There had been remarkable development in nucleos(t)ide analogues (NAs) and evolution in treatment strategies in last 15 years. Currently, there are five NAs available for chronic hepatitis B treatment, namely lamivudine, telbivudine and entecavir (nucleoside analogues), adefovir dipivoxil and tenofovir disoproxil fumarate (nucleotide analogues). The advantages of relatively infrequent side effects and easy administration per oral make NAs popular treatment options. The major drawback of earlier generation NAs is the risk of emergence of drug resistance. Current international guidelines recommend the use of more potent agents with high genetic barriers to resistance including entecavir and tenofovir as first line chronic hepatitis B treatment. However, there is no consensus regarding the subsequent treatment regimens in patients with suboptimal responses to NAs. De novo combination therapy of two NAs, response-guided therapy and roadmap concept in NAs with subsequent switch or add-on therapy can also potentially improve treatment efficacy and avoid resistance.
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