Lamivudine/interferon combination therapy in anti-HBe positive chronic hepatitis B patients: a controlled pilot study.
OBJECTIVE
In this study, lamivudine-interferon (LAM/IFN) combination therapy was compared to LAM monotherapy to verify if the combination treatment might improve efficacy and reduce the emergence of LAM-resistant mutants.


METHODS
Fifty patients with anti-HBe-positive chronic hepatitis B were treated for 12 months with LAM at 100mg/day (26 pts) or with IFN at 5MU t.i.w.+LAM 100mg/day (24 pts). Serum ALT, HBV DNA and IgM anti-HBc were monitored during treatment and a 6-month follow-up. The polymerase gene was amplified by PCR and the region coding for YMDD motif was directly sequenced.


RESULTS
All patients normalized ALT and cleared HBV DNA during treatment. The response was maintained until the end of therapy in the LAM/IFN group, while in 5/26 initial responders treated with LAM alone, a virological and biochemical breakthrough was observed after 6-10 months, and selection for YMDD variants resulted. After therapy discontinuation, most patients relapsed; the response rate after 6 months was 17% in the LAM/IFN group and 19% in the LAM group.


CONCLUSIONS
In anti-HBe-positive chronic hepatitis B, a 12-month course of LAM/IFN combination therapy is as beneficial as LAM monotherapy, however, the combination regimen appeared to prevent or delay the emergence of YMDD variants.
Santantonio
Teresa
T
Department of Internal Medicine, Immunology and Infectious Diseases, University of Bari, Bari, Italy. t.santantonio@clininf.uniba.it
Niro
Grazia Anna
GA
Sinisi
Emanuele
E
Leandro
Gioacchino
G
Insalata
Maria
M
Guastadisegni
Angela
A
Facciorusso
Domenico
D
Gravinese
Eleonora
E
Andriulli
Angelo
A
Pastore
Giuseppe
G
D000328:Adult; D000998:Antiviral Agents / Q000008:administration & dosage*; D024882:Drug Resistance, Viral; D004359:Drug Therapy, Combination; D005260:Female; D006511:Hepatitis B Antigens / Q000032:analysis; D019694:Hepatitis B, Chronic / Q000188:drug therapy*; D006801:Humans; D007372:Interferons / Q000008:administration & dosage*; D019259:Lamivudine / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage*; D016896:Treatment Outcome
D000998:Antiviral Agents; D006511:Hepatitis B Antigens; D018894:Reverse Transcriptase Inhibitors; D019259:Lamivudine; D007372:Interferons