Hence, Treg and Th17 cells arise in a mutually exclusive fashion, and a balance between the two T-cell subsets is crucial for the immune homeostasis. Furthermore, recent studies highlight that Th17 cell-differentiation can be regulated by nuclear receptor LXRs, known as LXRa and LXRb. These nuclear receptors act as important BMS-354825 modulators of lipid metabolism and cholesterol homeostasis by regulating genes, such as SREBP-1c, and ABCA-1. Therefore, considering the importance of cholesterol for the life cycle of the HCV, and the involvement of LXRs in the modulation of the immune response, we thought that cholesterol, via LXRs-mediated signaling, could represent a key element in regulating the differentiation of T lymphocytes in Th17 cells. In addition, CHC patients have high serum levels of oxysterols, endogenous ligands of LXRs and products of cholesterol oxidation. Furthermore, it has been reported a direct interaction between HCV-core protein and Retinoid X Receptor alpha, a well-known heterodimeric partner of LXRs. So the RXR/HCV-core complex might deregulate the LXRs activity during HCV infection, supporting the influence of HCV on LXRs and in turn on the frequency of Th17 cells, thus potentially affecting the host immune system. On these bases, we performed a pilot study to investigate if a Normocaloric Low Cholesterol Diet may be able to modulate Th17/Treg balance in patients affected by chronic HCV infection. With this experimental setting we directly compared the effect of NLCD in CHC patients compared to nonalcoholic fatty liver disease and non-alcoholic steatohepatitis patients, since the last two categories of patients are characterized by both hepatic steatosis and lipid disorders, similar to the ones observed in CHC patients, but in absence of the viral involvement. The importance of cholesterol in the HCV infection has been repeatedly described. Thus, HCV infection is able to alter host lipid metabolism, leading to a hepatic steatosis. In this regard we administered a diet low in cholesterol to assess the impact that it could have on CHC patients. In fact, we describe that a Normocaloric Low Cholesterol diet is able to restore the immune homeostasis recovering the balance between Th17 and Treg cells in CHC patients, but not in those affected by NAFLD/NASH. Thus, our findings corroborate the importance of cholesterol metabolism during HCV infection. Confirming several studies, we observed a remarkable higher frequency of Th17 cells in blood of CHC patients with respect to healthy individuals, and a slight increase in NAFLD/NASH subjects. Interestingly, NLCD was able to induce a consistent reduction of Th17-cell frequency in CHC patients, but not in our cohorts of NAFLD/NASH patients. As expected, after diet, we observed a decrease in serum levels of Th17-associated cytokines, i.e. IL-17 and IL-22, which was statistically significant only in CHC patients. Furthermore, we reported that Th17- cell frequency correlated, before and after NLCD.