Elemental zinc induces synthesis of intestinal mucosal metallothionein, which has a high affinity for copper and, thus, binds
dietary copper and limits its absorption.1 The copper bound to the intestinal mucosal metallothionein is eventually excreted in feces as enterocytes are shed.1 Elemental zinc can be supplemented in the acetate, sulfate, gluconate, or methionine forms. Zinc gluconate is the most common
formulation and is available over the counter. The dosage listed in Table 2 is for elemental zinc; clients may need help in selecting an appropriate product.
Zinc should be given one to two hours before a meal so the maximum amount of metallothionein will be available to bind copper.
If nausea is reported, zinc may be given with a small amount of canned dog food. D-penicillamine and trientine could theoretically
chelate zinc, but practically it is not a problem. Staggering the therapy should suffice.9
Ursodiol and glucocorticoids
Most of the information supporting the administration of ursodiol in patients with liver disease comes from studies in people.
Ursodiol, or ursodeoxycholic acid, is a hydrophilic bile acid that shifts the bile acid profile toward the less toxic hydrophilic
forms by competing with other bile acids for ileal absorption.8 In addition, the choleretic properties of ursodiol may increase copper excretion. Ursodiol may also reduce hepatocellular
injury and fibrosis, modulate immune responses, and prevent bile acid-induced peroxidation by acting indirectly as an antioxidant.8
The goal of glucocorticoid therapy in patients with copper-associated hepatopathy is primarily to reduce inflammation. Since
prednisolone is the active metabolite of prednisone and prednisone conversion may be impaired in dogs with substantial hepatic
dysfunction, we prefer to use prednisolone in patients with liver disease. Prednisone and prednisolone have a 12- to 36-hour
duration of action, and alternate-day dosing is ideal.8 Chronic corticosteroid use will increase ALP and GGT activities with minimal increases in hepatocellular leakage enzyme
activities (ALT, AST); these changes do not reflect ongoing inflammation from copper-associated damage.
SAMe and vitamin E
S-adenosylmethionine (SAMe), a precursor of the antioxidant glutathione, is used as an antioxidant in liver disease. Also,
it is recommended to help combat the oxidative effects of copper in copper-associated hepatopathy.8
Vitamin E is a potent antioxidant commonly used in treating liver disease, particularly copper-associated hepatopathies. Vitamin
E is depleted in people with copper storage (Wilson's) disease, and its concentrations are decreased in chronic cholestasis.8 Advise owners to avoid giving their dogs selenium-containing preparations because of possible selenium toxicosis.
MONITORING AND MAINTENANCE THERAPY
Follow-up liver biopsies with copper quantification are required to determine efficacy and duration of chelation therapy.
No consensus has been established about when it is appropriate to perform follow-up biopsies in these patients. In our experience,
repeating the biopsy after 12 months of chelation therapy is helpful. The decision to perform subsequent biopsies can be based
on serial monitoring of hepatic enzyme activities.
After effective chelation therapy, institute maintenance therapy to prevent copper reaccumulation. This therapy usually consists
of zinc supplementation along with dietary copper restriction. Intermittent copper chelation therapy may be required to maintain
normal hepatic copper concentrations in severely affected individuals.
Any patient with evidence of liver disease may have increased hepatic copper concentrations, either as a primary disorder
or secondary to hepatocellular dysfunction and cholestasis. If a liver biopsy is performed for histologic analysis, submit
a second sample for quantitative copper analysis—especially in known copper hepatopathy-associated breeds—since diagnosis
and treatment may mitigate or reverse copper-associated changes.
Brier Bostrum, DVM
Audrey K. Cook, BVM&S, MRCVS, DACVIM, DECVIM-CA
Department of Small Animal Clinical Sciences
College of Veterinary Medicine and Biomedical Sciences
Texas A&M University
College Station, TX 77843