Patients having a minor homozygote (rs8099917 GG or rs12979860 TT) were not found in this study, which is consistent with a recent report of the rarity of a minor homozygote in Japanese patients.3 IL28B minor patients were significantly associated with a higher γ-glutamyl transpeptidase (γ-GTP) level and higher frequency of mutations at amino acid positions 70 and 91 of the HCV core region (glutamine or histidine mutation at amino acid position 70; methionine

mutation at amino acid position 91). NVR rate was significantly higher in IL28B minor patients than in IL28B major patients. Hepatic expression levels of cytoplasmic viral sensors (RIG-I, MDA5, and LGP2) were significantly higher Idelalisib price in IL28B minor patients

than in IL28B major patients (Fig. 1). Similarly, expressions of ISG15 and USP18 were significantly higher in IL28B minor patients than in IL28B major patients (Fig. 1). In contrast, the hepatic expression of the adaptor molecule (IPS-1) was significantly lower in IL28B minor patients than that in IL28B major patients (Fig. 1). Hepatic expression of RNF125 was similar among IL28B genotypes (Fig. 1). IFNλ (IL28A/B) expression was higher in IL28B minor patients, but not statistically significant (Fig. 1). Because expression of RIG-I and IPS-1 were negatively correlated, the expression ratio of Ganetespib order RIG-I/IPS-1 in IL28B minor patients was significantly higher than in IL28B major patients (Fig. 1). Next, to assess the relationship between baseline medchemexpress hepatic gene expression and treatment efficacy, we compared levels of gene expression involving innate immunity and IFNλ based on the final virological

response (Fig. 2). Overall, hepatic expressions of cytoplasmic viral sensors and the ISG15/USP18 system in NVR patients were significantly higher than those in VR patients. In a similar but opposite manner, hepatic expressions of IPS-1 and RNF125 in NVR patients were significantly lower than that in VR patients, and the expression of IFNδ was higher in NVR patients, but the differences were not statistically significant. Expression ratio of RIG-I/IPS-1 was significantly higher in NVR patients than that in VR patients. Because hepatic expressions of the RIG-I/IPS-1 and ISG15/USP18 systems were significantly related both to IL28B minor and NVR patients, RIG-I and ISG15 expression levels and the RIG-I/IPS-1 ratio between VR and NVR patients were further stratified by IL28B genotype (Fig. 3). Even in the subgroup of IL28B minor patients, the expressions of RIG-I and ISG15 were significantly higher in NVR patients than those in VR patients. Similar tendencies were observed in a subgroup of IL28B major patients, in whom the RIG-I/IPS-1 expression ratio was significantly higher in NVR patients than in VR patients.