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IL28B and the control of hepatitis C virus infection.

ABSTRACT: Treatment-induced control and spontaneous clearance of hepatitis C virus (HCV) infection are affected by various host factors. Polymorphisms in the region of the gene IL28B are associated with HCV clearance, implicating the gene product, interferon (IFN)-?3, in the immune response to HCV. Although it is not clear how the IL28B haplotype affects HCV clearance, IFN-?3 up-regulates interferon-stimulated genes, similar to IFN-? and IFN-? but via a different receptor. There is also evidence that IFN-?3 affects the adaptive immune response. The IL28B genotype can be considered, along with other factors, in predicting patient responses to therapy with pegylated IFN-? and ribavirin. We review the genetic studies that uncovered the association between IL28B and HCV clearance, the biology of IFN-?3, the clinical implications of the genetic association, and areas of future research.

SUBMITTER: Balagopal A

PROVIDER: S-EPMC3072961 | biostudies-literature | 2010 Dec

REPOSITORIES: biostudies-literature

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IL28B and the control of hepatitis C virus infection.

Balagopal Ashwin A Thomas David L DL Thio Chloe L CL

Gastroenterology 20101013 6

Treatment-induced control and spontaneous clearance of hepatitis C virus (HCV) infection are affected by various host factors. Polymorphisms in the region of the gene IL28B are associated with HCV clearance, implicating the gene product, interferon (IFN)-λ3, in the immune response to HCV. Although it is not clear how the IL28B haplotype affects HCV clearance, IFN-λ3 up-regulates interferon-stimulated genes, similar to IFN-α and IFN-β but via a different receptor. There is also evidence that IFN- ...[more]

PMID: 20950615

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Project description:BACKGROUND:Recent clinical studies have shown that the presence of CC genotype in the rs12979860 region of IL28B gene is associated with an increase in the probability of spontaneous clearance of hepatitis C virus (HCV). Moreover, IL28B polymorphism seems to influence the probability of developing liver steatosis in chronic HCV patients. AIMS:The aims of our clinical study were 1) to verify the distribution of IL28B genotypes (CC, CT or TT) among subjects with spontaneous clearance of HCV infection and 2) to examine the correlation between IL28B polymorphism and hepatic steatosis among these subjects. METHODS AND PATIENTS:We enrolled 41 subjects with spontaneous resolution of HCV infection (detectable serum anti-HCV but undetectable HCV-RNA) and 134 healthy controls from the same geographical area. The IL28B single-nucleotide polymorphism (SNP) rs12979860 was genotyped by using a Pyrosequencing™ technique. The presence of steatosis was assessed by liver biopsy or ultrasound examination in the 41 study subjects. RESULTS:CC, CT and TT-genotypes of the SNP rs1979860 were found in 66%, 24% and 10% of the subjects who spontaneously cleared HCV and in 31%, 54% and 15% of controls, respectively (p?=?0.0003). Among the study subjects, females with CC-genotype were significantly more represented (p?=?0.02). Hepatic steatosis did not correlate with IL28B genotype (p?=?0,14) but only with a high body mass index (BMI) value (p?=?0.03). CONCLUSIONS:Female subjects carrying IL28B CC-genotype are significantly more represented among Italian patients who spontaneously cleared HCV infection. In addition, among these subjects, the presence of liver steatosis does not correlate with IL28B genotype but is solely related to the occurrence of high BMI. Thus, the association between IL28B polymorphism and steatosis in chronic HCV patients requires the presence of active HCV replication to occur, while in subjects who have cleared the infection, the mechanism(s) inducing liver steatosis are independent from IL28B profile.

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IL28B and the control of hepatitis C virus infection.

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IL28B and the control of hepatitis C virus infection.

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