title: Optimized threshold for serum HCV RNA to predict treatment outcomes in hepatitis C patients receiving peginterferon alfa-2a/ribavirin.
abstract: It is unclear whether the current threshold for 'high' hepatitis C virus (HCV) RNA level (800,000 IU/mL) is optimal for predicting sustained virological response (SVR). We retrospectively analysed pretreatment HCV RNA levels and SVR rates in 1529 mono-infected and 176 HIV-HCV co-infected patients treated with peginterferon alfa-2a (40 kD) plus ribavirin. We improved the threshold for differentiating low and high viral load by fitting semiparametric generalized additive logistic regression models to the data and constructing receiver operating characteristics curves. Among HCV genotype 1 mono-infected patients, the difference in SVR rates between those with low and high baseline HCV RNA levels was 27% (70%vs 43%) when 400,000 IU/mL was used and 16% (59%vs 43%) when 800,000 IU/mL was used. In HIV-HCV genotype 1 co-infected patients, the difference was 51% (71%vs 20%) when 400,000 IU/mL was used and 43% (61%vs 18%) when 800,000 IU/mL was used. A lower threshold (200,000 IU/mL) was identified for genotype 1 mono-infected patients with 'normal' alanine aminotransferase (ALT) levels. No threshold could be identified in HCV genotype 2 or 3 patients. A threshold HCV RNA level of 400,000 IU/mL is optimal for differentiating high and low probability of SVR in genotype 1-infected individuals with elevated ALT.
authors.affiliation: Johann Wolfgang Goethe University Medical Center, Frankfurt am Main, Germany. zeuzem@em.uni-frankfurt.de
authors.forename: S
authors.initials: S
authors.lastname: Zeuzem
authors.forename: M
authors.initials: M
authors.lastname: Rodríguez-Torres
authors.forename: K
authors.initials: K
authors.lastname: Rajender Reddy
authors.forename: P
authors.initials: P
authors.lastname: Marcellin
authors.forename: M
authors.initials: M
authors.lastname: Diago
authors.forename: A
authors.initials: A
authors.lastname: Craxi
authors.forename: P
authors.initials: P
authors.lastname: Pockros
authors.forename: M
authors.initials: M
authors.lastname: Rizzetto
authors.forename: D
authors.initials: D
authors.lastname: Bernstein
authors.forename: M L
authors.initials: ML
authors.lastname: Shiffman
authors.forename: A
authors.initials: A
authors.lastname: Lin
authors.forename: F
authors.initials: F
authors.lastname: Tatsch
authors.forename: S
authors.initials: S
authors.lastname: Hadziyannis
mesh_terms: D000328:Adult; D000410:Alanine Transaminase / Q000097:blood; D000998:Antiviral Agents / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D016174:Hepacivirus / Q000235:genetics / Q000502:physiology*; D006526:Hepatitis C / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D012367:RNA, Viral / Q000097:blood*; D012372:ROC Curve; D011994:Recombinant Proteins / Q000627:therapeutic use; D012189:Retrospective Studies; D012254:Ribavirin / Q000627:therapeutic use*; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; D000410:Alanine Transaminase; C100416:peginterferon alfa-2a