In vivo pharmacology evaluation in chronic DMN induced rat liver fibrosis models showed that 1x/week treatments for 5 weeks improved overall animal health condition as reflected by improved survival and body weight. Specific evaluation of liver fibrosis parameters including

hepatic hydroxyproline levels, image-quantified Sirius Red staining, semi-quantitative histopathology score of liver fibrosis following H&E staining and Trichrome staining all provided strong evidence of collagen deposition reduction and liver fibrosis resolution. GLP-toxicological studies in non-human primate showed a >20-fold safety margin with no significant adverse effect. Phase I clinical trial has been completed in 66 healthy individuals in U.S. for single-dose escalation study evaluating the safety, tolerability, and pharmacokinetics of ND-L02-s0201 injection. The escalation study successfully reached the highest planned dose at 0.8 mg/kg (concentration based on siRNA NDT-05-0038) with no steroid-based AZD1208 clinical trial premedication applied. All doses were well tolerated with no adverse effect noted during clinical observation. Disclosures: Wenbin Ying – Management find more Position: Nitto Denko Technical Corporation The following people have nothing to disclose: Jun Zhang, Yun Liu, Li Wang, Jihua Liu, Jian Liu, Jingyuan Yu, Jean-Pierre

Clamme, Jiping Yao, Lishuang Xu, Donald A. Kaiser, Yasunobu Tanaka, Miyono Miyazaki, Keiko Kajiwara, Kenjiro Minomi, Yoshiro Niitsu Background/Aims: Diagnosis of liver cirrhosis at pre-clinical stage is challenging due to lack of any finding. We evaluated outcomes of subclinical cirrhosis (SC) diagnosed by transient elastography (Fibroscan). Methods: Patients with chronic liver disease (CLD) and a valid Fibroscan were divided into: 1) SC (Fibroscan >13kPa and no thrombocytopenia, GNA12 nor signs of advanced liver disease

on ultrasound or endoscopy); 2) non-cirrhotic CLD (Fibroscan <13kPa). Patients with Fibroscan >13kPa and signs of advanced liver disease were excluded. We used multivariate logistic regression analysis for factors associated with baseline SC. Incidence of severe outcomes (HCC, variceal bleeding, ascites) and any outcome (severe outcomes, thrombocytopenia, ultrasonographic or endoscopic signs) was computed. Multivariate Cox proportional hazard models adjusted for age, sex, HIV coinfection, diabetes and SC were used. Results: 702 patients (median age 49 years, 60% male) were included in 2010-2013. 101 (14%) had SC, 601 (86%) had non-cirrhotic CLD. Histology was available for 25% of SC patients and 65% of them had advanced fibrosis or cirrhosis. Factors associated with SC at baseline were older age (OR=1.1; 95% CI 1.0-1.3), HIV co-infection (OR=3.5; 1.8-6.8) and higher APRI (OR=2.6; 1.9-3.7). Over 726 person-years (PY) of follow-up, incidence rate of any outcome was higher in those with SC (10.4/100 PY; 95% CI 4.3-16.6) compared to those with non-cirrhotic CLD (2.9/100 PY; 1.6-4.2). Incidence rate of severe outcomes was 3.5/100 PY (0.1-6.