title: Pegylated interferon plus optimized weight-based ribavirin dosing negate the influence of weight and body mass index on early viral kinetics and sustained virological response in chronic hepatitis C.
abstract: OBJECTIVE
  Elevated body mass index (BMI) in chronic hepatitis C (CHC) has been associated with reduced rates of sustained virological response (SVR). The aims of this study were to determine whether early viral kinetics (and subsequently SVR) are influenced by weight or BMI by measuring HCV RNA at week 4 using two PCR assays with differing sensitivities.
  
  
  METHODS
  Patients with CHC treated with peginterferon plus weight-based ribavirin were included in this retrospective study. Body mass index, pretreatment viral load, genotype and liver histology were abstracted from the clinical database. HCV RNA PCR (lower limit of detection (LLD) <50 IU/mL) at treatment week 4 and 6 months after completion of therapy were recorded to determine the presence of rapid virological response (RVR-50) and SVR, respectively. In those who achieved RVR-50, stored week 4 serum was retested using Taqman (LLD < 15 IU/mL, RVR-15).
  
  
  RESULTS
  Of 134 patients included (genotype 1 57%, BMI 26.7 ± 4.5 kg/m², ribavirin dose 13.9 ± 2.6 mg/kg/day), 59% achieved SVR. RVR-50 was observed in 39.6% and RVR-15 in 27.6%. Neither body weight nor BMI influenced RVR-50, RVR-15 or SVR. The positive predictive values (PPVs) of RVR-50 and RVR-15 for SVR were 88.7% and 97.3% (P = 0.23). RVR-50 and RVR-15 superceded genotype and viral load as the strongest independent predictors of SVR (OR 9.25 (1.9-45.11) and OR 30.74 (3.08-317.96), respectively).
  
  
  CONCLUSIONS
  RVR is the strongest predictor of SVR. Early viral kinetics is not influenced by body weight or BMI when weight-based ribavirin is prescribed.
authors.affiliation: Department of Medicine, Toronto Western Hospital, University Health Network, Toronto, ON, Canada.
authors.forename: V
authors.initials: V
authors.lastname: Pattullo
authors.forename: N C
authors.initials: NC
authors.lastname: Ravindran
authors.forename: T
authors.initials: T
authors.lastname: Mazzulli
authors.forename: D K H
authors.initials: DK
authors.lastname: Wong
authors.forename: E J
authors.initials: EJ
authors.lastname: Heathcote
mesh_terms: D000998:Antiviral Agents / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use; D015992:Body Mass Index; D001835:Body Weight / Q000187:drug effects; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000187:drug effects* / Q000235:genetics / Q000502:physiology; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000627:therapeutic use; D008297:Male; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000627:therapeutic use; D011237:Predictive Value of Tests; D012367:RNA, Viral / Q000097:blood; D011994:Recombinant Proteins; D012254:Ribavirin / Q000008:administration & dosage* / Q000494:pharmacology / Q000627:therapeutic use; D013997:Time Factors; D016896:Treatment Outcome; D019562:Viral Load / Q000187:drug effects*
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C417083:peginterferon alfa-2b; C100416:peginterferon alfa-2a