Page 26 - Copper-associated hepatitis in the Labrador retriever diagnosis, treatment and genetics

Chapter 1
expression in non-lymphatic cells can also be induced by toxins, like copper. Homozygosity for the DLA-DRB1*00601 of the dog leukocyte antigen (DLA) system genotype was found to be associated with an increased risk for Dobermann hepatitis in Finnish Dobermanns130. Dobermann hepatitis behaves exceptionally compared with other copper storage diseases with respect to the very severe prognosis when left untreated, the strong female predisposition and the relatively mild increase in hepatic copper concentration associated with severe disease. Female predisposition is a common feature for auto-immune diseases both in humans and in dogs. Possibly, there is a combined role for copper accumulation and auto-immune deregulation in the pathogenesis of Dobermann hepatitis. Currently genome wide association, followed by next generation sequencing of associated regions and RNA sequencing efforts are performed in the combined Dutch and Finnish cohorts of Dobermann hepatitis liver samples within the LUPA initiative131.
Dalmatian
One report from the USA37 has convincingly demonstrated that this breed has an inherited copper storage disease causing hepatitis and liver cirrhosis. Preceding case reports132;133 already had indicated the presence of a copper storage disease in the American population. The mean hepatic copper concentrations that were reported ranged from 650 to 9,424 μg/g dwl. In the liver biopsies, necro-inflammatory alterations were present in regions with copper-laden hepatocytes and Kupffer cells. Several cases in the Netherlands and Germany have been diagnosed (personal communication J. Rothuizen), so this disease is also present in European Dalmatians. However, currently reliable incidence estimates are lacking. There seems to be no sex predisposition in this breed.
Labrador retriever
An increased incidence of chronic hepatitis was reported in the Labrador retriever previously134, however, Hoffman et al. were the first to demonstrate an association of increased hepatic copper concentrations and hepatitis in this breed in Dutch Labrador retrievers39. Soon thereafter, copper-associated hepatitis in the American Labrador retriever population was recognized as well135;136. There is a strong female predisposition and breeding bitches in the post-partum period have an increased risk for clinical illness. Hormonal
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