Entecavir plus adefovir combination therapy versus lamivudine add-on adefovir for lamivudine-resistant chronic hepatitis B: A meta-analysis

To determine whether adefovir (ADV) in combination with entecavir (ETV) is more effective than with lamivudine (LAM) in patients with lamivudine-resistant chronic HBV infection, electronic databases were searched through May 10th, 2013 to obtain relevant trials which met the inclusion criteria. Meta-analysis was performed on randomized controlled trials (RCTs) and non-randomized studies. Four trials containing a total of 323 patients were included. Serum HBV DNA reductions after 3 and 6 months of treatment in the ETV+ADV group were greater than that of LAM+ADV group (mean difference (MD)=0.90, 95% confidence interval (CI): 0.74-1.07, P<0.00001; MD=0.81, 95% CI: 0.57-1.06, P<0.00001). The rate of 6 months HBV DNA undetectability with ETV and ADV was higher than that of LAM and ADV (relative risk (RR)=1.63, 95% CI: 1.14-2.34, P<0.007). There were higher rates of serum ALT normalization than those in LAM+ADV group after 6 months of treatment (RR=1.40, 95% CI: 1.11-1.77, P<0.005). The ETV+ADV group had lower viral breakthrough and genotypic mutation rates than LAM+ADV group after 12 months of treatment (RR=0.24, 95% CI: 0.10-0.58, P=0.002). The combination of ETV plus ADV is a more effective rescue therapy than LAM add-on ADV in patients with LAM-resistant HBV.