Source Centre for Liver Disease, Mater Misericordiae University Hospital, Dublin, Ireland; School of Medicine and Medical Science, University College Dublin, Ireland. jdpryan@yahoo.co.uk.

Pegylated interferon-α (PEG-IFNα) forms an integral part of the current treatment for Hepatitis C virus (HCV) infection. PEG-IFNα suppresses HCV production by augmenting the innate anti-viral immune response. Recent studies have reported the induction of hepcidin, the iron regulatory hormone, by IFNα in-vitro. As hepcidin plays an important role in innate immunity, we hypothesized that this finding may be of clinical relevance to HCV, and investigated the changes in iron homeostasis during the first 24hrs of treatment.

Blood samples were obtained from HCV patients immediately prior to, and 6,12, and 24hrs following the first dose of PEG-IFNα/ribavirin(RBV). Samples were analyzed for hepcidin, cytokine, iron levels and HCV viral load, and hepcidin mRNA expression was quantified in peripheral blood mononuclear cells. Hepcidin induction by IFN-α was further analyzed in cell culture. In HCV patients, a single dose of PEG-IFNα/RBV resulted in a significant increase in serum hepcidin, peaking at 12hrs, coinciding with a 50% reduction in serum iron (SI) and transferrin saturation (TS) over the 24hr period. Patients with a ≥2log decline in HCV viral load over the first 24hrs had significantly lower SI and TS levels at 12 and 24hrs. Moreover, 24hr SI levels were an independent predictor of the immediate HCV viral decline, an indicator of ultimate treatment outcome. In cell culture, a direct induction of hepcidin by IFN-α was seen, controlled by the STAT3 transcription factor.

Hepcidin induction occurs following the initiation of PEG-IFNα treatment for HCV, and is mediated via STAT3 signalling. The subsequent hypoferremia was greatest in those with the most significant decline in viral load, identifying systemic iron withdrawal as a marker of immediate interferon-α efficacy in HCV patients.