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Test ID: CUT    
Copper, Liver Tissue

Useful For Suggests clinical disorders or settings where the test may be helpful

Diagnosing Wilson disease and primary biliary cirrhosis

Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test

Homeostatic regulation of copper metabolism is very complex. The liver is the key organ to facilitate copper storage and incorporation of copper into the transport protein ceruloplasmin. Intestinal absorption and biliary excretion also play major roles in the regulation of copper homeostasis.

 

Abnormal copper metabolism is associated with liver disease. Elevated serum copper concentrations are seen in portal cirrhosis, biliary tract disease, and hepatitis, probably because excess copper that would normally be excreted in the bile is retained in circulation. In primary biliary cirrhosis, ceruloplasmin is high, resulting in high serum copper. Lesser elevations of hepatic copper are found in chronic copper poisoning, obstructive jaundice, and certain cases of hepatic cirrhosis. Reduced serum copper concentration is typical of Wilson disease (hepatolenticular degeneration). Wilson disease is characterized by liver disease, neurologic abnormalities, and psychiatric disturbances. Kayser-Fleischer rings are normally present and urinary copper excretion is increased, while serum copper and ceruloplasmin are low.

Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.

10-35 mcg/g dry weight

 

>1,000 mcg/g dry weight: VERY HIGH

This finding is strongly suggestive of Wilson disease. If this finding is without supporting histology and other biochemical test results, contamination during collection, handling, or processing should be considered. Fresh tissue would be appropriate for copper measurement. Genetic test for Wilson disease (WDMS / Wilson Disease Mutation Screen, ATP7B DNA Sequencing) is also available at Mayo Clinic. Please call Mayo Medical Laboratories at 800-533-1710 or 507-266-5700 if you need further assistance.

 

250-1,000 mcg/g dry weight: HIGH

This finding is suggestive of possible Wilson disease. If this finding is without supporting histology and other biochemical test results, contamination during collection, handling, or processing should be considered. Fresh tissue would be appropriate for copper measurement. Genetic test for Wilson disease (WDMS / Wilson Disease Mutation Screen, ATP7B DNA Sequencing) is also available at Mayo Clinic. Please call Mayo Medical Laboratories at 800-533-1710 or 507-266-5700 if you need further assistance.

 

35-250 mcg/g dry weight: HIGH

Excessive copper at this level can be associated with cholestatic liver disease, such as primary biliary cirrhosis, primary sclerosing cholangitis, autoimmune hepatitis, and familial cholestatic syndrome. Heterozygous carriers for Wilson disease occasionally have modestly elevated values, but rarely higher than 125 mcg/g of dry weight. In general, the liver copper content is higher than 250 mcg/g dried tissue in patients with Wilson disease. If this finding is without supporting histology and other biochemical test results, contamination during collection, handling, or processing should be considered. Fresh tissue would be appropriate for copper measurement. Genetic test for Wilson disease (WDMS / Wilson Disease Mutation Screen, ATP7B DNA Sequencing) is also available at Mayo Clinic. Please call Mayo Medical Laboratories at 800-533-1710 or 507-266-5700 if you need further assistance.

Interpretation Provides information to assist in interpretation of the test results

The constellation of symptoms associated with Wilson disease (WD), which includes Kayser-Fleischer rings, behavior changes, and liver disease, is commonly associated with liver copper concentration >250 mcg/g dry weight.

 

>1,000 mcg/g dry weight: VERY HIGH. This finding is virtually diagnostic of WD; such patients should be showing all the signs and symptoms of WD.

 

250 mcg/g dry weight to 1,000 mcg/g dry weight: HIGH. This finding is suggestive of WD unless signs and symptoms, supporting histology, and other biochemical results (low serum ceruloplasmin, low serum copper, and high urine copper) are not evident.

 

35 mcg/g dry weight to 250 mcg/g dry weight: HIGH. Excessive copper at this level can be associated with cholestatic liver disease, such as primary biliary cirrhosis, primary sclerosing cholangitis, autoimmune hepatitis, and familial cholestatic syndrome. The heterozygous carriers for WD occasionally have modestly elevated values, but rarely higher than 125 mcg/g of dry weight. In general, the liver copper content is higher than 250 mcg/g dried tissue in WD patients.

 

In patients with elevated levels of copper without supporting histology and other biochemical test results, contamination during collection, handling, or processing should be considered. Fresh tissue would be appropriate for copper measurement. Genetic test for WD (WDMS / Wilson Disease Mutation Screen, ATP7B DNA Sequencing) is available at Mayo Clinic.

Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances

Specimen handling should be minimized.

 

Elevated copper levels without supporting histology or other biochemical test results should instigate an investigation into whether the specimen has been contaminated.

 

A minimum tissue dry weight of 0.3 mg is required for analysis. This is the equivalent of a piece of tissue from a 22-gauge needle approximately 0.5 cm long, or approximately 0.3 cm in length when taken with an 18-gauge needle. Since the specimen must be manipulated during analysis, more than the minimal amount described in the previous sentence must be submitted for analysis.

 

Paraffin blocks that have been cut for slides may be contaminated if the microtome was previously used to cut specimens that had been fixed with a copper-containing solution. Many fixatives, such as Hollandes, contain high levels of copper. Any object that has been exposed to these fixatives (eg, cutting boards, towels, containers, utensils) that comes into contact with the tissue can potentially contaminate the specimen. Rinsing and washing will not remove the copper contaminant. Therefore, submission of fresh-frozen, unfixed tissue is strongly recommended.

 

Gadolinium is known to interfere with most metals tests. If gadolinium-containing contrast media has been administered a specimen should not be collected for 96 hours.

 

See Improving Test Success in Iron Liver Tissue Specimens in Publications.

Clinical Reference Provides recommendations for further in-depth reading of a clinical nature

1. Korman J, Volenberg I, Balko J, et al: Screening for Wilson disease in acute liver failure: a comparison of currently available diagnostic tests. Hepatology 2008 Oct;48(4):1167-1174

2. Roberts EA, Schlisky ML: Diagnosis and Treatment of Wilson Disease: AASLD Practice Guidelines. Hepatology 2008;47:2089-2111

3. de Bie P, Muller P, Wijmenga C, Klomp LW: Molecular pathogenesis of Wilson and Menkes disease: correlation of mutations with molecular defects and disease phenotypes. J Med Genet 2007 November;44(11):673-688

4. Merle U, Schaefer M, Ferenci P, Stremmel W: Clinical presentation, diagnosis and long-term outcome of Wilson's disease: a cohort study. Gut 2007;56:115-120