(Chang et al 2006a). At week 48, histologic improvement (necroinﬂammation score) occurred in signiﬁcantly higher proportion of patients treated with ETV compared to LAM (72% vs 62%, p = 0.009). Serum HBV DNA levels became undetectable by PCR methods in 67% and 36% (p 0.001) of the patients treated with ETV and LAM, respectively. Moreover, the mean reduction from baseline in the serum HBV DNA levels at week 48 was 6.9 log and 5.4 log in the ETV and LAM group respectively (p 0.001). Although ETV achieved a signiﬁcantly greater suppression of HBV DNA levels than LAM, the rate of HBeAg loss and HBeAg seroconversion did not differ signiﬁcantly between the two treatment groups being 22% and 21% in the ETV vs 20% and 18% in the LAM arm (Chang et al 2006a, Table 1). At week 48, 21% of the patient in the ETV group and 19% of those in the LAM group had achieved a complete response, 70% and 46% respectively had only virologic response and 5% and 26% respectively had no response. Among patients with response at week 48, 82% in the ETV and 73% in the LAM group sustained their response 24 weeks after discontinuation of treatment. There was no evidence of emergence of ETV resistant variants among 339 evaluated patients and although 6 (2%) of ETV treated individuals experienced a virologic rebound during the ﬁrst year of therapy, samples obtained from these patients retained full phenotypic susceptibility to ETV. The adverse events were similar in the two groups. In the ETV group 3% of patients experienced alanine amino- transferase ﬂares (ALT levels more than twice the baseline level and more than 10 times the ULN) during treatment while such ﬂares were observed in 6% of the patients in the LAM group. All ﬂares in the ETV group were associated with a decline of HBV DNA levels by 2 log10 and all but one were self-limited with continuation of treatment, without any evidence of hepatic decompensation. On the other hand half of Entrcavir in hepatitis B the ﬂares in the LAM group were associated with increasing HBV DNA levels and in one patient hepatic decompensation developed. Post-treatment ALT ﬂares were observed in 1% in the ETV group and in 7% of patients in the LAM group (Chang et al 2006a). The efﬁcacy of extension of ETV and LAM treatment to week 96 in those HBeAg-positive patients who had only a virological response at week 48 without HBeAg seroconver- sion, have also been evaluated (Gish et al 2005). During this period return of ALT to normal was achieved in 50% of the ETV and 42% of the LAM-treated patients. The cumulative virologic response rate at week 96 (Table 1), deﬁned by HBV DNA 300copies/mL, was 80% in the ETV and 39% in the LAM group (p 0.001). Despite the signiﬁcantly greater suppression of HBV DNA in the ETV group, the cumula- tive HBeAg seroconversion rate did not differ signiﬁcantly between the two treatment groups (Table 1) Furthermore, patients achieving only virologic response during the second year of therapy could receive double dose of ETV (1 mg) for at least one additional year. Thus 122 from 151 eligible HBeAg-positive patients were enrolled and evaluated at week 144. Serum HBV DNA 300copies/mL and ALT normaliza- tion were observed in 87% and 85% of patients respectively, while HBeAg loss and HBeAg seroconversion were achieved in 31% and 16% of them (Chang et al 2006b). Efﬁcacy in HBeAg-negative patients In a randomized double-blind trial, treatment with ETV 0.5 mg was compared to LAM 100 mg once daily for at least 52 weeks (Lai et al 2006b). According to the study protocol, similarly with the trial in HBeAg-positive patients, clinical- management decisions were made at week 52 on the basis of the results of HBV DNA levels (b-DNA) and ALT levels on serum samples obtained at week 48. Response was deﬁned as Table 1 Comparison of entecavir vs lamivudine in HBeAg positive and HBeAg-negative treatment-naïve patients with chronic hepatitis B (CHB) Undetectable HBV DNA ALT normal HBeAg loss HBeAg seroconversion Histologic improvement HBV resistance HBeAg (+) CHB LAM Year 1 Year 2 36% 39% 60% 20% 18% 62% 13% 77% 28% 25% ETV Year 1 67% 68% 22% 21% 72% 0% Year 2 80% 84% 32% 31% 0% HBeAg (−) CHB LAM Year 1 Year 2 72% 77% 71% 61% 6% 84% ETV Year 1 90% 78% 70% 0% Abbreviations: CHB, chronic hepatitis B; ETV, entecavir; LAM, lamivudine;ALT, alanine aminotransferase; HBV, hepatitis B virus; NA, non applicable; vs, versus. (Gish et al 2005; Chang et al 2006a; Lai et al 2006b; Shouval et al 2006). Therapeutics and Clinical Risk Management 2007:3(6) Year 2 94% 89% 0% 1081