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. 2012 Mar;56(3):557-63.
doi: 10.1016/j.jhep.2011.10.004. Epub 2011 Oct 23.

Single nucleotide polymorphism upstream of interleukin 28B associated with phase 1 and phase 2 of early viral kinetics in patients infected with HCV genotype 1

Charles D Howell  1 , Alexis Gorden, Kathleen A Ryan, Alexander J Thompson, Chadi Ibrahim, Michael Fried, Nezam H Afdhal, John G McHutchison, Kevin V Shianna, David B Goldstein, Alan R Shuldiner, Braxton D Mitchell
Affiliations

Single nucleotide polymorphism upstream of interleukin 28B associated with phase 1 and phase 2 of early viral kinetics in patients infected with HCV genotype 1

Charles D Howell et al. J Hepatol. 2012 Mar.

Abstract

Background & aims: We studied the relationship between IL28B gene-related SNP rs12979860 and early viral kinetics (day 0-28) during peginterferon and ribavirin treatment, in 173 African Americans (AA) and 188 Caucasian Americans (CA) with HCV genotype 1.

Methods: We studied the relationship between IL28B 16 gene-related SNP rs12979860 and early viral kinetics (day 0-28) 17 during peginterferon and ribavirin treatment, in 171 African 18 Americans (AA) and 188 Caucasian Americans (CA) with HCV 19 genotype 1.

Results: Compared to non-C/C genotypes, C/C was associated with greater declines in serum HCV RNA during phase 1 (day 0-2), phase 2 (day 7-28), and day 0-28 and higher response (undetected HCV RNA) rates at weeks 4 and 12 in AA and CA. A static phase and increases in HCV RNA from day 2 to 7 were more common in patients with non-C/C genotypes. C/C was also associated with higher week 24, 48, and 72 response rates in CA (p<0.01) but not in AA. At baseline, SNP genotype was the only independent predictor of phase 1; SNP genotype and phase 1 were independent predictors of phase 2 (p<0.001). There were no racial differences in HCV RNA declines during phase 1, day 2-7, phase 2, and day 0-28 with the same SNP genotype. AA with C/C and C/T genotypes had lower week 24, 48, and 72 (SVR) rates than did CA (p=0.03). SNP C/C predicted higher SVR rates in AA and CA with high baseline HCV RNA (≥ 600,000 IU/ml), and in CA with ≥ 1 log(10)IU/ml decrease in HCV RNA from day 0 to 28.

Conclusions: SNP rs12979860 is strongly associated with both phase 1 and phase 2 HCV RNA kinetics in AA and CA with HCV genotype 1.

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Conflict of interest statement

Conflict of interest

C.H. serves on the Roche-Genentech Pegasys Advisory Board.

Figures

Fig. 1
Fig. 1. Serum HCV RNA day 0–28 AA (A) and CA (B)
Serum HCV RNA concentrations were measured as per Materials and methods. Results compared using Kruskal-Wallis tests.
Fig. 2
Fig. 2. Early HCV RNA kinetics phases (day 0–28)
Changes in serum HCV RNA concentrations, (A) phase 1 (day 0–2), (B) day 2–7; (C) phase 2 (day 7–28); (D) day 0–28. Results compared by ANOVA.
Fig. 3
Fig. 3. SVR by SNP rs12979860 genotype in AA (A) and CA (B)
Results compared by regression analysis and additive genetic model.
See this image and copyright information in PMC

Comment in

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