*Regulation of Iron Metabolism in NAFLD/NASH DOI: http://dx.doi.org/10.5772/intechopen.107221*

in this study demonstrated that hepcidin expression in β-cells is directly regulated by iron. Iron is important for normal insulin secretion. However, excessive amounts of iron can affect β-cell function in hemochromatosis models [82–84], causing iron accumulation in the islets, a reduction in insulin secretion and an increase in the apoptosis of β-cells. In contrast, a reduction in the iron pool was shown to protect against diabetes and loss of β-cell function in an obese (ob/ob) mouse model [85]. These observations suggest that hepcidin produced by β-cells may be involved in the intrinsic regulation of pancreatic iron and glucose homeostasis [22].

In accordance with this study, the possibility of replacing phlebotomy with placenta-derived drugs, Laennec and Porcine, was evidenced through the pharmacological mechanism of inducing hepcidin production and suppressing iron-related oxidative stress [86]. Furthermore, these results strongly suggest that Laennec and Porcine are considerably effective not only for H.H but also for other iron loading diseases, such as β-thalassemia, MDS, NASH complicated with T2DM, and autoimmune liver disease [primary biliary cirrhosis (PBC) and autoimmune hepatitis (AIH)] [73–75]. The efficacy of removing iron from the liver will improve the prognosis of patients with these types of iron-loading hepatic disorders. Thus, more experimental and clinical studies are required to confirm the claim that hepcidin plays an important role in chronic liver diseases and complicating T2DM [87]. These are promising drugs that can suppress iron-induced oxidative injury as well as iron deposition in multiple organs, which will improve the prognosis of patients who developed iron-overloading disorders (**Figures 5**–**8**) [73–75].

In addition, in some types of β-thalassemia (especially intermediate), inducing hepcidin by administering Laennec and Porcine can improve the iron-overloading conditions in these patients without affecting the underlying cause of their haemolytic anaemia.

In general, serum hepcidin levels are typically elevated in individuals with NASH [68]. As this in itself fails to explain the cause of iron loading in NASH, one might consider that dysregulated iron metabolism occurs in NASH independently of hepcidin. One of the possible mechanisms by which hepcidin inducer Laennec is capable of improving iron metabolism in NAFLD/NASH might be the induction of the alternative route of hepcidin, which might be relevant in the progression of NAFLD/NASH. Furthermore, there might be some kind of 'hepcidin resistance' in NAFLD/NASH patients, which is observed in T2DM patients as 'insulin resistance'.

In conclusion, the present study suggests that s-ferritin elevation in our patients is a marker of metabolic syndrome with hepatic steatosis and insulin resistance and not of iron overload. The direct pathogenic mechanism, however, remains unknown. In the absence of in vivo data, any iron-independent role of hepcidin in the host defence remains speculative.
