Genetic variation in IL28B predicts hepatitis C treatment-induced viral clearance

  title={Genetic variation in IL28B predicts hepatitis C treatment-induced viral clearance},
  author={Dongliang Ge and Jacques Fellay and Alexander J Thompson and Jason S. Simon and Kevin V. Shianna and Thomas J. Urban and Erin L. Heinzen and Ping Qiu and Arthur H. Bertelsen and Andrew J. Muir and Mark S. Sulkowski and John McHutchison and David B. Goldstein},
Chronic infection with hepatitis C virus (HCV) affects 170 million people worldwide and is the leading cause of cirrhosis in North America. Although the recommended treatment for chronic infection involves a 48-week course of peginterferon-α-2b (PegIFN-α-2b) or -α-2a (PegIFN-α-2a) combined with ribavirin (RBV), it is well known that many patients will not be cured by treatment, and that patients of European ancestry have a significantly higher probability of being cured than patients of African… 


It is reported that a genetic polymorphism near the IL28B gene, encoding interferon- lambda-3 (IFN-lambda-3), is associated with an approximately twofold change in response to treatment, both among patients of European ancestry and African-Americans.

IL28B polymorphism and genetic biomarkers of viral clearance in hepatitis C virus infection.

A association between genetic variation in the region of the IL28B gene and treatment outcome in HCV-1 patients and patients who carry the good response variant are two- to three-fold more likely to be cured.

The Role of Pharmacogenetics in the Treatment of Chronic Hepatitis C Infection

The pharmacogenetic data for boceprevir and telaprevir triple therapy in patients with HCV‐1 infection, as well as viral genomic polymorphisms and genetic variants that may protect against anemia are reviewed.

Pharmacogenetics: A SNP for hepatitis C treatment failure

  • C. V. Ooij
  • Medicine, Biology
    Nature Reviews Genetics
  • 2009
In patients who have the marker that is associated with treatment failure, the levels of IL28 mRNA in the blood were significantly lower than in individuals who did not carry the marker, which suggests that the causal variants might affect the expression of this gene.

Immunologic al and Genetic Markers Predicting Treatment Outcome in Hepatitis C Virus Infection

The specific sCD26 activity was found to predict the effectiveness of peg-IFN/RBV therapy in chronic hepatitis C, and enhance the value of established outcome predictors.

IL28B polymorphism is associated with treatment response in patients with genotype 4 chronic hepatitis C.

IL28B polymorphism, Explanation for Different Responses to Therapy in Hepatitis C Patients

SVR as a hepatitis C treatment outcome can be predicted by various baseline predictors such as HCV RNA levels, the dose and duration of therapy, body mass index, age, insulin resistance, gender, stage of fibrosis and co-infection with other hepatitis viruses or HIV.

Individualized Therapy for Hepatitis C Infection: Focus on the Interleukin-28B Polymorphism in Directing Therapy

In the era of increased overall virologic response rates and good tolerability of the rapidly developing non-IFN oral direct-acting antiviral therapy regimens, the need for individualized treatment is likely to diminish and various predictors of response, including IL28B will likely be of reduced importance in the near future.



IL28B is associated with response to chronic hepatitis C interferon-α and ribavirin therapy

The data suggest that host genetics may be useful for the prediction of drug response, and they also support the investigation of the role of IL28B in the treatment of HCV and in other diseases treated with IFN-α.

Genetic variation in IL28B and spontaneous clearance of hepatitis C virus

It is shown that the C/C genotype strongly enhances resolution of HCV infection among individuals of both European and African ancestry, the strongest and most significant genetic effect associated with natural clearance ofHCV.

Interferon signaling and treatment outcome in chronic hepatitis C

The concept that activation of the endogenous IFN system in CHC not only is ineffective in clearing the infection but also may impede the response to therapy, most likely by inducing a refractory state of the IFN signaling pathway, is supported.

Gene expression and hepatitis C virus infection

This paper reviews the published literature on gene expression associated with HCV infection (HCV infection, fibrosis progression), and also according to response to treatment, and recommends combination of pegylated interferons with ribavirin for treatment of hepatitis C.

Peginterferon alfa-2a and ribavirin in patients with chronic hepatitis C who have failed prior treatment.

BACKGROUND & AIMS The most effective therapy currently available for treatment of chronic hepatitis C virus (HCV) is the combination of peginterferon and ribavirin. This study evaluated the

Intrahepatic interferon‐stimulated gene responses: Can they predict treatment responses in chronic hepatitis C infection?

The authors have identified molecular pathways associated with IFN responsiveness within the liver associated with HCV infection through gene array analysis and confirmed key findings by real-time reverse-transcription polymerase chain reaction.

Peginterferon alfa-2b and ribavirin for the treatment of chronic hepatitis C in blacks and non-Hispanic whites.

Black patients with chronic hepatitis C have a lower rate of response to treatment with peginterferon alfa-2b and ribavirin than non-Hispanic white patients, a difference that is not explained by differences in the viral genotype.

Telaprevir with peginterferon and ribavirin for chronic HCV genotype 1 infection.

Treatment with a telaprevir-based regimen significantly improved sustained virologic response rates in patients with genotype 1 HCV, albeit with higher rates of discontinuation because of adverse events.

Pegylated interferon-alpha-2a plus ribavirin for treatment-naive Asian patients with hepatitis C virus genotype 1 infection: a multicenter, randomized controlled trial.

  • Chen‐Hua LiuChun-Jen Liu J. Kao
  • Medicine
    Clinical infectious diseases : an official publication of the Infectious Diseases Society of America
  • 2008
In treatment-naive Asian patients with HCV-1 infection, 48 weeks of pegylated IFN-alpha-2a plus ribavirin therapy is associated with a higher SVR rate, compared with 24 weeks of such therapy.

Treatment responses in Asians and Caucasians with chronic hepatitis C infection.

Genotype 1 CHC in Asian subjects is associated with higher rates of virological response compared to that in Caucasians, and this difference remained significant after adjusting for other predictive variables.