20). Selleckchem Cobimetinib Furthermore, the AUROCs
for ALT ≤1.5 ULN vs. >1.5 ULN and ALT ≤2 ULN vs. ALT >2 ULN demonstrated similar diagnostic performances (all p>0.09). The NRIs for ALT-strati-fied cut-offs were -0.03, -0.06, and -0.1 8 for ≥F2, ≥F3, and F4, respectively, suggesting no improvement in fibrosis stage reclas-sification with ALT stratification. Subsequently, all NRIs were negative (≤-0.03) for ALT ≤1.5 ULN vs. >1.5 ULN and ALT ≤2 ULN vs. ALT >2 ULN. Conclusions: In this study we propose new cut-offs to grade fibrosis in CHB patients. ALT-stratified cut-offs did not improve the diagnostic performance of TE in CHB. Disclosures: Jordan J. Feld – Advisory Committees or Review Panels: Roche, Merck, Vertex, Gilead, Abbott, Tibotec, Theravance, Achillion; Speaking and Teaching: Merck, Roche, Abbott David K. Wong
– Grant/Research Support: Gilead, BMS, Vertex, BI Robert J. de Knegt – Advisory Committees or Review Panels: MSD, Roche, Norgine, Janssen Cilag; Grant/Research Support: Gilead, MSD, Roche, Janssen Cilag, BMS; Speaking and Teaching: Gilead, MSD, Roche, Janssen Cilag Harry L. Janssen – Consulting: Abbott, Bristol Myers Squibb, Debio, Gilead Sciences, Merck, Medtronic, Novartis, Roche, Santaris; Grant/Research Support: Anadys, Bristol Myers Squibb, Gilead Sciences, Innogenetics, Kirin, Merck, Medtronic, Novartis, Roche, Santaris The following people have nothing to disclose: Heng Chi, Bettina E. Hansen, ABT 263 Erik H. Buster Chronic hepatitis B virus (HBV) infection is a major disease world-wide for which there remains an unmet medical need. Current therapies have little effect on the viral proteins that allow
Idelalisib purchase sustained infection and progression of disease, and prevent the patient from mounting an effective immune response. We are developing a small interfering RNA (siRNA)-based therapeutic named ARC-520 that is designed to decrease viral protein load by the mechanism of RNA interference (RNAi). We have shown that a single intravenous injection of ARC-520 results in multi-log repression of viral RNA, proteins and DNA with long duration of effect (more than one month) in transient and transgenic mouse models of chronic HBV infection, without toxicity. Here, we present studies that demonstrate dose dependent reduction of HBV DNA in serum and liver, HBV transcripts in liver, HBsAg, HBeAg and core antigen from single or multiple doses of ARC-520 in mice. Multiple doses of ARC-520 enabled an extended duration of effect. Recently we extended our investigations of ARC-520 to treatment of a chimpanzee chronically infected with HBV since 1 979. This animal was 36 years old, weighed 51 kg and had a very high viral titer of HBV genotype B (1E+10 GE/ml serum). A single intravenous injection of 2 mg/kg of ARC-520 was well-tolerated and resulted in decreases in serum levels of HBsAg, HBeAg and HBV DNA.