title: Peginterferon alfa-2a and ribavirin in patients with chronic hepatitis C who have failed prior treatment.
abstract: OBJECTIVE
  The most effective therapy currently available for treatment of chronic hepatitis C virus (HCV) is the combination of peginterferon and ribavirin. This study evaluated the effectiveness of this treatment in patients who were nonresponders to previous interferon-based therapy.
  
  
  METHODS
  The first 604 patients enrolled in the Hepatitis C Antiviral Long-Term Treatment Against Cirrhosis (HALT-C) Trial were evaluated. All were HCV RNA positive, previous nonresponders to interferon, with or without ribavirin, and had bridging fibrosis or cirrhosis on liver biopsy (Ishak fibrosis stage 3-6). Patients were retreated with peginterferon alfa-2a 180 microg/wk plus ribavirin 1000-1200 mg/day. Those with no detectable HCV RNA in serum at week 20 continued treatment for a total of 48 weeks and were then followed for an additional 24 weeks.
  
  
  RESULTS
  Thirty-five percent of patients had no detectable HCV RNA in serum at treatment week 20, and 18% achieved sustained virologic response (SVR). Factors associated with an SVR included previous treatment with interferon monotherapy, infection with genotypes 2 or 3, a lower AST:ALT ratio, and absence of cirrhosis. Reducing the dose of ribavirin from > or =80% to < or =60% of the starting dose during the first 20 weeks of treatment was associated with a decline in SVR from 21% to 11% (P < or = 0.05). In contrast, reducing the dose of peginterferon or reducing ribavirin after week 20, when HCV RNA was already undetectable, did not significantly affect SVR.
  
  
  CONCLUSIONS
  Selected nonresponders to previous interferon-based therapy can achieve SVR following retreatment with peginterferon alfa-2a and ribavirin.
authors.affiliation: Hepatology Section, Virginia Commonwealth University, Richmond, 23298, USA. mshiffma@hsc.vcu.edu
authors.forename: Mitchell L
authors.initials: ML
authors.lastname: Shiffman
authors.forename: Adrian M
authors.initials: AM
authors.lastname: Di Bisceglie
authors.forename: Karen L
authors.initials: KL
authors.lastname: Lindsay
authors.forename: Chihiro
authors.initials: C
authors.lastname: Morishima
authors.forename: Elizabeth C
authors.initials: EC
authors.lastname: Wright
authors.forename: Gregory T
authors.initials: GT
authors.lastname: Everson
authors.forename: Anna S
authors.initials: AS
authors.lastname: Lok
authors.forename: Timothy R
authors.initials: TR
authors.lastname: Morgan
authors.forename: Herbert L
authors.initials: HL
authors.lastname: Bonkovsky
authors.forename: William M
authors.initials: WM
authors.lastname: Lee
authors.forename: Jules L
authors.initials: JL
authors.lastname: Dienstag
authors.forename: Marc G
authors.initials: MG
authors.lastname: Ghany
authors.forename: Zachary D
authors.initials: ZD
authors.lastname: Goodman
authors.forename: James E
authors.initials: JE
authors.lastname: Everhart
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000009:adverse effects; D004359:Drug Therapy, Combination; D005260:Female; D019698:Hepatitis C, Chronic / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage* / Q000009:adverse effects; D008103:Liver Cirrhosis / Q000821:virology; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols; D011446:Prospective Studies; D011994:Recombinant Proteins; D012254:Ribavirin / Q000008:administration & dosage* / Q000009:adverse effects; D017211:Treatment Failure
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; C417083:peginterferon alfa-2b; C100416:peginterferon alfa-2a