Liver Iron Load Influences Hepatic Fat Fraction in End-Stage Renal Disease Patients on Dialysis: A Proof of Concept Study

EBioMedicine. 2019 Jan:39:461-471. doi: 10.1016/j.ebiom.2018.11.020. Epub 2018 Nov 28.

Abstract

Background: Nonalcoholic fatty liver disease (NAFLD) is a spectrum of diseases including steatosis, nonalcoholic steatohepatitis (NASH), cirrhosis, and end-stage liver failure. Hepatic iron accumulation has been linked to hepatic fibrosis severity in NASH and NAFLD. Iron overload induced by parenteral (IV) iron therapy is a potential clinical problem in dialysis patients. We analyzed the hypothetical triggering and aggravating role of iron on NAFLD in patients on dialysis.

Methods: Liver iron concentration (LIC) and hepatic proton density fat fraction (PDFF) were analyzed prospectively in 68 dialysis patients by magnetic resonance imaging (MRI). Follow up of LIC and PDFF was performed in 17 dialysis patients during iron therapy.

Findings: PDFF differed significantly among dialysis patients classified according to LIC: patients with moderate or severe iron overload had increased fat fraction (PDFF: 7.9% (0.5-14.8%)) when compared to those with normal LIC (PDFF: 5% (0.27-11%)) or mild iron overload (PDFF: 5% (0.30-11.6%); P = 0.0049). PDFF correlated with LIC, and ferritin and body mass index. In seven patients monitored during IV iron therapy, LIC and PDFF increased concomitantly (PDFF: initial 2.5%, final 8%, P = 0.0156; LIC: initial 20 μmol/g, final 160 μmol/g: P = 0.0156), whereas in ten patients with iron overload, PDFF decreased after IV iron withdrawal or major dose reduction (initial: 8%, final: 4%; P = 0.0098) in parallel with LIC (initial: 195 μmol/g, final: 45 μmol/g; P = 0.002).

Interpretation: Liver iron load influences hepatic fat fraction in dialysis patients. Iron overload induced by iron therapy may aggravate or trigger NAFLD in dialysis patients.

Trial registration number (isrctn): 80100088.

Keywords: Dialysis; Iron overload; Liver iron concentration (LIC); Liver proton density fat fraction (liver-PDFF); MRI; NAFLD.

Publication types

  • Clinical Trial
  • Observational Study

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Anemia / drug therapy*
  • Cross-Sectional Studies
  • Female
  • Humans
  • Iron / administration & dosage
  • Iron / adverse effects*
  • Iron Overload / chemically induced
  • Iron Overload / diagnostic imaging*
  • Kidney Failure, Chronic / therapy*
  • Liver / chemistry*
  • Liver / diagnostic imaging
  • Magnetic Resonance Imaging
  • Male
  • Middle Aged
  • Non-alcoholic Fatty Liver Disease / complications*
  • Proof of Concept Study
  • Prospective Studies
  • Protons
  • Renal Dialysis

Substances

  • Protons
  • Iron