title: Age and total ribavirin dose are independent predictors of relapse after interferon therapy in chronic hepatitis C revealed by data mining analysis.
abstract: BACKGROUND
  This study aimed to define factors associated with relapse among responders to pegylated interferon (PEG-IFN) plus ribavirin (RBV) therapy in chronic hepatitis C.
  
  
  METHODS
  A cohort of genotype 1b chronic hepatitis C patients treated with PEG-IFN plus RBV and who had an undetectable HCV RNA by week 12 (n=951) were randomly assigned to model derivation (n=636) or internal validation (n=315) groups. An independent cohort (n=598) were used for an external validation. A decision tree model for relapse was explored using data mining analysis.
  
  
  RESULTS
  The data mining analysis defined five subgroups of patients with variable rates of relapse ranging from 13% to 52%. The reproducibility of the model was confirmed by internal and external validations (r(2)=0.79 and 0.83, respectively). Patients with undetectable HCV RNA at week 4 had the lowest risk of relapse (13%), followed by patients <60 years with undetectable HCV RNA at week 5-12 who received ≥3.0 g/kg of body weight of RBV (16%). Older patients with a total RBV dose <3.0 g/kg had the highest risk of relapse (52%). Higher RBV dose beyond 3.0 g/kg was associated with further decrease of relapse rate among patients <60 years (up to 11%) but not among older patients whose relapse rate remained stable around 30%.
  
  
  CONCLUSIONS
  Data mining analysis revealed that time to HCV RNA negativity, age and total RBV dose was associated with relapse. To prevent relapse, ≥3.0 g/kg of RBV should be administered. Higher dose of RBV may be beneficial in patients <60 years.
authors.affiliation: Division of Gastroenterology and Hepatology, Musashino Red Cross Hospital, Tokyo, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Kurosaki
authors.forename: Naoki
authors.initials: N
authors.lastname: Hiramatsu
authors.forename: Minoru
authors.initials: M
authors.lastname: Sakamoto
authors.forename: Yoshiyuki
authors.initials: Y
authors.lastname: Suzuki
authors.forename: Manabu
authors.initials: M
authors.lastname: Iwasaki
authors.forename: Akihiro
authors.initials: A
authors.lastname: Tamori
authors.forename: Kentaro
authors.initials: K
authors.lastname: Matsuura
authors.forename: Sei
authors.initials: S
authors.lastname: Kakinuma
authors.forename: Fuminaka
authors.initials: F
authors.lastname: Sugauchi
authors.forename: Naoya
authors.initials: N
authors.lastname: Sakamoto
authors.forename: Mina
authors.initials: M
authors.lastname: Nakagawa
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Yatsuhashi
authors.forename: Namiki
authors.initials: N
authors.lastname: Izumi
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D054316:Biomarkers, Pharmacological / Q000032:analysis; D015331:Cohort Studies; D057225:Data Mining; D054796:Drug Dosage Calculations; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000187:drug effects / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000517:prevention & control* / Q000821:virology; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000008:administration & dosage* / Q000627:therapeutic use; D011379:Prognosis; D012367:RNA, Viral / Q000096:biosynthesis; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use; D012008:Recurrence; D015203:Reproducibility of Results; D012254:Ribavirin / Q000008:administration & dosage* / Q000627:therapeutic use; D019562:Viral Load / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D054316:Biomarkers, Pharmacological; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C100416:peginterferon alfa-2a