Efficacy and resistance in de novo combination lamivudine and adefovir dipivoxil therapy versus entecavir monotherapy for the treatment-naive patients with chronic hepatitis B: a meta-analysis

Background: Currently, there is no consensus on the efficacy and resistance of de novo combination therapy versus monotherapy for treatment naive patients of chronic hepatitis B (CHB). Objectives: The aim of this study was to evaluate the effectiveness and resistance of de novo combination of lamivudine (LAM) and adefovir dipivoxil (ADV) compared with entecavir (ETV) monotherapy for nucleos(t)ide-naive patients with CHB. Study design: Publications on the effectiveness and resistance of LAM plus ADV versus ETV monotherapy for nucleos(t) ide-naive patients with CHB were identified by a search of PubMed, Embase, the Cochrane Library, Web of science, OVID, and CBM (Chinese Biological Medical Literature) until May 1, 2013. Biochemical response, hepatitis B e antigen seroconversion, and viroligic response were extracted and combined to obtain an integrated result. Viral resistance and safety were reviewed. Results: Five eligible studies (328 patients in total) were included in the analysis. LAM plus ADV combination therapy produced more rapid HBV DNA reduction rate at 12 weeks than that of ETV monotherapy. At 48 weeks, the combination group had superior viroligic response rates compared with ETV group (90.0% vs. 78.9%, P=0.01). The difference in the ALT normalization and HBeAg seroconversion rates was not found. At week 96, LAM + ADV was more effective than ETV in ALT normalization [RR = 1. 11, 95% CI (1.02, 1.21), P = 0.01] and HBeAg seroconversion [RR = 2.00, 95% CI (1.26, 3.18, P=0.003)], and no significant difference was found in the virologic response (P = 0.23). No viral resistance occurred in combination therapy and six patients in ETV group were experienced with viral breakthrough. Both groups were well tolerated. Conclusion: The de novo LAM plus ADV combination therapy for treatment-naive patients with CHB was greater than ETV monotherapy in both biochemical response and HBeAg seroconversion rate up to 96 weeks. The rate of emergence of viral resistance in the combination group was less than that in the ETV monotherapy.