The new era of Hepatitis C management is marked by newly available tests for IL28B polymorphisms, US Food and Drug Administration (FDA) approval of the first direct acting antivirals (DAA; boceprevir and telaprevir), monitoring of drug-related mutations. With the previous standard of care (PEGylated interferon-alpha and ribavirin), baseline predictors were regularly used to determine treatment candidacy, and recently, IL28B genetic polymorphisms have been identified as the strongest baseline predictors of treatment response.

The approval of the HCV NS3-4A protease inhibitors telaprevir and boceprevir in 2011 was the first therapeutic advance for patients infected with HCV in over a decade. Either drug in combination with pegIFN/RBV has been shown to substantially improve response rates in HCV genotype 1 patients compared to the standard of care (SOC) with pegIFN/RBV alone. Identification of several single nucleotide polymorphisms (SNPs) around the IL28B gene that is strongly associated with treatment outcomes in HCV genotype-1 infected individuals.

The gold standard treatment for chronic hepatitis C virus (HCV) infection is PEGylated interferon (PEG-IFN) in combination with ribavirin. Most patients treated with PEG-IFN achieve a sustained virological response (SVR). However host genetic factors play a vital role in the spontaneous and treatment-induced clearance of HCV infection from these infected patients. In the current study, polymorphisms of IL28B (rs8099917 and rs12979860) were analyzed and their association with the virological response to PEG-IFN alpha treatment was determined.

Single nucleotide polymorphisms near the interleukin 28B (IL-28B) gene have been identified as strong predictors of both spontaneous or Peg-interferon (Peg-IFN) and ribavirin (RBV) induced clearance of hepatitis C virus (HCV). Several studies have shown that, in patients with genotype 1 (GT-1), rs12979860 C/C and rs8099917 T/T substitutions are associated with a more than twofold increase in sustained virological response rate to Peg-IFN and RBV treatment. Although new treatment regimens based on combination of DAA with or without IFN are in the approval phase, until combination regimens with a backbone of Peg-IFN will be used, we can expect that IL28B holds its importance.

IL28B variants are also associated with decreased frequency of spontaneous clearance of HCV. Interferon-λ induces the JAK/STAT pathway, which up-regulates genes with antiviral effects against HCV. The newly identified SNPs likely mark a functional variant that affects response to interferon-α.

A goal of genomic research is to yield information that leads to treatment decisions based on a patient’s genetic makeup. Personalized clinical decision-making for treatment of patients with chronic hepatitis C requires estimates of the probability that a patient will achieve SVR which consider not only IL28B genotype, but also other factors that are associated with treatment response.

Polymorphisms related to the gene encoding IL-28B are the strongest genetic predictors of HCV clearance, both by interferon-based treatment or by the natural immune system.

geneOmbio offers IL28B genotyping tests for HCV and HBV patients for prediction of response to the therapies. This test is performed on blood sample collected from infected patient. Two most important mutations in IL28B gene are detected by DNA sequencing and the interpretation is drawn on the basis of type of mutation detected.

– Prajakta Shinde

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