Demographic and histopathologic features of dogs with abnormally high concentrations of hepatic copper

Abstract

Background Copper associated hepatopathy (CAH) has become an important and prevalent disease since the 1990's, coincidental with changes in copper (Cu) content in commercial dog foods. Knowing the demographic and histopathologic features related to hepatic Cu concentrations might aid in diagnosing CAH in dogs. Hypothesis/Objectives The primary aim was to identify demographic and histopathologic features associated with abnormally high hepatic Cu concentrations. Animals Dogs that underwent liver histopathology and Cu quantification at a veterinary diagnostic laboratory between July 2010 and February 2020. Methods Data was retrospectively collected from an electronic database. A Gaussian multiple regression model on the log scale was used to evaluate associations between hepatic Cu and a set of demographic and histologic features selected with machine learning methods. Results Of 4559 cases meeting criteria, 50% had hepatic Cu > 400 and 19% had Cu > 1000 ppm (parts per million) dry weight (reference range 120‐400). Median hepatic Cu was 391 ppm, range 4.5 to 31500. Age was negatively associated (P < .02), but specific breeds (Doberman pinscher, Labrador retriever, and West Highland white terrier) were positively associated with abnormally high hepatic Cu (P < .001). Severity of inflammation (mild, moderate, and severe) and necrosis/apoptosis were associated with abnormally high hepatic Cu (P < .01). Conclusion and Clinical Importance Abnormally high hepatic Cu is prevalent in hepatic biopsies from dogs. Machine learning modeling showed that necroinflammation, not cholestasis or cirrhosis, on hepatic histopathology, is predictive of higher hepatic Cu and might be a reliable histologic predictor of CAH.

Copper‐associated chronic hepatitis in Cavalier King Charles spaniels

“…However, the occurrence of several unique histological features that commonly characterised many of the cases, together with the high prevalence of the ATP7B variant, might support a breed predilection. Moreover, the recently reported association between the CKCS breed and abnormally high [Cu] h , 23 and the much higher allelic frequency of the ATP7B variant in these CKCS (0.42) than that recently reported in 144 samples from dogs of multiple breeds in the UK (0.135) 26 further support the possibility of a breed‐specific proclivity. The protracted history in some of the dogs and the fact that others were incidentally diagnosed allude to a long subclinical stage.…”

“…Reports of CuCH in Cavalier King Charles spaniels (CKCS) are scarce and anecdotal 4,22 . One recent publication has alluded to the possibility of a breed‐specific CuCH in CKCS, reporting an association between increased [Cu] h and CKCS in the United States 23 . However, this study did not elaborate on the clinical, laboratory or histological changes in affected dogs.…”

“…4,22 One recent publication has alluded to the possibility of a breed-specific CuCH in CKCS, reporting an association between increased [Cu] h and CKCS in the United States. 23 However, this study did not elaborate on the clinical, laboratory or histological changes in affected dogs. Therefore, we aimed to characterise the clinical signs, laboratory findings, histological features, genetic background and outcome of the disease, thereby increasing awareness of CuCH in this particular breed.…”

Prevalence of canine hepatopathy among a clinic population fed commercial dry food: Age and Dietary factors influence the disease prevalence

“…The other common and important hepatic disorder in dogs is copper-associated hepatopathy. The prevalence of this disease has increased over time and is related to the changes in copper content in commercial dog foods [22] [23]. In dogs with copper-associated hepatopathy, asymptomatic elevations in liver enzyme activity are often present that later progress to liver failure [24].…”

Characterization of clinical presentation, histological features, ultrasonographic findings, and survival in 29 dogs with granulomatous hepatitis

“… 26 , 27 An overall increase in hepatic copper content has been reported in several studies over the last several years in both breeds that are and those that are not predisposed to copper‐associated hepatitis. 16 , 17 , 28 , 29 , 30 , 31 , 32 , 33 These increases in hepatic copper concentration may reflect the higher concentrations of copper in dog foods that have accompanied an increase in the bioavailability of copper additives and the popularity of boutique diets with high copper concentrations.…”