title: Prediction of response to pegylated interferon/ribavirin combination therapy for chronic hepatitis C genotype 1b and high viral load.
abstract: BACKGROUND
  This study explores pretreatment predictive factors for ultimate virological responses to pegylated interferon-α (1.5 μg/kg/week) and ribavirin (600-1000 mg/day) (PEG-IFN/RBV) combination therapy for patients infected with hepatitis C virus (HCV)-1b and a high viral load.
  
  
  METHODS
  A total of 75 patients underwent PEG-IFN/RBV combination therapy for 48 weeks. HCV amino acid (aa) substitutions in non-structural protein 5a, including those in the IFN/RBV resistance-determining region (IRRDR) and the IFN sensitivity-determining region and the core regions, as well as the genetic variation (rs8099917) near the interleukin 28B (IL28B) gene (genotype TT) were analyzed.
  
  
  RESULTS
  Of the 75 patients, 49 % (37/75) achieved a sustained virological response (SVR), 27 % (20/75) showed relapse, and 24 % (18/75) showed null virological response (NVR). Multivariate logistic regression analysis identified IRRDR with 6 or more mutations (IRRDR ≥6) [odds ratio (OR) 11.906, p < 0.0001] and age <60 years (OR 0.228, p = 0.015) as significant determiners of SVR and IL28B minor (OR 14.618, p = 0.0019) and platelets <15 × 10(4)/mm(3) (OR 0.113, p = 0.0096) as significant determiners of NVR. A combination of IRRDR ≥6 and age <60 years improved SVR predictability (93.3 %), and that of IRRDR ≤5 and age ≥60 years improved non-SVR predictability (84.0 %). Similarly, a combination of IL28B minor and platelets <15 × 10(4)/mm(3) improved NVR predictability (85.7 %), and that of IL28B major and platelets ≥15 × 10(4)/mm(3) improved non-NVR (response) (97.1 %) predictability.
  
  
  CONCLUSIONS
  IRRDR ≥6 and age <60 years were significantly associated with SVR. IL28B minor and platelets <15 × 10(4)/mm(3) were significantly associated with NVR. Certain combinations of these factors improved SVR and NVR predictability and could, therefore, be used to design therapeutic strategies.
authors.affiliation: Department of Gastroenterology, Kobe Asahi Hospital, 3-5-25 Bououji-cho, Nagata-ku, Kobe 653-0801, Japan. asahi-hp@arion.ocn.ne.jp
authors.forename: Soo Ryang
authors.initials: SR
authors.lastname: Kim
authors.forename: Ahmed
authors.initials: A
authors.lastname: El-Shamy
authors.forename: Susumu
authors.initials: S
authors.lastname: Imoto
authors.forename: Ke Ih
authors.initials: KI
authors.lastname: Kim
authors.forename: Yoshi-hiro
authors.initials: YH
authors.lastname: Ide
authors.forename: Lin
authors.initials: L
authors.lastname: Deng
authors.forename: Ikuo
authors.initials: I
authors.lastname: Shoji
authors.forename: Yasuhito
authors.initials: Y
authors.lastname: Tanaka
authors.forename: Yutaka
authors.initials: Y
authors.lastname: Hasegawa
authors.forename: Mitsuhiro
authors.initials: M
authors.lastname: Ota
authors.forename: Hak
authors.initials: H
authors.lastname: Hotta
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000235:genetics / Q000821:virology; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage / Q000627:therapeutic use*; D007372:Interferons; D007378:Interleukins / Q000235:genetics*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011110:Polymorphism, Genetic; D012254:Ribavirin / Q000008:administration & dosage / Q000627:therapeutic use*; D017421:Sequence Analysis; D016896:Treatment Outcome; D019562:Viral Load; D017361:Viral Nonstructural Proteins; D000095022:Interferon Lambda
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D007372:Interferons; D007378:Interleukins; D012254:Ribavirin; D017361:Viral Nonstructural Proteins; C000624353:interferon-lambda, human; D000095022:Interferon Lambda