Bitetto et al. described how vitamin D serum level is complementary to the interleukin 28B (IL28B; rs12979860) polymorphism in predicting the achievement of sustained virological response (SVR) in treatment-naive patients receiving standard pegylated interferon (Peg-IFN) and ribavirin (RBV) for the treatment of genotype 1 chronic hepatitis C virus (HCV).1
It should be also noted how vitamin D serum levels may be influenced by polymorphisms in the gene coding for a related metabolic enzyme (cytochrome P450 27B1 [CYP27B1]).2 The association between responsiveness to therapy for difficult-to-treat HCV infections and IL28B (rs12979860 and rs8099917) single-nucleotide polymorphisms (SNPs) were evaluated.1, 3
Prior to the discovery of these new predictive factors, both dosage and pharmacokinetic exposure of RBV have been repeatedly found to be associated with the therapeutic outcome of chronic HCV hepatitis.4, 5 No data are, however, yet available on the interplay between RBV pharmacokinetics and these newly introduced predictive factors.
In the analysis of 91 patients with chronic genotype 1/4 HCV hepatitis who received standard Peg-IFN/RBV treatment, we found that further to IL28B (rs8099917) SNP (odds ratio [OR] = 2.83, 95% confidence interval [CI] = 1.08-7.39, P = 0.034) and CYP27B1 (rs4646536) SNP (OR = 3.90, 95% CI = 1.37-11.14, P = 0.011), the presence of RBV concentrations >2500 ng/mL (OR = 3.08, 95% CI = 1.21-7.85, P = 0.019) was an independent predictor of SVR.
It is worth noting (Fig. 1) how no patients with all three unfavorable factors had SVR, whereas a tendency to higher rates of SVR was seen according to the combination of favorable genetic and RBV pharmacokinetic factors. These results reveal that rs8099917 G allele, rs4646536 C allele (related to low 25-hydroxyvitamin D3 serum concentrations), and RBV plasma concentrations (<2500 ng/mL) could predict which patients are likely to experience treatment failure in this group of difficult-to-treat HCV-infected patients.
Based on these findings, we believe that in addition to these recently characterized human genetic factors, the individual pharmacokinetic exposure to RBV should not be neglected among the predictors of anti-HCV treatment outcome.