Combination alpha-interferon and lamivudine therapy for alpha-interferon-resistant chronic hepatitis B infection: results of a pilot study

J Hepatol. 1998 Jun;28(6):923-9. doi: 10.1016/s0168-8278(98)80338-3.


Background/aims: Alpha-interferon achieves seroconversion in about one third of naive patients. Attempts to achieve seroconversion in patients who have previously failed alpha-interferon have proved disappointing. Combination chemotherapy (alpha-interferon with a nucleoside analogue) might provide a treatment alternative for these patients. We have undertaken a phase 2 study in 20 patients who had previously failed at least one course of alpha-interferon. The study was designed to assess the safety, tolerability and efficacy of the combination.

Methods: All patients were treated for 16 weeks with alpha-interferon in combination with 12 or 16 weeks of Lamivudine (3'TC). Patients were followed for 16 weeks post-treatment. Pharmacokinetic studies were performed to identify/exclude significant pharmacokinetic drug interaction.

Results: The combination was well tolerated, and side-effects of the combination were indistinguishable from the recognised side-effects of alpha-interferon. Pharmacokinetic studies performed on days 1 and 29 did not show any significant interaction. All patients achieved HBV DNA clearance during treatment, but 19 relapsed at the end of treatment. HBeAg/anti-HBe seroconversion was observed for four patients, but was sustained for a single patient (who also had sustained DNA clearance).

Conclusions: Combination therapy with alpha-interferon and lamivudine given for 16 weeks appears safe and is well tolerated. However, for this group of patients who had previously failed interferon monotherapy, the efficacy of combination interferon/lamivudine therapy appears disappointing, and other treatment strategies should be investigated.

Publication types

  • Clinical Trial
  • Clinical Trial, Phase II
  • Controlled Clinical Trial
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aged
  • Alanine Transaminase / blood
  • Amylases / blood
  • Antiviral Agents / adverse effects
  • Antiviral Agents / pharmacokinetics
  • Antiviral Agents / therapeutic use*
  • DNA, Viral / blood
  • Double-Blind Method
  • Drug Therapy, Combination
  • Female
  • Hepatitis B e Antigens / blood
  • Hepatitis B virus / isolation & purification
  • Hepatitis B, Chronic / therapy*
  • Humans
  • Interferon alpha-2
  • Interferon-alpha / adverse effects
  • Interferon-alpha / pharmacokinetics
  • Interferon-alpha / therapeutic use*
  • Lamivudine / adverse effects
  • Lamivudine / pharmacokinetics
  • Lamivudine / therapeutic use*
  • Male
  • Metabolic Clearance Rate
  • Middle Aged
  • Pilot Projects
  • Recombinant Proteins
  • Time Factors


  • Antiviral Agents
  • DNA, Viral
  • Hepatitis B e Antigens
  • Interferon alpha-2
  • Interferon-alpha
  • Recombinant Proteins
  • Lamivudine
  • Alanine Transaminase
  • Amylases