• combination therapy;
  • famciclovir;
  • interferon alpha;
  • lamivudine;
  • nucleoside analogue;
  • precore mutant chronic hepatitis B

Background/Aims: Hepatitis B e antigen-negative/hepatitis B virus (HBV) DNA-positive chronic hepatitis B (CHBe−) exhibits a high relapse rate on monotherapy with lamivudine or interferon-alpha (IFN-α). We investigated, whether sequential therapy with famciclovir or lamivudine followed by combination with IFN-α-2a improves durable virologic response in CHBe− characterized by mutation analysis of the HBV precore genome region.

Methods: Fourteen patients were treated with famciclovir (n=3) or lamivudine for 4 weeks to reduce the viral load, and subsequently with the combination of the nucleoside analogue and IFN-α-2a until 16 weeks beyond the loss of serum HBV-DNA.

Results: Median duration of therapy was 29.0 weeks (range 20.6–48.3 weeks). Serum HBV-DNA was undetectable and alanine aminotransferase had normalized in all patients at the end of treatment. Seven (50%) patients maintained a sustained response 12 months after end of treatment. Only two of them had been infected by HBV with the G1896A mutation. Most patients (5/7) with the G1896A mutation relapsed within 4 months after therapy.

Conclusion: Sequential combination therapy can induce sustained virologic response in a subgroup of CHBe−, but most with the G1896A precore mutant HBV relapse. Trials of CHBe− should be based on characterization of HBV mutants.