IL28B polymorphisms influence stage of fibrosis and spontaneous or interferon-induced viral clearance in thalassemia patients with hepatitis C virus infection

Haematologica. 2012 May;97(5):679-86. doi: 10.3324/haematol.2011.050351. Epub 2011 Dec 16.

Abstract

Background: Polymorphisms in the interleukin-28B are important determinants in the spontaneous and drug-induced control of hepatitis C virus infection.

Design and methods: We assessed the association of rs8099917 and rs12979860 polymorphisms with spontaneous viral clearance, severity of liver fibrosis, and response to interferon-monotherapy in 245 thalassemia major patients with hepatitis C virus infection.

Results: Ninety-eight patients (40%) had a spontaneous viral clearance while 147 patients (60%) developed a chronic infection. Spontaneous viral clearance was more frequent among patients with the T/T genotype of rs8099917 polymorphism (OR 2.130; P = 0.008) or C/C genotype of rs12979860 polymorphism (OR 2.425; P = 0.001). During observation, 131 patients with chronic infection underwent a liver biopsy; age (OR 1.058; P = 0.01) G/T or G/G genotypes of rs8099917 polymorphism (OR 3.962; P = 0.001), and C/T or T/T genotypes of rs12979860 polymorphism (OR 3.494; P = 0.005) were associated with severe liver fibrosis, independent of liver iron concentration. Finally, T/T genotype of rs8099917 polymorphism (OR 3.014; P = 0.03) or C/C genotype of rs12979860 polymorphism (OR 3.285; P = 0.01), age (OR 0.902; P = 0.001), female gender (OR 3.418; P = 0.01) and 2 or 3 virus C genotypes (OR 4.700; P=0.007) were independently associated with sustained virological response in 114 patients treated with alpha-interferon. Conclusions Polymorphisms in the interleukin-28B are associated with the control of hepatitis C virus infection in thalassemia major patients, and understanding allelic patterns has an important role in determining prognosis and therapeutic management.

Publication types

  • Multicenter Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Antibodies, Viral / immunology
  • Antiviral Agents / therapeutic use
  • Cohort Studies
  • Female
  • Follow-Up Studies
  • Hepacivirus / genetics
  • Hepatitis C, Chronic / drug therapy
  • Hepatitis C, Chronic / genetics*
  • Hepatitis C, Chronic / virology
  • Humans
  • Interferon Inducers / therapeutic use
  • Interferon-alpha / therapeutic use*
  • Interferons
  • Interleukins / genetics*
  • Liver Cirrhosis / etiology*
  • Liver Cirrhosis / pathology
  • Male
  • Polymorphism, Single Nucleotide / genetics*
  • Prognosis
  • Viral Load / genetics*
  • Young Adult
  • beta-Thalassemia / drug therapy
  • beta-Thalassemia / genetics*
  • beta-Thalassemia / virology

Substances

  • Antibodies, Viral
  • Antiviral Agents
  • interferon-lambda, human
  • Interferon Inducers
  • Interferon-alpha
  • Interleukins
  • Interferons