title: Predicting response to peginterferon alpha-2a, lamivudine and the two combined for HBeAg-negative chronic hepatitis B.
abstract: OBJECTIVE
  In a trial of patients with hepatitis B e antigen (HBeAg)-negative chronic hepatitis B, 24 week post-treatment biochemical and virological response rates with peginterferon alpha-2a with or without lamivudine were significantly higher than with lamivudine alone. The effect of pre-treatment factors on post-treatment responses was investigated.
  
  
  METHODS
  Multivariate analyses were performed using available data from 518 patients treated with peginterferon alpha-2a with or without lamivudine, or with lamivudine alone. A post-treatment response was defined as alanine aminotransferase (ALT) normalisation and hepatitis B virus (HBV) DNA level of <20,000 copies/ml.
  
  
  RESULTS
  In logistic regression analyses across all treatment arms, peginterferon alpha-2a (with or without lamivudine) therapy, younger age, female gender, high baseline ALT, low baseline HBV DNA and HBV genotype were identified as significant predictors of combined response at 24 weeks post-treatment. In the peginterferon alpha-2a and lamivudine monotherapy arms, patients with genotypes B or C had a higher chance of response than genotype D infected patients (p<0.001), the latter responding better to the combination than to peginterferon alpha-2a monotherapy (p = 0.015). At 1 year post-treatment, response rates by intention-to-treat analysis were 19.2% for the peginterferon alpha-2a, 19.0% for the combination, and 10.0% for the lamivudine groups, with genotypes B or C associated with a sustained combined response to peginterferon alpha-2a with or without lamivudine therapy.
  
  
  CONCLUSIONS
  Baseline ALT and HBV DNA levels, patient age, gender, and infecting HBV genotype significantly influenced combined response at 24 weeks post-treatment, in patients treated with peginterferon alpha-2a and/or lamivudine. At 1 year post-treatment HBV genotype was significantly predictive of efficacy for patients treated with peginterferon alpha-2a with or without lamivudine.
authors.affiliation: University of Pisa and Foundation IRCCS, Policlinico di Milano, Milan, Italy. bonino@med-club.com
authors.forename: F
authors.initials: F
authors.lastname: Bonino
authors.forename: P
authors.initials: P
authors.lastname: Marcellin
authors.forename: G K K
authors.initials: GK
authors.lastname: Lau
authors.forename: S
authors.initials: S
authors.lastname: Hadziyannis
authors.forename: R
authors.initials: R
authors.lastname: Jin
authors.forename: T
authors.initials: T
authors.lastname: Piratvisuth
authors.forename: G
authors.initials: G
authors.lastname: Germanidis
authors.forename: C
authors.initials: C
authors.lastname: Yurdaydin
authors.forename: M
authors.initials: M
authors.lastname: Diago
authors.forename: S
authors.initials: S
authors.lastname: Gurel
authors.forename: M-Y
authors.initials: MY
authors.lastname: Lai
authors.forename: M R
authors.initials: MR
authors.lastname: Brunetto
authors.forename: P
authors.initials: P
authors.lastname: Farci
authors.forename: M
authors.initials: M
authors.lastname: Popescu
authors.forename: P
authors.initials: P
authors.lastname: McCloud
mesh_terms: D000328:Adult; D000367:Age Factors; D000410:Alanine Transaminase / Q000097:blood; D000998:Antiviral Agents / Q000627:therapeutic use*; D015415:Biomarkers / Q000097:blood; D004279:DNA, Viral / Q000097:blood; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D006513:Hepatitis B e Antigens / Q000097:blood; D006515:Hepatitis B virus / Q000145:classification / Q000235:genetics / Q000302:isolation & purification; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D019259:Lamivudine / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D011379:Prognosis; D011994:Recombinant Proteins; D012737:Sex Factors; D016896:Treatment Outcome
chemical_list: D000998:Antiviral Agents; D015415:Biomarkers; D004279:DNA, Viral; D006513:Hepatitis B e Antigens; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D019259:Lamivudine; D011092:Polyethylene Glycols; D000410:Alanine Transaminase; C100416:peginterferon alfa-2a