risk. During follow-up, increases in Ishak stage, hepatic collagen, and ELF were associated with progression to cirrhosis. Changes in NAS were not significant, but worsening lobular inflammation was associated with increased progression (HR 3.21; 95% CI 1.14, 9.04). After a median of 26.7 months (range, 0.1–42.3), 49 cirrhotic subjects (19.0%) experienced clinical events (ascites [n = 19], encephalopathy [n = 13], variceal hemorrhage [n = 6], newly-diagnosed varices [n = 4], ≥2-point increase in Child-Pugh score and/or MELD ≥ 15 [n = 6], death [n = 1]). Factors associated with disease progression included higher BL hepatic collagen and ELF, increases in these markers over time, and lack of improvement in Ishak stage (Table). Changes in NAS were not significant although the absence of improved lobular inflammation was associated with increased risk (HR 2.33; 95% CI 1.01–5.35). Table: Factors Associated with Disease Progression in Patients with Advanced Fibrosis Due to NASH Variable* Bridging Fibrosis (Progression to Cirrhosis) Cirrhosis (Adjudicated Clinical Events) HR (95% CI) P-Value HR (95% CI) P-Value Ishak stage Baseline 4 vs. 3 Baseline 6 vs. 5 2.76 (1.52, 5.00) N/A <0.001 N/A N/A 1.25 (0.68, 2.29) N/A 0.480 No change or worsening 1 vs. improvement Worsening vs. no change or improvement N/A 2 44.01 (17.01, 114.33) N/A <0.001 9.63 (1.33, 69.81) N/A 0.025 N/A Hepatic collagen,% Baseline Change from baseline 1.27 (1.18, 1.36) 1.24 (1.19, 1.30) <0.001 <0.001 1.07 (1.03, 1.11) 1.04 (1.01, 1.07) <0.001 0.017 ELF Baseline Change from baseline 3.13 (2.31, 4.22) 1.59 (1.18, 2.13) <0.001 0.002 2.37 (1.69, 3.31) 1.54 (1.10, 2.15) <0.001 0.012 NAS Baseline ≤ 2 vs. 3–4 Baseline ≥ 5 vs. 3–4 N/A 3 1.64 (0.83, 3.27) N/A 0.16 0.99 (0.47, 2.10) 0.78 (0.40, 1.54) 0.99 0.48 No change vs. improvement Worsening vs. improvement 1.43 (0.71, 2.86) 1.20 (0.58, 2.51) 0.31 0.62 1.69 (0.84, 3.37) 0.87 (0.38, 1.98) 0.14 0.74 N/A, not applicable. *Changes from baseline adjusted for baseline value. 1 Combined no change or worsening as reference group for subjects with cirrhosis (Ishak stage 5 or 6) at baseline because cirrhotic subjects with Ishak stage 6 fibrosis cannot have an increase in fibrosis stage. 2 No subjects with bridging fibrosis at baseline who had Ishak improvement had a clinical event. 3 No subjects with bridging fibrosis and a NAS ≤ 2 at baseline had a clinical event. Conclusions: In patients with advanced fibrosis due to NASH, the primary determinant of disease progression is fibrosis and its change over time. GS-005 Replacement of the murine common bile duct with a bioengineered conduit incorporating primary human cholangiocyte organoids F. Sampaziotis 1,2 , A.W. Justin 1 , O.C. Tysoe 1 , S. Sawiak 1 , R.L. Gieseck 3 , M.C. de Brito 1 , N.L. Berntsen 4 , M.J. Gomez-Vazquez 1 , D. Ortmann 1 , L. Yiangou 1 , J. Bargehr 1 , A. Bertero 1 , M.C. Zonneveld 1 , M.T. Pedersen 5 , M. Pawlowski 1 , N. Georgakopoulos 1 , N. Pirmadjid 1 , G.M. Skeldon 6 , E.M. Godfrey 2 , W. Shu 6 , P.M. Materek 1 , K.E. Snijders 1 , S.E. Brown 1 , C.A. Rimland 1 , I. Simonic 2 , S. Davies 2 , K. Jensen 5 , W.T. Gelson 2 , G. Alexander 1 , S. Sinha 1 , N.R. Hannan 7 , T. Wynn 3 , T.H. Karlsen 4 , E. Melum 4 , A.E. Markaki 1 , K. Saeb-Parsy 1 , L. Vallier 1 . 