Page 24 - Copper-associated hepatitis in the Labrador retriever diagnosis, treatment and genetics

Chapter 1
Bedlington terrier
Although there are some reports of atypical copper toxicosis in Bedlington terriers, a homozygous COMMD1 exon 2 deletion is causative for BTCT in the majority of dogs40. Impaired biliary copper excretion leads to a massive accumulation of copper in the liver, which is the highest that is recognized in any dog breed. Copper concentrations as high as 2,000 μg/g dwl are already recognized in 1 year old dogs, however, often no histological signs of hepatitis are present then84;122. Hepatitis develops around 2-5 years of age and the dogs become clinically ill. Successful treatment is possible with D-penicillamine. Without treatment the hepatic copper concentration tends to increase over time and usually reach values of 5,000 μg/g dwl, but in some cases extremely high liver copper levels of 15,000 μg/g dwl have been reported. A tendency of decrease in hepatic copper concentration is present in old animals or in advanced stages of liver cirrhosis122.
West Highland white terrier
Hepatitis associated with hepatic copper accumulation was first reported in this breed in the Unites States36. Later, the same authors reported a larger group of 71 dogs, of which many were related123. The disease had a clear familial distribution and when two affected dogs were mated, all dogs in the offspring showed increased hepatic copper concentrations, indicating a hereditary background. Of the 71 cases investigated by Thornburg et al., 44 had a highly increased copper concentration with an equal distribution over both sexes. Copper concentrations do not reach extremely high values, as in the Bedlington terriers, the highest value reported was 6,800 μg/g dwl, however the majority of affected West Highland White terriers has copper concentrations around 2,000 μg/g dwl.
Dobermann
Dobermanns have been reported to have a very severe form of hepatitis and cirrhosis, which is almost exclusively seen in females and has a fatal course within weeks or a few months after diagnosis. Reports from the USA124, Finland125, and the Netherlands38;126-128 describe increased copper concentrations and a predominant monocellular infiltrate in the liver of affected Dobermanns. In the Dutch population a random sample of 15% of a cohort of three year old Dobermanns was followed over time. In 6% of these dogs, copper-associated
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