ETV is the most potent antiviral agent. It can reduce serum HBV DNA by 6.9 log10 in HBeAg-positive patients and by 5 log10 in HBeAg-negative patients. Although more powerful in its antiviral potency, the 1-year HBeAg seroconversion rate is not superior than other NA (21% at 1 year and 31% after 2 years of ETV treatment).26 A phase III clinical trial involving 648 patients randomized to receive

either ETV 0.5 mg/day or LAM 100 mg/day for 48 weeks was conducted to compare the safety and efficacy of ETV versus LAM in patients with HBeAg-negative chronic hepatitis B.27 Patients treated with ETV showed a significantly higher rate of histological improvement, HBV DNA reduction and undetectable HBV DNA (< 60 IU/mL), compared with patients treated with LAM. Of note is the very low resistance rate (1.2%) observed in the nucleoside-naïve Ruxolitinib molecular weight HBeAg-negative patients treated with ETV for up to 5 years. In a randomized LAM-controlled ETV trial in HBeAg-positive patients, the

HBV DNA levels (< 80 vs > 80 IU/mL) at week 24 were also useful in predicting the HBeAg seroconversion rates (30% vs 17%) and undetectable HBV DNA (96% vs 50%) at week 52 of ETV therapy.28 A large-scale phase III trial involving 921 HBeAg-positive and 466 HBeAg-negative patients showed that virological response to Ldt was superior to that for LAM after 1 and 2 years of treatment.17,18 In HBeAg-negative patients, a RG7204 clinical trial higher proportion treated with Ldt than LAM achieved undetectable HBV DNA levels (88% vs 71% at 1 year and 82% vs 57% at 2 years) with the polymerase chain reaction method (COBAS Amplicor HBV Monitor, Roche Molecular Systems) with a detection limit of 60 IU/mL. Ldt was associated with a lower rate of resistance than LAM was. The resistance rates at 1 and 2 years for Ldt were 2.3% and 11%, respectively. Notably, the resistance rate was quite low at 1 year in HBeAg-negative patients who had undetectable HBV DNA levels at week 24, compared with patients whose HBV DNA levels were ≧ 2000 IU/mL (0% vs 30%) (Table 2).17 Further analysis using a multivariate logistic regression model to evaluate baseline and/or early on-treatment

variables showed that: (i) HBeAg-positive selleck patients with baseline HBV DNA < 9 log10 copies/mL, ALT ≧ 2xULN and non-detectable HBV DNA at week 24 achieved undetectable HBV DNA in 89%, HBeAg seroconversion in 52% and Ldt resistance in 1.8% at 2 years; and (ii) HBeAg-negative patients with baseline HBV DNA < 7 log10 copies/mL and undetectable serum HBV DNA at week 24 achieved undetectable HBV DNA in 91% and Ldt resistance in 2.3% at 2 years.29 More recently, a phase III study was reported that involved 266 HBeAg-positive and 375 HBeAg-negative patients who were randomized in a 2:1 ratio to receive TDF 300 mg (n = 176 in HBeAg-positive and 250 in HBeAg-negative) or ADV 10 mg (n = 90 in HBeAg-positive and 125 in HBeAg-negative) for 48 weeks.