After infection,

the mice were treated with 90mg/kg/day of TDF for 2 weeks. Results: Core-associated HBV replication intermediates of wild type Dabrafenib order clones, lamivudine-resistant clones (rtL180M/M204V) and lamivudine plus entecavir-resistant clones (rtL180M/S202G/M204V) in transiently HBV transfected HepG2 cells were suppressed by TDF in a dose-dependent manner. Clones with lamivudine plus adefovir-resistant mutations (rtA181T/N236T) showed resistance against TDF. Comparing the changes of serum HBV DNA levels in the mice by TDF treatment, the reduction of HBV DNA with rtA181T/N236T clone was less than with wild type (-2.0Log, -2.8Log, respectively). In the in vitro and in vivo analyses using a lamivudine-resistant clone (rtL180M/M204V) and EGFR inhibitor a lamivudine plus adefovir-resistant clone (rtL180M/M204V/N236T), the latter developed a strong resistance to TDF. Therefore, rtN236T substitution could be a key mutation for TDF susceptibility. IC50 (inhibitory concentration 50) of genotype A clones was approximately 20% higher than that of genotype C clones in vitro. The reduction of serum HBV DNA in the mouse with wild type genotype A was also less than with wild type genotype

C (-1.8Log, -2.8Log, respectively). These genotypic differences were determined by amino acid sequences at amino acids 223 and 224 in HBV RT region. Conclusions: The present study indicates that TDF susceptibilities vary among HBV genotypes and drug-resistant HBV clones.

Examination of amino acid sequences in the HBV RT region will give us useful information to select nucleot(s)ide analogues to treat patients with chronic hepatitis B virus infection. Disclosures: Kazuaki Chayama – Consulting: Abbvie; Grant/Research Support: Dainippon Sumitomo, Chugai, Mitsubishi Tanabe, DAIICHI SANKYO, Toray, BMS, MSD; Speaking and Teaching: Chugai, Mitsubishi Tanabe, DAIICHI SANKYO, KYORIN, Nihon Medi-Physics, BMS, Dainippon Sumitomo, MSD, ASKA, MCE公司 Astellas, AstraZeneca, Eisai, Olympus, GlaxoSmithKline, ZERIA, Bayer, Minophagen, JANSSEN, JIMRO, TSUMURA, Otsuka, Taiho, Nippon Kayaku, Nippon Shinyaku, Takeda, AJINOMOTO, Meiji Seika, Toray The following people have nothing to disclose: Eisuke Murakami, Masataka Tsuge, Nobuhiko Hiraga, Tomokazu Kawaoka, Atsushi Ono, Daiki Miki, Hiromi Abe, Michio Imamura, Hiroshi Aikata, Hidenori Ochi, C. Nelson Hayes Aim: It is controversial to monitor disease activity using ALT level in HBeAg (-) chronic hepatitis B (CHB) infection. Current guidelines favor liver biopsy in HBeAg (-) CHB with persistently normal ALT (PNALT) and high serum HBVDNA levels. In this study, we aimed to determine fibrosis stage and histological activity index (HAI) in HBeAg (-) CHB patients with PNALT and high HBVDNA. We evaluated the possible risk factors associated with significant histological abnormalities.