Low Serum Hepcidin in Patients with Autoimmune Liver Diseases

PLoS One. 2015 Aug 13;10(8):e0135486. doi: 10.1371/journal.pone.0135486. eCollection 2015.

Abstract

Hepcidin, a liver hormone, is important for both innate immunity and iron metabolism regulation. As dysfunction of the hepcidin pathway may contribute to liver pathology, we analysed liver hepcidin mRNA and serum hepcidin in patients with chronic liver diseases. Hepcidin mRNA levels were determined in liver biopsies obtained from 126 patients with HCV (n = 21), HBV (n = 23), autoimmune cholestatic disease (primary biliary cirrhosis and primary sclerosing cholangitis; PBC/PSC; n = 34), autoimmune hepatitis (AIH; n = 16) and non-alcoholic fatty liver disease (NAFLD; n = 32). Sera sampled on the biopsy day from the same patients were investigated for serum hepcidin levels. Hepatic hepcidin mRNA levels correlated positively with ferritin and negatively with serum γ-GT levels. However, no correlation was found between serum hepcidin and either ferritin or liver hepcidin mRNA. Both serum hepcidin and the serum hepcidin/ferritin ratio were significantly lower in AIH and PBC/PSC patients' sera compared to HBV, HCV or NAFLD (P<0.001 for each comparison) and correlated negatively with serum ALP levels. PBC/PSC and AIH patients maintained low serum hepcidin during the course of their two-year long treatment. In summary, parallel determination of liver hepcidin mRNA and serum hepcidin in patients with chronic liver diseases shows that circulating hepcidin and its respective ratio to ferritin are significantly diminished in patients with autoimmune liver diseases. These novel findings, once confirmed by follow-up studies involving bigger size and better-matched disease subgroups, should be taken into consideration during diagnosis and treatment of autoimmune liver diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Cholangitis, Sclerosing / blood
  • Cholangitis, Sclerosing / genetics
  • Cholangitis, Sclerosing / pathology*
  • Diagnosis, Differential
  • Down-Regulation
  • Female
  • Ferritins / blood
  • Hepatitis B / blood
  • Hepatitis B / genetics
  • Hepatitis B / pathology
  • Hepatitis C / blood
  • Hepatitis C / genetics
  • Hepatitis C / pathology
  • Hepatitis, Autoimmune / blood
  • Hepatitis, Autoimmune / genetics
  • Hepatitis, Autoimmune / pathology*
  • Hepcidins / blood*
  • Hepcidins / genetics*
  • Humans
  • Liver / metabolism
  • Liver / pathology
  • Liver Cirrhosis, Biliary / blood
  • Liver Cirrhosis, Biliary / genetics
  • Liver Cirrhosis, Biliary / pathology*
  • Male
  • Middle Aged
  • Non-alcoholic Fatty Liver Disease / blood
  • Non-alcoholic Fatty Liver Disease / genetics
  • Non-alcoholic Fatty Liver Disease / pathology

Substances

  • HAMP protein, human
  • Hepcidins
  • Ferritins

Grants and funding

This work was supported by program 09SYN-12-682, which is implemented under the auspices of NSRF and the National Range Action “COOPERATION” and co-funded by the Greek Government and the European Union - European Regional Development Fund. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.