title: Pegylated interferon alfa-2b alone or in combination with lamivudine for HBeAg-positive chronic hepatitis B: a randomised trial.
abstract: BACKGROUND
  Treatment of HBeAg-positive patients with chronic hepatitis B is not effective in most. A combination of immunomodulatory pegylated interferon alfa-2b and antiviral lamivudine might improve the rate of sustained response.
  
  
  METHODS
  307 HBeAg-positive patients with chronic hepatitis B were assigned combination therapy (100 microg/week pegylated interferon alfa-2b and 100 mg/day lamivudine) or monotherapy (100 microg/week pegylated interferon alfa-2b and placebo) for 52 weeks. During weeks 32-52 the pegylated interferon dose was 50 microg/week in both treatment groups. The analyses were based on the modified intention-to-treat population after exclusion of 24 patients from one centre withdrawn for misconduct, ten who lost HBeAg before the study start, and seven who received no study medication. All included patients were followed up for 26 weeks after treatment.
  
  
  RESULTS
  49 (36%) of 136 patients assigned monotherapy and 46 (35%) of 130 assigned combination therapy had lost HBeAg at the end of follow-up (p=0.91). More of the combination-therapy than of the monotherapy group had cleared HBeAg at the end of treatment (57 [44%] vs 40 [29%]; p=0.01) but relapsed during follow-up. Patterns were similar when response was assessed by suppression of serum hepatitis B virus (HBV) DNA or change in concentrations of alanine aminotransferase. Response rates (HBeAg loss) varied by HBV genotype (p=0.01): A, 42 (47%) patients; B, ten (44%); C, 11 (28%); and D, 26 (25%).
  
  
  CONCLUSIONS
  Treatment with pegylated interferon alfa-2b is effective for HBeAg-positive chronic hepatitis B. Combination with lamivudine in the regimen used is not superior to monotherapy. HBV genotype is an important predictor of response to treatment.
authors.affiliation: Department of Gastroenterology, Erasmus MC, University Medical Center Rotterdam, Rotterdam, Netherlands. h.janssen@erasmusmc.nl
authors.forename: Harry L A
authors.initials: HL
authors.lastname: Janssen
authors.forename: Monika
authors.initials: M
authors.lastname: van Zonneveld
authors.forename: Hakan
authors.initials: H
authors.lastname: Senturk
authors.forename: Stefan
authors.initials: S
authors.lastname: Zeuzem
authors.forename: Ulus S
authors.initials: US
authors.lastname: Akarca
authors.forename: Yilmaz
authors.initials: Y
authors.lastname: Cakaloglu
authors.forename: Christopher
authors.initials: C
authors.lastname: Simon
authors.forename: Thomas M K
authors.initials: TM
authors.lastname: So
authors.forename: Guido
authors.initials: G
authors.lastname: Gerken
authors.forename: Robert A
authors.initials: RA
authors.lastname: de Man
authors.forename: Hubert G M
authors.initials: HG
authors.lastname: Niesters
authors.forename: Pieter
authors.initials: P
authors.lastname: Zondervan
authors.forename: Bettina
authors.initials: B
authors.lastname: Hansen
authors.forename: Solko W
authors.initials: SW
authors.lastname: Schalm
mesh_terms: D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage*; D004279:DNA, Viral / Q000097:blood; D004311:Double-Blind Method; D004337:Drug Carriers; D004359:Drug Therapy, Combination; D005260:Female; D005838:Genotype; D006514:Hepatitis B Surface Antigens / Q000097:blood; D006513:Hepatitis B e Antigens / Q000097:blood*; D006515:Hepatitis B virus / Q000235:genetics / Q000302:isolation & purification; D019694:Hepatitis B, Chronic / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology / Q000821:virology; D006801:Humans; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage*; D019259:Lamivudine / Q000008:administration & dosage*; D008099:Liver / Q000473:pathology; D008297:Male; D011092:Polyethylene Glycols; D011994:Recombinant Proteins
chemical_list: D000998:Antiviral Agents; D004279:DNA, Viral; D004337:Drug Carriers; D006514:Hepatitis B Surface Antigens; D006513:Hepatitis B e Antigens; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D019259:Lamivudine; D011092:Polyethylene Glycols; C417083:peginterferon alfa-2b