28 Interestingly, considering only noninvasive parameters, the AUC of the model that includes vitamin D levels to predict severe fibrosis remains good. This suggests the potential use of serum 25(OH)D levels as a noninvasive marker

of liver fibrosis, a use that needs to be tested and validated in large prospective cohort studies in patients with CHC of all genotypes, and in chronic liver disease of other origins. It is conceivable that a reduced 25(OH)D level might by itself favor progression of fibrosis. Different experimental models showed that vitamin D, www.selleckchem.com/products/byl719.html via interaction with vitamin D receptor, protects against oxidative stress production,29 can influence the migration, proliferation, and gene expression of fibroblasts,30, 31 and reduces the inflammatory

and fibrogenic activity of liver stellate cells.32, 33 However further prospective cohort studies will Everolimus research buy be needed to determine the causal association between vitamin D deficiency and fibrosis in patients with CHC. Another interesting finding of this study is the evidence that lower 25(OH)D serum levels were an independent negative risk factor for SVR. Again, this observation will require further validation in different, large cohorts of patients, but is supported by experimental data that suggest a role of vitamin D in the modulation of the immune response,32, 33 and by recent clinical data36 reporting higher early virological response rate in CHC treated with standard of care plus vitamin D, compared with those treated with standard of care only. Finally, in line with data from the literature, we found that steatosis35 and lower cholesterol levels, a known surrogate marker of fibrosis severity,26 were independently associated with lower SVR rate. We did not find any association this website between IR and SVR, in keeping the conflicting data reported in the literature on the role of IR as a predictor of SVR.36 The main limitation of this study lies in its cross-sectional nature and its inability to dissect the temporal relation between 25(OH)D and fibrosis. A further methodological drawback is the potentially limited external validity of the results for different

populations and settings. Another limitation of this study is the lack of data on the potential confounders that may influence the levels of vitamin D, such as exposure to sunshine, dietary intake, and the prevalence of osteoporosis. However, all of the subjects involved in this study lived in Sicily, where sunshine is abundant, even if we cannot rule out differences in sun exposure between healthy controls and CHC patients. However, data on the prevalence of osteoporosis were not available, nor was the dietary intake of vitamin D, which, however, remains a rather crude measure of vitamin D status because of recall bias. The lack of these data in both cases and controls makes a systematic error very unlikely. Also, data on osteoporosis were not available in both groups.