Is copper hepatotoxic in primary biliary cirrhosis?

Area of Science:

• Hepatology
• Biochemistry
• Pathology

Background:

• Primary biliary cirrhosis (PBC) is associated with liver copper retention due to cholestasis.
• Copper retention is hypothesized to be hepatotoxic in PBC, similar to Wilson's disease, justifying D-penicillamine use.

Purpose of the Study:

• To investigate the role of liver copper retention in the pathogenesis of liver dysfunction in primary biliary cirrhosis.
• To test the hypothesis that copper is hepatotoxic in PBC.

Main Methods:

• Studied 64 patients with PBC, assessing liver copper concentrations, liver cell synthetic function, and liver cell damage.
• Utilized biochemical tests, histology, and electron microscopy with x-ray probe microanalysis on liver biopsies.

Main Results:

• 54 out of 64 PBC patients had increased liver copper concentrations.
• No correlation was found between liver copper levels and biochemical or histological markers of liver cell damage.
• Electron microscopy revealed copper and sulfur in lysosomes, but organelle changes typical of Wilson's disease were absent.

Conclusions:

• Liver cell synthetic function was preserved in PBC patients with copper retention.
• Biochemical, histological, and histochemical differences suggest distinct copper handling in PBC compared to Wilson's disease.
• This study found no evidence that copper plays a significant role in the pathogenesis of liver dysfunction in primary biliary cirrhosis.