Pegylated interferon alfa-2b alone or in combination with lamivudine for HBeAg-positive chronic hepatitis B: a randomised trial

Harry L A Janssen, Monika van Zonneveld, Hakan Senturk, Stefan Zeuzem, Ulus S Akarca, Yilmaz Cakaloglu, Christopher Simon, Thomas M K So, Guido Gerken, Robert A de Man, Hubert G M Niesters, Pieter Zondervan, Bettina Hansen, Solko W Schalm, HBV 99-01 Study Group

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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 The analyses were based on the modified intention-to-treat population after exclusion of 24 patients from one centre withdrawn for misconduct, ten who lost HBeAg before the study start, and seven who received no study medication.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.

FINDINGS: 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%).

INTERPRETATION: 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.

Original languageEnglish
Pages (from-to)123-9
Number of pages7
JournalThe Lancet
Issue number9454
Publication statusPublished - 11-Jan-2005
Externally publishedYes


  • Adult
  • Antiviral Agents
  • DNA, Viral
  • Double-Blind Method
  • Drug Carriers
  • Drug Therapy, Combination
  • Female
  • Genotype
  • Hepatitis B Surface Antigens
  • Hepatitis B e Antigens
  • Hepatitis B virus
  • Hepatitis B, Chronic
  • Humans
  • Interferon-alpha
  • Lamivudine
  • Liver
  • Male
  • Polyethylene Glycols
  • Recombinant Proteins

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