title: Increase in platelet count based on inosine triphosphatase genotype during interferon beta plus ribavirin combination therapy.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  Natural IFN-β/ribavirin therapy is safe for patients with the ITPA-CC genotype, even if their pretreatment platelet counts are low.
authors.affiliation: The Center for Liver Disease, Shin-kokura Hospital, Kitakyushu, Japan. h-nomura@shin-kokura.gr.jp
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Nomura
authors.forename: Yugo
authors.initials: Y
authors.lastname: Miyagi
authors.forename: Hironori
authors.initials: H
authors.lastname: Tanimoto
authors.forename: Nobuyuki
authors.initials: N
authors.lastname: Yamashita
authors.forename: Kiyoaki
authors.initials: K
authors.lastname: Ito
authors.forename: Naohiko
authors.initials: N
authors.lastname: Masaki
authors.forename: Masashi
authors.initials: M
authors.lastname: Mizokami
mesh_terms: D000368:Aged; D000998:Antiviral Agents / Q000009:adverse effects* / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D006454:Hemoglobins / Q000378:metabolism; D016174:Hepacivirus; D019698:Hepatitis C, Chronic / Q000097:blood* / Q000188:drug therapy / Q000235:genetics*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000009:adverse effects / Q000627:therapeutic use; D016899:Interferon-beta / Q000009:adverse effects* / Q000627:therapeutic use; D007372:Interferons; D007378:Interleukins / Q000235:genetics; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D010976:Platelet Count; D011092:Polyethylene Glycols / Q000009:adverse effects / Q000627:therapeutic use; D020641:Polymorphism, Single Nucleotide; D011755:Pyrophosphatases / Q000235:genetics*; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use; D012254:Ribavirin / Q000009:adverse effects* / Q000627:therapeutic use; D018709:Statistics, Nonparametric; D000097630:Inosine Triphosphatase; D000095022:Interferon Lambda
chemical_list: D000998:Antiviral Agents; D006454:Hemoglobins; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D016899:Interferon-beta; D007372:Interferons; D007378:Interleukins; D011092:Polyethylene Glycols; D011755:Pyrophosphatases; D011994:Recombinant Proteins; D012254:Ribavirin; D000097630:Inosine Triphosphatase; C000624353:interferon-lambda, human; D000095022:Interferon Lambda; C417083:peginterferon alfa-2b