AIM: To evaluate the long-term efficacy adefovir(ADV)-based combination therapies in entecavir(ETV)-resistant chronic hepatitis B(CHB) patients. METHODS: F i fty CHB pat ient s wi t h genotypic resistance to ETV at 13 medical centers in South Korea were included for the analysis. All the patients received rescue therapy with the combination of ADV plus ETV(ADV/ETV,n = 23) or ADV plus lamivudine(LMV)(ADV/LMV,n = 27) for more than 12 mo. Patients were monitored at least every 3-4 mo during ADV-based combination therapy by clinical examination as well as biochemical and virological assessments. Hepatitis B virus(HBV) DNA levels were measured by realtime PCR and logarithmically transformed for analysis. Cumulative rates of virologic response(VR; HBV DNA < 20 IU/m L) were calculated using the Kaplan-Meier method,and the difference was determined by a logrank test. Multivariate logistic regression and Cox proportional hazards models were used to identify independent risk factors significantly associated with short-term and long-term VR,respectively.RESULTS: Baseline median HBV DNA levels were 5.53(2.81-7.63) log10 IU/m L. The most commonly observed ETV genotypic mutation sites were rt184 and rt202. Patients were treated for a median of 27(12-45) mo. Overall,cumulative VR rates at 6,12,24,and 36 mo were 26%,36%,45%,and 68%,respectively. Patients treated with the ADV/ETV combination showed higher cumulative VR rates(35%,43%,65%,and 76%,respectively) than those with the ADV/LAM combination(18%,30%,30%,and 62%,respectively; P = 0.048). In the multivariate analysis,low baseline HBV DNA levels(< 5.2 log10 IU/m L) and initial virologic response at 3 mo(IVR-3; HBV DNA < 3.3 log10 IU/m L after 3 mo) were independent predictive factors for VR. Patients with favorable predictors achieved cumulative VR rates up to 90% at 36 mo. During the same period,the cumulative incidence of virologic breakthrough was as low as 6% in patients with the both favorable predictors.CONCLUSION: If tenofovir is not available,ADV/ETV combination could be considered in ETV-resistant patients with low HBV DNA titers,and may becontinued if IVR-3 is achieved. AIM: To evaluate the long-term efficacy adefovir (ADV) -based combination therapies in entecavir (ETV) -resistant chronic hepatitis B (CHB) patients. METHODS: F i fty CHB patient s wi th genotypic resistance to ETV at 13 medical All of the patients received rescue therapy with the combination of ADV plus ETV (ADV / ETV, n = 23) or ADV plus lamivudine (LMV) (ADV / LMV, n = 27) than 12 months. Patients were monitored at least every 3-4 months during ADV-based combination therapy by clinical examination as well as biochemical and virological assessments. Hepatitis B virus (HBV) DNA levels were measured by realtime PCR and logarithmically transformed for analysis. Cumulative rates of virologic response (VR; HBV DNA <20 IU / m L) were calculated using the Kaplan-Meier method, and the difference was determined by a logrank test. Multivariate logistic regression and Cox proportional hazards models were used to identify independent risk factors significantl y associated with short-term and long-term VR, respectively. RESULTS: Baseline median HBV DNA levels were 5.53 (2.81-7.63) log10 IU / m L. The most commonly observed ETV genotypic mutation sites were rt184 and rt202. Overall, the cumulative VR rates at 6, 12, 24, and 36 mo were 26%, 36%, 45%, and 68%, respectively. Patients treated with the ADV / ETV Combination showed higher cumulative VR rates (35%, 43%, 65%, and 76% respectively) than those with the ADV / LAM combination (18%, 30%, 30%, and 62%, respectively; . In the multivariate analysis, low baseline HBV DNA levels (<5.2 log10 IU / m L) and initial virologic response at 3 mo (IVR-3; HBV DNA <3.3 log10 IU / m L after 3 months) were independently predictive factors for VR. Patients with favorable predictors of the cumulative VR rates up to 90% at 36 mo. During the same period, the cumulative incidence of virologic breakthrough was as low as 6% in patients with the both favorable predictors. CONCLUSION: If tenofovir is not available, ADV / ETV combination could be considered in ETV-resistant patients with low HBV DNA titers, and may becontinued if IVR-3 is achieved.