Diagnosing and Treating Copper-Associated Hepatitis

Copper-associated hepatitis is becoming a commonly recognized cause of liver disease in dogs and was initially identified in Bedlington terriers. A mutation in the COMMD1 gene has been identified and there is a genetic test available if you are working with a breeder for screening. While a genetic mutation has been postulated in other breeds, it has yet to be proven. It is important to be aware of the other breeds commonly affected, including Labrador retrievers, Doberman pinschers, Dalmatians, West Highland white terriers, Anatolian shepherds, and Skye terriers.

SYMPTOMS

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Some affected dogs will have no clinical signs and you might only notice a problem on routine lab work. Other affected dogs can present with anorexia, weight loss, lethargy, vomiting, polyuria, polydipsia, and diarrhea. In severe cases causing liver failure, owners may describe signs of hepatic encephalopathy. A physical exam can be normal or can show signs of liver disease, such as icterus, abdominal distension, bruising, muscle wasting, and an enlarged liver.
 

DIAGNOSIS

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Diagnosis requires a liver biopsy, and clotting times and bile acids should be performed in addition to routine labs. There are multiple methods for obtaining a biopsy sample. At DVMS, we frequently perform ultrasound-guided liver biopsies. These are relatively quick procedures and owners can often take the dog home the same day. Samples should be submitted for histopathology and for quantitative copper measurement, along with any other testing dictated by the individual case.

Pathologists can apply a special stain for copper. However, you may have to make a specific request for this at submission. Make sure your pathologist describes where the copper accumulation is occurring, so that you can use this information to determine if your patient has primary copper-associated hepatitis or if the copper accumulation is secondary to another disease process in the liver. In primary copper toxicosis, the accumulation occurs in centrilobular hepatocytes and in regenerative nodules. In most cases of secondary copper accumulation, the copper is typically only found in cells adjacent to the primary injury. With special stains, the pathologist can give a qualitative assessment of copper levels, but it is important to get a quantitative level. At DVMS, we submit one of the biopsy samples obtained to a lab specializing in copper quantification.

TREATMENT

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Treatment for copper-associated hepatitis needs to be tailored to the individual patient. DVMS' board-certified internists, Janet Bailey, DVM, DACVIM, and Melissa Riensche, DVM, DACVIM, spend a great deal of time with the owners of affected pets determining the right treatment plan. Dietary therapy with a low copper diet is important. There are also many medications available and it is important to consider side effects, cost, and compliance by the patient and owners when selecting a treatment plan. In general, copper chelating medications such as D-penacillamine or trientine are paired with medications to support the liver, such as s-adenosyl methionine, milk thistle, and vitamin E. Based on the results of the biopsies, medications for inflammation, secondary infections, and cholestasis, as well as anti-fibrotic medications are considered. If there are signs of encephalopathy present, that is treated concurrently. Ideally, a repeat liver biopsy is obtained after two to six months of treatment to reassess copper levels. In most cases, clinical signs, liver enzymes, and bile acids are monitored, and when they normalize, it is time to consider stopping chelator therapy and starting preventative treatment with zinc acetate. However, some dogs will need low doses of chelators for the rest of their lives.

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PROGNOSIS

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The prognosis is heavily dependent on the stage of disease at diagnosis. Dogs that are diagnosed early, with minimal fibrosis present on biopsies, tend to do very well with treatment. They will likely need some medications and dietary restrictions for the rest of their lives.

DVMS IS HERE TO HELP YOU WITH ALL ASPECTS OF YOUR LIVER DISEASE CASES

Consider referral for any dog with elevated liver enzymes without a known cause, when you receive a biopsy result that is complex and you would like further interpretation, or when you would like input on long-term treatment and management. We are here to help your patients have the best quality of life possible.

We welcome your call at 480.635.1110 EXT.7 to learn more, make a referral,
or discuss a case for referral consideration.

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