title: Differential antiviral effects of pegylated interferon-α2a and pegylated interferon-α2b in chronic hepatitis C.
abstract: OBJECTIVE
  Pegylated interferon (peg-IFN)-α2a and -α2b show different pharmacokinetic properties but are used interchangeably for hepatitis C treatment in traditional dual combinations and with newer agents. We assessed whether peg-IFN antiviral effects vary with peg-IFN subtype, affecting viral response in a differential manner.
  
  
  METHODS
  Chronic hepatitis C patients treated with ribavirin combined with peg-IFN-α2a (N = 109) or -α2b (N = 114) were studied. Hepatitis C virus RNA quantitation was performed by Cobas TaqMan 5 min before treatment start and subsequently after 48/72 h and 7, 14, 28 and 90 days. Antiviral effect was assessed in terms of viraemia changes over treatment. Histology grading and staging, interleukin-28B (IL28B) status and baseline viral genotype, alanine aminotransferase, gamma glutamyltransferase and glucose were analysed.
  
  
  RESULTS
  Viraemia decline after 48/72 h and 7 days was significantly greater with peg-IFN-α2b (1.96 and 2.12 vs 1.49 and 1.20 log10 IU/mL with peg-IFN-α2a; p < 0.001). Differences were of larger extent in patients with advanced fibrosis (p = 0.002), genotype 1 infection (p = 0.002) and CT/TT genotypes of IL28B (p = 0.001). A rebound in viral load was observed significantly more often after the first dose in patients treated with peg-IFN-α2b (78 vs 28 % in those with peg-IFN-α2a; p = 0.0001). Differences between peg-IFNs disappeared by day 28 of treatment.
  
  
  CONCLUSIONS
  There are significant pharmacodynamic differences between peg-IFN-α2a and -α2b in the early phase of chronic hepatitis C treatment. The greater early viral decline observed with peg-IFN-α2b was essentially confined to 'difficult to treat' patients. Whether this could affect response-guided treatment decision making, as well as triple drug regimens, needs to be assessed.
authors.affiliation: Internal Medicine Section, Department of Cardiothoracic Sciences, University of Naples S.U.N., Ospedale Monaldi, Via Leonardo Bianchi snc, 80131, Naples, Italy, emanuele.durante@unina2.it.
authors.forename: Emanuele
authors.initials: E
authors.lastname: Durante-Mangoni
authors.forename: Antonio
authors.initials: A
authors.lastname: Parrella
authors.forename: Domenico
authors.initials: D
authors.lastname: Iossa
authors.forename: Roberto
authors.initials: R
authors.lastname: Andini
authors.forename: Rosa
authors.initials: R
authors.lastname: Molaro
authors.forename: Carminia
authors.initials: C
authors.lastname: Battimelli
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Sodano
authors.forename: Riccardo
authors.initials: R
authors.lastname: Utili
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage*; D015331:Cohort Studies; D005260:Female; D019698:Hepatitis C, Chronic / Q000175:diagnosis* / 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*; D011994:Recombinant Proteins / Q000008:administration & dosage; D012189:Retrospective Studies; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; C417083:peginterferon alfa-2b; C100416:peginterferon alfa-2a