Combined lamivudine and famciclovir therapy for patients with chronic hepatitis B

OBJECTIVE:  No single antiviral drug is able to eradicate hepatitis B virus (HBV) infection. It has been shown in vitro that lamivudine and panciclovir (the active metabolite of famciclovir) act synergistically to inhibit HBV replication. To study the therapeutic efficacy of combined lamivudine and famciclovir therapy in patients with chronic hepatitis B. METHODS:  Twenty-one patients with chronic hepatitis B, who had been given lamivudine monotherapy for more than 6 months without improve­ment, had increased serum alanine aminotransferase (ALT) and HBV-DNA levels, and were positive for hepatitis B surface antigen (HBsAg); 17 were positive for HBeAg. The diagnosis was verified by histology in 12 HBeAg-positive cases. All patients were given combined therapy with lami­vudine (100 mg q.d.) and famciclovir (500 mg t.i.d.) orally for 4 months, and then with lamivudine alone for 5−10 months. RESULTS:  Serum HBV-DNA levels were initially 1 × 108.19 ± 1.18 copies/mL, then decreased to 1 × 105.25 ± 1.18 copies/mL at the end of the combined treatment and 1 × 105.25 ± 1.82 copies/mL in the follow-up period (P < 0.01). Serum ALT decreased from 225 ± 110 U/L before the trial to 79 ± 50 U/L at the end of the combined treatment and 81 ± 48 U/L in the follow-up period (P < 0.01). In 17 HBeAg-positive patients, eight (47.1%) had HBeAg/anti-hepatitis B e antigen (HBeAg) seroconversion with a significant decrease of HBV-DNA (<1 × 104 copies/mL) and normal ALT (P < 0.01). Of four HBeAg-negative patients, three had decreased levels of HBV-DNA, to below 1 × 104 copies/mL, which was associated with a significant decrease in ALT. Two patients had recurrent flare-ups in the follow-up period, but both HBV-DNA and ALT were lower than the pretreatment levels. In 10 patients who underwent a second liver biopsy, improvements in inflammatory activity and fibrosis were seen in eight (80%) and four (40%) cases, respectively (P < 0.05). CONCLUSIONS:  The combination treatment of lamivudine and famciclovir has synergistic or additive anti-HBV effects, and may be an alternative therapy for patients with active chronic hepatitis B.