Dataset Information

IL-28B As a Predictor of Sustained Virologic Response in Patients with Chronic Hepatitis C Virus Infection.

ABSTRACT: Genome-wide association studies have recently identified single nucleotide polymorphisms in proximity to the interleukin-28B (IL-28B) gene that can predict sustained virologic response (SVR) in patients with chronic hepatitis C virus (HCV) infection who are undergoing therapy with pegylated interferon (IFN) a and ribavirin. IL-28B encodes IFN-?3, a type III IFN involved in host antiviral immunity. Favorable variants of the 2 most widely studied IL-28B polymorphisms, rs1 2979860 and rs8099917, are strong pretreatment predictors of early viral clearance and SVR in patients with genotype 1 HCV infection. Variations in the distribution of IL-28B alleles may partly explain differences in SVR rates among ethnic groups. Further investigations have implicated IL-28B in the development of chronic HCV infection versus spontaneous resolution of acute infection and suggest that IL-28B may be a key factor involved in host immunity against HCV. Clinical trials of IFN-? as a therapeutic agent for chronic HCV infection are currently underway. The use of IL-28B polymorphisms as a predictive tool will have a major impact on treatment strategies for chronic HCV infection, particularly in the context of emerging therapies and direct-acting antiviral agents.

SUBMITTER: Gonzalez SA

PROVIDER: S-EPMC3151409 | biostudies-literature | 2011 Jun

REPOSITORIES: biostudies-literature

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IL-28B As a Predictor of Sustained Virologic Response in Patients with Chronic Hepatitis C Virus Infection.

Gonzalez Stevan A SA Keeffe Emmet B EB

Gastroenterology & hepatology 20110601 6

Genome-wide association studies have recently identified single nucleotide polymorphisms in proximity to the interleukin-28B (IL-28B) gene that can predict sustained virologic response (SVR) in patients with chronic hepatitis C virus (HCV) infection who are undergoing therapy with pegylated interferon (IFN) a and ribavirin. IL-28B encodes IFN-λ3, a type III IFN involved in host antiviral immunity. Favorable variants of the 2 most widely studied IL-28B polymorphisms, rs1 2979860 and rs8099917, ar ...[more]

PMID: 21869868

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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.

Project description:BACKGROUND & AIMS:The combination of ledipasvir and sofosbuvir has been approved for treatment of genotype 1 hepatitis C virus (HCV) infection, including an 8-week regimen for treatment-naïve patients without cirrhosis and a baseline level of HCV RNA <6 million IU/mL. We analyzed data from a multicenter, prospective, observational study to determine real-world sustained virologic responses 12 weeks after treatment (SVR12) with regimens containing ledipasvir and sofosbuvir and identify factors associated with treatment failure. METHODS:We collected data from 2099 participants in the HCV-TARGET study with complete virologic data (per-protocol population). We analyzed data from 1788 patients receiving ledipasvir-sofosbuvir (282 for 8 weeks, 910 for 12 weeks, 510 for 24 weeks, and 86 for a different duration) and 311 receiving ledipasvir-sofosbuvir plus ribavirin (212 for 12 weeks and 81 for 24 weeks, 18 for other duration) to estimate SVR12 (with 95% confidence interval [CI]), and logistic regression methods to identify factors that predicted an SVR12. RESULTS:The overall study population was 25% black, 66% with HCV genotype 1A infection, 41% with cirrhosis, 50% treatment-experienced, and 30% receiving proton pump inhibitors at start of treatment. In the per-protocol population, SVR12s were achieved by 96% of patients receiving ledipasvir-sofosbuvir for 8 weeks (95% CI, 93%-98%), 97% receiving the drugs for 12 weeks (95% CI, 96%-98%), and 95% receiving the drugs for 24 weeks (95% CI, 93%-97%). Among patients also receiving ribavirin, SVR12 was achieved by 97% of the patients receiving the drugs for 12 weeks (95% CI, 94%-99%) and 95% receiving the drugs for 24 weeks (95% CI, 88%-99%). Of the 586 patients who qualified for 8 weeks of treatment, only 255 (44%) received the drugs for 8 weeks. The rate of SVR12 among those who qualified for and received 8 weeks of therapy was similar in those who qualified for 8 weeks but received 12 weeks therapy (96%; 95% CI, 92%-99% vs 98%; 95% CI, 95%-99%). Factors that predicted SVR12 were higher albumin (?3.5 g/dL), lower total bilirubin (?1.2 g/dL), absence of cirrhosis, and absence of proton pump inhibitor use. CONCLUSIONS:Regimens containing ledipasvir and sofosbuvir are highly effective for a broad spectrum of patients with HCV genotype 1 infection treated in different clinical practice settings. Expanded use of 8-week treatment regimens for eligible patients is supported by these real-world results. Modification of proton pump inhibitor use may increase rates of SVR. ClinicalTrials.gov no. NCT01474811.

Dataset Information

IL-28B As a Predictor of Sustained Virologic Response in Patients with Chronic Hepatitis C Virus Infection.

Publications

IL-28B As a Predictor of Sustained Virologic Response in Patients with Chronic Hepatitis C Virus Infection.

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