title: Durable hepatitis B surface antigen decline in hepatitis B e antigen-positive chronic hepatitis B patients treated with pegylated interferon-α2b: relation to response and HBV genotype.
abstract: BACKGROUND
  On-treatment decline of serum hepatitis B surface antigen (HBsAg) may reflect the immunomodulatory effect of pegylated interferon (PEG-IFN) for hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB). We compared HBsAg decline across HBV genotypes between combined responders (HBeAg loss and HBV DNA<10,000 copies/ml at week 78), HBeAg responders (HBeAg loss with HBV DNA>10,000 copies/ml) and non-responders.
  
  
  METHODS
  HBsAg was measured at baseline, on-treatment and 6 months post-treatment in 221 HBeAg-positive CHB patients treated with PEG-IFN with or without lamivudine for 52 weeks, and in a representative subgroup of 142 patients at long-term follow-up (LTFU; mean 3.0 years).
  
  
  RESULTS
  On-treatment HBsAg decline significantly varied according to HBV genotype (A and B more than C and D; P<0.001). On-treatment HBsAg decline also differed between patients with a combined response (n=43) and those without (n=178; 3.34 versus 0.69 log IU/ml decline at week 52; P<0.001). Among patients without a combined response, no difference was observed between HBeAg responders (n=41) versus non-responders (n=137). HBsAg decline was sustained in combined responders and progressed to 3.75 log IU/ml at LTFU. Patients with a combined response achieved pronounced HBsAg declines, irrespective of HBV genotype, and those who achieved HBsAg levels <1,000 IU/ml at week 78 had a high probability of a sustained response and HBsAg clearance through LTFU.
  
  
  CONCLUSIONS
  On-treatment HBsAg decline during PEG-IFN therapy for HBeAg-positive CHB depends upon HBV genotype. Patients with a combined response to PEG-IFN achieve a pronounced HBsAg decline, irrespective of HBV genotype, which is sustained through 3 years of off-treatment follow-up.
authors.affiliation: Department of Gastroenterology and Hepatology, Erasmus MC University Medical Center, Rotterdam, the Netherlands.
authors.forename: Milan J
authors.initials: MJ
authors.lastname: Sonneveld
authors.forename: Vincent
authors.initials: V
authors.lastname: Rijckborst
authors.forename: Yilmaz
authors.initials: Y
authors.lastname: Cakaloglu
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Simon
authors.forename: E Jenny
authors.initials: EJ
authors.lastname: Heathcote
authors.forename: Fehmi
authors.initials: F
authors.lastname: Tabak
authors.forename: Tomasz
authors.initials: T
authors.lastname: Mach
authors.forename: Charles A B
authors.initials: CA
authors.lastname: Boucher
authors.forename: Bettina E
authors.initials: BE
authors.lastname: Hansen
authors.forename: Stefan
authors.initials: S
authors.lastname: Zeuzem
authors.forename: Harry L A
authors.initials: HL
authors.lastname: Janssen
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage* / Q000627:therapeutic use; D054316:Biomarkers, Pharmacological / Q000097:blood*; D004279:DNA, Viral / Q000097:blood*; D005260:Female; D005500:Follow-Up Studies; D005838:Genotype; D006514:Hepatitis B Surface Antigens / Q000097:blood*; D006513:Hepatitis B e Antigens / Q000097:blood; D006515:Hepatitis B virus / Q000235:genetics*; D019694:Hepatitis B, Chronic / Q000097:blood / Q000188:drug therapy* / Q000821:virology; D006801:Humans; D016898:Interferon-alpha / Q000008:administration & dosage* / Q000627:therapeutic use; D019259:Lamivudine / Q000008:administration & dosage / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D011092:Polyethylene Glycols / Q000008:administration & dosage* / Q000627:therapeutic use; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000627:therapeutic use; D016896:Treatment Outcome; D019562:Viral Load / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D054316:Biomarkers, Pharmacological; D004279:DNA, Viral; D006514:Hepatitis B Surface Antigens; D006513:Hepatitis B e Antigens; D016898:Interferon-alpha; D011994:Recombinant Proteins; D019259:Lamivudine; D011092:Polyethylene Glycols; C100416:peginterferon alfa-2a