Hepatic copper concentrations in 546 dogs (1982–2015)

Abstract

BackgroundCopper associated hepatitis (CAH) has been increasingly recognized in dogs, and speculation exists that hereditary defects in copper metabolism have been exacerbated by increased environmental copper exposure. However, no broad epidemiological investigations have been performed to investigate quantitative hepatic copper concentrations ([Cu]H) over time in both dogs that are (predisposed breed [PB]), and are not (non‐predisposed breed [NPB]), considered at‐risk for CAH.ObjectivesTo investigate [Cu]H in dogs and explore temporal, demographic, and histologic associations spanning 34 years.Animals546 archived liver specimens.MethodsRetrospective study. Searches of the Michigan State University Veterinary Diagnostic Laboratory database identified dogs that had undergone hepatic histopathologic assessment. Cases with archived tissue were reviewed and classified by breed, time period, and presence or absence of hepatitis. Inductively coupled plasma mass spectrometry was used to determine [Cu]H.ResultsIn time period 2009–2015, median [Cu]H were 101 μg/g and 313 μg/g greater than median [Cu]H in time period 1982–1988 for NPB and PB dogs, respectively (P < .001 for both comparisons). The proportion of dogs with [CU]H > 300 μg/g increased in NPB (28% to 49%) and PB dogs (48% to 71%) during these periods (P = .002 for both comparisons). Median [Cu]H in dogs with hepatitis increased 3‐fold over time in both NPB (P = .004) and PB populations (P < .001).Conclusions and Clinical ImportanceThe frequent recognition of CAH in recent years is likely due to the observed increases in [Cu]H over time. Importantly, effects are not limited to PB dogs.

ACVIM consensus statement on the diagnosis and treatment of chronic hepatitis in dogs

“…The most common toxic injury causing CH in dogs is a consequence of hepatic copper (Cu) excess . Copper‐associated CH (CuCH) may develop in any breed, including mixed breeds, but the Bedlington Terrier (BT), Dalmatian, Labrador Retriever (LR), Doberman Pinscher, and West Highland White Terrier are predisposed.…”

“…The increasing frequency of CH cases beginning in the late 1990s correlates with the change in the premixes used to supplement Cu in commercial dog foods, which resulted in higher amounts of bioavailable Cu in diets . The panel believes that the National Research Council (NRC) and Association of American Feed Control Officials dietary guidelines, along with a change to more bioavailable Cu chelate premixes in commercial dog food, are linked with an increased prevalence of hepatic Cu accumulation in dogs (Table ) .…”

Ammonium tetrathiomolybdate treatment of copper‐associated hepatopathy in dogs

“…Copper‐associated hepatopathy (CAH) is characterized by progressive hepatic copper accumulation leading to hepatitis, cirrhosis, and eventual death if left untreated . The disease has garnered considerable attention from the veterinary community in recent years . Once thought to be a rare condition affecting only Bedlington Terriers, CAH is widely recognized in Labrador Retrievers, Doberman Pinschers, West Highland White Terriers, and Dalmatians .…”

“…Once thought to be a rare condition affecting only Bedlington Terriers, CAH is widely recognized in Labrador Retrievers, Doberman Pinschers, West Highland White Terriers, and Dalmatians . More recently, CAH has been recognized in various breeds and crosses not typically considered predisposed to CAH . The genetic basis for disease in Bedlington Terriers is well described, but the etiology in other breeds is complex and multifactorial …”

“…More recently, CAH has been recognized in various breeds and crosses not typically considered predisposed to CAH . The genetic basis for disease in Bedlington Terriers is well described, but the etiology in other breeds is complex and multifactorial …”