title: Predicting sustained virological response and anaemia in chronic hepatitis C patients treated with peginterferon alfa-2a (40KD) plus ribavirin.
abstract: OBJECTIVE
  To assess the likelihood of a sustained virological response (SVR) vs. the likelihood of anaemia in patients with chronic hepatitis C.
  
  
  METHODS
  Data from 1732 patients treated with peginterferon alfa-2a (40KD) plus ribavirin in two randomized, multinational studies were pooled. Probabilities of SVR and anaemia were modelled using the generalized additive logistic model, with numerous clinical variables considered for entry into the model. Baseline haemoglobin was only considered in the analysis for anaemia.
  
  
  RESULTS
  The probability of anaemia increased from 6 to 16% as a function of the ribavirin dose kg(-1) (12-16 mg kg(-1)), whereas the relationship between SVR and ribavirin dose kg(-1) was influenced by hepatitis C virus (HCV) genotype. The probability of an SVR was not influenced by the ribavirin dose kg(-1) in patients with HCV genotype 2 or 3 infection, but increased as a function of ribavirin dose kg(-1) in patients with HCV genotype 1 infection (40-50% increase in probability of SVR for 12-16 mg kg(-1) dose ribavirin increase). The probability of an SVR in patients included with HCV genotype 1 decreased with increasing HCV RNA level to about 3 million copies ml(-1), but was relatively independent of increasing HCV RNA level thereafter. In addition, older age, a higher ribavirin apparent oral clearance and cirrhosis had a negative impact on achieving an SVR, but improved with increasing alanine aminotransferase (ALT) quotient. Sex and ribavirin dose kg(-1) were the most important prognostic factors for anaemia, followed by baseline haemoglobin, age, baseline ALT quotient and cirrhosis.
  
  
  CONCLUSIONS
  This study supports individualizing ribavirin dosages by HCV genotype and body weight, and highlights several clinical variables that influence the likelihood of an SVR compared with anaemia in chronic hepatitis C patients treated with peginterferon alfa-2a (40KD) plus ribavirin.
authors.affiliation: Exprimo NV, Lummen, Belgium, F. Hoffmann-La Roche Nutley, NJ, USA.
authors.forename: Eric
authors.initials: E
authors.lastname: Snoeck
authors.forename: Janet R
authors.initials: JR
authors.lastname: Wade
authors.forename: Frank
authors.initials: F
authors.lastname: Duff
authors.forename: Matthew
authors.initials: M
authors.lastname: Lamb
authors.forename: Karin
authors.initials: K
authors.lastname: Jorga
mesh_terms: D000328:Adult; D000368:Aged; D000740:Anemia / Q000139:chemically induced; D000998:Antiviral Agents / Q000009:adverse effects*; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000009:adverse effects*; D008297:Male; D008875:Middle Aged; D008954:Models, Biological; D015337:Multicenter Studies as Topic; D011092:Polyethylene Glycols / Q000009:adverse effects*; D016032:Randomized Controlled Trials as Topic; D011994:Recombinant Proteins; D012254:Ribavirin / Q000009:adverse effects*; D018570:Risk Assessment; D012307:Risk Factors; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C100416:peginterferon alfa-2a