Hepcidin expression levels involve efficacy of pegylated interferon-α treatment in hepatitis B-infected liver

Int Immunopharmacol. 2022 Jun:107:108641. doi: 10.1016/j.intimp.2022.108641. Epub 2022 Feb 22.

Abstract

Background: Hepcidin is the master iron regulator hormone produced by the liver. The association of serum hepcidin with pegylated interferon therapy in patients with chronic hepatitis C infection has been studied. However, the role of serum hepcidin level in predicting the effect of pegylated interferon treatment in patients with chronic hepatitis B (CHB) infection is yet to be elucidated. Our study aims to investigate the correlation between hepcidin expression levels and the curative effect of interferon-alpha therapy in patients with CHB.

Methods: A total of 47 patients with CHB who accepted pegylated interferon-α (PEG-IFN- α) treatment were recruited. The serum level of hepcidin was estimated by ELISA. The alternation in the gene expression level of hepcidin was detected by RT-PCR, and immunofluorescence cell staining was performed to detect hepcidin peptide. The induction of antiviral proteins was analyzed by Western blotting. The predictive value of early on-treatment variation in serum hepcidin during treatment progress was assessed by receiver operating characteristic analysis.

Results: High levels of early on-treatment serum hepcidin were observed in patients who achieved a decline in HBsAg > 1 log10 IU/mL or HBV DNA > 1 log10 IU/mL. In vitro, an elevation of the hepcidin expression in HepG2.2.15 cells induced by PEG-IFN-α treatment was noted. Furthermore, combined treatment with hepcidin and PEG-IFN-α increased the levels of antiviral proteins. The predictive cut-off value of hepcidin for HBsAg decline > 1 log10 IU/mL was 239 pg/mL, and the sensitivity and specificity were 72.73% and 70.97%, respectively. The predictive cut-off value of hepcidin for the decline in HBV DNA > 1 log10 IU/mL was 190.4 pg/mL, and the sensitivity and specificity were 72.73% and 61.11%, respectively. Early-on treatment changes in the hepcidin level signified the predictive value of the PEG-IFN-α curative effect.

Conclusions: A higher early-on treatment hepcidin level indicates a higher possibility of HBsAg and HBV DNA decline in patients with CHB during PEG-IFN-α treatment. A high early-on treatment serum hepcidin level is significant in predicting the PEG-IFN-α therapeutic effect in patients with CHB.

Keywords: Hepatitis B Virus; Hepcidin; IFN Therapy; Predictive Value.

MeSH terms

  • Antiviral Agents / pharmacology
  • Antiviral Agents / therapeutic use
  • DNA, Viral
  • Hepatitis B Surface Antigens*
  • Hepatitis B e Antigens
  • Hepatitis B virus
  • Hepatitis B, Chronic*
  • Hepcidins
  • Humans
  • Interferon-alpha / therapeutic use
  • Polyethylene Glycols / pharmacology
  • Polyethylene Glycols / therapeutic use
  • Recombinant Proteins / pharmacology
  • Recombinant Proteins / therapeutic use
  • Treatment Outcome

Substances

  • Antiviral Agents
  • DNA, Viral
  • Hepatitis B Surface Antigens
  • Hepatitis B e Antigens
  • Hepcidins
  • Interferon-alpha
  • Recombinant Proteins
  • Polyethylene Glycols