Efficacy of entecavir and adefovir combination therapy for patients with lamivudine- and entecavir-resistant chronic hepatitis B

Background The optimal treatment of patients with chronic hepatitis B (CHB) who develop resistance to both lamivudine (LMV) and entecavir (ETV) after sequential monotherapy of LMV and ETV remains little known. Methods We evaluated the efficacy of entecavir (ETV) plus adefovir dipivoxil (ADV) combination therapy for patients with resistance to LMV and ETV. We reviewed the medical records of 12 patients, and treated all 12 patients with ETV plus ADV combination therapy for at least 18 months. Quantitative hepatitis B virus (HBV) DNA levels, serologic markers, and hepatic panel values were monitored at baseline and 3-month intervals thereafter for 18 months. Results The baseline mean serum HBV DNA level was 7.26 ± 1.11 log copies/ml. The mean reductions in serum HBV DNA levels from baseline to 3, 6, 9, 12, 15, and 18 months were -1.98 ± 1.03, -2.87 ± 1.02, -3.32 ± 1.10, -3.92 ± 1.30, -4.36 ± 1.22, and -4.57 ± 1.18 log copies/ml, respectively. Complete virological response (HBV DNA of <2 log copies/ml) at 6, 12, and 18 months was observed in 1 (8.3%), 4 (33.3%), and 6 (50.0%) patients, respectively. The 2 patients with baseline HBV DNA of <6 log copies/ml achieved complete virological response at 18 months, while 4 of 10 patients with baseline HBV DNA of ≥ 6 log copies/ml achieved complete virological response at 18 months. None of the 12 patients experienced virological breakthrough during follow-up. Conclusions ETV plus ADV combination therapy effectively reduced serum HBV DNA levels in patients with CHB who developed resistance to both LMV and ETV. Additional long-term studies are needed to assess the effect of long-term treatment with these drugs. © 2012 Springer Science+Business Media, LLC.