title: Prediction of virologic response in difficult-to-treat chronic hepatitis C patients during high-dose interferon induction therapy.
abstract: OBJECTIVE
  To determine (i) whether early viral kinetics or other markers during a modified treatment regimen are predictors of treatment outcome and (ii) whether fast responders can be treated for 24 weeks, without compromising the sustained virologic response (SVR) rate.
  
  
  METHODS
  One hundred "difficult-to-treat" chronic hepatitis C patients (46 previous non-responders/relapsers (any genotype), 54 treatment-naive patients genotypes 1 and 4) were treated with triple antiviral induction therapy: amantadine hydrochloride and ribavirin, combined with 6 weeks interferon alfa-2b induction (weeks 1-2: 18 MU/day, weeks 3-4: 9 MU/day, weeks 5-6: 6 MU/day), thereafter combined with weekly peginterferon alfa-2b. Fast responders (>or=3 log(10) HCV RNA decline at week 4) were randomized to 24 or 48 weeks. Slow responders (<3 log(10) HCV RNA decline at week 4) were treated for 48 weeks. Treatment was stopped in patients with detectable HCV RNA at week 24.
  
  
  RESULTS
  Thirty-six patients achieved SVR: 28 of 60 fast responders (47%) versus 8 of 32 slow responders (25%, p<0.05). Relapse rates among fast responders treated for 24 or 48 weeks were 27% and 20%, respectively (p=NS). SVR in fast responders was independent of baseline HCV RNA >or= or <600,000 IU/mL. All treatment-naive patients with HCV RNA <5 IU/mL at week 1 or 2 achieved SVR; all treatment-naive patients with HCV RNA >or=5 IU/mL at week 16 became non-SVR. In previous non-responders/relapsers, the predictive value for SVR was 83% if HCV RNA was <5 IU/mL at week 2; all previous non-responders/relapsers with HCV RNA >or=5 IU/mL at week 8 became non-SVR.
  
  
  CONCLUSIONS
  With high-dose interferon induction, SVR and non-SVR can be predicted reliably within 16 weeks. Fast responders can be treated for 24 weeks, and SVR is independent of baseline viral load in fast responders.
authors.affiliation: AMC Liver Center, Department of Gastroenterology and Hepatology. h.c.gelderblom@amc.uva.nl
authors.forename: Huub C
authors.initials: HC
authors.lastname: Gelderblom
authors.forename: Hans L
authors.initials: HL
authors.lastname: Zaaijer
authors.forename: Marcel G W
authors.initials: MG
authors.lastname: Dijkgraaf
authors.forename: Jan
authors.initials: J
authors.lastname: Van Der Meer
authors.forename: Christine J
authors.initials: CJ
authors.lastname: Weegink
authors.forename: Peter L M
authors.initials: PL
authors.lastname: Jansen
authors.forename: Marcel G H M
authors.initials: MG
authors.lastname: Beld
authors.forename: Henk W
authors.initials: HW
authors.lastname: Reesink
mesh_terms: D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000008:administration & dosage*; D005260:Female; D005838:Genotype; D016174:Hepacivirus / Q000235:genetics / Q000302:isolation & purification; D019698:Hepatitis C, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols; D012367:RNA, Viral / Q000097:blood; D011994:Recombinant Proteins; D019562:Viral Load
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; C417083:peginterferon alfa-2b