In the present study, we showed the existence of different rs8099917 genotype frequencies and HCV viral genotypes in patients with different treatment responses. Carriers with the rs8099917 TT genotype and non-G1 HCV genotype had a high chance of achieving SVR and a lower likelihood of either NVR or REL. In contrast, carriers with the rs8099917 TG/GG genotype and G1 HCV genotype had a high risk of NVR or REL. Combining the two pretreatment predictors, IL-28B genetic variants and HCV genotype accurately predicted treatment efficacy of every patient before therapy. This strategy could conceivably play a very important role in the HCV treatment decision-making process because of the high frequency of the favorable allele and the high frequency of SVR in China [18
]. This study is anticipated to open a new window for genotype-based personalized medicine for Chinese patients with CHC.
Nowadays, several studies have reported that genetic variants near IL-28B are associated with response to treatment of chronic HCV infection with a combination of PEG-IFN and RBV [8
]. The IL-28B gene allele frequency was reported to vary according to ethnicity. In the current study, we found that G variants (TG
GG) carriers had a significantly higher risk of NVR and REL. Moreover, logistic regression analysis showed that G allele was an independent predictive factors of NVR and REL, which was similar to reports from Japanese patients in previous studies [11
]. These results may provide useful information for a personalized treatment regimen.
In the current study, it is noteworthy that a high rate of Chinese patients with the TT genotype of rs8099917 attained a SVR. Similarly, Tanaka Y, et al.
reported that rs8099917 had a strong association with response to therapy and the TT genotype of the rs8099917 polymorphism was associated with a high SVR rate [11
]. Suppiah et al.
also reported that the highest rate of SVR was in the group of patients with the TT genotype of rs8099917 and that the presence of the G allele was the most powerful predictive factor for NVR [9
] . Overall, our results were in agreement with the results reported by Suppiah et al.
and Tanaka et al.
Logistic regression model identified the rs8099917 G allele as the most significant factor for predicting NVR (OR
14.02), whereas the prediction of REL using the SNP had lower statistical power (OR
2.27) compared to NVR prediction, indicating that these SNPs are strongly associated with the outcome of NVR. The REL patients with the TT genotype might be able to achieve a SVR following prolonged therapy with PEG-IFN/RBV. Clinically, many factors, such as age, gender, pretreatment HCV RNA levels, higher pretreatment AST levels, liver fibrosis status, and insulin resistance are important factors in the outcome of PEG-IFN-α/RBV therapy [5
]. Nevertheless, this result was not observed in our study, it is possible that such a finding is attributable to relatively small numbers of subjects in the cohort.
It is widely accepted that both host and virus factors can influence the SVR[7
]. Ge et al.
reported that among Caucasian patients with G1, the rs12979860 (3 kilobases upstream of the IL-28B gene) wild CC genotype was an independent predictor favoring SVR [10
]. McCarthy et al.
demonstrated a similar finding with respect to off-treatment viral loads in Caucasian patients with G1 [25
]. Our study included 47% non-G1 infected patients, and surprisingly, the percent of patients with a favorable IL-28B genotype was higher in the non-G1 group (77.9%). There is the possibility that the rs8099917 TT genotype may help select patients with non-G1 infections. The influence of host genotype could be slightly stronger among individuals infected by the non-G1 than among those infected by the G1. We found that G1 infected patients had an increased risk of NVR and REL than non-G1, and this data generated from the current study could provide important information for patients who either would or would not benefit from PEG-IFN-α/RBV treatment before starting treatment. However, these results need additional confirmation in other cohorts.
It is anticipated that this study, which identified a highly genetic association between NVR and REL in patients with different viral genotypes, will have a lasting impact, particularly in the development of individualized treatment strategies. Also, the higher frequency of the TT genotype in Chinese patients may explain (at least partially) why Chinese patients have superior responses to PEG-IFN-α/RBV therapy than other nationalities. The strong associations between IL-28B (rs8099917) genotypes and SVR are consistent in different ethnic groups [10
]. The IL-28B genotype may guide clinical decision making regarding whether or not to initiate therapy, how long to continue therapy for avoiding unpleasant side effects associated with treatment. Nevertheless, there are also NVR (9.1%) and REL (13.0%) patients, even when the favorable TT genotype and non-G1 was identified in patients included in the current study. These results indicate that further prospective studies comparing the treatment efficacy are warranted.
The major limitation of this study is the small number of included cases resulting in low statistical power. Further, whether or not geographic variations in the HCV core protein mutations in the interferon sensitivity-determining region contribute to a relatively much higher SVR rate in the current study remains uncertain [23
]. In this study it was not possible to compare HCV genotype frequencies and IL-28B genotypes between individuals with either cleared or chronic infection because samples from the acute phase of HCV infection were unavailable in individuals with spontaneous HCV clearance.