title: Response to peginterferon alfa-2a (40KD) in HBeAg-negative CHB: on-treatment kinetics of HBsAg serum levels vary by HBV genotype.
abstract: OBJECTIVE
  We investigated whether HBV genotype influences on-treatment HBsAg kinetics and/or the end-of-treatment HBsAg levels associated with long-term virological response in HBeAg-negative chronic hepatitis B patients treated with peginterferon alfa-2a±lamivudine in the Phase III trial.
  
  
  METHODS
  All patients (n=230) who participated in long-term follow-up were included according to the availability of HBsAg level measurements. Long-term virological response was defined as HBV DNA ≤ 10,000cp/ml (1786IU/ml) at 5 years post-treatment. Genotype-specific end-of-treatment HBsAg levels associated with long-term virological response (identified by ROC analysis) were assessed in 199 patients with HBsAg measurements available at baseline and end-of-treatment. HBsAg kinetics according to genotype and long-term virological response were investigated in the 117 patients with additional samples available at weeks 12, 24, and 72.
  
  
  RESULTS
  Baseline HBsAg levels were significantly higher for A than B, C, and D genotypes (p<0.05). On-treatment HBsAg kinetics varied according to HBV genotype. The difference between responders and non-responders was greatest for genotype A from weeks 12-24; for genotypes B and D from baseline to week 12; there was no significant difference over any timeframe for genotype C. High positive predictive values for long-term virological response could be obtained by applying end-of-treatment genotype-specific cut-offs: 75%, 47%, 71%, and 75% for genotypes A (<400IU/ml), B (<50IU/ml), C (<75IU/ml), and D (<1000IU/ml), respectively.
  
  
  CONCLUSIONS
  On-treatment HBsAg kinetics vary between HBV genotypes. Genotype-specific monitoring timeframes and end-of-treatment thresholds could ameliorate response-guided treatment of HBeAg-negative chronic hepatitis B.
authors.affiliation: U.O. Epatologia-Azienda Ospedaliero Universitaria Pisana, Pisa, Italy. Electronic address: brunetto@med-club.com.
authors.forename: Maurizia R
authors.initials: MR
authors.lastname: Brunetto
authors.forename: Patrick
authors.initials: P
authors.lastname: Marcellin
authors.forename: Beatrice
authors.initials: B
authors.lastname: Cherubini
authors.forename: Cihan
authors.initials: C
authors.lastname: Yurdaydin
authors.forename: Patrizia
authors.initials: P
authors.lastname: Farci
authors.forename: Stephanos J
authors.initials: SJ
authors.lastname: Hadziyannis
authors.forename: Vivien
authors.initials: V
authors.lastname: Rothe
authors.forename: Loredana
authors.initials: L
authors.lastname: Regep
authors.forename: Ferruccio
authors.initials: F
authors.lastname: Bonino
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000998:Antiviral Agents / Q000627:therapeutic use*; D005260:Female; D005838:Genotype; D006514:Hepatitis B Surface Antigens / Q000097:blood*; D006513:Hepatitis B e Antigens / Q000097:blood*; D006515:Hepatitis B virus / Q000145:classification / Q000235:genetics*; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*; D007700:Kinetics; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D011994:Recombinant Proteins / Q000627:therapeutic use
chemical_list: D000998:Antiviral Agents; D006514:Hepatitis B Surface Antigens; D006513:Hepatitis B e Antigens; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; C100416:peginterferon alfa-2a
keywords: ALT; CHB; EOT; Genotype; HBV; HBeAg; HBeAg-negative chronic hepatitis B; HBsAg; HBsAg quantification; IFN; LVR; NPV; PPV; Peginterferon alfa-2a; ROC; Response-guided; alanine aminotransferase; chronic hepatitis B; end-of-treatment; hepatitis B e antigen; hepatitis B s antigen; hepatitis B virus; interferon; long-term virological response; negative predictive value; positive predictive value; receiver-operating characteristic