Copper Deficiency in Liver Diseases: A Case Series and Pathophysiological Considerations

Abstract

Copper is an indispensable trace element. It serves as a cofactor for enzymes involved in cellular energy metabolism, antioxidant defense, iron transport, and fibrogenesis. Although these processes are central in the pathogenesis of liver disorders, few studies have attributed them to copper deficiency. We herein describe in detail a case series of liver disease patients (n = 12) who presented with signs of copper deficiency based on serum and liver copper measurements. Median age of the group at the time of presentation was 39 (range 18‐64 years). Six patients were female. The median serum copper was 46 μg/dL (normal range: 80‐155 μg/dL for women and 70‐140 μg/dL for men). Seven of the 12 patients had hepatic copper concentration less than 10 μg/g dry weight (normal range: 10‐35 μg/g). Most cases presented with acute‐on‐chronic liver failure (n = 4) and decompensated cirrhosis (n = 5). Only 3 patients had a condition known to be associated with copper deficiency (ileocolonic Crohn’s disease following resection n = 1, Roux‐en‐Y gastric bypass n = 2) before presenting with hepatic dysfunction. Notable clinical features included steatohepatitis, iron overload, malnutrition, and recurrent infections. In 2 of the 3 patients who received copper supplementation, there was an improvement in serum copper, ceruloplasmin, and liver function parameters. Conclusion: Copper deficiency in the serum or liver occurs in a wide range of liver diseases. Given the biological essentiality of copper, the mechanism and clinical significance of this association require systematic study.