Test Catalog

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 using liver tissue specimens

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.

<50 mcg/g dry weight

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 above 250 mcg/g dry weight.


VERY HIGH >1000 mcg/g dry weight:

This finding is strongly suggestive of Wilson disease.


HIGH 250-1000 mcg/g dry weight:

This finding is suggestive of possible Wilson disease.  


MODERATELY HIGH 50-250 mcg/g dry weight:

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 any of the above findings are without supporting histology and other biochemical test results, contamination during collection, handling, or processing should be considered. Genetic testing for Wilson disease (WDZ / Wilson Disease, Full Gene Analysis, Varies) is available at Mayo Clinic Laboratories, call 800-533-1710 if you need additional assistance.


In patients with elevated levels of copper without supporting histology and other biochemical test results, contamination during collection, handling, or processing should be considered.

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 Hollande's, contain high levels of copper. Any object that has been exposed to these fixatives (eg, cutting boards, towels, containers, utensils) and 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.

Clinical Reference Recommendations for 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

5. Rifai N, Horwath AR, Wittwer CT, eds. Tietz Textbook of Clinical Chemistry and Molecular Diagnostics. 6th ed. Elsevier; 2018