title: Changes in anti-viral effectiveness of interferon after dose reduction in chronic hepatitis C patients: a case control study.
abstract: BACKGROUND
  High dose interferon induction treatment of hepatitis C viral infection blocks viral production over 95%. Since dose reduction is often performed due to clinical considerations, the effect of dose reduction on hepatitis C virus kinetics was studied.
  
  
  METHODS
  A new model that allowed longitudinal changes in the parameters of viral dynamics was used in a group of genotype-1 patients (N = 15) with dose reduction from 10 to 3 million units of interferon daily in combination with ribavirin, in comparison to a control group (N = 9) with no dose reduction.
  
  
  RESULTS
  Dose reduction gave rise to a complex viral kinetic pattern, which could be only explained by a decrease in interferon effectiveness in blocking virion production. The benefit of the rapid initial viral decline following the high induction dose is lost after dose reduction. In addition, in some patients also the second phase viral decline slope, which is highly predictive of success of treatment, was impaired by the dose reduction resulting in smaller percentage of viral clearance in the dose reduction group.
  
  
  CONCLUSIONS
  These findings, while explaining the failure of many induction schedules, suggest that for genotype-1 patients induction therapy should be continued till HCVRNA negativity in serum in order to increase the sustained response rate for chronic hepatitis C.
authors.affiliation: Dept of Hepatology & Gastroenterology, University Hospital Rotterdam, The Netherlands. fcbekkering@hotmail.com
authors.forename: F C
authors.initials: FC
authors.lastname: Bekkering
authors.forename: A U
authors.initials: AU
authors.lastname: Neumann
authors.forename: J T
authors.initials: JT
authors.lastname: Brouwer
authors.forename: R S
authors.initials: RS
authors.lastname: Levi-Drummer
authors.forename: S W
authors.initials: SW
authors.lastname: Schalm
mesh_terms: D000998:Antiviral Agents / Q000008:administration & dosage*; D016022:Case-Control Studies; 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*; D008954:Models, Biological; D012367:RNA, Viral / Q000097:blood; D011994:Recombinant Proteins
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins