The relationship between copper and steatosis in Wilson's disease

Abstract

Background and aims: The histological similarities seen in Wilson's disease (WD) and non-alcoholic steatohepatitis (NASH) led us to verify possible correlations between glucose and/or lipid and/or iron metabolism alterations and hepatic steatosis in WD patients.

Methods: Thirty-five WD patients (20 females, 15 males, mean age 40.1 ± 5.4 years), and 44 NASH patients (25 females, 19 males, mean age 42.8 ± 6.7 years) were enrolled in the study. BMI, total/HDL/LDL-cholesterol, triglycerides and glucose serum levels were established in all subjects. HOMA index was calculated. Percutaneous liver biopsy with quantitative evaluation of steatosis and copper tissue content was performed in all WD patients and in NASH control group.

Results: Significant difference was seen in baseline serum levels of glucose, HOMA index, total cholesterol, triglycerides, and ferritin between the WD group and NASH group (P<0.05) but steatosis scored was similar between two groups. No correlation between the level of steatosis and metabolic factors studied was highlighted. In WD, hepatic parenchymal copper concentration was 753 ± 65.3 mcg/g dry weight against 54.5 ± 16.9 mcg/g dry weight in NASH patients (P<0.05). Higher liver copper concentrations were seen in patients with severe steatosis compared to those with mild (P=0.004) and moderate, (P=0.038) steatosis. Positive significant correlation between liver copper content and steatosis scores (r=0.87; r(2)=0.76) was observed.

Conclusions: The hepatic steatosis in WD is not induced by metabolic comorbidities but by the accumulation of copper in the liver tissue. The hypothesise that the metabolic alterations could be co-factors in the pathogenesis of steatosis in these patients cannot be excluded.