1 University of Cambridge; 2 Cambrige University Hospitals NHS Foundation Trust, Cambridge, United Kingdom; 3 National Institutes of Health, Bethesda, United States; 4 Norwegian PSC Research Center, OUS Rikshospitalet, Oslo, Norway; 5 University of Copenhagen, Copenhagen, Denmark; 6 Heriot-Watt University, Edinburgh; 7 University of Nottingham, Nottingham, United Kingdom E-mail: fotiss@yahoo.com Background and Aims: Treatment of common bile duct disorders such as biliary atresia is limited to liver transplantation or hepatojejunostomy due to the lack of suitable tissue for surgical reconstruction. Here we explore the potential of bioengineered biliary tissue consisting of human extrahepatic cholangiocyte organoids (ECOs) and biodegradable scaffolds for biliary reconstruc- tion in vivo. Methods: Primary human cholangiocytes were isolated by mechan- ical dissociation from deceased organ donors with ethical approval and informed consent (n = 8). Propagation of ECOs was achieved using our established protocol. Transcriptomic characterization was performed using the Illumina HumanHT-12v4 array. ECOs were seeded on Polyglycolic Acid (PGA) or densified collagen scaffolds. Biliary reconstruction was achieved by partially replacing the gallbladder wall with an ECO populated PGA-scaffold patch (ECO- patch; n = 8), or replacing a length of the native common bile duct with ECO populated collagen tubes (ECO-tubes) through end-to-end anastomosis (n = 4). All experiments were performed in immune compromised mice. Fibroblast-populated (n = 5, PGA; n = 4, collagen) or acellular scaffolds (n = 2, PGA) were used as negative controls. Biliary tree patency was confirmed using magnetic resonance cholangiopancreatography (MRCP) or cholangiogram. Results: ECOs closely correlate with primary cholangiocytes in terms of transcriptomic profile (r:0.92), and functional properties (ALP, GGT, bile acid transfer). ECO-populated scaffolds form biliary tissue- resembling structures, maintain their functional properties (ALP, GGT) and marker expression (CK7, CK19, HNF1B). All ECO-trans- planted animals exhibited prolonged survival (ECO-patch vs. acellu- lar controls, P = 0.0027; ECO-tubes vs. fibroblasts, P = 0.0082; log-rank test). The transplanted cells integrated in the biliary epithelium, continued expressing biliary markers (CK7, CK19, HNF1B), exhibited ALP activity and a patent lumen. All reconstructions with fibroblasts failed, the biliary epithelium was replaced by fibrotic tissue and the lumen of the gallbladder or neo-bile duct was occluded. Conclusions: We demonstrate that ECO-populated biodegradable scaffolds maintain key biliary characteristics and can reconstruct/ replace parts of the biliary tree following transplantation. To our knowledge, this is the first demonstration for the application of regenerative medicine in the management of cholangiopathies and first report of an organ reconstruction using human primary cells expanded in vitro. GS-006 EXPEDITION-I: efficacy and safety of glecaprevir/pibrentasvir in adults with chronic hepatitis C virus genotype 1, 2, 4, 5 or 6 infection and compensated cirrhosis X. Forns 1 , S. Lee 2 , J. Valdes 3 , S. Lens 1 , R. Ghalib 4 , H. Aguilar 5 , F. Felizarta 6 , T. Hassanein 7 , H. Hinrichsen 8 , D. Rincon 9 , R. Morillas 10 , S. Zeuzem 11 , Y. Horsmans 12 , D. Nelson 13 , Y. Yu 3 , T. Pilot-Matias 3 , C.-W. Lin 3 , F. Mensa 3 . 1 Liver Unit, Hospital Clinic, CIBEREHD, IDIBAPS, Barcelona, Spain; 2 University of Calgary, Calgary, Canada; 3 ABBVIE, North Chicago; 4 Texas Digestive Disease Consultants, Arllington; 5 Louisiana Research Center, LLC, Shreveport; 6 Private Practice, Bakersfield; 7 Southern California Liver Centers and Southern California Research Center, Coronado, United States; 8 Gastroenterology- Hepatology Center Kiel, Kiel, Germany; 9 Liver Unit, Hospital General Universitario Gregorio Marañón, Madrid; 10 Liver Section and CIBERehd, Departmentof Gastroenterology, Hospital Universitari Germans Trias i Pujol, Badalona, Spain; 11 J.W. Goethe University, Frankfurt, Germany; ORAL PRESENTATIONS S3 Journal of Hepatology 2017 vol. 66 | S1–S32