The pathogenesis of chronic hepatitis in Doberman pinschers is unknown, but most affected dogs have high hepatic copper concentrations. Examining early treatment of this disease is important because, once it becomes clinical, hepatitis in these dogs responds poorly to treatment. D-penicillamine, a chelating agent used in copper storage hepatopathies, works by reductive chelation and by increasing excretion of copper in the urine. This study was performed to evaluate the treatment of subclinical hepatitis in Doberman pinschers using D-penicillamine.
Five client-owned Doberman pinschers were selected from a group previously studied for associations between hepatic copper concentration and subclinical hepatitis. In the previous study, the dogs had been examined every 6 months for 3 to 4 years. Subclinical hepatitis was present continuously in these dogs, and annual quantitative measurements of copper concentration had gradually increased during that period. In the present study, the same dogs were evaluated after being given 200 mg D-penicillamine PO Q12 H for 4 months. Subsequent results showed significant decreases in hepatic copper concentrations in all dogs. Subclinical hepatitis had also decreased in all 5 dogs and disappeared completely in 3. No adverse effects were noted by the owners. Because of the small sample size, the authors were unable to conclude that the subclinical hepatitis was caused by increased copper concentrations or that the improvement seen in hepatitis after treatment was caused by decreased hepatic copper. However, they did think it was reasonable to conclude that D-penicillamine treatment was responsible for decreasing both hepatic copper concentrations and hepatic inflammation in these dogs and that early treatment of this disease is feasible.
Commentary: Copper retention in the liver causes hepatitis in several breeds, most notably Bedlington terriers followed closely by Doberman pinschers. The exact mechanisms of copper-induced hepatitis are unknown. A number of drugs have been used to prevent copper absorption or to facilitate its removal from the body, but no prospective study that definitively evaluates the efficacy and dosage of these drugs has been done. This study is an important first step in that it shows that D-penicillamine effectively reduced hepatic copper concentration at the relatively low dose of 6 mg/kg Q12 H with concomitant improvement in pathologic conditions of the liver. This is good news for all breeds that experience copper-induced hepatitis.
Improvement in liver pathology after 4 months of d-penicillamine in 5 Doberman pinschers with subclinical hepatitis. Mandigers PJJ, van den Ingh TS, Bode P, Rothuizen J. J VET INTERN MED 19:40-43, 2005.