title: Usefulness of viral kinetics for early prediction of a sustained virological response in HCV-1 non-responders re-treated with pegylated interferon and ribavirin.
abstract: OBJECTIVE
  Undetectable HCV RNA at 12 weeks is the stopping rule recommended in HCV patients in whom previous treatment has failed. Whether earlier virological criteria may be useful for deciding treatment discontinuation remains subject of debate. The aim of this study was to identify, in HCV-1 non-responders and relapsers to IFN or Peg-IFN and ribavirin, the earliest and most accurate predictor of failure to respond to a new treatment combining Peg-IFN and ribavirin.
  
  
  METHODS
  Prediction of SVR was assessed using the area under the ROC (AUROC) curve of reduction in viral load at different time points.
  
  
  RESULTS
  This study included 151 patients (32% with extensive fibrosis or cirrhosis). A SVR was reached in 34% (21% in non-responders and 59% in relapsers). In non-responders, 1 month was the most accurate time point for predicting SVR (AUROC: 0.787 ± 0.075, p = 0.0001). Thirty-seven percent of non-responders did not have a 1-log drop in viral load at 1 month. All these patients had detectable HCV RNA at 3 months (p < 0.0001) and only 4% attained a SVR (p = 0.004). The same high negative predictive value for SVR was found in sensitivity analysis restricted to non-responders to Peg-IFN and ribavirin. In contrast, in relapsers, undetectable HCV RNA at 3 months was the earliest criterion with high negative predictive value (92%, p < 0.0001).
  
  
  CONCLUSIONS
  All HCV-1 non-responders who did not have a 1-log drop in viral load at 1 month remained HCV-RNA-detectable at 3 months, and only 4% attained a SVR. This new criterion can be used early on as a first stopping rule.
authors.affiliation: Service d'Hépato-Gastroentérologie, Hôpital Huriez, CHRU Lille, Lille, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Deltenre
authors.forename: Marion
authors.initials: M
authors.lastname: Corouge
authors.forename: Valérie
authors.initials: V
authors.lastname: Canva
authors.forename: Hélène
authors.initials: H
authors.lastname: Castel
authors.forename: Faustine
authors.initials: F
authors.lastname: Wartel
authors.forename: Sébastien
authors.initials: S
authors.lastname: Dharancy
authors.forename: Alexandre
authors.initials: A
authors.lastname: Louvet
authors.forename: Mouna
authors.initials: M
authors.lastname: Lazrek
authors.forename: Christophe
authors.initials: C
authors.lastname: Moreno
authors.forename: Jean
authors.initials: J
authors.lastname: Henrion
authors.forename: Philippe
authors.initials: P
authors.lastname: Mathurin
mesh_terms: D000998:Antiviral Agents / Q000627:therapeutic use*; D019540:Area Under Curve; D003661:Decision Support Techniques; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics / Q000502:physiology*; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology*; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D011237:Predictive Value of Tests; D012367:RNA, Viral / Q000097:blood*; D012372:ROC Curve; D011994:Recombinant Proteins / Q000627:therapeutic use; D012008:Recurrence; D012254:Ribavirin / Q000627:therapeutic use*; D013997:Time Factors; D017211:Treatment Failure; D019562:Viral Load
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C100416:peginterferon alfa-2a