Changes in the Serum Hepcidin-to-ferritin Ratio with Erythroferrone after Hepatitis C Virus Eradication Using Direct-acting Antiviral Agents

Intern Med. 2019 Oct 15;58(20):2915-2922. doi: 10.2169/internalmedicine.2909-19. Epub 2019 Jun 27.


Objective Hepcidin is a master iron regulator hormone produced by the liver, but precise mechanism underlying its involvement in iron overload in hepatitis C virus (HCV) infection remains unclear. We investigated the serum hepcidin levels against iron overload before and after HCV eradication. Methods We prospectively investigated the iron metabolism characteristics in 24 patients with HCV genotype 1b infection before and after treatment. We also assessed the serum erythroferrone (ERFE) levels to investigate its association with iron metabolism changes. Patients were treated with Ledipasvir 90 mg and Sofosbuvir 400 mg once daily for 12 weeks and observed for 12 more weeks in order to evaluate their sustained virological response. Results Serum hepcidin levels at baseline were in the normal range, although serum ferritin levels were increased. After HCV eradication, both serum ferritin and hepcidin levels were significantly decreased at 24 weeks from baseline (p<0.001, p=0.006, respectively). However, the serum hepcidin-to-ferritin ratios were significantly increased (p<0.001). In addition, the serum ERFE levels were significantly decreased (p<0.001). Increases in the serum hepcidin-to-ferritin ratios were correlated with decreases in the serum ERFE levels (ρ=-0.422, p=0.039). Conclusion Serum hepcidin levels were relatively low against ferritin levels in HCV infection. However, after HCV eradication, the serum hepcidin-to-ferritin ratios were increased. These results indicate the improvement of inadequate hepcidin secretion against iron overload after HCV eradication. Downregulation of ERFE may have affected the improvement of iron metabolism.

Keywords: direct-acting antiviral agents; erythroferrone; ferritin; hepatitis C virus; hepcidin.

Publication types

  • Clinical Trial

MeSH terms

  • Adult
  • Aged
  • Antiviral Agents / therapeutic use*
  • Benzimidazoles / therapeutic use
  • Female
  • Ferritins / blood*
  • Fluorenes / therapeutic use
  • Hepacivirus / isolation & purification
  • Hepatitis C, Chronic / blood
  • Hepatitis C, Chronic / complications
  • Hepatitis C, Chronic / drug therapy*
  • Hepatitis C, Chronic / virology
  • Hepcidins / blood*
  • Humans
  • Iron / blood
  • Iron Overload / blood
  • Iron Overload / virology
  • Male
  • Middle Aged
  • Peptide Hormones / blood*
  • Prospective Studies
  • Sofosbuvir
  • Uridine Monophosphate / analogs & derivatives
  • Uridine Monophosphate / therapeutic use


  • Antiviral Agents
  • Benzimidazoles
  • Erfe protein, human
  • Fluorenes
  • HAMP protein, human
  • Hepcidins
  • Peptide Hormones
  • ledipasvir, sofosbuvir drug combination
  • Ferritins
  • Iron
  • Uridine Monophosphate
  • Sofosbuvir