You are here

Article Text

Article menu
Download PDFPDF
Liver disease
Lamivudine and alpha interferon combination treatment of patients with chronic hepatitis B infection: a randomised trial
  1. S W Schalma,
  2. J Heathcoteb,
  3. J Cianciarac,
  4. G Farrelld,
  5. M Shermanb,
  6. B Willemse,
  7. A Dhillonf,
  8. A Mooratg,
  9. J Barberg,
  10. D F Grayg,
  11. International Lamivudine Study Group
  1. aDepartment of Hepatology and Gastroenterology, Erasmus University Hospital Rotterdam, Rotterdam, Netherlands, bDivision of Gastroenterology, Toronto Hospital, Toronto, Canada, cDepartment of Hepatology and Infectious Diseases, Medical Academy of Warsaw, Warsaw, Poland, dStorr Liver Unit, University of Sydney at Westmead Hospital, Sydney, Australia, eDepartment of Gastroenterology and Hepatology, University Hospital Montréal, Campus St Luc, Montréal, Québec, Canada, fDepartment of Histopathology, Royal Free Hospital, London, UK, gGlaxo Wellcome Research and Development, Greenford, UK
  1. Professor S W Schalm, Department of Hepatology and Gastroenterology, Room Ca 326, University Hospital Rotterdam, PO Box 2040, 3000 CA Rotterdam, Netherlands

Abstract

BACKGROUND, AIM, AND METHODS Alpha interferon is the generally approved therapy for HBe antigen positive patients with chronic hepatitis B, but its efficacy is limited. Lamivudine is a new oral nucleoside analogue which potently inhibits hepatitis B virus (HBV) DNA replication. To investigate the possibility of an additive effect of interferon-lamivudine combination therapy compared with interferon or lamivudine monotherapy, we conducted a randomised controlled trial in 230 predominantly Caucasian patients with hepatitis B e antigen (HBeAg) and HBV DNA positive chronic hepatitis B. Previously untreated patients were randomised to receive: combination therapy of lamivudine 100 mg daily with alpha interferon 10 million units three times weekly for 16 weeks after pretreatment with lamivudine for eight weeks (n=75); alpha interferon 10 million units three times weekly for 16 weeks (n=69); or lamivudine 100 mg daily for 52 weeks (n=82). The primary efficacy end point was the HBeAg seroconversion rate at week 52 (loss of HBeAg, development of antibodies to HBeAg and undetectable HBV DNA).

RESULTS The HBeAg seroconversion rate at week 52 was 29% for the combination therapy, 19% for interferon monotherapy, and 18% for lamivudine monotherapy (p=0.12 and p=0.10, respectively, for comparison of the combination therapy with interferon or lamivudine monotherapy). The HBeAg seroconversion rates at week 52 for the combination therapy and lamivudine monotherapy were significantly different in the per protocol analysis (36% (20/56) v 19% (13/70), respectively; p=0.02). The effect of combining lamivudine and interferon appeared to be most useful in patients with moderately elevated alanine aminotransferase levels at baseline. Adverse events with the combination therapy were similar to interferon monotherapy; patients receiving lamivudine monotherapy had significantly fewer adverse events.

CONCLUSIONS HBeAg seroconversion rates at one year were similar for lamivudine monotherapy (52 weeks) and standard alpha interferon therapy (16 weeks). The combination of lamivudine and interferon appeared to increase the HBeAg seroconversion rate, particularly in patients with moderately elevated baseline aminotransferase levels. The potential benefit of combining lamivudine and interferon should be investigated further in studies with different regimens of combination therapy.

  • chronic hepatitis B
  • hepatitis B virus
  • nucleoside analogue
  • lamivudine
  • alpha interferon
  • combination therapy
  • HBeAg seroconversion

https://doi.org/10.1136/gut.46.4.562

Statistics from Altmetric.com

    Request Permissions

    If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.

    View Full Text

    Footnotes

    • ↵† An initial eight week pretreatment period with lamivudine was included in the combination arm design to reduce HBV DNA load before the combination treatment as low HBV DNA levels have been significantly associated with improved response to interferon.3 6

    • ↵‡ The original study design had a lamivudine monotherapy arm with a six month treatment duration for comparison with the combination and interferon treatment arms. However, emerging results from phase II studies11 indicated lamivudine therapy of longer than six months duration was required for significant HBeAg seroconversion. The protocol was consequently amended to extend the duration of the lamivudine monotherapy arm to 12 months.

    • Abbreviations used in this paper:
      HBV
      hepatitis B virus
      HBsAg
      hepatitis B surface antigen
      HBeAg
      hepatitis B e antigen
      ALT
      alanine aminotransferase
      ULN
      upper limit of normal

    Linked Articles