title: Validation of a stopping rule at week 12 using HBsAg and HBV DNA for HBeAg-negative patients treated with peginterferon alfa-2a.
abstract: OBJECTIVE
  It was recently demonstrated that none of the hepatitis B e antigen (HBeAg)-negative patients without any serum hepatitis B surface antigen (HBsAg) decline and with <2log hepatitis B virus (HBV) DNA decline at week 12 of a 48-week peginterferon alfa-2a (PEG-IFN) treatment course achieved a sustained response (SR). We aimed at validating this stopping rule in two independent trials.
  
  
  METHODS
  HBeAg-negative patients receiving 48 or 96 weeks of PEG-IFN in the phase III registration trial (N=85) and PegBeLiver study (N=75) were stratified according to the presence of any HBsAg decline and/or 2log HBV DNA decline at week 12. SR was defined as HBV DNA <2000IU/ml and normal alanine aminotransferase 24 weeks after treatment.
  
  
  RESULTS
  The original PARC trial included 102 patients (genotype A/D/other: 14/81/7), 25 (25%) had an SR. The validation dataset consisted of 160 patients (genotype A/B/C/D/other: 10/18/34/91/7), 57 (36%) achieved an SR. The stopping rule performed well across the two studies (p=0.001) and its negative predictive value [NPV] was 95% in the validation dataset harbouring genotypes A-D. Its performance was best for genotype D. Moreover, among the 34 patients treated for 96 weeks, none of the 7 (21%) without HBsAg decline and with <2log HBV DNA decline at week 12 achieved an SR (NPV 100%).
  
  
  CONCLUSIONS
  We confirmed in two independent studies that the combination of HBsAg and HBV DNA levels at week 12 identifies HBeAg-negative patients with a very low chance of SR to either 48 or 96 weeks of PEG-IFN therapy.
authors.affiliation: Dept. of Gastroenterology and Hepatology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
authors.forename: Vincent
authors.initials: V
authors.lastname: Rijckborst
authors.affiliation: Dept. of Gastroenterology and Hepatology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands; Dept. of Biostatistics, Erasmus MC, University Medical Center, Rotterdam, The Netherlands.
authors.forename: Bettina E
authors.initials: BE
authors.lastname: Hansen
authors.affiliation: Dept. of Internal Medicine 3, Gastroenterology and Hepatology, Medical University of Vienna, Vienna, Austria.
authors.forename: Peter
authors.initials: P
authors.lastname: Ferenci
authors.affiliation: Hepatology Unit, University Hospital Pisa, Pisa, Italy.
authors.forename: Maurizia R
authors.initials: MR
authors.lastname: Brunetto
authors.affiliation: Dept. of Infectious Diseases, Istanbul University Cerrahpasa Medical School, Istanbul, Turkey.
authors.forename: Fehmi
authors.initials: F
authors.lastname: Tabak
authors.affiliation: Dept. of Gastroenterohepatology, Istanbul University Medical School, Istanbul, Turkey.
authors.forename: Yilmaz
authors.initials: Y
authors.lastname: Cakaloglu
authors.affiliation: Liver Unit, Cardarelli Hospital, Naples, Italy.
authors.forename: A Galeota
authors.initials: AG
authors.lastname: Lanza
authors.affiliation: Infectious Disease Unit, SS Anna and Sebastiano Hospital, Caserta, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Messina
authors.affiliation: SPARC Consulting, Milan, Italy.
authors.forename: Claudio
authors.initials: C
authors.lastname: Iannacone
authors.affiliation: Roche, Monza, Italy.
authors.forename: Benedetta
authors.initials: B
authors.lastname: Massetto
authors.affiliation: Roche, Basel, Switzerland.
authors.forename: Loredana
authors.initials: L
authors.lastname: Regep
authors.affiliation: First Gastroenterology Unit, Fondazione IRCCS Cà Granda, Ospedale Maggiore Policlinico, Università di Milano, Milan, Italy.
authors.forename: Massimo
authors.initials: M
authors.lastname: Colombo
authors.affiliation: Dept. of Gastroenterology and Hepatology, Erasmus MC, University Medical Center, Rotterdam, The Netherlands. Electronic address: h.janssen@erasmusmc.nl.
authors.forename: Harry L A
authors.initials: HLA
authors.lastname: Janssen
authors.affiliation: First Gastroenterology Unit, Fondazione IRCCS Cà Granda, Ospedale Maggiore Policlinico, Università di Milano, Milan, Italy.
authors.forename: Pietro
authors.initials: P
authors.lastname: Lampertico
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000627:therapeutic use; D015415:Biomarkers / Q000097:blood; D004279:DNA, Viral / Q000097:blood*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005838:Genotype; D006509:Hepatitis B / Q000097:blood* / Q000188:drug therapy*; D006514:Hepatitis B Surface Antigens / Q000097:blood*; D006515:Hepatitis B virus / Q000235:genetics*; D006801:Humans; D016898:Interferon-alpha / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000627:therapeutic use*; D011237:Predictive Value of Tests; D011994:Recombinant Proteins / Q000627:therapeutic use; D012189:Retrospective Studies; D013997:Time Factors; D016896:Treatment Outcome; D028761:Withholding Treatment
chemical_list: D000998:Antiviral Agents; D015415:Biomarkers; D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens; D016898:Interferon-alpha; D011994:Recombinant Proteins; D011092:Polyethylene Glycols; C100416:peginterferon alfa-2a