To confirm the presence of an independent association between impaired liver VDR expression and the diagnosis of NASH, we compared clinical and metabolic

parameters of patients affected by NASH with those obtained in the comparison subjects. The two groups were comparable for sex, age, and BMI. In all these subjects, we measured fasting blood glucose Dorsomorphin datasheet (mg/dL), basal insulin (μU/mL), and adiponectin, and calculated the HOMA-IR. No significant differences were found between metabolic parameters of NASH patients and the comparison group [25(OH)D3, 54.7 ± 30.7 nmol/L versus 52.9 ± 11.02 nmol/L, P value not significant; basal insulin, 18.4 ± 11 μU/mL versus 19.8 ± 12.4 μU/mL, P value not significant; HOMA-IR, 5.5 ± 4.7 versus 3.87 ± 2.6, P value not

significant; MEK inhibitor adiponectin (p = 0.25), 16.03 ± 8.7 ng/mL versus 17.8 ± 13.3 ng/mL], excluding fasting blood glucose (106.3 ± 26.2 mg/dL versus 93.6 ± 9 mg/dL, P = 0.038). The bivariate correlation analysis showed the presence of a negative association between VDR expression in cholangiocytes and in hepatocytes and the diagnosis of NASH (Spearman’s coefficient, −0.5, P = 0.001, and Spearman’s coefficient, −0.4, P = 0.01, respectively), whereas no correlation was found between liver VDR positivity and basal insulin, HOMA-IR, adiponectin, or BMI. Stepwise multiple regression analysis considering liver VDR expression as dependent variable and sex, age, BMI, HOMA-IR, adiponectin, and the diagnosis of NASH as independent variables confirmed the presence of a strong association between low liver VDR expression and the diagnosis of NASH independently from all other metabolic parameters (unstandardized β coefficient, −18.7; standardized β coefficient, 0.51; P = 0.027). In the CHC population mean serum 25(OH)D3 levels were comparable with those observed

in patients affected by NASH (50.75 ± 26.7 versus 54.7 ± 30.7 nmol/L; P value not significant) before and correlated with CYP2R1 expression on hepatocytes (Spearman’s coefficient, 0.50; P = 0.02). VDR expression was found in both the nuclei and cytosol of cholangiocytes and hepatocytes and was strongly associated with hepatic reactivity for CYP27A1 and CYP2R1 (Table 3), but did not correlate with either serum 25(OH)D3 levels or other clinical and biochemical parameters. The degree of VDR expression on cholangiocytes and the expression of CYP27A1 were significantly reduced compared with those observed in the comparison group (Spearman’s coefficient, −0.69, P < 0.001, and Spearman’s coefficient, −0.5, P < 0.001, respectively), as shown in Table 2. Interestingly, the portal inflammation was inversely correlated with VDR positivity on inflammatory cells (Spearman’s coefficient, −0.55; P < 0.009), and on hepatocytes (Spearman’s coefficient, −0.43; P < 0.