Low hepatic manganese concentrations in patients with hepatic steatosis - A cohort study of copper, iron and manganese in liver biopsies

J Trace Elem Med Biol. 2021 Sep:67:126772. doi: 10.1016/j.jtemb.2021.126772. Epub 2021 May 7.

Abstract

Background and aims: Hepatic steatosis is the most common histopathological finding on liver biopsy, with the most prevalent etiology being NAFLD. The pathogenesis of hepatic steatosis and NAFLD is multifactorial, however, studies on the importance of manganese in NAFLD are limited. We aimed to study hepatic manganese content, and other trace elements, in relation to hepatic steatosis in patients with chronic liver diseases of different etiology, mainly NAFLD.

Methods: Patients with chronically elevated liver function tests underwent a diagnostic work-up, including routine blood tests and two liver biopsies. One of the biopsies was sent for histopathological evaluation, and the other for ultra-trace elemental determinations. Steatosis was graded using conventional histopathological methodology, and fat content was also quantitated in biopsy samples by measuring the steatotic area of the section using stereological point counting (SPC). Ultra-trace elemental analysis was utilized for determining manganese, iron, and copper using inductively coupled plasma sector field mass spectrometry (ICP-SFMS).

Results: 76 patients were included in the study. Hepatic manganese concentrations in patients with steatosis were lower than in patients without hepatic steatosis (3.8 ± 1.1 vs. 6.4 ± 1.8, P < 0.001). Similar results were seen for blood manganese levels and hepatic steatosis. We found a strong inverse correlation between steatosis grade and hepatic manganese content (ρ=-0.743, P < 0.001). Also, low levels of manganese independently predicted the presence of steatosis (aOR 0.07 [95%CI: 0.01-0.63]).

Conclusion: Patients with NAFLD, or other CLD and concomitant hepatic steatosis, showed lower levels of hepatic manganese content with increasing grade of steatosis.

Keywords: Liver biopsy; NASH; Non-alcoholic steatohepatitis; Trace elements.

MeSH terms

  • Biopsy
  • Cohort Studies
  • Copper
  • Humans
  • Iron
  • Liver*
  • Manganese
  • Non-alcoholic Fatty Liver Disease*
  • Trace Elements

Substances

  • Trace Elements
  • Manganese
  • Copper
  • Iron