title: Clinical milestones for the prediction of severe anemia by chronic hepatitis C patients receiving telaprevir-based triple therapy.
abstract: OBJECTIVE
  Anemia is a common adverse effect of telaprevir (TVR) in combination with pegylated interferon (PegIFN)α and ribavirin (RBV) therapy. It occurs at a higher incidence with the TVR relative to PegIFNα and RBV alone. We herein evaluate the baseline and on-treatment predictors of the development of severe anemia by chronic hepatitis C virus (HCV) patients receiving TVR-based triple therapy.
  
  
  METHODS
  This prospective, multicenter study consisted of 292 patients (median age: 62 years) infected with HCV genotype 1. All received 12 weeks of TVR in combination with 24 weeks of PegIFNα2b and RBV. The definition of severe anemia during antiviral treatment is hemoglobin (Hb)<85 g/L.
  
  
  RESULTS
  101 (34.6%) patients developed severe anemia during the treatment period. Multivariable logistic regression analysis of possible pretreatment predictors of the development of severe anemia extracted baseline Hb < 135 g/L (Hazard ratio [HR], 2.53; p = 0.0013), estimated glomerular filtration rate <80 ml/min/1.73 m(2) (HR, 1.83; p = 0.0265), and inosine triphosphatase (ITPA) CC genotype (rs1127354) (HR, 2.91; p = 0.0024). For patients with ITPA CC (n = 227), multivariable logistic regression analysis of possible pretreatment and on-treatment predictors of the development of severe anemia extracted Hb level at week 2 (HR, 0.96; p = 0.0085) and the initial four weeks of weight-adjusted TVR (HR, 1.05; p = 0.0281).
  
  
  CONCLUSIONS
  Anemia remains a risk for all patients treated with TVR-based triple therapy. However, ITPA polymorphism (rs1127354) is useful for predicting the development of severe anemia and will be helpful in the management of treatment.
authors.affiliation: Department of General Internal Medicine, Kyushu University Hospital, Fukuoka, Japan.
authors.forename: Eiichi
authors.initials: E
authors.lastname: Ogawa
authors.forename: Norihiro
authors.initials: N
authors.lastname: Furusyo
authors.forename: Makoto
authors.initials: M
authors.lastname: Nakamuta
authors.forename: Eiji
authors.initials: E
authors.lastname: Kajiwara
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Nomura
authors.forename: Kazufumi
authors.initials: K
authors.lastname: Dohmen
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Takahashi
authors.forename: Takeaki
authors.initials: T
authors.lastname: Satoh
authors.forename: Koichi
authors.initials: K
authors.lastname: Azuma
authors.forename: Akira
authors.initials: A
authors.lastname: Kawano
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Tanabe
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Kotoh
authors.forename: Shinji
authors.initials: S
authors.lastname: Shimoda
authors.forename: Jun
authors.initials: J
authors.lastname: Hayashi
mesh_terms: D000368:Aged; D000740:Anemia / Q000201:enzymology / Q000209:etiology* / Q000235:genetics; D000998:Antiviral Agents / Q000008:administration & dosage / Q000009:adverse effects*; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D006454:Hemoglobins / Q000378:metabolism; D016174:Hepacivirus / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000097:blood / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage; D008297:Male; D008875:Middle Aged; D009842:Oligopeptides / Q000008:administration & dosage / Q000009:adverse effects*; D011092:Polyethylene Glycols / Q000008:administration & dosage; D020641:Polymorphism, Single Nucleotide; D011446:Prospective Studies; D011755:Pyrophosphatases / Q000235:genetics; D011994:Recombinant Proteins / Q000008:administration & dosage; D012254:Ribavirin / Q000008:administration & dosage; D012307:Risk Factors; D000097630:Inosine Triphosphatase
chemical_list: D000998:Antiviral Agents; D006454:Hemoglobins; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D009842:Oligopeptides; D011092:Polyethylene Glycols; D011755:Pyrophosphatases; D011994:Recombinant Proteins; D012254:Ribavirin; C486464:telaprevir; C511829:ITPA protein, human; D000097630:Inosine Triphosphatase; C417083:peginterferon alfa-2b
keywords: AUROC; Anemia; CI; HCV; HR; Hb; Hepatitis C virus; ITPA; Inosine triphosohatase; PegIFN; Pegylated interferon; RBV; RVR; Ribavirin; SNP; SVR; TVR; Telaprevir; area under the receiver operating characteristic curve; confidence interval; eGFR; estimated glomerular filtration rate; hazard ratio; hemoglobin; hepatitis C virus; inosine triphosphatase; pegylated interferon; rapid virological response; ribavirin; single nucleotide polymorphism; sustained virological response; telaprevir