Comparison of copper concentration between non-alcoholic fatty liver disease patients and normal individuals: A meta-analysis

Non-alcoholic fatty liver disease (NAFLD) is the most prevalent chronic liver disease worldwide. Copper metabolism plays an important role in the pathogenesis of NAFLD. However, the relationship between serum/hepatic copper concentration and NAFLD is still debated. A literature search was performed using electronic databases to find publications up to September 2022, where the relationship between serum/hepatic copper or ceruloplasmin concentration and NAFLD was evaluated. Finally, 6 articles with 9 unique outcomes involving 2,607 NAFLD patients and 1,441 non-NAFLD normal individuals were included. The pooled results showed that hepatic copper concentration was significantly decreased in NAFLD patients (SMD = −0.98, 95% CI = [−1.21; −0.74], p < 0.0001), and the sensitivity analysis also confirmed this. Nevertheless, serum copper (SMD = −0.02, 95% CI = [−0.32; 0.28], p = 0.88) and ceruloplasmin (SMD = −0.03, 95% CI = [−0.69; 0.63], p = 0.93) were not associated with NAFLD. This meta-analysis revealed that low hepatic copper concentration was found in NAFLD patients and serum copper and ceruloplasmin were not associated with NAFLD. Larger cohort studies and related trials are needed to further validate the result of this meta-analysis in the future.