Serum ferritin levels, an indicator of hepatic iron stores, remained unchanged overall (Supporting Fig. 3). As previously reported, HCV viral load declined significantly following PEG-IFN-α/RBV administration, with the lowest levels seen at 24 hours during the period of this study (Fig. 3A; T = 0 versus T = 24 HCV viral load, P < 0.0001). Notably, SI and TS levels were significantly lower at 12 and 24 hours in HCV patients experiencing

a ≥2 log decline in HCV viral load (Fig. 3B,C; SI at 12 hours, P = 0.033; 24 hours, P = 0.029; TS at 12 hours, P = 0.026; 24 hours, P = 0.017). this website SI levels at 24 hours were found to be an independent predictor of the decline in viral load over 24 hours, controlling for both HCV genotype and IL28b genotype (Table 2; R square 0.47; coefficient B −0.12, SE −0.20, −0.02; P = 0.013). However, this effect appeared to be confined to HCV genotype 1 patients, in whom the change in

HCV viral load correlated significantly with that of SI over the 24-hour period (Supporting Fig. S4a; r = 0.49, P = 0.041). Moreover, SI at 24 hours was associated with both EVR and SVR at univariate analysis in the group as Apoptosis inhibitor a whole (Supporting Table 1; EVR: odds ratio [OR] 1.3, 95% confidence interval [CI] 1.024-1.65, P = 0.031; SVR: OR 1.199, 95% CI 0.977-1.473, P = 0.083), although the study was underpowered to perform multivariate logistic analysis. Also of relevance, the correlation between hepcidin and iron learn more changes during the 24-hour period was strongest in those ultimately achieving an SVR (Fig. 3D,E). The inflammatory induction of hepcidin is chiefly mediated by interleukin 6 (IL-6), whereas other cytokines have also been

implicated.22, 23 To investigate the stimulus for hepcidin production following PEG-IFN-α/RBV, serum levels of a panel of cytokines were measured in a subgroup of 22 patients at time 0, 12, and 24 hours. These included IL-1, IL-6, IFN-α, and interferon-gamma-inducible protein-10 (IP-10), a serum marker of IFN-α response.24 Although serum IL-1 and IL-6 increased significantly upon PEG-IFN-α/RBV treatment, their induction was not proportional to that of hepcidin (Supporting Fig. 5a-d). However, serum hepcidin did correlate significantly with increased IFN-α and IP-10 levels at 12 hours (Fig 4A-D; rho = 0.44, P = 0.042 and rho = 0.59, P = 0.004 respectively). Although the assay used to detect serum IFN-α did not discriminate between endogenous and administered IFN-α, the serum IFN-α levels attained would suggest that exogenous (pegylated) IFN-α was also detected.25 Peak (12-hour) serum hepcidin levels further correlated significantly with the peak (24-hour) serum CRP levels (Fig. 4E,F). Treatment of human hepatoma cells with IFN-α resulted in a rapid time-dependent induction of hepcidin mRNA expression, peaking at 2-3 hours (Fig. 5A; P < 0.001).