title: Rapid virological response is the most important predictor of sustained virological response across genotypes in patients with chronic hepatitis C virus infection.
abstract: OBJECTIVE
  The probability of response to peginterferon and ribavirin is associated with numerous host and virological factors. Attainment of a rapid virological response (RVR), defined as undetectable HCV RNA at week 4 during treatment with peginterferon and ribavirin, is highly predictive of sustained virological response (SVR). The aim of the present study was to determine the relative importance of the kinetics of antiviral response compared to baseline host and virological factors for predicting SVR.
  
  
  METHODS
  A retrospective analysis of 1383 patients, encompassing genotypes 1-4, treated with peginterferon alfa-2a and ribavirin, was performed. Baseline characteristics were compared across HCV genotypes and pretreatment factors associated with RVR were identified. The relative significance of RVR compared to other baseline factors for predicting SVR was analyzed by multiple logistic regression analysis.
  
  
  RESULTS
  RVR was achieved by 16% of patients with genotype 1 and 71% and 60% of those with genotype 2 and 3, respectively. Among patients who achieved RVR, the rate of SVR was high across all genotypes and ranged from 88% to 100% (genotypes 1-4). Baseline factors predictive of RVR included genotype, younger age, lower initial viral load, higher ALT ratio, absence of advanced fibrosis, and younger age. Notably, the presence of RVR generated the highest odds ratio (5.47, 95% confidence interval 3.97-7.52) for predicting SVR in multiple logistic regression analysis of these factors.
  
  
  CONCLUSIONS
  Attainment of RVR varies by genotype and is associated with several baseline factors. Patients who achieve RVR have the highest rates of SVR, regardless of genotype. These findings have important implications for predicting and managing response-guided combination antiviral therapies.
authors.affiliation: University of North Carolina, Chapel Hill, NC 27599, USA. mfried@med.unc.edu
authors.forename: Michael W
authors.initials: MW
authors.lastname: Fried
authors.forename: Stephanos J
authors.initials: SJ
authors.lastname: Hadziyannis
authors.forename: Mitchell L
authors.initials: ML
authors.lastname: Shiffman
authors.forename: Diethelm
authors.initials: D
authors.lastname: Messinger
authors.forename: Stefan
authors.initials: S
authors.lastname: Zeuzem
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000145:classification / Q000187:drug effects* / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000627:therapeutic use; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000627:therapeutic use; D012367:RNA, Viral / Q000097:blood; D011994:Recombinant Proteins; D012189:Retrospective Studies; D012254:Ribavirin / Q000008:administration & dosage / Q000627:therapeutic use; D013997:Time Factors; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C100416:peginterferon alfa-2a