A study was carried out to determine whether early viral dynamics retain prediction of the outcome of peginterferon (PEG-IFN) and ribavirin combination therapy based on different genetic polymorphisms near the IL28B gene, the strongest baseline predictor of response to this therapy. A total of 272 patients infected with hepatitis C virus (HCV) genotype 1b were grouped according to genetic polymorphisms near the IL28B gene (rs8099917). The ability of reduced HCV RNA levels at 4 and 12 weeks after starting therapy to predict a sustained virologic response was evaluated based on these genotypes. Among patients with the TT genotype for rs8099917 (associated with a favorable response), the rates of sustained virologic response were higher in patients with a ≥3 log(10) reduction in serum HCV RNA levels at 4 weeks after starting therapy (P < 0.0001). In contrast, among patients with the TG/GG genotype (associated with an unfavorable response), there were no differences in this rate based on the reduction in HCV RNA levels at 4 weeks. Early viral dynamics at 4 weeks after starting therapy retains its predictive value for sustained virologic response in patients with the TT genotype for rs8099917, but not in patients with the TG/GG genotype. Patients who are likely to achieve sustained virologic response despite unfavorable TG/GG genotype cannot be identified based on early viral dynamics during therapy. In contrast, lack of early virologic response at 12 weeks retains a strong predictive value for the failure of sustained virologic response regardless of IL28B polymorphisms, which remains useful as a factor to stop therapy.
Toyoda, H., Kumada, T., Tada, T., Hayashi, K., Honda, T., Katano, Y., … Matsuda, F. (2012). Predictive value of early viral dynamics during peginterferon and ribavirin combination therapy based on genetic polymorphisms near the IL28B gene in patients infected with HCV genotype 1b. Journal of Medical Virology, 84(1), 61–70. https://doi.org/10.1002/jmv.22272