Abstract
BackgroundSingle nucleotide polymorphisms (SNPs) of interleukin-28B (IL28B) have received considerable interest for their association with sustained virological response (SVR) when treating patients of genotype-1 hepatitis C virus (GT1-HCV) chronic infection with pegylated interferon and ribavirin (PegIFN/RBV). This study was to investigate the predictive power of IL28B SNPs for on-treatment responses and SVR in treatment-naïve patients with GT1-HCV chronic infection.Methodology/Principal FindingsWe analyzed ten SNPs of IL28B in 191 treatment-naïve patients with GT1-HCV chronic infection who received PegIFN/RBV. In these patients, rapid virological response (RVR), early virological response (EVR) and SVR were achieved in 69.6%, 95.8% and 68.6% of the patients, respectively. Multivariate analysis (odds ratio; 95% confidence interval; P value) indicated age (0.96; 0.93–0.99; 0.012), low baseline viral load (4.65; 2.23–9.66; <0.001) and CC genotype of rs12979860 (7.74; 2.55–23.53; <0.001) but no other SNPs were independent predictors for SVR. In addition, none of the ten SNPs examined were associated with baseline viral load and stages of liver fibrosis. Regarding RVR, low baseline viral load (2.83; 1.40–5.73; 0.004) and CC genotype of rs12979860 (10.52; 3.45–32.04; <0.001) were two critical predictors. As for EVR, only CC genotype of rs12979860 (36.21; 6.68–196.38; <0.001) was the predictor. Similarly, for end of treatment response (ETR), CC genotype of rs12979860 (15.42; 4.62–51.18; <0.001) was the only predictor. For patients with RVR, only low baseline viral load (3.90; 1.57–9.68; 0.003) could predict the SVR. For patients without RVR, only rs12979860 (4.60; 1.13–18.65; 0.033) was the predictor for SVR.Conclusions/Significancers12979860 is the critical predictor for RVR, EVR, ETR and SVR in treatment-naïve patients of GT1-HCV chronic infection. Furthermore, this SNP is the only predictor for SVR in patients without RVR. These results have provided evidence that rs12979860 is the ideal IL28B SNP for genetic testing in treating patients of GT1-HCV chronic infection.
Highlights
A combination therapy of pegylated interferon-alpha and ribavirin (PegIFN/RBV) is a well-accepted standard of care for patients with chronic hepatitis C (CHC) [1]
Which single nucleotide polymorphisms (SNPs) would be the most influential on sustained virological response (SVR) was still undetermined. We investigated these issues and tried to increase our understanding of the predictive ability of 10 SNPs of IL28B for rapid virological response (RVR), early virological response (EVR) and SVR in a cohort of patients with genotype-1 hepatitis C virus (GT1-HCV) chronic infection treated with PegIFN/RBV from a large medical center
We identified rs12979860, one of the 10 SNPs of IL28B, to be the most powerful predictor for RVR, EVR, end-of-treatment response (ETR) and SVR in GT1 HCV infected patients treated with PegIFN/ RBV
Summary
A combination therapy of pegylated interferon-alpha and ribavirin (PegIFN/RBV) is a well-accepted standard of care for patients with chronic hepatitis C (CHC) [1]. As for the response-guided approach, rapid virological response (RVR) is regarded as an important predictor for SVR [5,10,11] It is a guide for shortening treatment duration from 48 weeks to 24 weeks for HCV genotype 1 with low viral load [4,5,12,13] and from 24 weeks to 12–16 weeks for genotype 2/3 chronic infection [10,14,15]. The prevalence rates of cc genotype of rs1297860 paralleled with the SVR in each population [17] These genotypes of IL28B correlated with the spontaneous clearance of hepatitis C virus [18] and with viral responses during treatment [21]. We investigated these issues and tried to increase our understanding of the predictive ability of 10 SNPs of IL28B for RVR, EVR and SVR in a cohort of patients with GT1-HCV chronic infection treated with PegIFN/RBV from a large medical center
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