Increase in platelet count based on inosine triphosphatase genotype during interferon beta plus ribavirin combination therapy

J Gastroenterol Hepatol. 2012 Sep;27(9):1461-6. doi: 10.1111/j.1440-1746.2012.07171.x.

Abstract

Background and aim: The inosine triphosphatase (ITPA) genotype is associated with ribavirin-induced anemia and pegylated interferon α (PEG IFN-α)-induced platelet reduction during PEG IFN-α plus ribavirin combination therapy. Natural IFN-β plus ribavirin therapy is associated with increases in platelet counts during treatment. We investigated decreases in platelet counts according to ITPA genotype during natural IFN-β/ribavirin therapy to determine if patients with low platelet counts were eligible for this combination therapy.

Methods: A total of 187 patients with chronic hepatitis C received PEG IFN-α/ribavirin or natural IFN-β/ribavirin therapy. Decreases in platelet counts based on ITPA genotype were investigated during treatment through 24 weeks.

Results: Platelet counts decreased during week 1 of PEG IFN-α/ribavirin therapy, but increased during week 2, after which platelet counts decreased gradually. Platelet counts decreased until week 4 of natural IFN-β/ribavirin therapy, after which platelet counts increased. Platelet counts after week 8 were higher relative to pretreatment platelet counts. Patients with the ITPA-CC genotype showed a smaller decrease in platelet counts during natural IFN-β/ribavirin therapy than those with the ITPA-CA/AA genotype; platelet counts after week 8 of this therapy were higher than pretreatment platelet counts, regardless of pretreatment platelet counts. Multivariate logistic regression analyses showed that natural INF-β/ribavirin therapy was the only significant independent predictor for an increase in platelets through week 8.

Conclusion: Natural IFN-β/ribavirin therapy is safe for patients with the ITPA-CC genotype, even if their pretreatment platelet counts are low.

Publication types

  • Clinical Trial

MeSH terms

  • Aged
  • Antiviral Agents / adverse effects*
  • Antiviral Agents / therapeutic use
  • Drug Therapy, Combination
  • Female
  • Genotype
  • Hemoglobins / metabolism
  • Hepacivirus
  • Hepatitis C, Chronic / blood*
  • Hepatitis C, Chronic / drug therapy
  • Hepatitis C, Chronic / genetics*
  • Humans
  • Inosine Triphosphatase
  • Interferon Lambda
  • Interferon alpha-2
  • Interferon-alpha / adverse effects
  • Interferon-alpha / therapeutic use
  • Interferon-beta / adverse effects*
  • Interferon-beta / therapeutic use
  • Interferons
  • Interleukins / genetics
  • Logistic Models
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Platelet Count
  • Polyethylene Glycols / adverse effects
  • Polyethylene Glycols / therapeutic use
  • Polymorphism, Single Nucleotide
  • Pyrophosphatases / genetics*
  • Recombinant Proteins / adverse effects
  • Recombinant Proteins / therapeutic use
  • Ribavirin / adverse effects*
  • Ribavirin / therapeutic use
  • Statistics, Nonparametric

Substances

  • Antiviral Agents
  • Hemoglobins
  • Interferon alpha-2
  • Interferon-alpha
  • Interferon-beta
  • Interferons
  • Interleukins
  • Polyethylene Glycols
  • Pyrophosphatases
  • Recombinant Proteins
  • Ribavirin
  • Inosine Triphosphatase
  • interferon-lambda, human
  • Interferon Lambda
  • peginterferon alfa-2b