Both groups had similar rates of histologic regression between baseline and Week 240. Patients with HVL generally took high throughput screening compounds longer to achieve HBV DNA <400 copies/mL but had caught up with the non-HVL patients by Week 96. The authors stated that no patient with baseline HVL had persistent viremia at Week 240 or amino acid substitutions associated with TDF resistance. These results are remarkable and suggest that monotherapy with a potent NUC that has a high barrier to resistance such as TDF

is sufficient in maintaining viral suppression during long-term treatment even in patients with HVL. However, the results should be interpreted with caution. Persistent viremia in this study was defined as never having HBV DNA <400 copies/mL and this endpoint was only reported on patients who remained on treatment at Week 240. Thus, patients with HBV DNA <400 copies/mL at a single timepoint and higher levels of HBV DNA subsequently would not be considered to have persistent viremia and those who were no longer on treatment at Week 240 were not counted. Of the 129 patients with baseline HVL, 46 discontinued the

study before Week 240 of whom 28 had HBV DNA <400 copies/mL at the last visit. In the remaining 83 patients, 73 had HBV DNA <400 copies/mL, three had HBV DNA ≥400 copies/mL, and HBV DNA of the other seven were unknown at Week 240. Thus, based on intention to treat analysis, only 56.6% (73/129) patients Selleck SB431542 had HBV DNA <400 copies/mL at Week 240. If the last result was carried forward, 78.3% (101/129) patients had HBV DNA <400 copies/mL. By contrast, HBV DNA <400 copies/mL at Week 240 was achieved in 76.0% (389/512) non-HVL patients by intention to treat analysis and in 91.0% (466/512) if the last result was carried forward. Furthermore, 35 HVL patients were eligible to add FTC between Week 72 Casein kinase 1 and 240 and 28 eligible plus one noneligible patient had FTC added. Adding FTC did not appear to affect HBV DNA outcomes, with 66% (19/29) on FTC/TDF and 86% (6/7) on TDF having HBV DNA <400 copies/mL at Week 240 or last visit. The difference was not statistically significant

but this may be related to the small number of patients. HBV DNA levels of the 11 patients with HBV DNA ≥400 copies/mL were not provided. That patients with HVL take longer to achieve virologic response had also been observed by other investigators. Yuen et al.[6] studied 222 NUC-naïve patients and found that 100% and 76.5% of patients with baseline HBV DNA < and ≥8 log10 copies/mL, respectively, had undetectable HBV DNA at Year 3 of ETV therapy. The only patient in whom ETV resistance was detected had baseline HBV DNA 8.1 log10 copies/mL. In a randomized trial comparing ETV monotherapy versus combination of ETV plus TDF in NUC naïve patients, Lok et al.[14] showed that 76.4% and 83.2% patients, respectively, achieved the primary endpoint of HBV DNA <50 IU/mL (∼300 copies/mL) at Week 96 (P = 0.088).