Again, CYP27B1-1260 rs10877012 genotype had no significant influence on SVR in patients with good-response IL28B rs12979860 genotype (SVR rates 88% vs. 65% vs. 73% for AA vs. CA vs. CC, respectively; P=0.62). However, SVR rates in HCV EPZ-5676 chemical structure genotype 1 and 4 patients with poor-response IL28B rs12979860 genotype were 42% vs. 39% vs. 30% in CYP27B1-1260 rs10877012 AA vs. AC vs. CC, respectively (univariate P=0.11; multivariate P=0.09, OR=1.46, 95% CI=0.940�C2.288), but the association formally lost statistical significance, most likely due to the low number (n=24) of HCV genotype 1 and 4 patients with CYP27B1-1260 rs10877012 AA and poor-response IL28B rs12979860 genotype. With respect to the low frequency of the beneficial minor A allele, CYP27B1-1260 rs10877012 does not appear to be a suitable parameter for clinical decision making.

Nevertheless, our genetic analyses point to a relevant role of vitamin D metabolism in the response to treatment with PEG-IFN-�� and ribavirin of chronic hepatitis C. Serum Concentrations of 25-hydroxyvitamin D in Patients with Chronic Hepatitis C Serum concentrations of 25(OH)D3 were determined in 496 patients at baseline of treatment with PEG-IFN-�� and ribavirin (n=269) or at the time of liver biopsy in patients who were not treated (n=227). Mean and median 25(OH)D3 serum concentrations were 15.6 and 13.4 ng/mL (SD=9.07; range 3.8�C76.9 ng/mL), respectively, which are significantly lower than those determined in the general population (e. g. 22.2 and 20 ng/mL in Reusch et al., n>6.000) [24], [28].

Among patients with chronic hepatitis C, 32%, 42%, and 26% had 25(OH)D3 serum levels <10, ��10 to <20, and ��20 ng/mL, respectively. Because of the seasonal fluctuation of 25(OH)D3 serum levels, we calculated median 25(OH)D3 serum levels separately for each month. Although season had a substantial impact on median 25(OH)D3 serum levels, at least 50% of HCV-infected individuals suffered from vitamin D insufficiency (<20 ng/mL) even during summer, while approximately 50% suffered from vitamin D deficiency (<10 ng/mL) between November and April (Figure 2). Figure 2 Seasonal variation of 25(OH)D3 serum levels in patients with chronic hepatitis C. In a univariate analysis, age, male sex, infection with HCV genotype 3, excessive alcohol consumption, presence of diabetes, advanced liver fibrosis, and season of blood sampling were significantly associated with low Anacetrapib 25(OH)D3 serum levels (< median; Table 5). In logistic regression analyses, age, advanced liver fibrosis, presence of diabetes, and season of blood sampling were independent and significant predictors of low 25(OH)D3 serum levels (Table 5). Table 5 Factors associated with 25-hydroxyvitamin D serum levels (�� median) in patients with chronic hepatitis C.