Additional Supporting Information may be found in the online version of this article.

HEP_25666_sm_SuppInfo.doc20KSupporting Information
HEP_25666_sm_SuppFig1.tiff131KSupporting Information Figure 1. Hepcidin changes according to HFE genotype. Serum hepcidin increased significantly from baseline in all patients except for one individual who had undergone therapeutic venesection for HFE Hereditary Hemochromatosis (C282Y homozygote) prior to treatment with PEG/RBV, in whom hepcidin remained undetectable at all time points. Indeed, venesection is known to strongly suppress hepcidin production.(1) One other patient with a HFE genotype associated with Hemochromatosis, i.e. C282Y/H63D compound heterozygote, did not have significant baseline iron overload (serum ferritin 238μg/L) and had an appropriate increase in hepcidin following PEG/RBV.
HEP_25666_sm_SuppFig2.tiff134KSupporting Information Figure 2. Serum iron levels at 24hrs according to IL28b genotype. IL28b polymorphisms impact upon HCV Genotype 1 infection predominantly. In this study, 18 patients had genotype 1 HCV. A non-significant trend toward lower serum iron levels at 24 hours with a favorable C/C IL28b genotype (i.e. homozygous for the rs12979860 polymorphism (n=9) compared with heterozygotes (C/T; n=8); non-significant, p=0.12) was noted.
HEP_25666_sm_SuppFig3.tiff80KSupporting Information Figure 3. Changes in serum ferritin during the first 24 hours of PEG-IFNa/RBV treatment. Serum ferritin did not change significantly during the first 24 hours of PEG-IFNa/RBV treatment.
HEP_25666_sm_SuppFig4.tif154KSupporting Information Figure 4. Changes in serum iron and HCV viral load according to HCV genotype during the first 24 hours of PEG-IFNa/RBV treatment The overall change in serum iron correlated significantly with that of HCV viral load from baseline to nadir (variables Log10 transformed) in patients with HCV genotype 1 but not genotype 3 (S4a: Genotype 1, r= 0.49, p=0.041; S4b: Genotype 3, r=0.05, p=0.86).
HEP_25666_sm_SuppFig5.tiff162KSupporting Information Figure 5. Cytokine and hepcidin changes during the first 24 hours of PEG-IFNa/RBV treatment Despite significant increases in interleukin 6 (IL-6) at 12 and 24 hours post PEG-IFNa/RBV (Fig. S5a; T=0 vs T=12 and T=24, ***p<0.0001) and IL-1b at 12 hours (Fig. S5c; T=0 vs T=12, p=0.02), no significant correlations between serum levels of these cytokines and that of hepcidin were seen (Fig. S5b and S5d).
HEP_25666_sm_SuppFig6.tiff58KSupporting Information Figure 6. Knock down efficiency of STAT3. STAT3 mRNA expression was assessed in Hep3b cells 48hrs after transfection with STAT3-specific or control (scrambled) siRNAs. STAT3 mRNA expression was assessed by qPCR normalised to GAPDH expression, and expressed here as fold change (***p<0.0001).
HEP_25666_sm_SuppTab1.doc39KSupporting Information Table 1. Factors associated with Sustained Virological Response (SVR) Logistic regression analysis

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