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

Abstract

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.

Relevance of the Core 70 and IL-28B polymorphism and response-guided therapy of peginterferon alfa-2a ± ribavirin for chronic hepatitis C of Genotype 1b: a multicenter randomized trial, ReGIT-J study

“…Regarding the correlation between treatment response and SVR, Thompson et al [38] reported that RVR and cEVR rates were lower in patients with the IL-28B minor genotype than in those with the major genotype but the SVR rate was not affected by the IL-28B genotype in patients with RVR or cEVR. In recent studies published after recognition of IL-28B polymorphism, virological response at week 4 and 12 was highly associated with SVR [39, 40]. In our present results, if RVR or EVR is achieved, a high SVR rate can be obtained regardless of the IL-28B polymorphism or Core 70 mutation status.…”

Host Genetic Variants in the Pathogenesis of Hepatitis C

“…Early viral dynamics, in a Japanese study, had only a predictive value for therapy response in patients with rs8099917 TT-genotype. Non reaching RVR at week 4 was per se a predictive factor for non-SVR in these cohorts regardless of IL28B [41]. Huang et al analyzed rs8099917 to identify GT-1 patients responding to a short treatment of 24 weeks with Peg-INF/RBV.…”

Impact of Donor and Recipient Single Nucleotide Polymorphisms of IL28B rs8099917 in Living Donor Liver Transplantation for Hepatitis C

“…A prospective study with a fixed DNA sampling protocol is required. Second, the nucleotide sequences of the core and non-structural 5A regions, another recently suggested important factor [36], have not been investigated in concert with IL28B polymorphisms. In fact, few studies to date have performed a combined analysis of both IL28B polymorphisms and HCV RNA nucleotide sequences, most likely due to the additional logistic burden.…”