ObjectiveTo evaluate the efficacy and safety of the combined therapy with entecavir (ETV) and adefovir dipivoxil (ADV) in patients with lamivudine (LAM)-resistant chronic hepatitis B (CHB). MethodsA total of 45 patients who were diagnosed with LAM-resistant CHB and admitted to the Kunshan People's Hospital from May 2011 to May 2013 were recruited in this study and randomly divided to two groups. The treatment group included 23 CHB patients who received the combined therapy with ETV and ADV. The control group included 22 CHB patients who received the combined therapy with LAM and ADV. The changes in levels of HBV DNA, alanine aminotransferase (ALT), aspartate aminotransferase (AST), total bilirubin (TBil), albumin (Alb), and HBV serum markers before and after 4, 12, 24, and 48 weeks of treatment, as well as the rate of mutations other than that at rtM204I after 48 weeks of treatment, were measured in both groups. Comparison of continuous data between groups was made by t test, and comparison of categorical data by fourfold table chi-square test. ResultsThe levels of ALT and AST in the treatment group were significantly lower than those in the control group after 4 and 12 weeks of treatment (t=3.124, 5.271, 4.476, 5.125, all P<0.01), as well as 24 and 48 weeks of treatment (t=2.240, 2.307, 2.886, 2908, all P<0.05). The serum HBV DNA clearance rates in the treatment group after 4, 12, 24, and 48 weeks of treatment were 739%, 86.8%, 95.7%, and 100%, respectively, all of which were significantly higher than those in the control group (χ2=11.79, 575, 10.29, 5.89, respectively, all P<0.05). However, there was no significant difference in the HBeAg seroconversion rate among HBeAg-positive patients between the two groups. No mutations other than that at rtM204I were found in the treatment group, while four new mutations were detected in the control group (χ2=4.59, P<0.05). ConclusionThe combined therapy with ETV and ADV has good therapeutic effect in treating LAM-resistant CHB patients, and the clinical application is highly recommended.