Primary sclerosing cholangitis is a chronic, cholestatic syndrome characterized by fibrosing inflammation of the bile ducts that may lead to cirrhosis and death from liver failure. Previous reports have suggested abnormal hepatic copper metabolism in this disease. Therefore, in 70 patients, we prospectively determined the levels of hepatic copper, serum copper, and serum ceruloplasmin, and the rate of urinary copper excretion to assess the diagnostic and prognostic usefulness of these tests. Virtually all patients had at least one abnormal copper test. Hepatic copper levels were elevated in 87% of patients [292 ± 38 μg/g dry wt (mean ± SE)] and 24-h urinary copper levels in 64% of patients [135 ± 15 μg/24 h (mean ± SE)] to values comparable to those seen in Wilson's disease or primary biliary cirrhosis. In advanced histologic stages of primary sclerosing cholangitis, progressively higher mean levels of hepatic and urinary copper were found. In the liver, mean copper content (in micrograms per gram dry weight) in disease stages I and II was 147 ± 36 (mean ± SE); in stage III (fibrosis), 302 ± 68; and in stage IV (cirrhosis), 379 ± 69. In the urine, mean copper excretion (in micrograms per 24 h) in stages I and II was 72 ± 14 (mean ± SE); in stage III, 100 ± 14; and in stage IV, 207 ± 30. Higher hepatic and urinary copper levels at initial evaluation were associated with decreased survival during a median follow-up period of 2.6 yr: patients with hepatic copper > 250 μg/g dry wt and urinary copper excretion > 200 μg/ 24 h at initial evaluation had an 18-mo survival of <60%. We conclude that abnormal copper metabolism is a universal feature of primary sclerosing cholangitis, that hepatic copper accumulates and urinary copper excretion increases as the disease progresses, and that the hepatic copper concentration and the 24-h urinary copper determination are useful prognostic indicators in this disease.
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