IL28B SNP rs12979860 Is a Critical Predictor for On-Treatment and Sustained Virologic Response in Patients with Hepatitis C Virus Genotype-1 Infection

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.

Response to treatment in Brazilian patients with chronic hepatitis C is associated with a single-nucleotide polymorphism near the interleukin-28B gene

“…The current study was the first to investigate a large number of Brazilian patients and the frequency of the C allele was assessed in a cohort of 263 patients with liver fibrosis due to infection with HCV genotype 1. The C allele was present in 39% of patients, which is lower than the frequencies reported from Europe, Asia and Oceania, but similar to that observed in Africa (IBGE 2000, Thomas et al 2009, Lin et al 2011, and this finding may be due to the large proportion of African descendants in the Brazilian population. The present study confirmed that the IL28B polymorphism is a good predictor of SVR, independent of other factors, such as age, gender, stage of liver fibrosis and VL.…”

Nanomedicines in the treatment of hepatitis C virus infection in Asian patients: optimizing use of peginterferon alfa

“…93 In East Asian HCV-1 patients who received 24 weeks of PEG-IFN α-2a plus RBV therapy, the IL-28B genotypes played a minor role to affect the overall SVR rates if they achieved RVR. 80,94,95 In line with the report by Thompson et al, IL-28B genotypes strongly affected the SVR rates in East Asian HCV-1 patients if they failed to achieve RVR. 96,98 However, the role of IL-28B genotypes was limited in East Asian HCV-1 patients who failed to achieve RVR if Wk-8R was taken into consideration.…”

“…91,92 Furthermore, IL-28B genotypes are associated with the RVR rates in HCV-infected patients, especially in those with HCV-1 infection. 78,80,91,[93][94][95][96][97] Because the favorable IL-28 genotype highly predicts RVR and SVR in HCV-1 patients, Asian HCV-1 patients, who carry the highest frequency of the favorable IL-28B genotype, have greater SVR rates than HCV-1 patients of other ethnicities.…”

A Follow-up Study for Chinese Chronic Hepatitis C Patients Treated with the Combination of PEG-IFNα-2a (PEGASYS) and Ribavirin

“…4 Moreover, IL-28B gene polymorphisms were the strongest predictors of response to pegylated interferon and RBV in patients chronically infected with HCV genotypes 1 and 4. 5 Some studies found that the protective rs12979860 C allele frequency was 91.0%-97.5% in east Asia population, which may be the possible reason why domestic patients had a higher SVR than aboard. Therefore, therapy of CHC recently entered a new era with the deployment of direct-acting antivirals (DAAs), and IL-28B genotyping will be also useful for personalized CHC treatment in the forthcoming era of DAAs.…”