title: Early on-treatment prediction of response to peginterferon alfa-2a for HBeAg-negative chronic hepatitis B using HBsAg and HBV DNA levels.
abstract: Peginterferon alfa-2a results in a sustained response (SR) in a minority of patients with hepatitis B e antigen (HBeAg)-negative chronic hepatitis B (CHB). This study investigated the role of early on-treatment serum hepatitis B surface antigen (HBsAg) levels in the prediction of SR in HBeAg-negative patients receiving peginterferon alfa-2a. HBsAg (Architect from Abbott) was quantified at the baseline and during treatment (weeks 4, 8, 12, 24, 36, and 48) and follow-up (weeks 60 and 72) in the sera from 107 patients who participated in an international multicenter trial (peginterferon alfa-2a, n = 53, versus peginterferon alfa-2a and ribavirin, n = 54). Overall, 24 patients (22%) achieved SR [serum hepatitis B virus (HBV) DNA level < 10,000 copies/mL and normal alanine aminotransferase levels at week 72]. Baseline characteristics were comparable between sustained responders and nonresponders. From week 8 onward, serum HBsAg levels markedly decreased in sustained responders, whereas only a modest decline was observed in nonresponders. However, HBsAg declines alone were of limited value in the prediction of SR [area under the receiver operating characteristic curve (AUC) at weeks 4, 8, and 12 = 0.59, 0.56, and 0.69, respectively]. Combining the declines in HBsAg and HBV DNA allowed the best prediction of SR (AUC at week 12 = 0.74). None of the 20 patients (20% of the study population) in whom a decrease in serum HBsAg levels was absent and whose HBV DNA levels declined less than 2 log copies/mL exhibited an SR (negative predictive value = 100%).
  
  
  CONCLUSIONS
  At week 12 of peginterferon alfa-2a treatment for HBeAg-negative CHB, a solid stopping rule was established with a combination of declines in serum HBV DNA and HBsAg levels from the baseline. Quantitative serum HBsAg in combination with HBV DNA enables on-treatment adjustments of peginterferon therapy for HBeAg-negative CHB.
authors.affiliation: Gastroenterology and Hepatology, Erasmus MC-University Medical Center, Rotterdam, the Netherlands.
authors.forename: Vincent
authors.initials: V
authors.lastname: Rijckborst
authors.forename: Bettina E
authors.initials: BE
authors.lastname: Hansen
authors.forename: Yilmaz
authors.initials: Y
authors.lastname: Cakaloglu
authors.forename: Peter
authors.initials: P
authors.lastname: Ferenci
authors.forename: Fehmi
authors.initials: F
authors.lastname: Tabak
authors.forename: Meral
authors.initials: M
authors.lastname: Akdogan
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Simon
authors.forename: Ulus S
authors.initials: US
authors.lastname: Akarca
authors.forename: Robert
authors.initials: R
authors.lastname: Flisiak
authors.forename: Elke
authors.initials: E
authors.lastname: Verhey
authors.forename: Anneke J
authors.initials: AJ
authors.lastname: Van Vuuren
authors.forename: Charles A B
authors.initials: CA
authors.lastname: Boucher
authors.forename: Martijn J
authors.initials: MJ
authors.lastname: ter Borg
authors.forename: Harry L A
authors.initials: HL
authors.lastname: Janssen
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use*; D004279:DNA, Viral / Q000097:blood*; D004311:Double-Blind Method; D005260:Female; D006514:Hepatitis B Surface Antigens / Q000097:blood*; D006513:Hepatitis B e Antigens; D006515:Hepatitis B virus / Q000235:genetics*; D019694:Hepatitis B, Chronic / Q000097:blood* / Q000188:drug therapy*; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000627:therapeutic use*; D008297:Male; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D011237:Predictive Value of Tests; D011994:Recombinant Proteins; D012074:Remission Induction; D012189:Retrospective Studies; D013997:Time Factors
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens; D006513:Hepatitis B e Antigens; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; C100416:peginterferon alfa-2a