Early viral kinetics during hepatitis C virus genotype 6 treatment according to IL28B polymorphisms

World J Gastroenterol. 2014 Aug 14;20(30):10599-605. doi: 10.3748/wjg.v20.i30.10599.

Abstract

Aim: To investigate the early viral kinetics and interleukin-28B (IL28B) polymorphisms of hepatitis C genotype 6 during pegylated interferon and ribavirin therapy.

Methods: Sixty-five patients with chronic hepatitis C virus (HCV) infection treated with pegylated interferon and ribavirin (PEG-IFN/RBV) were included, of whom 15 (23.1%), 16 (24.6%) and 34 (52.3%) patients were infected with hepatitis C genotype 1 (HCV-1), genotype 3 (HCV-3) and genotype 6 (HCV-6), respectively. Serum HCV-RNA levels were measured frequently during the first 4-wk of therapy. DNA extracted from samples was analyzed for the IL28B single nucleotide polymorphism (SNP) rs12979860 by polymerase chain reaction and direct sequencing.

Results: During the first 4-wk of therapy, the mean viral decline for patients with HCV-6 (5.55 ± 1.82 log₁₀IU/mL) was comparable to that of patients with HCV-3 (5.55 ± 1.82 log₁₀IU/mL vs 5.86 ± 1.02 log₁₀IU/mL, P = 0.44) and was significantly higher than patients with HCV-1 (5.55 ± 1.82 log₁₀IU/mL vs 4.23 ± 1.99 log₁₀IU/mL, P = 0.04). In the HCV-6 group, the first phase (days 0-2) viral decline was significantly higher in patients with the favorable rs12979860 CC than non-CC genotypes (2.46 ± 1.01 log₁₀IU/mL/wk vs 1.70 ± 0.67 log₁₀IU/mL, respectively, P = 0.045). A statistically insignificant decrease in the second-phase (days 7-28) decline was also found in patients with the CC genotype than those with the non-CC genotype, though not significantly different (1.24 ± 0.64 log₁₀IU/mL/wk vs 0.80 ± 0.65 log₁₀IU/mL/wk, respectively, P = 0.172). At baseline, the SNP genotype was an independent predictor of rapid virological response but not of sustained virological response.

Conclusion: The IL28B genotype was linked to an impact on early viral kinetics in response to PEG-IFN/RBV therapy in HCV-6 infected patients.

Keywords: Early viral kinetics; Genotype 6; Hepatitis C virus; Interleukin-28B; rs12979860.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Antiviral Agents / therapeutic use*
  • Biomarkers / blood
  • Drug Therapy, Combination
  • Female
  • Genotype
  • Hepacivirus / drug effects*
  • Hepacivirus / genetics
  • Hepacivirus / growth & development
  • Hepacivirus / immunology
  • Hepatitis C, Chronic / complications*
  • Hepatitis C, Chronic / diagnosis
  • Hepatitis C, Chronic / genetics
  • Hepatitis C, Chronic / immunology
  • Humans
  • Interferon-alpha / therapeutic use*
  • Interferons
  • Interleukins / genetics*
  • Kinetics
  • Male
  • Middle Aged
  • Polyethylene Glycols / therapeutic use*
  • Polymorphism, Single Nucleotide*
  • Prospective Studies
  • RNA, Viral / blood
  • Recombinant Proteins / therapeutic use
  • Ribavirin / therapeutic use*
  • Treatment Outcome
  • Viral Load

Substances

  • Antiviral Agents
  • Biomarkers
  • interferon-lambda, human
  • Interferon-alpha
  • Interleukins
  • RNA, Viral
  • Recombinant Proteins
  • Polyethylene Glycols
  • Ribavirin
  • Interferons
  • peginterferon alfa-2a