title: Ranking predictors of a sustained viral response for patients with chronic hepatitis C treated with pegylated interferon and ribavirin in Scotland.
abstract: OBJECTIVE
  From the literature on the hepatitis C virus, the existence of a gap between a sustained virologic response (SVR) attainable in randomized clinical trials (RCTs) versus routine practice is not clear. Further, in terms of the pretreatment prediction of SVR, to date, studies have focused only on reporting the magnitude of association (MOA) between each predictor and an SVR. They fail to acknowledge that a predictor with a large MOA is of little value to clinicians if it has low variability in the treatment population.
  
  
  METHODS
  Hepatitis C virus clinical databases were used to derive a large, representative cohort of Scottish pegylated interferon and ribavirin initiates.
  
  
  RESULTS
  Overall, 39% [123/315, 95% confidence interval (CI) 34-45%] of genotype 1 and 70% (414/594, 95% CI 66-73%) of genotype 2/3 patients achieved an SVR; this compares with the pooled estimates of 47% for genotype 1 (95% CI 41-52%) and 80% for genotype 2/3 (95% CI 75-85%) RCT participants. Significant predictors of SVR identified from logistic regression were ranked on the basis of the akaike information criteria (reflecting an approach that will account for each predictor's MOA and variability) as follows: (i) genotype, % increase in akaike information criteria of the final model when variables are excluded, 58.49%; (ii) γ-glutamyl transferase, 18.64%; (iii) platelet count, 6.48%; (iv) alanine aminotransferase quotient, 4.63%; (v) ever infected with hepatitis B virus, 4.31% and (vi) sex, 3.10%.
  
  
  CONCLUSIONS
  (i) The proportion of patients attaining an SVR in Scottish routine practice is marginally lower than in RCTs and (ii) other than genotype, γ-glutamyl transferase emerges as a valuable predictor of an SVR in routine practice. Further, we demonstrate an approach to more clearly discern the predictive value of response predictors.
authors.affiliation: Department of Mathematics and Statistics, University of Strathclyde, Scotland, UK. Hamish.innes@nhs.net
authors.forename: Hamish A
authors.initials: HA
authors.lastname: Innes
authors.forename: Sharon J
authors.initials: SJ
authors.lastname: Hutchinson
authors.forename: Samuel
authors.initials: S
authors.lastname: Allen
authors.forename: Diptendu
authors.initials: D
authors.lastname: Bhattacharyya
authors.forename: Peter
authors.initials: P
authors.lastname: Bramley
authors.forename: Bill
authors.initials: B
authors.lastname: Carman
authors.forename: Toby E S
authors.initials: TE
authors.lastname: Delahooke
authors.forename: John F
authors.initials: JF
authors.lastname: Dillon
authors.forename: David J
authors.initials: DJ
authors.lastname: Goldberg
authors.forename: Nicholas
authors.initials: N
authors.lastname: Kennedy
authors.forename: Peter R
authors.initials: PR
authors.lastname: Mills
authors.forename: John
authors.initials: J
authors.lastname: Morris
authors.forename: Judith
authors.initials: J
authors.lastname: Morris
authors.forename: Chris
authors.initials: C
authors.lastname: Robertson
authors.forename: Adrian J
authors.initials: AJ
authors.lastname: Stanley
authors.forename: Peter
authors.initials: P
authors.lastname: Hayes
mesh_terms: D000217:Acyltransferases / Q000097:blood; D000328:Adult; D017677:Age Distribution; D000410:Alanine Transaminase / Q000097:blood; D000998:Antiviral Agents / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000145:classification / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000097:blood / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010976:Platelet Count; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D011379:Prognosis; D011446:Prospective Studies; D011994:Recombinant Proteins / Q000627:therapeutic use; D012189:Retrospective Studies; D012254:Ribavirin / Q000627:therapeutic use*; D017678:Sex Distribution; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D015415:Biomarkers; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; D000217:Acyltransferases; C019181:glutamine phenylacetyltransferase; D000410:Alanine Transaminase; C417083:peginterferon alfa-2b; C100416:peginterferon alfa-2a