Genotypic and phenotypic analyses20, 21 were also performed on isolates from all patients experiencing virologic breakthrough (≥1 log10 increase from nadir) at the time breakthrough occurred. All data analyses are descriptive.

Tabulations by treatment group are presented for each of the efficacy and safety variables. Continuous variables are summarized using the mean, median, minimum, and maximum values. Binary variables are summarized by counts and percentages. Efficacy endpoints were assessed among patients with available samples. An additional sensitivity analysis using the last observation carried forward method (LOCF) was conducted for the endpoint of HBV DNA <300 copies/mL at Week 240 (Year 5). In this analysis, selleck products the last observed HBV DNA levels signaling pathway were carried forward for those patients without Year 5 measurements, i.e., patients who had either discontinued prior to Year 5 or who were still on study but had a missing HBV DNA measurement

at Year 5. Safety analyses for the cohort include all adverse events that occurred on-treatment in study ETV-901 and all deaths that occurred on-study (during treatment in ETV-901 or during off-treatment follow-up). Serum HBV DNA was quantified by a central laboratory using the Roche COBAS Amplicor PCR assay (v. 2.0; lower limit of quantification 300 copies/mL [57 IU/mL]; Pleasanton, CA). In study ETV-022, HBV serologies (HBsAg, anti-HBs, HBeAg, anti-HBe) were assessed

in a central laboratory using the Abbott AxSYM microparticle enzyme immunoassay (Abbott Laboratories, North Chicago, IL) and DiaSorin enzyme immunoassay. In study ETV-901, HBV serologies were assessed in local laboratories using available methodologies. ALT was assessed by local laboratories in studies ETV-022 and ETV-901. Genotyping of HBV DNA involved PCR amplification of the HBV reverse transcriptase domain, followed by nucleotide sequence analysis. MCE In phenotypic analyses, substitutions that emerged on-treatment were cloned into HBV expression vectors, which were transfected into HepG2 hepatoma cells in the presence of entecavir. The amounts of replicated, encapsulated HBV DNA was immunocaptured from the culture media and quantified to determine the susceptibility to entecavir.20–22 The study was designed by the sponsor in collaboration with expert hepatologists. The sponsor collected the data, carried out the statistical analyses, and coordinated the writing of the article with all authors. Of the 354 patients who were randomized to treatment with entecavir 0.