Differences in Tissue Copper and Zinc Content Between Normal Livers and Those with Cirrhosis with or Without Hepatocellular Carcinoma

This study aimed to compare the contents of copper (Cu), zinc (Zn), magnesium (Mg), and iron (Fe) in healthy liver tissue from deceased liver donors (DGs), in cirrhotic tissue from patients without (CIR) or with hepatocellular carcinoma (CIR-HCC) and in HCC tissue from the latter patients. Liver tissue samples were obtained from cirrhotic liver transplant recipients, with (n = 14) and without HCC (n = 14), and from DGs (n = 18). In patients with HCC, both cirrhotic and tumor tissue was collected. The tissue metal content was measured using atomic absorption spectrometry. The Cu content of DG tissue was significantly lower than that of CIR-HCC and HCC tissue but not CIR tissue. The tissue Zn and Mg contents were significantly higher in DG tissue than in CIR, CIR-HCC, and HCC tissues. No difference was observed for Fe. The Cu/Zn ratio progressively increased in DG, CIR, CIR-HCC, and HCC tissues. The increased Cu content in cirrhotic and tumor tissue of HCC patients and the fact that the latter had the highest value for the Cu/Zn ratio indirectly suggest the potential role of these metals in hepatocarcinogenesis. These findings support a pathophysiological basis for further experimental studies to investigate the potential therapeutic implications of pharmacological agents targeting metal homeostasis in this malignancy.