0mg. As the rate of genotypic resistance to ETV (ETV-R) is reported high currently, HIF inhibitor changing ETV to the other agent may be needed even in patients whose resistance to ETV was not identified. However, appropriate indication and time point have not been proposed yet. This study was aimed to stratify ETV therapy in LAM-R patients. Methods: One hundred and nine CHB patients who developed LMV-R and then received ETV 1.0mg up to 5 years were evaluated prospectively. Virologic response (VR, HBV

DNA <20 IU/mL) and ETV-R during 5 years of treatment were evaluated as primary end points. We divided subjects into non-detection group (HBV DNA <20 IU/mL) and detection group (HBV DNA >20 IU/mL) at 6 months and 12 months of switching to ETV for prediction of long term response. Results: The mean age of the patients was 45±1 1 years,

the proportion of male and HBeAg-positive patient was Barasertib 72% (79/109) and 77% (84/109), respectively. VR rates were 0%, 20%, 24%, 32%, 37%, and 39% and the mean serum HBV DNA levels were 6.89±1.03, 3.26±1.81, 3.06±1.82, 2.49±1.53, 2.43±1.35 and 1.73±0.87 log 10 IU/ml at baseline, month 12, 24, 36, 48 and 60, respectively. Genotypic resistance to ETV occurred at 30±12 months (median 24 months, 12-66 months). Resistance rates were 4.6%, 19%, 32%, 36%, and 37% at baseline, month 12, 24, 36, 48 and 60, respectively. When we predicted long term responses according to delectability of HBV DNA at 6 months of treatment, VR (100% vs. 28%, p <0.001) was higher and ETV-R (0% vs. 45%, p = 0.001)

was lower in non-detection group than in detection group. Likewise, at 12 months of treatment, VR (96% vs. 21%, p <0.001) was higher and ETV-R (12% vs. 49%, p = 0.001) was lower in non-detection group than detection group. Multivariate analysis showed non-detection of HBV DNA at 6 months as well as 12 months were independent factors associated with VR. To evaluate predictive value for VR, area under the receiver operating characteristic Protein kinase N1 curve (AUROC) was used. AUROC (0.865; 95% confidence interval [CI], 0.789-0.940; P <0.001) of non-detection of HBV DNA at 12 months showed slightly better than that of 6 months (AUROC, 0.828; 95% confidence interval [CI], 0.742-0.914; P <0.001). Conclusion: Resistance rates were high in patients with detectable HBV DNA at 12 months of ETV therapy. Therefore, switching to or adding a potent nucleotide analogue (e.g. tenofovir) is warranted in LAM-R CHB patients whose HBV DNA is detected after 12 months of ETV therapy.