title: Plasma/erythrocyte ribavirin x100 ratio as an indicator of sustained virological response in HCV genotype 1 patients with early virological response.
abstract: BACKGROUND
  On-treatment predictors during antiviral therapy of HCV are useful because they allow discontinuation of an unnecessary treatment in non-responders. Our aim was to evaluate the usefulness of plasma and erythrocyte ribavirin levels in predicting sustained virological response (SVR) in HCV genotype 1 patients undergoing antiviral treatment.
  
  
  METHODS
  A total of 40 HCV genotype 1 patients treated with pegylated interferon-alpha2a 180 microg weekly plus ribavirin 1,000 or 1,200 mg daily (according to body weight) were included in the study. Plasma and erythrocyte ribavirin levels were evaluated in all patients at week 12 by HPLC. At week 24, ribavirin levels were reassessed in those achieving early virological response (EVR).
  
  
  RESULTS
  A total of 27 patients achieved EVR, whereas 17 achieved SVR. There was no difference among EVR and non-EVR patients in terms of plasma and erythrocyte ribavirin concentrations at week 12. At week 24, EVR patients obtaining SVR exhibited higher mean +/-sd levels of ribavirin in plasma and lower levels in erythrocytes compared with non-SVR patients (in plasma 12.8 +/-10 versus 5.8 +/-4 microM [P<0.02] and in erythrocytes 1,053 +/-504 versus 1,613 +/-589 microM [P<0.03]). When the plasma ribavirin/erythrocyte ribavirin x100 ratio was compared, the difference was enhanced (1.5 +/-1.3 versus 0.4 +/-0.3 microM; P<0.01). Receiver operating characteristic curve analysis identified a cutoff for plasma ribavirin/erythrocyte ribavirin x100 ratio in predicting SVR of 0.71 with a negative predictive value of 0.8 and a positive predictive value of 0.9, whereas those related to EVR were 1 and 0.6, respectively.
  
  
  CONCLUSIONS
  Plasma ribavirin/erythrocyte ribavirin x100 ratio at week 24 seems to be a good indicator of SVR in HCV genotype 1 patients achieving EVR.
authors.affiliation: Hepatology Unit, University of Rome, Rome, Italy. baiocchi@uniroma2.it
authors.forename: Leonardo
authors.initials: L
authors.lastname: Baiocchi
authors.forename: Francesco
authors.initials: F
authors.lastname: De Leonardis
authors.forename: Marco
authors.initials: M
authors.lastname: Delle Monache
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Nosotti
authors.forename: Renato L
authors.initials: RL
authors.lastname: Conti
authors.forename: Ilaria
authors.initials: I
authors.lastname: Lenci
authors.forename: Marco
authors.initials: M
authors.lastname: Carbone
authors.forename: Daniele
authors.initials: D
authors.lastname: Di Paolo
authors.forename: Silvia
authors.initials: S
authors.lastname: Cucchiarelli
authors.forename: Mario
authors.initials: M
authors.lastname: Angelico
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000097:blood* / Q000627:therapeutic use; D004359:Drug Therapy, Combination; D004912:Erythrocytes / Q000737:chemistry*; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000145:classification / Q000187:drug effects* / Q000235:genetics; 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; D010949:Plasma / Q000737:chemistry*; D011092:Polyethylene Glycols / Q000627:therapeutic use; D011237:Predictive Value of Tests; D012367:RNA, Viral / Q000097:blood; D011994:Recombinant Proteins; D012254:Ribavirin / Q000097:blood* / Q000627:therapeutic use; D012680:Sensitivity and Specificity; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C100416:peginterferon alfa-2a