title: Retreating chronic hepatitis C with daily interferon alfacon-1/ribavirin after nonresponse to pegylated interferon/ribavirin: DIRECT results.
abstract: Up to 50% of patients with chronic hepatitis C fail to respond to initial therapy with pegylated interferon (PEG-IFN) and ribavirin (RBV). With unsuccessful viral eradication, these patients remain at risk for developing progression of their liver disease. Retreatment with PEG-IFN/RBV yields sustained virologic response (SVR) rates that are under 10%. A wholly synthetic interferon, interferon alfacon-1 or consensus interferon (CIFN) given with RBV, was evaluated in patients who failed initial PEG-IFN/RBV therapy. The intent-to-treat analysis included 487 patients; 245 received CIFN 9 microg/day and RBV, and 242 received CIFN 15 microg/day and RBV. Within this group of patients, 59.3% had documented advanced fibrosis at baseline liver biopsy (stage F3 or F4). SVR rates were 6.9% (17/245 patients) in the 9 microg group and 10.7% (26/242) in the 15 microg group. In the intent-to-treat analysis, SVR rates were higher among patients with a >2-log(10) decrease in hepatitis C virus RNA during prior PEG-IFN/RBV therapy: 11% (4/38) in the 9 mug group and 23% (7/31) in the 15 microg group. Among patients with lower baseline fibrosis scores (F0-F3), SVR rates were 7.8% (15/192) in the 9 microg group and 13.1% (23/175) in the 15 microg group. In this same group of patients (F0-F3), if a >2-log(10) decrease in hepatitis C virus RNA with previous PEG-IFN/RBV treatment was achieved, SVR rates improved to 10.7% and 31.6% in the 9 microg and 15 microg groups, respectively. CIFN/RBV combination retreatment was safe and well tolerated.
  
  
  CONCLUSIONS
  Retreatment of PEG-IFN and RBV nonresponders with CIFN and RBV is safe and efficacious and can be considered a retreatment strategy for patients failing previous therapy with PEG-IFN/RBV, especially in interferon-sensitive patients with lower baseline fibrosis scores.
authors.affiliation: Saint Louis University Liver Center, Saint Louis University School of Medicine, St. Louis, MO 63110-0250, USA. baconbr@slu.edu
authors.forename: Bruce R
authors.initials: BR
authors.lastname: Bacon
authors.forename: Mitchell L
authors.initials: ML
authors.lastname: Shiffman
authors.forename: Flavia
authors.initials: F
authors.lastname: Mendes
authors.forename: Reem
authors.initials: R
authors.lastname: Ghalib
authors.forename: Tarek
authors.initials: T
authors.lastname: Hassanein
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Morelli
authors.forename: Shobha
authors.initials: S
authors.lastname: Joshi
authors.forename: Kenneth
authors.initials: K
authors.lastname: Rothstein
authors.forename: Paul
authors.initials: P
authors.lastname: Kwo
authors.forename: Norman
authors.initials: N
authors.lastname: Gitlin
mesh_terms: D000998:Antiviral Agents / Q000008:administration & dosage*; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D007370:Interferon Type I / Q000008:administration & dosage*; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D011994:Recombinant Proteins; D019233:Retreatment; D012254:Ribavirin / Q000008:administration & dosage*; D017211:Treatment Failure
chemical_list: D000998:Antiviral Agents; D007370:Interferon Type I; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C050739:interferon alfacon-1; C417083:peginterferon alfa-2b; C100416:peginterferon alfa-2a