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458 Hepatopathy, Copper-Associated

• Laparoscopic biopsies are preferred over Technician Tips SUGGESTED READING
needle biopsies due to the larger tissue sample • Avoid jugular venipuncture until coagulation Dirksen K, et al: Sensitivity and specificity of plasma
VetBooks.ir Prevention • Blood for bile acids is collected after a Retrievers. J Vet Intern Med 31(4):1017-1027,
is assessed as normal.
obtained.
ALT, ALP, and bile acids for hepatitis in Labrador
12-hour fast (preprandial) and 2 hours after
2017.
Avoid prolonged use of glucocorticoids when
possible. feeding a fatty meal (postprandial). AUTHOR: Julie E. Trzil, DVM, MS, DACVIM
EDITOR: Leah A. Cohn, DVM, PhD, DACVIM

Hepatopathy, Copper-Associated Client Education
Sheet

BASIC INFORMATION ○ In Bedlingtons, a defect in the COMMD1 Advanced or Confirmatory Testing
gene leads to decreased biliary excretion Determination of hepatic copper concentra-
Definition of copper. tion: quantitative analysis on hepatic wedge
Accumulation of copper within hepatocytes, ○ Genetic basis for copper accumulation or needle biopsies, digital image analysis of
leading to hepatotoxicosis in other breeds is unknown, but some scanned rhodanine-stained histopathology slides;
evidence for mutation in ATP7B (a copper qualitative and semiquantitative assessment of
Epidemiology transporter) in Labradors rhodamine- or rubeanic acid–stained slides
SPECIES, AGE, SEX • Secondary copper accumulation is due to • Normal hepatic copper levels: 200-400 mcg/g
• Dogs: common; copper accumulates slowly, and cholestatic disease and impairment in biliary dry weight (DW) in dog and < 190 mcg/g
clinical signs typically appear in middle age excretion. This is a rare cause of copper DW in cats
• Cats: rare, younger (median age, 2 years) accumulation in the dog but occurs in cats. • In Bedlingtons, genetic test, microsatellite
• Emerging evidence suggests that many dogs marker (C04107) available, but may miss disease
GENETICS, BREED PREDISPOSITION accumulate excess copper in the liver associ- in some pedigrees (5%-10% false-negatives).
• Autosomal recessive in Bedlington terriers ated with excess dietary copper content. No test for COMMD1 mutation is available.
• Predisposition in Dalmatians, West Highland • Accumulating copper puts oxidant stress on • In Bedlingtons, copper levels gradually
white terriers, Labrador retrievers, Doberman the liver, predisposing it to damage. increase with age and can reach very high
pinschers and standard poodles • Excess copper damages hepatocytes by levels (>10,000 mcg/g DW).
• Can happen sporadically in any breed of inducing the formation of free radicals. • Lower copper levels (500-2000 mcg/g DW)
dog or cat • Rarely, copper storage hepatopathy is associ- typically occur in Labradors and Dobermans.
ated with renal Fanconi syndrome (p. 322). • Cats > 700 mcg/g DW is consistent with
Clinical Presentation primary copper hepatopathy.
DISEASE FORMS/SUBTYPES DIAGNOSIS Histopathologic findings:
• Subclinical • Inborn errors such as occur in Bedlingtons:
• Chronic hepatitis/cirrhosis Diagnostic Overview initial finding is centrilobular copper accumu-
• Acute liver disease with hemolytic anemia The disorder may be suspected in two contexts: lation with hepatocellular vacuolation, followed
(rare) as part of any necroinflammatory or cholestatic by degeneration/necrosis and then inflamma-
liver disease (detected as part of evaluation tion and fibrosis; progresses to become more
HISTORY, CHIEF COMPLAINT of liver biopsy specimens) or in cases where panlobular with periportal orientation
• Patients usually present with features of copper accumulation is the dominant feature of • In secondary copper accumulation, copper
chronic hepatic disease such as polyuria and hepatopathy in a dog (e.g., Bedlington terrier) staining is located primarily in areas of
polydipsia, lethargy, vomiting, abdominal with or without overt clinical signs. Definitive inflammation or degeneration (periportal),
distention, or encephalopathy (p. 440) or, diagnosis requires quantification of hepatic with more accumulation in macrophages.
less commonly, with acute liver failure (p. copper content from a liver biopsy specimen. • Cats with primary copper hepatopathy are pre-
442) and hemolytic anemia (p. 59). disposed to develop hepatocellular carcinoma.
• In early stages, patients may be asymptomatic Differential Diagnosis
with just increased serum liver enzyme Chronic: TREATMENT
activities, particularly serum alanine ami- • Infectious, immune, or toxic causes of
notransferase (ALT). inflammatory hepatic disease Treatment Overview
• Hepatic neoplasia Decrease hepatic copper concentration, decrease
Etiology and Pathophysiology • Congenital portosystemic shunts copper absorption, and attenuate oxidant injury
• Copper is absorbed in the small intestine Acute:
and extracted by hepatocytes. Copper is • Infectious, immune, drug, or toxin-induced Acute General Treatment
chaperoned around the hepatocyte before (zinc) hemolytic anemia Manage the complications of acute or chronic
being released into the serum or excreted in • Exposure to hepatotoxic drugs or environ- hepatic disease (pp. 174 and 452).
bile. A small amount is stored in lysosomes. mental toxins
• Copper homeostasis is maintained by biliary • Infectious canine hepatitis, leptospirosis Chronic Treatment
excretion of excess copper. In dogs other than Bedlingtons and Dalmatians,
• Abnormal hepatic copper accumulation Initial Database the need to treat elevated hepatic copper
occurs because of a primary inborn error of Tests to rule out hemolytic anemia (p. 59), concentrations is based on distribution of the
metabolism or secondary to increased dietary cirrhotic/fibrosing liver disease (p. 174), acute copper in the biopsy, the presence of concurrent
consumption or acquired cholestatic liver hepatic injury (p. 442), and chronic idiopathic liver injury or inflammation, and evaluation
disease. hepatitis (p. 452) of clinicopathologic markers of liver injury.
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