Dataset Information

IL28B favorable genotype and ultrarapid viral response as the earliest treatment predictors of a sustained viral response in a Georgian cohort infected with the hepatitis C genotype 1.

ABSTRACT: OBJECTIVES:The early identification of factors contributing to the successful treatment of hepatitis C infection is important for researchers and clinicians. Studies carried out on the role of an ultrarapid viral response (URVR) for the prediction of a sustained viral response (SVR) have shown its high positive predictive value (PPV). However, data on the combined effect of URVR with IL28B genotypes for the prediction of SVR are lacking. Our aim was to study the role of URVR and IL28B genotypes in the prediction of SVR among patients in Georgia infected with genotype 1. METHODS:Of a total of 156 patients enrolled in the study, 143 were included in the final analyses. Viral load testing for monitoring the viral response was carried out at 3, 24, 48, and 72 h and at 1, 2, and 4 weeks after the initiation of treatment. IL28B single nucleotide polymorphisms in rs12979860 were genotyped using real-time PCR methods. RESULTS:Our study showed that URVR was the earliest treatment predictor among genotype 1 patients harboring the IL28B C/C genotype (PPV-100%). Moreover, the C/C genotype was found to have a high PPV among genotype 1 patients without URVR or a rapid viral response, unlike patients infected with genotype 2 or 3. URVR and IL28B C/C genotypes were not as predictive of an SVR among genotype 2 and 3 patients; however, rapid viral responses were highly predictive of an SVR in these patients. CONCLUSION:Our results suggest that testing for IL28B genotypes and viral load at weeks 1 and 2 may improve the ability to predict an SVR among hepatitis C virus genotype 1 patients; this information may be useful to ensure patient compliance with treatment.

SUBMITTER: Karchava M

PROVIDER: S-EPMC3368996 | biostudies-literature | 2012 Jul

REPOSITORIES: biostudies-literature

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IL28B favorable genotype and ultrarapid viral response as the earliest treatment predictors of a sustained viral response in a Georgian cohort infected with the hepatitis C genotype 1.

Karchava Marine M Sharvadze Lali L Chkhartishvili Nikoloz N Nelson Kenrad K Gochitashivli Nino N Gatserelia Lana L Dvali Natia N Dolmazashvili Ekaterine E Dzigua Lela L Badridze Nino N Zhamutashvili Maia M Tsertsvadze Tengiz T

European journal of gastroenterology & hepatology 20120701 7

<h4>Objectives</h4>The early identification of factors contributing to the successful treatment of hepatitis C infection is important for researchers and clinicians. Studies carried out on the role of an ultrarapid viral response (URVR) for the prediction of a sustained viral response (SVR) have shown its high positive predictive value (PPV). However, data on the combined effect of URVR with IL28B genotypes for the prediction of SVR are lacking. Our aim was to study the role of URVR and IL28B ge ...[more]

PMID: 22569080

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Project description:UNLABELLED:Recent studies have shown that a single-nucleotide polymorphism upstream of the interleukin-28B (IL28B) gene plays a major role in predicting therapeutic response in hepatitis C virus (HCV)-infected patients treated with pegylated interferon (PEG-IFN)/ribavirin. We sought to investigate the mechanism of the IL28B polymorphism, specifically as it relates to early HCV viral kinetics, IFN pharmacokinetics, IFN pharmacodynamics, and gene expression profiles. Two prospective cohorts (human immunodeficiency virus [HIV]/HCV-coinfected and HCV-monoinfected) completing treatment with IFN/ribavirin were enrolled. Patients were genotyped at the polymorphic site rs12979860. In the HIV/HCV cohort, frequent serum sampling was completed for HCV RNA and IFN levels. DNA microarray of peripheral blood mononuclear cells and individual expression of IFN-stimulated genes (ISGs) were quantified on IFN therapy. The IL28B-favorable (CC) genotype was associated with improved therapeutic response compared with unfavorable (CT or TT) genotypes. Patients with a favorable genotype had greater first- and second-phase viral kinetics (P = 0.004 and P = 0.036, respectively), IFN maximum antiviral efficiency (P = 0.007) and infected cell death loss (P = 0.009) compared with unfavorable genotypes. Functional annotation analysis of DNA microarray data was consistent with depressed innate immune function, particularly of natural killer cells, from patients with unfavorable genotypes (P <0.004). Induction of innate immunity genes was also lower in unfavorable genotypes. ISG expression at baseline and induction with IFN was independent of IL28B genotype. CONCLUSION:Carriers of the IL28B-favorable genotype were more likely to have superior innate immune response to IFN therapy compared with unfavorable genotypes, suggesting that the unfavorable genotype has aberrant baseline induction of innate immune response pathways resulting in impaired virologic response. IL28B genotype is associated with more rapid viral kinetics and improved treatment response outcomes independent of ISG expression.

Project description:BACKGROUND:Single 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 FINDINGS:We 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/SIGNIFICANCE:rs12979860 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.

Dataset Information

IL28B favorable genotype and ultrarapid viral response as the earliest treatment predictors of a sustained viral response in a Georgian cohort infected with the hepatitis C genotype 1.

Publications

IL28B favorable genotype and ultrarapid viral response as the earliest treatment predictors of a sustained viral response in a Georgian cohort infected with the hepatitis C genotype 1.

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