 Entecavir ETV is a cyclopentyl guanosine analogue, and a potent and selective inhibitor of HBV replication in vitro.4 In the phase III registration trials it resulted in superior virologic, biochemical and histological efficacy after one year of therapy compared to LAM in both HBeAg-positive and HBeAg-negative chronic HBV patients. 5, 6 Moreover, ETV proved to have a high genetic barrier to resistance with only 1.2 of NA-naïve HBV patients demonstrating genotypic resistance to ETV after five years of ETV monotherapy.7 In LAM-refractory chronic HBV patients ETV appeared to be less potent and the frequency of resistance was increased. 8, 9 After five years of treatment 51 of LAM-refractory patients showed genotypic ETV resistance, and in 43 a virologic breakthrough was observed as well. 7 Recently we presented the promising results of a large European cohort of patients treated with ETV for a median period of 12 months. We concluded that ETV should not be used in patients with a prior history of LAM-resistance. However, prior treatment with ADV did not influence the efficacy of ETV in these patients.10 