Low IL10 serum levels as key factor for predicting the sustained virological response to IFNα/ribavirin in Brazilian patients with HCV carrying IL28B CT/TT genotype

Hum Immunol. 2014 Aug;75(8):895-900. doi: 10.1016/j.humimm.2014.06.017. Epub 2014 Jun 30.

Abstract

Propose: IL28B polymorphisms rs12979860 CC genotype was associated to protection of HCV infection and sustained virological response (SVR) in HCV infected patients treated with pegIFNα/ribavirin (IFNα/RIB), however, this polymorphism frequency varies depending on genetic components. Studies with larger number of Brazilian individuals, determining IL28B polymorphisms is lacking. Regarding to treatment response, the levels of IL10 seem to influence response to IFNα/RIB therapy. Thus, the IL28B polymorphism frequency was investigated in health controls and infected HCV patients, as well as, in patients who reach SVR vs Non-SVR. Also, to gain insight into the interplay between IL28B genotypes, IL10 levels and therapy response, a subgroup of genotyped HCV patients SVR and Non-SVR were analyzed regarding the IL10 production.

Methods: It was enrolled 487 HCV infected patients and 234 healthy individuals. Patients with response to IFNα/RIB were classified as SVR (n = 81) and Non-SVR (n = 123). TAQMAN probes were used for genotyping the SNP rs12979860, resulting in CC, CT or TT genotypes. In one hundred one patients, the levels IL10 were measured at week 4 of IFNα/RIB.

Results: CC genotype was associated to SVR (p = 0.029) and its frequency was higher in healthy individuals vs patients (p = 0.02). Patients carrying CT/TT with IL10<10 pg/mL, had a chance of 2.72 to achieve SVR in multivariate model (p = 0.043).

Conclusion: CC genotype was associated to SVR and protection to HCV infection. Moreover, IL28B genotyping and IL10 serum levels could be further explored as a useful algorithm for identify the CT/TT SVR patients.

Keywords: HCV; IL10; IL28b; Polymorphism; Therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Antiviral Agents / therapeutic use*
  • Drug Therapy, Combination
  • Female
  • Gene Expression
  • Genotype
  • Hepacivirus / drug effects
  • Hepacivirus / immunology
  • Hepatitis C, Chronic / drug therapy*
  • Hepatitis C, Chronic / genetics*
  • Hepatitis C, Chronic / immunology
  • Hepatitis C, Chronic / virology
  • Humans
  • Interferon alpha-2
  • Interferon-alpha / therapeutic use
  • Interferons
  • Interleukin-10 / blood
  • Interleukin-10 / genetics*
  • Interleukin-10 / immunology
  • Interleukins / genetics*
  • Interleukins / immunology
  • Male
  • Middle Aged
  • Polyethylene Glycols / therapeutic use
  • Polymorphism, Genetic
  • Prognosis
  • Recombinant Proteins / therapeutic use
  • Ribavirin / therapeutic use
  • Viral Load / drug effects

Substances

  • Antiviral Agents
  • interferon-lambda, human
  • IL10 protein, human
  • Interferon alpha-2
  • Interferon-alpha
  • Interleukins
  • Recombinant Proteins
  • Interleukin-10
  • Polyethylene Glycols
  • Ribavirin
  • Interferons
  • peginterferon alfa-2b
  • peginterferon alfa-2a