Department of Gastroenterology, Liver Center, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea.
One year trial with entecavir plus adefovir resulted in a higher rate of virological response (VR) compared with lamivudine plus adefovir in multiple drug-refractory chronic hepatitis B (CHB) patients. This extension study enrolled 89 of 90 patients who completed a 52-week randomized trial comparing treatment with entecavir plus adefovir (EA) to lamivudine plus adefovir (LA). At the baseline of the original study, all patients had lamivudine-resistant hepatitis B virus (HBV) and serum HBV DNA >2000 IU/mL despite prior lamivudine plus adefovir therapy. Forty-five patients initially randomized to entecavir plus adefovir (EA-EA) and the other 44 patients randomized to lamivudine plus adefovir (LA-EA) received entecavir plus adefovir for an additional 52 weeks. The proportion of patients with VR (serum HBV DNA <60 IU/mL) gradually increased in both groups, and was comparable at week 104 (42.2% in the EA-EA group and 34.1% in the LA-EA group, P=0.51). The mean reduction in serum HBV DNA from baseline was similar in the two groups (-2.8 log10 IU/mL and -2.8 log10 IU/mL, respectively, P=0.87). At week 104, the number of patients who retained the preexisting HBV mutants resistant to adefovir or entecavir has decreased from 8 to 2 in the EA-EA group and 15 to 6 in the LA-EA group (P=0.27). Both study groups had favorable safety profiles. In conclusion, up to 104 weeks of entecavir plus adefovir treatment was associated with a progressive VR, decrease of preexisting drug-resistant mutants, and no selection for additional resistance mutants of HBV in multiple drug-refractory CHB patients.