title: Prediction of sustained virological response by ribavirin plasma concentration at week 4 of therapy in hepatitis C virus genotype 1 patients.
abstract: BACKGROUND
  Pegylated interferon/ribavirin combination is currently the standard treatment for chronic hepatitis C virus (HCV) infection. Body weight adjustment of ribavirin is crucial for response. However, previous studies found no relation between ingested dose and plasma concentration. The aim of this study was to define the ribavirin trough plasma concentration at week 4 (W4) associated with sustained virological response (SVR).
  
  
  METHODS
  Thirty-one HCV genotype 1 patients (8 naive and 23 non-responders to a previous pegylated interferon/ribavirin therapy) were treated with pegylated interferon/ribavirin and assessed by HPLC for ribavirin plasma concentration at W4.
  
  
  RESULTS
  Eleven patients (35%) achieved SVR, whereas 20 (65%) were non-responders. The median ribavirin plasma concentration at W4 (1.90 mg/l) varied from 1.62 mg/l in patients with subsequent non-response to 2.28 mg/l in sustained responders (P=0.007). Receiver operating characteristic curve analysis indicated that the 2.01 mg/l threshold gave the best sensitivity and specificity (73% and 80%, respectively, area under the curve =0.80; P=0.007). Sixty-seven percent of patients with median ribavirin plasma concentration >2 mg/l achieved SVR versus only 16% below this level (P=0.007). Multivariate regression analysis indicated that a ribavirin plasma concentration >2 mg/l at W4 was associated with SVR independent of gender, age, weight, baseline viral load and response to previous therapy.
  
  
  CONCLUSIONS
  These results, which remain to be confirmed in large clinical trials, highlight the potential relevance of ribavirin plasma level monitoring at an early stage of treatment. This monitoring could be of help in guiding antiviral therapy by offering dose adjustment in patients with ribavirin plasma level below the 2 mg/l threshold.
authors.affiliation: Hospices Civils de Lyon, Hôtel Dieu, Service d'hépatologie et de gastroentérologie, 69002 Lyon, France.
authors.forename: Marianne
authors.initials: M
authors.lastname: Maynard
authors.forename: Pierre
authors.initials: P
authors.lastname: Pradat
authors.forename: Marie-Claude
authors.initials: MC
authors.lastname: Gagnieu
authors.forename: Claude
authors.initials: C
authors.lastname: Souvignet
authors.forename: Christian
authors.initials: C
authors.lastname: Trepo
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D002851:Chromatography, High Pressure Liquid; D016903:Drug Monitoring; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000145:classification / Q000187:drug effects* / Q000235:genetics*; D006526:Hepatitis C / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000627:therapeutic use*; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D010949:Plasma / Q000737:chemistry; D011092:Polyethylene Glycols; D011237:Predictive Value of Tests; D012372:ROC Curve; D011994:Recombinant Proteins; D012254:Ribavirin / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D012680:Sensitivity and Specificity; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C417083:peginterferon alfa-2b