title: The magnitude of week 4 HCV RNA decay on pegylated interferon/ribavirin accurately predicts virological failure in patients with genotype 1.
abstract: BACKGROUND
  Current stopping rules during pegylated interferon (peg-IFN)/ribavirin (RBV) treatment rely on week 12 HCV RNA response, but earlier identification of non-responders offers clinical and economic advantages.
  
  
  OBJECTIVE
  To evaluate, among 129 HCV-genotype-1-infected, treatment-naive patients receiving peg-IFN/RBV, the feasibility of predicting treatment failure using receiver operating characteristics (ROC) curves after measuring week 4 HCV RNA decreases, and to assess baseline predictors of not achieving sustained virological response (SVR).
  
  
  RESULTS
  Peg-IFN-alpha2b was used in 84.5% of patients. Fifty-three (41%) reached SVR. The best cutoff value of HCV RNA decrease at week 4 to predict non-SVR corresponded to 1 log10 IU/ml: sensitivity and negative predictive value: 100%; specificity: 64%; positive predictive value: 66%; ROC curve area: 0.91 (95% confidence interval [CI]: 0.86-0.96). By applying this threshold, treatment could have been discontinued at week 4 in 64% of virological non-responders (49/76). By univariate analysis, baseline HCV RNA > 800,000 IU/ml (P = 0.029), older age (P = 0.011), and higher aspartate aminotransferase (AST) levels (P = 0.005) or AST/alanine aminotransferase ratio values (P = 0.04) were associated with failure. After multivariate analysis, only baseline HCV RNA >800,000 IU/ml (odds ratio [OR]: 2.12; 95% CI: 1.005-4.488; P = 0.048) and higher AST levels (OR: 1.01; 95% CI: 1.003-1.024; P = 0.011) remained statistically significant.
  
  
  CONCLUSIONS
  The lack of > or = log10 IU/ml decrease in baseline HCV RNA at week 4 was 100% predictive of treatment failure, independently associated with HCV RNA > 800,000 IU/ml and higher AST levels.
authors.affiliation: Service of Gastroenterology, Hospital Ramón y Cajal, Universidad de Alcalá de Henares, Madrid, Spain. rbarcena.hrc@salud.madrid.org
authors.forename: Rafael
authors.initials: R
authors.lastname: Bárcena
authors.forename: Ana
authors.initials: A
authors.lastname: Moreno
authors.forename: Santos
authors.initials: S
authors.lastname: del Campo
authors.forename: Alfonso
authors.initials: A
authors.lastname: Muriel
authors.forename: María L
authors.initials: ML
authors.lastname: Mateos
authors.forename: Elena
authors.initials: E
authors.lastname: Garrido
authors.forename: Miguel
authors.initials: M
authors.lastname: García
authors.forename: Carmen
authors.initials: C
authors.lastname: Quereda
authors.forename: Santiago
authors.initials: S
authors.lastname: Moreno
authors.forename: Alberto
authors.initials: A
authors.lastname: Moreno
mesh_terms: D001219:Aspartate Aminotransferases / Q000097:blood; D015331:Cohort Studies; D004359:Drug Therapy, Combination; D023381:Endpoint Determination; D005260:Female; D005819:Genetic Markers; D016174:Hepacivirus / Q000235:genetics* / Q000302:isolation & purification; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols; D011237:Predictive Value of Tests; D012367:RNA, Viral / Q000097:blood*; D011994:Recombinant Proteins; D012189:Retrospective Studies; D012254:Ribavirin / Q000627:therapeutic use*; D013030:Spain; D013045:Species Specificity; D013997:Time Factors; D017211:Treatment Failure; D014505:Urban Population; D019562:Viral Load
chemical_list: D005819:Genetic Markers; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; D001219:Aspartate Aminotransferases; C417083:peginterferon alfa-2b