinical study in Holland of 101 dogs with hepatitis identified a significantly different breed distribution involving English and American Cocker Spaniels, Labrador and Golden Retrievers, West Highland White Terriers, Jack Russell Terriers, and German Pointers.¹ The latter study did not separate acute and chronic hepatitis and copper storage disease.

Definitive Diagnosis

Definitive diagnosis of canine chronic hepatitis can only be made on the basis of hepatic histopathology as outlined in Chapters 29 and 61. Finding elevated serum liver enzyme activity and compatible signs on hepatic ultrasound is not sufficient to make a diagnosis, as these findings are very nonspecific and do not differentiate primary chronic hepatitis from other liver pathologies.

Therapy

Chapters 40, 43, 46, and 61 detail treatment for canine chronic hepatitis.