Sequential combination therapy of HBe antigen-negative/virus-DNA-positive chronic hepatitis B with famciclovir or lamivudine and interferon-alpha-2a.
OBJECTIVE
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-alpha). We investigated, whether sequential therapy with famciclovir or lamivudine followed by combination with IFN-alpha-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-alpha-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.


CONCLUSIONS
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.
Schiefke
Ingolf
I
Department of Medicine II, University of Leipzig, Leipzig, Austria.
Klecker
Chris
C
Maier
Melanie
M
Oesen
Ute
U
Etzrodt
Gunnar
G
Tannapfel
Andrea
A
Liebert
Uwe G
UG
Berr
Frieder
F
D015075:2-Aminopurine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use*; D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000368:Aged; D000410:Alanine Transaminase / Q000097:blood; D000998:Antiviral Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D004279:DNA, Viral / Q000097:blood; D004359:Drug Therapy, Combination; D000077595:Famciclovir; D005260:Female; D006513:Hepatitis B e Antigens / Q000097:blood / Q000235:genetics / Q000276:immunology; D006515:Hepatitis B virus / Q000235:genetics / Q000302:isolation & purification*; D019694:Hepatitis B, Chronic / Q000097:blood / Q000188:drug therapy* / Q000473:pathology; D006801:Humans; D007279:Injections, Subcutaneous; D000077190:Interferon alpha-2; D016898:Interferon-alpha / Q000008:administration & dosage / Q000627:therapeutic use*; D019259:Lamivudine / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D009154:Mutation; D011994:Recombinant Proteins; D016896:Treatment Outcome; D019562:Viral Load; D014766:Viremia / Q000188:drug therapy / Q000473:pathology
D000998:Antiviral Agents; D004279:DNA, Viral; D006513:Hepatitis B e Antigens; D000077190:Interferon alpha-2; D016898:Interferon-alpha; D011994:Recombinant Proteins; D019259:Lamivudine; D015075:2-Aminopurine; D000410:Alanine Transaminase; D000077595:Famciclovir