Lamivudine vs lamivudine and interferon combination treatment of HBeAg(-) chronic hepatitis B

J Viral Hepat. 2005 May;12(3):262-8. doi: 10.1111/j.1365-2893.2005.00566.x.


To determine whether combination treatment of HBeAg(-) chronic hepatitis B is beneficial we studied 78 patients with HBeAg(-), HBV DNA-positive chronic hepatitis B who were randomized to lamivudine, 100 mg, qd, for 12 months or lamivudine-interferon (9 MU, t.i.w.) in combination. In the combination arm, 2 months of lamivudine treatment preceded 10 months of combination treatment. Biochemical, virologic and histologic responses were assessed at the end of treatment, after six and a median 27 months of drug-free follow-up (short- and long-term follow-up, respectively). Virologic response was defined as undetectable HBV DNA with a hybridization assay and biochemical response as normal alanine aminotransferase (ALT). Change in HBV DNA was also assessed by real-time polymerase chain reaction (PCR). Presence of YMDD mutants at the end of treatment was investigated with a line probe assay. Both treatment regimes led to a median 2 log decline in HBV DNA levels. Virologic end of treatment responses were 90 and 92% with mono- and combination treatment, respectively. Corresponding virologic responses at short- and long-term follow-up were 59 and 54%, and 27 and 25%, respectively. Patients having a baseline HBV DNA value > or =200 pg/mL were more likely to relapse within 6 months off therapy than those patients with a baseline HBV DNA level <200 pg/mL (P = 0.041). YMDD mutants were observed in 53% of patients receiving lamivudine compared with 24% of patients receiving the combination regime (P = 0.017). In conclusion, efficacy of combination treatment is similar to lamivudine monotherapy. However, combination treatment decreases the development of YMDD mutant strains compared with lamivudine monotherapy.

Publication types

  • Clinical Trial
  • Comparative Study
  • Randomized Controlled Trial

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Dose-Response Relationship, Drug
  • Drug Administration Schedule
  • Drug Therapy, Combination
  • Female
  • Follow-Up Studies
  • Hepatitis B e Antigens / immunology*
  • Hepatitis B, Chronic / diagnosis
  • Hepatitis B, Chronic / drug therapy*
  • Hepatitis B, Chronic / immunology
  • Humans
  • Interferon alpha-2
  • Interferon-alpha / therapeutic use*
  • Lamivudine / administration & dosage*
  • Liver Function Tests
  • Male
  • Middle Aged
  • Probability
  • Recombinant Proteins
  • Risk Assessment
  • Severity of Illness Index
  • Statistics, Nonparametric
  • Treatment Outcome


  • Hepatitis B e Antigens
  • Interferon alpha-2
  • Interferon-alpha
  • Recombinant Proteins
  • Lamivudine