title: Low- and standard-dose peginterferon alfa-2a for chronic hepatitis C, genotype 2 or 3: efficacy, tolerability, viral kinetics and cytokine response.
abstract: BACKGROUND
  Chronic infection with hepatitis C, genotype 2/3, responds better than other genotypes to peginterferon and ribavirin treatment. We hypothesized that a lower dose of peginterferon would be as effective, but less toxic than standard doses.
  
  
  OBJECTIVE
  To test the hypothesis that a lower dose of peginterferon would be as effective as, but less toxic than, standard doses.
  
  
  METHODS
  A total of 30 patients were treated with low-dose peginterferon alfa-2a (90 microg/week) and 27 patients with standard doses (180 microg/week) for 24 weeks in combination with 800 mg/day of ribavirin. Patients who failed treatment were offered 48 weeks of standard-dose treatment. Viral and serum inducible protein 10 (IP-10) levels were measured and early viral kinetic parameters were calculated.
  
  
  RESULTS
  Sustained virological response was achieved in 68% of the low-dose and 87% of the standard-dose patients (per protocol, P = 0.79 for non-inferiority). Re-treatment was successful in all patients who tolerated full dose and duration. The standard-dose group had greater first-phase declines of viral levels and faster time to negativity. The second-phase slope was not dose-dependent. IP-10 induction was significantly greater with the standard dose. Although fatigue and general feeling during treatment were worse for standard dose, haematological toxicity and depression did not differ between groups.
  
  
  CONCLUSIONS
  A lower dose of peginterferon is associated with some symptomatic benefit, but the response is not equivalent to standard dosing.
authors.affiliation: Liver Diseases Branch, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892-1800, USA. rotmany@mail.nih.gov
authors.forename: Y
authors.initials: Y
authors.lastname: Rotman
authors.forename: B B
authors.initials: BB
authors.lastname: Borg
authors.forename: A
authors.initials: A
authors.lastname: Soza
authors.forename: J J
authors.initials: JJ
authors.lastname: Feld
authors.forename: A A
authors.initials: AA
authors.lastname: Modi
authors.forename: R
authors.initials: R
authors.lastname: Loomba
authors.forename: G
authors.initials: G
authors.lastname: Lutchman
authors.forename: E
authors.initials: E
authors.lastname: Rivera
authors.forename: E
authors.initials: E
authors.lastname: Doo
authors.forename: M G
authors.initials: MG
authors.lastname: Ghany
authors.forename: T
authors.initials: T
authors.lastname: Heller
authors.forename: A U
authors.initials: AU
authors.lastname: Neumann
authors.forename: T J
authors.initials: TJ
authors.lastname: Liang
authors.forename: J H
authors.initials: JH
authors.lastname: Hoofnagle
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use*; D016207:Cytokines / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000008:administration & dosage*; D012333:RNA, Messenger / Q000378:metabolism; D011994:Recombinant Proteins; D012254:Ribavirin / Q000008:administration & dosage*; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D016207:Cytokines; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012333:RNA, Messenger; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C100416:peginterferon alfa-2a