Combination therapy with lamivudine and famciclovir for chronic hepatitis B infection.

Background & Aims: Lamivudine suppresses hepatitis B replication, but drug-resistant mutants emerge with long-term therapy. In vitro data suggest that lamivudine and famciclovir might synergistically inhibit hepadnaviral replication. We reviewed our experience with lamivudine and famciclovir in 24 patients with chronic hepatitis B infection.

Methods: Patients with chronic hepatitis B infection and detectable HBV DNA received lamivudine and famciclovir combination therapy. The primary end point was HBV DNA suppression at week 48. Follow-up was reviewed for those who remained on combination therapy beyond the first 48 weeks.

Results: Thirteen treatment-naïve HBeAg-positive subjects received 48 weeks of therapy; all had undetectable HBV DNA levels (less than 2.5 pg/mL) at week 48. Three patients underwent HBeAg seroconversion at week 48 and discontinued therapy. Ten patients remained on combination therapy; 3 developed YMDD (tyrosine-methionine-aspartate-aspartate) mutations at year 2, although HBV DNA levels remained below 2.5 pg/mL at a mean of 39 months. A second heterogeneous group of 5 subjects including interferon therapy failures and those with HBeAg-negative infection also received 48 weeks of combination therapy, with 1 subject developing redetection of HBV DNA by week 48. YMDD mutations were noted in the other 4 subjects at year 2, although just 1 subject had HBV DNA greater than 2.5 pg/mL at 39 months of therapy.

Conclusions: In this small pilot study, 48 weeks of therapy with lamivudine and famciclovir was effective in suppressing HBV replication. A randomized controlled trial is required to define the role of combination therapy with lamivudine and famciclovir in delaying the clinical emergence of resistant strains.