title: Increase of ribavirin dose improves sustained virological response in HCV-genotype 1 patients with a partial response to peg-interferon and ribavirin.
abstract: OBJECTIVE
  In patients with chronic hepatitis C receiving Peg interferon/ribavirin (PEG-IFN/RBV) who do not achieve ≥ 2 log-reduction in HCV-RNA at week 12 (null responders, NR) and in those with ≥ 2 log-decrease but detectable at week 24 (partial responders, PR) the probability to achieve the sustained virological response (SVR) is almost null. The aim of this study was to investigate the efficacy of individualized schedule of progressively increased RBV doses in the setting of PEG-IFN/RBV treatment.
  
  
  METHODS
  PR or NR to PEG-IFN/RBV instead of discontinuing treatment were enrolled to receive increasing doses of RBV until a target theoretical concentration ([tRBV]) of ≥ 15 μmol/L (by pharmacokinetic formula based on glomerular filtration rate). HCV-RNA was assessed every 4 weeks and, if detectable, RBV dose was gradually increased until negativization. Twelve weeks later, patients with detectable HCV-RNA discontinued therapy while those with undetectable HCV-RNA continued for further 48 weeks.
  
  
  RESULTS
  Twenty genotype-1 patients (8 NR and 12 PR) were enrolled. After 12 weeks 9 (45%) were still HCV-RNA positive and were discontinued, while remaining 11 had undetectable HCV-RNA. One stopped treatment for side effects. Ten completed treatment. Five (all PR) achieved SVR. Side effects incidence was similar to that observed during PEG-IFN/RBV.
  
  
  CONCLUSIONS
  In conclusion, RBV high doses, according to individualized schedule, increase SVR in PR on a similar extent to that of triple therapy but without increase of side effects. Such treatment should be considered in PR with no access or intolerant to protease inhibitors (PI).
authors.affiliation: Department of Medical and Surgical Sciences, University of Bologna-Bologna, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Conti
authors.affiliation: Department of Medical and Surgical Sciences, University of Bologna-Bologna, Italy.
authors.forename: Ranka
authors.initials: R
authors.lastname: Vukotic
authors.affiliation: Department of Medical and Surgical Sciences, University of Bologna-Bologna, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Lorenzini
authors.affiliation: Department of Medical and Surgical Sciences, University of Bologna-Bologna, Italy.
authors.forename: Anna
authors.initials: A
authors.lastname: Riili
authors.affiliation: Department of Medical and Surgical Sciences, University of Bologna-Bologna, Italy.
authors.forename: Carmela
authors.initials: C
authors.lastname: Cursaro
authors.affiliation: Department of Medical and Surgical Sciences, University of Bologna-Bologna, Italy.
authors.forename: Alessandra
authors.initials: A
authors.lastname: Scuteri
authors.affiliation: Department of Medical and Surgical Sciences, University of Bologna-Bologna, Italy.
authors.forename: Elisabetta
authors.initials: E
authors.lastname: Loggi
authors.affiliation: Microbiology and Virology Unit, Sant'Orsola-Malpighi Hospital-Bologna, Italy.
authors.forename: Silvia
authors.initials: S
authors.lastname: Galli
authors.affiliation: Microbiology and Virology Unit, Sant'Orsola-Malpighi Hospital-Bologna, Italy.
authors.forename: Giuliano
authors.initials: G
authors.lastname: Furlini
authors.affiliation: Department of Medical and Surgical Sciences, University of Bologna-Bologna, Italy.
authors.forename: Mauro
authors.initials: M
authors.lastname: Bernardi
authors.affiliation: Department of Medical and Surgical Sciences, University of Bologna-Bologna, Italy.
authors.forename: Pietro
authors.initials: P
authors.lastname: Andreone
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000494:pharmacology / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D005919:Glomerular Filtration Rate / Q000187:drug effects / Q000502:physiology; D016174:Hepacivirus / Q000235:genetics*; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000235:genetics; D006801:Humans; D016898:Interferon-alpha / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000494:pharmacology / Q000627:therapeutic use*; D012367:RNA, Viral / Q000097:blood; D011994:Recombinant Proteins / Q000494:pharmacology / Q000627:therapeutic use; D012189:Retrospective Studies; D012254:Ribavirin / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C100416:peginterferon alfa-2a