title: Interferon-gamma with peginterferon alpha-2a and ribavirin in nonresponder patients with chronic hepatitis C (ANRS HC16 GAMMATRI).
abstract: OBJECTIVE
  Interferon-gamma-1b (IFN-γ-1b) improves alpha interferon (IFN-α) inhibition of hepatitis C virus (HCV) replication in replicon system. We described virological response after addition of IFN-γ to a combination of ribavirin/peginterferon (PEG-IFN)-α-2a or α-2b.
  
  
  METHODS
  In this non-comparative, multicenter trial, patients chronically infected by HCV who were nonresponders to a previous treatment by PEG-IFN and ribavirin were restarted on a regimen of PEG-IFN-α-2a (180 μg/week) + ribavirin (1000-1200 mg/day) for 16 weeks. If HCV-RNA decreased less than 2 log(10) copies/mL (nonresponders), and if PEG-IFN-α-2a and ribavirin dosages were unchanged while tolerance was good, IFNγ-1b (100 μg three times per week) was added for the last 32 weeks of treatment. Virological response was evaluated at week 28 (12 weeks after initiation of IFN-γ-1b).
  
  
  RESULTS
  Among the 48 patients started on dual therapy, 23 patients (47%) were nonresponders at week 12 and received IFN-γ-1b from week 16 onward. Their mean HCV-RNA (log(10) IU/mL) was 6.83 at baseline, 5.81 at week 12, and 5.63 at week 28. No patient reached undetectable HCV-RNA at week 28 (upper bound of 95% confidence interval: 14.8%); none had a decrease > 1 log(10) IU/mL. One case of grade 4 neutropenia was reported.
  
  
  CONCLUSIONS
  Among the strictly selected nonresponders, IFN-γ-1b (at a dosage of 100 μg thrice a week) in combination with PEG-IFN-α-2a and ribavirin failed to show virological efficacy.
authors.affiliation: CHU de Bordeaux, Pessac, France. patrice.couzigou@chu-bordeaux.fr
authors.forename: Patrice
authors.initials: P
authors.lastname: Couzigou
authors.forename: Sophie
authors.initials: S
authors.lastname: Pérusat
authors.forename: Marc
authors.initials: M
authors.lastname: Bourlière
authors.forename: Pascale
authors.initials: P
authors.lastname: Trimoulet
authors.forename: Thierry
authors.initials: T
authors.lastname: Poynard
authors.forename: Vincent
authors.initials: V
authors.lastname: Leroy
authors.forename: Patrick
authors.initials: P
authors.lastname: Marcellin
authors.forename: Juliette
authors.initials: J
authors.lastname: Foucher
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Bronowicki
authors.forename: Geneviève
authors.initials: G
authors.lastname: Chêne
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D016009:Chi-Square Distribution; D004359:Drug Therapy, Combination; D005260:Female; D005602:France; D006526:Hepatitis C / Q000235:genetics; D019698:Hepatitis C, Chronic / Q000175:diagnosis / Q000188:drug therapy*; D006801:Humans; D016898:Interferon-alpha / Q000009:adverse effects / Q000627:therapeutic use*; D007371:Interferon-gamma / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011092:Polyethylene Glycols / Q000009:adverse effects / Q000627:therapeutic use*; D012367:RNA, Viral / Q000097:blood; D011994:Recombinant Proteins / Q000009:adverse effects / Q000627:therapeutic use; D012254:Ribavirin / Q000009:adverse effects / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome; D019562:Viral Load
chemical_list: D000998:Antiviral Agents; D015415:Biomarkers; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; C554125:interferon gamma-1b; D011092:Polyethylene Glycols; D012254:Ribavirin; D007371:Interferon-gamma; C100416:peginterferon alfa-2a