title: Peginterferon alpha-2a and ribavirin versus peginterferon alpha-2a monotherapy in early virological responders and peginterferon alpha-2a and ribavirin versus peginterferon alpha-2a, ribavirin and amantadine triple therapy in early virological nonresponders: the SMIEC II trial in naïve patients with chronic hepatitis C.
abstract: OBJECTIVE
  The objective of this study was to compare the efficacy of anti-hepatitis C virus (anti-HCV) treatment schedules on the basis of an early virological response (EVR), defined as undetectable serum HCV-RNA (<50 IU/ml) after a 12-week induction course of peginterferon alpha-2a (PEG-IFN) 180 mcg/week.
  
  
  METHODS
  A total of 210 interferon-naïve patients (69% male; median age, 42 years) with histologically proven chronic hepatitis C infection (genotype 1: 62%) received PEG-IFN 180 mcg/week for 12 weeks. Patients with EVR (58%) were randomized to continue PEG-IFN monotherapy (n=64) or to add ribavirin (RBV), 800 mg/day (n=57), for 36 additional weeks. Patients without EVR (42%) were randomized to add RBV (n=42), or RBV plus amantadine, 200 mg/day (n=47), for 36 additional weeks. Sustained virological response (SVR, undetectable HCV-RNA 24 weeks after treatment completion) was compared among treatment groups.
  
  
  RESULTS
  Patients with EVR: SVR rate was 60.3% in the PEG-IFN group versus 67.2% in the PEG-IFN+RBV group (NS). In genotypes 2/3, SVR rates were 66.7 versus 73.1% (NS); in genotypes 1/4, SVR rates were 51.6 versus 61.3%, respectively (NS). Patients without EVR: SVR was 16.7% in the PEG-IFN+RBV group versus 31.9% in the triple therapy group (P=0.07). In patients with genotypes 1/4, SVR rates were 9.4 versus 29.7% (P=0.041).
  
  
  CONCLUSIONS
  In genotypes 1/4 patients without EVR, triple therapy results in higher SVR rates than standard dual therapy. This study confirms that addition of amantadine is beneficial in early-recognized 'difficult-to-treat' patients.
authors.affiliation: Hepatology Unit, Tor Vergata University, Rome, Italy. angelico@med.uniroma2.it
authors.forename: Mario
authors.initials: M
authors.lastname: Angelico
authors.forename: Beate
authors.initials: B
authors.lastname: Koehler-Horst
authors.forename: Paola
authors.initials: P
authors.lastname: Piccolo
authors.forename: Francesco
authors.initials: F
authors.lastname: Angelico
authors.forename: Silvia
authors.initials: S
authors.lastname: Gentile
authors.forename: Simona
authors.initials: S
authors.lastname: Francioso
authors.forename: Pierluigi
authors.initials: P
authors.lastname: Tarquini
authors.forename: Roberto Della
authors.initials: RD
authors.lastname: Vecchia
authors.forename: Laura
authors.initials: L
authors.lastname: Ponti
authors.forename: Giampaolo
authors.initials: G
authors.lastname: Pilleri
authors.forename: Angelo
authors.initials: A
authors.lastname: Barlattani
authors.forename: Antonio
authors.initials: A
authors.lastname: Grieco
authors.forename: Francesco
authors.initials: F
authors.lastname: Soccorsi
authors.forename: Paolo
authors.initials: P
authors.lastname: Guarascio
authors.forename: Luigi
authors.initials: L
authors.lastname: Demelia
authors.forename: Orazio
authors.initials: O
authors.lastname: Sorbello
authors.forename: Zaccaria
authors.initials: Z
authors.lastname: Rossi
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Forlini
authors.forename: Salvatore
authors.initials: S
authors.lastname: Zaru
authors.forename: Franco
authors.initials: F
authors.lastname: Bandiera
mesh_terms: D000328:Adult; D000367:Age Factors; D000547:Amantadine / Q000009:adverse effects / Q000627:therapeutic use*; D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D004359:Drug Therapy, Combination; D005260:Female; D016174:Hepacivirus / Q000235:genetics / Q000302:isolation & purification; D019698:Hepatitis C, Chronic / Q000188:drug therapy*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000009:adverse effects / Q000627:therapeutic use*; D011379:Prognosis; D012367:RNA, Viral / Q000097:blood; D011994:Recombinant Proteins; D012254:Ribavirin / Q000009:adverse effects / Q000627:therapeutic use*; D013997:Time Factors; D017211:Treatment Failure; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000998:Antiviral Agents; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D012367:RNA, Viral; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; D012254:Ribavirin; D000547:Amantadine; C100416:peginterferon alfa-2a