Clinical Exposures: Copper-associated hepatitis in a Doberman pinscher

Clinical Exposures: Copper-associated hepatitis in a Doberman pinscher

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Aug 01, 2011


Figure 1. A lateral abdominal radiograph of the dog in this case showing cranial displacement of the gastric axis and loss of serosal detail.
A 6-year-old spayed female Doberman pinscher was presented for an annual wellness examination. The dog weighed 68 lb (31 kg), which was 15 lb less than it weighed at its last visit five months before. The owner reported that the dog had been less interested in food for the past few weeks but was still eating. The owner also noted that the dog was exhibiting polyuria and polydipsia.

PHYSICAL EXAMINATION AND LABORATORY FINDINGS

The results of a physical examination were unremarkable. The dog's body condition score was 3/5.


Table 1: Relevant Serum Chemistry Profile Results
The complete blood count results were unremarkable. The relevant results of the serum chemistry profile are presented in Table 1.

DIAGNOSIS

Liver dysfunction was suspected based on these findings. The differential diagnoses included chronic hepatitis, neoplasia, chronic hepatopathy, and toxicosis.

A radiographic examination was performed, and the thoracic radiographs were unremarkable. The abdominal radiographs revealed cranial displacement of the gastric axis and loss of serosal detail, suggestive of microhepatia and ascites, respectively (Figure 1). An abdominal ultrasonographic examination showed a small, hypoechoic, heterogeneous, and irregularly marginated liver. A small amount of free peritoneal fluid was seen throughout the abdomen, which was consistent with ascites.

The radiographic and ultrasonographic changes associated with the liver indicated severe chronic liver disease, but other diffuse disease processes such as neoplasia could not be ruled out.

The owners elected euthanasia. Postmortem liver histologic changes were compatible with severe, chronic-active portal hepatitis, with strong positive results on staining for copper with rhodamine stain. The diagnosis was copper-associated chronic hepatitis.

DISCUSSION

Chronic hepatitis in Doberman pinschers, also known as Doberman hepatitis, is a disorder associated with histologic features of chronic active hepatitis, cholestasis, and cirrhosis. The disease is usually diagnosed in middle-aged spayed female dogs.1 The high incidence of chronic hepatitis in Doberman pinschers compared with some other breeds suggests the disease is hereditary.1-3

The pathogenesis of chronic hepatitis in Doberman pinschers has been debated for several years; the disease may be immune-mediated.1-3 Most affected dogs have chronic hepatitis and high liver copper concentrations, but the role of the high copper concentration is unclear.1-3 Whether the increased copper concentration is the result of concurrent cholestasis or whether the liver disease is a result of copper toxicosis is yet to be determined.4 Hepatic copper accumulation can result from increased uptake, a primary defect in hepatic copper metabolism, or altered biliary copper excretion.2,3

Copper-associated hepatitis is well-described in other breeds, such as Bedlington terriers,5 Labrador retrievers,6 and Dalmatians.7 The average canine copper liver concentration is 200 to 400 ppm per dry weight liver. Copper concentrations in breeds with primary copper storage disease vary between 600 to above 2,200 ppm.1

Affected Dobermans can start accumulating copper at the age of few months, but the clinical signs usually develop between 4 and 7 years of age.1 The signs are usually nonspecific and result from liver dysfunction.2,3 The initial clinical signs are usually subtle and intermittent and can begin as a calmer demeanor and loss of appetite.1,2 Gradually, the signs become more evident and can include salivation, nausea, and intermittent vomiting.1 In advanced stages, polyuria, polydipsia, icterus, diarrhea, ascites, and signs of hepatic encephalopathy may also be present. The progression of the clinical signs is variable but usually occurs over months.