Lamivudine compared with lamivudine and adefovir dipivoxil for the treatment of HBeAg-positive chronic hepatitis B☆

Background/Aims We aimed to evaluate nucleoside/nucleotide combination therapy in treatment-naive HBeAg-positive patients with chronic hepatitis B (CHB). Methods One hundred and fifteen HBeAg-positive patients received lamivudine 100mg daily plus placebo (monotherapy) or lamivudine 100mg plus adefovir dipoxil 10mg daily (combination therapy) for 104 weeks in a randomized double-blind study. Results Time-weighted average change in serum HBV DNA from baseline up to week 16 was −4.20 log 10 copies/mL for both groups ( p =0.936). At week 104, median serum HBV DNA change from baseline (log 10 copies/mL) for monotherapy and combination therapy was −3.41 versus −5.22, respectively. HBV DNA breakthrough was detected in 44% of monotherapy and 19% of combination therapy patients. The M204V/I mutation was detected in 43% (15/35) and 15% (6/41) of each group, respectively. ALT normalization at week 100 and 104 was 34% (19/56) in the monotherapy group and 45% (23/51) in the combination therapy group ( p =0.018). By week 104, HBeAg seroconversion occurred in 20% of monotherapy and 13% of combination therapy patients. Both regimens were well tolerated. Conclusions Lower rates of resistance to lamivudine, lower serum HBV DNA levels and higher rates of ALT normalization were seen in the combination therapy group after two years. However, serological outcomes were similar.