We appreciate the interest of Strnad et al. in our recent article.[1] Similar to our study, Strnad et al. demonstrate a significant increase in serum hepcidin levels in HCV genotype 1 patients soon after commencing pegylated interferon-α/ribavirin (PEG/RBV) therapy. However, the hepcidin assay used and the timepoints studied were different from ours, limiting comparisons between studies. Importantly, neither study found a significant association between baseline or dynamic changes in serum hepcidin levels and treatment outcomes.

Specifically, in our study we did not find any significant differences between baseline serum hepcidin levels according to gender, but male subjects experienced a greater increase in serum hepcidin following the first PEG/RBV dose than females (P = 0.052). The cause of this difference is unclear but could relate to gender-specific influences on expression of interferon stimulated genes before and after IFN-α treatment.[2] Indeed, anemia was commonly seen during PEG/RBV treatment and although no gender difference was noted, we agree that hepcidin induction is likely to contribute at least in part to this important adverse effect.

As noted elsewhere, significantly higher hepcidin levels 6 months following the end of treatment in those achieving a sustained virological response (SVR) may reflect a direct role for the hepatitis C virus in hepcidin dysregulation, which is ameliorated upon viral eradication.[3] Finally, the authors speculate as to the cause of the observed rise in hepcidin during treatment. Our study demonstrates a positive correlation between serum hepcidin and serum IFN-α levels in HCV patients and a clear induction of hepcidin by interferon-α treatment of cultured cells, suggesting a direct effect of IFN-α on hepcidin levels in hepatocytes during HCV therapy.

  • John Denis Ryan, M.B., B.Ch.

  • Sandro Altamura, Ph.D.

  • Martina Muckenthaler, Ph.D.

  • John Crowe, Ph.D., PRCPI

  • Center for Liver Disease

  • Mater Misericordiae University Hospital

  • Dublin, Ireland


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