A negative correlation tendency was found between serum prohepcidin levels and TS in patients with ALD kinase inhibitor Belinostat (r=-0.420, p=0.051, Fig. 2). However, the correlation was not statistically significant in the healthy, CH-C, or NAFLD groups. There was no significant correlation between serum prohepcidin and ferritin levels among the four groups of subjects. Figure 2 Negative correlation between the serum prohepcidin level and transferrin saturation (TS) in patients with alcoholic liver disease (ALD). Prohepcidin/ferritin ratios in CH-C, ALD, NAFLD, and healthy controls When we compared the prohepcidin/ferritin ratios among the four subject groups, there was no significant difference in the CH-C group (4.70��5.65, p=0.067), the ALD group (1.17��0.85, p=0.830) and the NAFLD group (1.37��1.49, p=0.

422) compared to the healthy control group (2.62��2.38), although the ratio in the CH-C group and the healthy control group showed relatively higher level than others. There was a negative correlation between the prohepcidin/ferritin ratio and TS in healthy controls (r=-0.448, p=0.025) and in patients with CH-C (r=0.-417, p=0.030). However, this correlation was not significant in patients with ALD or NAFLD. DISCUSSION In this study, we observed that both the serum prohepcidin and IL-6 levels were significantly elevated in CH-C patients compared to those in healthy controls, and both prohepcidin and IL-6 were positively correlated with each other in CH-C. ALD patients showed significantly higher serum iron and ferritin levels compared to healthy controls, but their serum prohepcidin levels were not different from those seen in healthy controls, despite the significantly elevated IL-6 levels.

Although the NAFLD group showed elevated serum iron and ferritin levels, GSK-3 neither the prohepcidin nor the IL-6 levels were elevated. Therefore, in CH-C, prohepcidin seems to be induced by IL-6. However, in ALD, prohepcidin is not induced by IL-6, probably due to the inhibitory effect of alcohol on hepcidin. Moreover, there was a negative correlation between the prohepcidin/ferritin ratio and TS in healthy and CH-C patients, while no such significant correlation was noted in ALD and NAFLD patients. This suggests that the prohepcidin response to body iron stores is functional in normal and CH-C patients, while it might be dysfunctional in ALD and NAFLD patients. Therefore, different regulatory mechanisms of iron metabolism and different roles of prohepcidin exist in different human liver diseases. Hepcidin is the product of the hepcidin antimicrobial peptide (HAMP) gene on human chromosome 19, and expression of hepcidin mRNA is mostly confined to the liver.