Age and total ribavirin dose are independent predictors of relapse after interferon therapy in chronic hepatitis C revealed by data mining analysis

Antivir Ther. 2012;17(1):35-43. doi: 10.3851/IMP1923.

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.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Age Factors
  • Aged
  • Antiviral Agents / administration & dosage*
  • Antiviral Agents / therapeutic use
  • Biomarkers, Pharmacological / analysis
  • Cohort Studies
  • Data Mining*
  • Drug Dosage Calculations
  • Female
  • Genotype
  • Hepacivirus / drug effects
  • Hepacivirus / genetics
  • Hepatitis C, Chronic / drug therapy*
  • Hepatitis C, Chronic / prevention & control*
  • Hepatitis C, Chronic / virology
  • Humans
  • Interferon-alpha / administration & dosage*
  • Interferon-alpha / therapeutic use
  • Male
  • Middle Aged
  • Polyethylene Glycols / administration & dosage*
  • Polyethylene Glycols / therapeutic use
  • Prognosis
  • RNA, Viral / biosynthesis
  • Recombinant Proteins / administration & dosage
  • Recombinant Proteins / therapeutic use
  • Recurrence
  • Reproducibility of Results
  • Ribavirin / administration & dosage*
  • Ribavirin / therapeutic use
  • Viral Load / drug effects

Substances

  • Antiviral Agents
  • Biomarkers, Pharmacological
  • Interferon-alpha
  • RNA, Viral
  • Recombinant Proteins
  • Polyethylene Glycols
  • Ribavirin
  • peginterferon alfa-2a