Th17 cells represent a pro-inflammatory subset, while the Treg cells have an antagonistic effect; the deregulation of Th17/Treg balance has been associated with pathophysiological changes observed during the inflammation and the progression of autoimmune diseases. So we investigated if the modulation of Th17-cells observed after NLCD in CHC patients was also associated with a modulation of Treg cells and then with a change in Th17/Treg ratio. Before diet, we observed an imbalanced ratio between the Th17 and Treg cells confirm an inflammatory status of the patients studied. In CHC patients after NLCD, we found a significant increase in Treg-cell frequency and in the Treg/Th17 ratio. Importantly, in NAFLD/NASH patients, no significant modulation of Th17/Treg balance, after NLCD, was observed. These findings indicate a different modulation of the immune response between CHC and NAFLD patients; in fact, the Th17-cell frequency regulation seems to be related not only to the metabolic status, but mostly to the presence of the HCV. Our study focused mainly on the frequency of Th17 cells, not only for their involvement in the progression of the disease, but especially because it has been described that their differentiation is regulated by cholesterol sensors and metabolic AZD6244 MEK inhibitor modulators, as LXRs. LXRs bind DNA as a heterodimer when joined to the RXR and regulates cholesterol and fatty acid metabolism genes, such as ABCA1 and SREBP1C. On these evidences, we evaluated the LXRs activity by the study of the relative expression of LXRs and their target genes, SREBP-1c and ABCA-1. Specifically, it has been showed that LXR-induced Srebp-1 inhibits Il17 transcription binding the Il17 promoter, thus regulating T17-cell proliferation and differentiation. After NLCD, we highlighted an increased mRNA-level expression of LXRs and of both their target genes in CHC patients, fact that, indirectly, supports an increased activity of the LXR nuclear receptors. The increase of transcriptional levels of LXRb in our cohorts of CHC patients was not expected, and, in our opinion, is quite intriguing. Further studies are needed to understand the role of LXRb during HCV infection. The same panel of genes was evaluated in NAFLD/NASH patients after NLCD, obtaining a different modulation than in CHC subjects. This supports our idea that NLCD can counteract the HCV influence on LXRs activity, restoring the immune system homeostasis. Consequently, the Th17-cell frequency is heavily influenced by cholesterol metabolism, since the NLCD improves Th17/Treg balance, modulating LXRs and their target genes. Finally, since TGF-b is known to be a regulator of Treg and Th17-cell differentiation, we looked at its serum concentration, in CHC and NAFLD/NASH patients before and after NLCD, taking into account that TGF-b, as well as HA, is a predictor of clinical worsening. In particular, the key role of TGF-b in inflammation is proved by the development of several anti-TGFb compounds for the treatment of a broad range of inflammatory, autoimmune diseases and cancer.