2% after five years among treatment-naïve subjects).47 The low resistance rate is related to both the profound viral suppression Roxadustat cell line as well as the requirement of at least three sites of genetic mutations in order to confer entecavir resistance. (Two of these three sites overlap with lamivudine resistance, both lamivudine and entecavir being nucleoside analogues.) This characteristic is referred to as “high genetic barrier”. Because of these merits, entecavir is now the first line agent for treatment-naïve CHB patients. However, it is not a drug of choice for patients with lamivudine-resistant

disease because of the common sharing of two out of the three required mutations between entecavir and lamivudine resulting in a high rate of development of entecavir resistant mutations.48,49 The chance of emergence

of entecavir-resistant HBV is as high as 51% in patients with pre-existing lamivudine resistant mutations after five years of entecavir treatment.47 ABT-263 molecular weight Because of this limitation, patients with lamivudine resistant HBV should be preferably treated by tenofovir which will be mentioned below, or adefovir if tenofovir is not widely available. HBsAg seroconversion occurs in 5.1% of patients after 96 weeks of entecavir.50 In patients who continue to receive entecavir, a further 1.4% have HBsAg seroconversion by year 5.45 While better treatment for lamivudine-resistant disease was still under investigation, telbivudine, another NA belonging to the L-nucleoside subgroup was approved for treatment for CHB in 2006. Telbivudine is more potent than lamivudine in reducing the HBV DNA levels by an addition of l log copies/mL after one year of therapy.51 The HBV DNA undetectable rates are 60% vs 40% for HBeAg-positive and 88% vs 71% for HBeAg-negative patients, respectively. Therefore the chance of drug resistance compared

to lamivudine-treated patients is lower in telbivudine-treated patients, although they share the same genetic mutation sites, and like lamivudine, a single mutation can cause resistance. However, the emergence of viral resistance to telbivudine (25% for HBeAg-positive patients and 11% for HBeAg-negative patients after two years)52 is still higher than adefovir and entecavir. The use of lamivudine and telbivudine has shown the OSBPL9 importance of selecting patients who achieve early potent HBV DNA suppression as a criterion for continuing therapy with these agents. Yuen et al. first demonstrate that HBV DNA levels after 24 weeks of lamivudine therapy is a reliable marker for predicting the chance of lamivudine resistance on continuous treatment.53 This concept of CHB treatment has also been proven in the GLOBE trial of telbivudine vs lamivudine.51,52 In addition to the measurement of HBV DNA treatment response at week 24, baseline HBV DNA levels and ALT levels are also important in selecting patients to be treated with these two agents. According to Zeuzem et al.