Science

Copper may play role in nonalcoholic fatty liver disease

Last Updated: 2010-05-07 16:37:30 -0400 (Reuters Health)

By Will Boggs, MD

NEW YORK (Reuters Health) - Low copper levels may contribute to nonalcoholic fatty liver disease (NAFLD), Austrian researchers reported online April 20th in the American Journal of Gastroenterology.

Biopsies from 124 patients with NAFLD had significantly lower copper content than biopsies from controls (17.7 vs 32.1 mcg/g of dry weight; p < 0.001) or from patients with other liver diseases (p < 0.05).

Hepatic copper concentrations were even lower in the 31 NAFLD patients with nonalcoholic steatohepatitis (NASH) -- a more severe form of the condition -- than in patients without NASH (15.1 vs 19 mcg/g; p = 0.038).

Furthermore, patients with NAFLD and metabolic syndrome had lower hepatic copper concentrations than NAFLD patients without metabolic syndrome (14.1 vs 20.5 mcg/g; p < 0.001).

In NAFLD patients, hepatic copper concentrations were inversely correlated with the degree of hepatic steatosis, fasting glucose concentrations, diabetes, insulin resistance, arterial hypertension, serum ferritin, and the sum of features of the metabolic syndrome present.

Serum copper and ceruloplasmin levels were also lower in patients with NAFLD compared with controls and patients with other liver diseases (except for those with hereditary hemochromatosis), but were only marginally correlated with hepatic copper concentrations in NAFLD patients.

"Our current lifestyle and dietary habits may seriously affect unrecognized areas of human biology," senior author Dr. Christian Datz from General Hospital Oberndorf told Reuters Health by e-mail. "The functions of trace metals may be one of these areas that is generally underappreciated in the development of diseases."

In addition to the 124 patients with NAFLD, the study population also included 27 controls having liver biopsy for unexplained liver enzyme elevations, 50 patients with genotype 1 chronic hepatitis C, 11 patients with autoimmune hepatitis, 13 patients with alcoholic liver disease, and 35 patients with hereditary hemochromatosis.

The researchers also studied the effect of dietary copper supply on liver histology and metabolic parameters in rats. In the rat study, a copper-restricted diet induced hepatic steatosis and insulin resistance, whereas rats on a normal or copper-supplemented diet showed no steatosis or insulin resistance.

"Our observation appears particularly surprising as NAFLD and diabetes are usually linked with overnutrition," Dr. Datz said.

"The most important point is to understand why these patients are copper deficient," Dr. Datz said. "Our rat data, however, suggest that higher than normal copper levels may have beneficial roles in insulin resistance and fatty liver and currently there is no evidence that this could not be the case in humans."

"We are planning studies to elucidate the origin and mechanisms behind decreased copper availability, i.e., whether decreased dietary uptake or loss via biliary excretion is the cause of our findings," Dr. Datz added.

He said his group also plans to study the interaction between copper and inflammatory pathways, in order to learn more about the role of copper in disease progression.

Am J Gastroenterol 2010.